Conditions: Diffuse Large B-cell Lymphoma
Keywords: DLBCL Efficacy MOR00208 Tafasitamab lenalidomide
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 81
Healthy volunteers: no

Brief summary:
This is a Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Lenalidomide Combined with MOR00208 in Participants with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL).

Detailed description:
The aim of this single-arm, multicentre, open-label Phase II study is to evaluate the Lenalidomide (LEN) combined with Tafasitamab (MOR00208) in adult participants with DLBCL who had relapsed after or were refractory to at least one, but no more than three previous systemic regimens administered for the treatment of their DLBCL and who were not candidates for high-dose chemotherapy and subsequent Autologous stem cell transplants and were thus considered to have exhausted their therapeutic options. One prior therapy line had to include an anti-CD20 targeted therapy (e.g., rituximab \[RTX\]).

MOR00208 and LEN were administered for up to 12 cycles (28 days each), followed by MOR00208 monotherapy until progression, in participants with at least stable disease or a better response.

Arms:
arm 1: MOR00208:

MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle.

Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle.

LEN:

Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings.

On days when both study drugs were given together, LEN was administered prior to MOR00208.

Interventions: intervention 1: Tafasitamab intervention 2: Lenalidomide
Intervention descriptions: intervention 1: 12 mg/kg intervention 2: 25 mg

Protocol document:
SAP_002.pdf: 
 
STATISTICAL ANALYSIS PLAN 
MorphoSys AG 
MOR208C203 
 
 
 
 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
Final Version 2.0 - Addendum Version 8.0 
 
 
MorphoSys AG 
 
Semmelweisstr. 7 
D-82152 Planegg 
GERMANY 
 
 
 
A Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the 
Safety and Efficacy of Lenalidomide Combined with MOR00208 in 
Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R- 
R DLBCL) 
 
Protocol No: MOR208C203 
 
 
 
 
 
 
 
IND Number: 
114,856 
EudraCT Number: 
2014-004688-19 


 
STATISTICAL ANALYSIS PLAN 
MorphoSys AG 
MOR208C203 
 
 
 
 
 
Sponsor: 
MorphoSys AG 
Author: 
SAP Version: 
Version 2.0 – Addendum Version 8.0, 10 
February, 2023 
Version Dates: 
Version 1.0, 02 November, 2015 
Version 2.0, 08 April, 2019 
Version 2.0 – Addendum Version 1.0, 09 
August, 2019 
Version 2.0 – Addendum Version 2.0, 05 
February, 2020 
Version 2.0 – Addendum Version 3.0, 24 
February, 2020 
Version 2.0 – Addendum Version 4.0, 10 
June, 2020 
Version 2.0 – Addendum Version 5.0, 02 
December, 2020 
Version 2.0 – Addendum Version 6.0, 21 
December, 2020 
Version 2.0 – Addendum Version 7.0, 31 
March, 2021 
 Version 2.0 – Addendum Version 8.0, 10 
February, 2023 
 
 
 
 
 
 
 
 
 
 
This document contains confidential information of MorphoSys AG. Any viewing or disclosure of 
such information that is not authorized in writing by MorphoSys AG is strictly prohibited. Such 
information may be used solely for the purpose of reviewing or performing this study. 


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STATISTICAL ANALYSIS PLAN 
SIGNATURE PAGE 
MorphoSys AG 
Semmelweisstr. 7 
D-82152 Planegg 
GERMANY 
 
 
A Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of 
Lenalidomide Combined with MOR00208 in Patients with Relapsed or Refractory Diffuse Large B-Cell 
Lymphoma (R-R DLBCL) 
Protocol No: MOR208C203 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Addendum 8.0 – Changes to Addendum 7.0 
 
SAP Section 
Changes 
Rationale 
SAP ADDENDUM 8.0 
• 
Definition of the distinction 
between combined therapy phase 
and monotherapy phase for 
observing Adverse Events per 
exposure time to treatment 
described in specific details  
(Section 20.11.3) 
 
 
 
 
• 
Forest Plots will be updated to the 
48-month landmark instead of the 
30 month landmark (Section 
20.8.2) 
• 
Modifying the algorithm for 
incorporating counts of 
treatment emergent 
Adverse Events when 
doses are skipped at the 
start of monotherapy phase 
or events beyond end of 
treatment for classification 
to the monotherapy period 
(Section 23.1.1) 
 
• 
This is due to the longer 
follow up time in the study 
(23.1.2) 
 
 
 
 
 
 
Addendum 7.0 – Changes to Addendum 6.0 
 
SAP Section 
Changes 
Rationale 
SAP ADDENDUM 7.0 
• 
Addition of analyses to address the 
impact of the Corona pandemic on 
trial conduct. 
• 
Regulatory requirement and 
sponsor responsibility to 
monitor the influence of the 
pandemic on trial conduct 
 
 
Addendum 6.0 – Changes to Addendum 5.0 
 
SAP Section 
Changes 
Rationale 
SAP ADDENDUM 6.0 
• 
Addition of a sensitivity analysis 
• 
Sensitivity analysis of 
scientific interest 
• 
Extension of search terms and 
phrases used to classify death 
• 
Modification of the search 
algorithm to account for new 
data entries in the data 
base 
• 
Extension of search terms used to 
identify patients who discontinued 
LEN as planned after 12 Cycles as 
per protocol 
• 
Modification of the search 
algorithm to account for new 
data entries in the data 
base 
 
 
Addendum 5.0 – Changes to Addendum 4.0 
 


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SAP Section 
Changes 
Rationale 
SAP ADDENDUM 5.0 
• 
Addition of multiple sensitivity 
analyses using the SAF instead of 
the FAS 
• 
Analyses applying the 
Intent-to-treat principle 
• 
Addition of multiple subgroup and 
supportive analyses 
• 
Addition of multiple safety-related 
tabulations 
• 
Additional subgroup and 
supportive analyses to 
address relevant scientific 
questions 
• 
Additional safety-related 
analyses to evaluate the 
safety of the treatment 
 
 
Addendum 4.0 - Changes to Addendum 3.0 
 
 
 
 
 
SAP Section 
Changes 
Rationale 
SAP ADDENDUM 4.0 
Additional subgroup analyses on 
centrally confirmed DLBCL 
patients. 
To account for updated central 
pathology information. 


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Addendum 3.0 - Changes to Addendum 2.0 
 
SAP Section 
Changes 
Rationale 
SAP ADDENDUM 3.0 
Update on the signature page: 
new “Head of Drug Safety & 
Pharmacovigilance” 
Department head has changed 
SAP ADDENDUM 3.0 
Forest plots for 24 month rates of 
PFS, DoR and OS in non- 
biomarker subgroups 
A graphical illustration facilitating 
data interpretation 
 
Addendum 2.0 - Changes to Addendum 1.0 
 
SAP Section 
Changes 
Rationale 
SAP ADDENDUM 2.0 
Efficacy assessment in 
subgroups of different BCL-2 
expression levels 
Relevant analysis from the 
medical and scientific point 
SAP ADDENDUM 2.0 
Efficacy in different age 
subgroups 
Relevant analysis from the 
medical and scientific point 
SAP ADDENDUM 2.0 
Identification of patients with a 
history of indolent lymphoma 
Improved detection algorithm 
covering a broader range of 
search terms 
SAP ADDENDUM 2.0 
Swimmers plot for patients with 
history of indolent lymphoma 
A graphical illustration facilitating 
data interpretation 
SAP ADDENDUM 2.0 
Deaths 
Improved algorithm to cover a 
broader range of terms 
SAP ADDENDUM 2.0 
Lenalidomide dose intensity 
Relevant information for 
interpreting both efficacy and 
safety data 
SAP ADDENDUM 2.0 
Categorization of the NHL 
reference diagnosis as 
determined by central pathology 
Mapping of the central pathology 
assessment with the terms used 
for reporting 
SAP ADDENDUM 2.0 
Efficacy endpoints are reported 
for selected NHL subtypes as 
determined by central pathology. 
Swimmer plots are generated by 
NHL subtypes 
Relevant for the interpretation of 
efficacy data 


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Addendum 1.0 - Changes to SAP Version 2.0 
 
SAP Section 
Changes 
Rationale 
8.2 Enrolled patients 
Some categories for study drug 
discontinuation were added. 
The updated patient disposition 
shows the patient flow more 
granular. 
All Sections 
All Listings specified for the FAS 
are produced for the SAF. 
One patient who is not in the FAS 
should also be represented in the 
Listings. 
SAP ADDENDUM 
A visualization for the distribution 
of compliance by Cycle was 
added. 
A graphical illustration is useful 
for interpretation. 
SAP ADDENDUM 
An analysis for the relative dose 
change was added. 
The information is relevant for 
interpretation of efficacy outcome 
variables. 
SAP ADDENDUM 
Additional analyses on drug 
safety were added: 
• 
TEAE by search category 
• 
Time to first TEAE 
• 
Tabulation of most frequent 
TEAEs with 10% cut-off 
• 
Reasons for temporary 
MOR00208 and LEN 
interruptions 
Helpful information to interpret 
drug safety. 
SAP ADDENDUM 
Additional efficacy analyses: 
• 
Time to PR 
• 
Time to best response 
• 
Event-free survival 
Helpful information to interpret 
the efficacy of the drug 
combination. 
SAP ADDENDUM 
Subgroup analyses: 
• 
Safety and efficacy in 
patients who discontinued 
LEN 
• 
Safety in patients who are 
treated with a reduced dose 
of LEN (incidence of TEAEs, 
duration of TEAEs) 
• 
Patients treated with different 
CMC batches (efficacy and 
safety are evaluated) 
• 
Efficacy by age category 
• 
OS by best response 
• 
Forest plots for various 
efficacy variables and 
Various subgroup analyses were 
added to obtain a clearer picture 
on the efficacy and safety of the 
drug combination in different 
subgroups. 


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different subgroups 
• 
Efficacy in patients ineligible 
for stem cell transplantation: 
definition of additional 
subgroups 
• 
Patients with high and low 
NK cell numbers at baseline: 
additional subgroup 
definition 
• 
Swimmers plot for 
responders 
APPENDIX 
APPENDIX: LIST OF MEDDRA 
QUERIES 
MedDRA queries necessary to 
perform some of the safety- 
relevant analyses specified in the 
SAP Addendum. 


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Changes to the Previous Version 
 
SAP Section 
Changes 
Rationale 
High Level Summary 
of changes 
The SAP has been re-written with 
1. 
Additional sections (Eg: 6. Definition 
and general Methodology), 
2. 
Additional definitions. (Eg: Reference 
start date and Study day) 
3. 
Additional details (Eg: censoring rules 
for PFS endpoint), 
In the previous SAP some of the 
details were missing. 
Additional Sections are added for 
the sake of completeness and 
providing added clarification on 
Statistical programming to be 
performed. 
Additional definitions are provided 
because they were not provided in 
the previous SAP and they are 
needed for the sake of 
completeness and clear guidance 
on Statistical programming. 
Additional Details are added for 
the sake of completeness and 
providing added clarification on 
Statistical programming to be 
performed. 
Signature Page 
1. – 6. Organizational changes 


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2 List of abbreviations 
and definition of terms 
Addition of 
1. 
ABC: Activated B-cell 
2. 
GCB: Germinal center B-cell 
3. 
GEP: Gene expression profiling 
4. 
HDC/HDT: High-dose chemotherapy 
5. 
IHC: Immuno-histochemistry 
6. 
INV: Investigator 
7. 
IV: Intravenous 
Removed 
8. 
ANC: Absolute neutrophil count 
9. 
CPH: Cox proportional hazards 
10. CS: Clinically significant 
11. DoBOR: Duration of best overall 
response 
12. ROC: Receiver operating characteristic 
1.-7. Abbreviations are now 
included due to addition of new 
details 
8.-12. Definitions and 
abbreviations are not used in this 
SAP version 
3 Introduction 
1. 
Section “1. Purpose and scope of the 
document” from the previous SAP 
version renamed to “3. Introduction” 
2. 
Section “2. Introduction” from the 
previous SAP version removed 
1. 
Details from section remained 
unchanged 
2. 
Information from this section 
are already documented in the 
protocol and are not 
necessary for the SAP 
4 Study Objectives 
and Endpoints 
1. 
Section “3. Study Objectives” and “4. 
Study endpoints” from the previous SAP 
version combined to one section 
2. 
Removed “Patients MUST have been 
treated with at least one dose of both 
study medications in order to qualify for 
the primary endpoint” in ORR endpoint 
definition 
3. 
Definition of secondary endpoints DCR, 
DoR, PFS, OS, TTNT removed 
4. 
Secondary endpoint definition for safety 
expanded to “Incidence , frequency and 
severity of treatment-emergent AEs” 
5. 
Addition of anti-MOR00208 antibody 
response classification in secondary 
endpoint of immunogenicity 
6. 
Endpoint definition for item 10: 
evaluation of efficacy parameters in 
cohorts with different International 
Prognostic Index classifications added 
7. 
Endpoint definition for study objective 
11: evaluation of TTP added 
8. 
Endpoint “Immune Response” from 
previous SAP version removed 
9. 
Endpoint “Biomarkers” from previous 
SAP version removed 
10. Definition for study endpoint 12 includes 
new biomarker subgroups, e.g. Cell-of- 
origin 
1. 
The new table with combined 
information on study 
objectives and endpoints 
provides direct link between 
objectives and endpoints 
2. 
Restriction for the primary 
endpoint not needed for the 
calculation of ORR 
3. 
A reference to the 
corresponding sections is 
presented for each endpoint 
with detailed description of the 
endpoints 
4. 
Detail added for the definition 
5. 
New definition added 
6. 
Endpoint definition added 
7. 
Endpoint definition added 
8. 
No corresponding study 
objective was defined in the 
SAP 
9. 
These endpoints are not 
considered in the new SAP 
version 
10. New biomarker subgroups of 
interest included according to 
L-MIND protocol 
5 Study Design 
1. 
Section “5. Study Design” from the 
1. 
Information from the previous 


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previous SAP version renamed to “5.1 
General study design” and definition of 
“primary refractory disease” and 
“Relapsed/recurrent disease” removed 
2. 
Section “6. Schedule of assessments” 
from the previous SAP version renamed 
to “5.2 Schedule of assessments” with a 
change of reference. Instead of the 
appendix, the new reference is to the 
protocol 
3. 
Section “Determination of Sample Size” 
renamed to “5.3 Determination of 
sample size” 
4. 
Section “5.4 Timing of analyses” added 
5. 
Section “9.7 Safety-Run-In” from the 
previous SAP version renamed to “5.4.1 
Safety run-in analysis” with changes in 
the wording 
6. 
Section “5.4.2 Primary Analysis” added 
7. 
Section “7.1 Final Analysis” from the 
previous SAP version renamed to “5.4.3 
Final analysis” with addition information 
regarding the timing of the final 
analysis. With regards to further 
exploratory analyses, the phrase is 
changed to “MorphoSys may perform 
further exploratory analyses…” 
SAP version remained 
unchanged. Definitions were 
removed, since they don’t 
belong to the study design 
2. 
Since the schedule of 
assessments is not essential 
for the SAP a reference to the 
protocol is sufficient and need 
not to be in the appendix of 
the SAP 
3. 
Since sample size 
considerations belong to the 
study design, it is moved to 
this section. Information from 
the previous SAP version 
remained unchanged 
4. 
Section added. Different 
subsections regarding the 
timing of analyses were 
presented in different sections 
and are now presented under 
one section for a better 
overview 
5. 
Information from the previous 
SAP remained similar with 
wording corrections 
6. 
Section with details added 
7. 
Information from previous 
SAP version remained 
unchanged with a minor word 
correction. Details on the 
timing of the final analysis 
added 
6 Definition and 
general Methodology 
Addition of new sections with details: 
6.1 Enrolment date 
All sections with information and 
definitions added 
6.2 Study drug and study treatment 
6.3 Study drug administration 
6.3.1 Date of first administration of study 
drug 
6.3.2 Date of last administration of study 
drug 
6.3.3 Date of first administration of study 
treatment 
6.3.4 Date of last administration of study 
treatment 
6.4 Reference start date and Study day 
6.5 Screening failure 
6.6 Time unit 
6.7 Baseline 


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6.8 On treatment assessment/event 
6.9 Start and end date for time to event 
variables 
6.10 Date of last contact 
6.11 Analysis Windows 
6.12 Selection of data in the event of 
multiple records in a window 
6.13 Analysis 
populations 
1. 
Addition of section “6.13.1 Screened 
patients” and “6.13.2 Enrolled patients” 
2. 
Information from section “8 Analysis 
populations” from the previous SAP 
version is incorporated in each 
subsection for each analysis set 
3. 
In section “6.13.3 Full analysis set 
(FAS)” restriction of “Patients in FAS 
have to have at least one post-baseline 
efficacy assessment” is replaced by “A 
listing showing the patients who have 
been excluded from the efficacy 
analysis will be provided” 
4. 
Section “6.13.4 Per protocol set (PPS)” 
includes definition of PPS with regards 
to protocol deviations and definition of 
protocol grouped into new categories 
5. 
Section “6.13.5 Safety set (SAF)” 
includes a more detailed description of 
SAF 
6. 
Section “6.13.8 Planned analyses for 
the different populations” added 
7. 
Section “6.13.9 Withdrawal of informed 
consent” added 
1. 
Definition added 
2. 
For a better overview, each 
analysis set is described in a 
separate subsection 
3. 
Exclusion from efficacy 
analysis also covers the case 
of patients without post- 
baseline assessment 
4. 
Details for the definition of 
PPS added 
5. 
More details are added to 
SAF definition 
6. 
Section added and provides 
more details 
7. 
Section added and provides 
more details 
6.14 Cheson criteria 
Section with its subsections 
6.14.1 Response criteria 
6.14.2 Disease progression 
6.14.3 Change in imaging modality 
added 
Section with its subsections and 
information added to provide more 
details 
7.1 General principles 
of statistical 
programming 
Information based on section “9.1.1 
Statistical Methods” from the previous SAP 
version. Statistical programming with SAS 
changed to version 9.4 or above 
Newer version of SAS software 
available 
7.2 Variable types and 
descriptive statistics 
Section “9.1.1 Statistical Methods” from the 
previous SAP version renamed to “7.2 
Variable types and descriptive statistics” 
with addition of definition of reference 
number of subjects and more detailed 
description of continuous and categorical 
variables. Addition of definition of “Time 
variables” and “Time to Event Variables”. 
Removed descriptions on significance levels 
Information on variable types and 
analysis methods added. Time to 
event variables and time variables 
added. Since descriptive analyses 
are performed without statistical 
tests, no significance level needs 
to be specified. With the change of 
CRO, no 
 SOPs are applicable, 
but 
SOPs 


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and reference to 
 SOPs and changed to 
SOPs 
7.3 Convention on 
missing data 
Section “9.1.2.1.2 Missing Data” from the 
previous SAP version renamed to “7.3 
Convention on missing data” with reference 
to each section for the handling of missing 
data 
For a better overview each method 
for handling missing data is 
presented in the respective section 
for the respective data 
7.4 Data included in 
the analysis and cut- 
off date 
Section added 
Section added and provides more 
details 
7.5 Specifications and 
Analysis Database 
Section added 
Section added and provides more 
details 
8 Patient disposition, 
background and 
baseline 
characteristics 
1. 
Description of patient disposition 
summaries added with extension on 
details given in section “9.2.1 Subject 
Disposition” from the previous SAP 
version 
2. 
Addition of section 
“8.1 Screened patients” 
“8.2 Enrolled patients” 
“8.3 Follow-up period” 
3. 
Section “9.2.2 Protocol Noncompliance” 
from previous SAP version renamed to 
“8.4 Protocol deviations” with a change 
in the structure of protocol deviations. 
Groups of protocol deviations are 
reduced to four categories 
4. 
Section “9.2.3 Background and 
Demographic Characteristics” from the 
previous SAP version renamed to “8.5 
Baseline and demographic 
characteristics” with an extension on 
variables to be summarized 
5. 
Addition of section 
“8.6.1 Coding and definitions” 
“8.6.2 DLBCL-specific medical history 
and diagnosis” 
6. 
Section “8.6.2.1 Handling of incomplete 
dates regarding DLBCL-specific 
medical history” added with information 
from section “8.2.7 medical Histories” 
from the previous SAP version 
7. 
Section “9.2.4 International Prognostic 
Index” from the previous SAP version 
renamed to “8.6.2.2 Calculation of the 
International Prognostic Index (IPI)” with 
deletion of sentences referring to 
analysis of IPI for DLBCL patients only 
8. 
Section “8.6.3 Reason for ASCT 
ineligibility” added 
9. 
Section “9.2.8 Pre-Medication for MOR 
infusion” from the previous SAP version 
renamed to “8.8 Pre-medication for 
1. 
Details added 
2. 
Sections added to provide 
more details 
3. 
The protocol deviations are 
categorized into four groups 
and provide a better overview 
4. 
Some variables for 
demographic characteristics 
added 
5. 
Sections added to provide 
more details 
6. 
Information remained 
unchanged, but is added as a 
separate section 
7. 
Information from the previous 
SAP version remained 
unchanged. Removal of 
restriction on DLBCL patients 
only, restriction results in an 
analysis set, which is not 
defined in 6.13 
8. 
Section added to provide 
more details 
9. 
Information from the previous 
SAP version remained 
unchanged. 


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MOR00208 infusion” 
8.7 Prior and 
concomitant 
medications and non- 
drug 
treatments/procedures 
1. 
Section “8.7.1 Coding” contains 
information from section “9.2.6 Prior 
and Concomitant medications and 
therapies” from the previous SAP 
version regarding the coding of 
prior/concomitant medications. 
Additional information on coding of 
surgical and medical procedures 
2. 
Section “8.7.2 Definitions” added with 
information from section “9.2.6 Prior 
and Concomitant medications and 
therapies” from the previous SAP 
version with additional details on each 
definition. Addition of time variables 
3. 
Section “8.7.3 Data presentation” added 
with information concomitant 
medications summary from the previous 
SAP version. Additional list of variables 
to be summarized provided 
4. 
Section “8.7.4 DLBCL-specific prior 
therapies” added with subsections 
regarding variables to be summarized, 
handling of missing dates, definitions of 
refractoriness, definitions of early/late 
relapse after first line treatment, 
imputation of missing values 
5. 
Section “8.7.5 Non-Study anti-cancer 
treatment” added 
1. 
Information from the previous 
SAP version remained 
unchanged. Information for 
surgical and medical 
procedures added 
2. 
Details added to the 
definitions. Additional details 
and variables provided 
3. 
Variables for summary tables 
added to provide more details 
4. 
Section with subsections and 
details added for more details 
5. 
Additional details and 
definitions are provided 
8.9 Study treatment 
1. 
Addition of section “8.9.1 Treatment 
cycles” 
2. 
Addition of section “8.9.2 Exposure” 
with information from previous SAP 
version and additional details for the 
definition of last date of exposure and 
exposure analysis 
3. 
Addition of sections 
“8.9.3 Dose reduction” 
“8.9.4 Dose interruption” 
“8.9.5 Permanent discontinuations” 
4. 
Section “8.9.6.1 MOR00208” for 
compliance includes information from 
the previous SAP version 
5. 
Section “8.9.6.2 LEN” added with 
extension on information from the 
previous SAP version 
1. 
Section added for more 
details 
2. 
Information added 
3. 
Sections added for more 
details 
4. 
Information from the previous 
SAP version remained 
unchanged with minor 
wording and editorial changes 
5. 
Information added for more 
details. Additional details and 
calculation descriptions are 
provided 
9 Primary Objective 
1. 
Section “9.3.1 Primary Efficacy 
Analysis” from the previous SAP 
version renamed to “9 Primary 
Objective” with addition of separate 
subsections 
2. 
Addition of subsections 
“9.1 Endpoint: Best objective response 
rate” 
“9.2 Main analysis” 
“9.3 Sensitivity Analysis” 
1. 
New structure provides a 
better overview of the primary 
endpoint 
2. 
The information from the 
previous SAP version 
remained mainly unchanged, 
but essential additional details 
added, such as formal details 
for the main analysis and the 
statement. Details regarding 


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“9.4 Concordance between IRC and 
investigator (INV) assessment” 
with information from previous SAP and 
addition of more details and analyses 
the concordance between IRC 
and INV assessment added 
10.1 Secondary 
objective 1 
1. 
Section “9.3.2.1 Disease control Rate 
(DCR)” from the previous SAP version 
renamed to “10.1 Secondary objective 
1” with addition of separate subsections 
2. 
Addition of subsections 
“10.1.1 Objective” 
“10.1.2 Endpoint: Disease control rate” 
“10.1.3 Main analysis” 
“10.1.4 Sensitivity analyses” 
with information from previous SAP 
version and addition of more details and 
analyses 
1. 
New structure provides a 
better overview of the 
endpoint 
2. 
The information from the 
previous SAP version 
remained mainly unchanged, 
but essential details are 
added similar to ORR 
10.2 Secondary 
objective 2 
1. 
Section “9.3.2.4 Progression-Free 
Survival (PFS)” from the previous SAP 
version renamed to “10.2 Secondary 
objective 2” with addition of separate 
subsections 
2. 
Addition of subsections 
“10.2.1 Objective” 
“10.2.2 Endpoint: Progression-free 
survival” 
“10.2.3 Disease assessments” 
“10.2.4 Censoring rules” 
“10.2.5 Main analysis” 
“10.2.6 Sensitivity analyses” 
with information from previous SAP 
version with addition of more details 
and analyses 
3. 
Censoring rule table added 
1. 
New structure provides a 
better overview of the 
endpoint 
2. 
The information from the 
previous SAP version 
remained mainly unchanged, 
but essential details and 
sections now provided 
3. 
Rules for censoring expanded 
10.3 Secondary 
objective 3 
1. 
Information is based on section “9.3.2.2 
Duration of Response (DoR), Duration 
of Best Overall Response (DoBOR), 
and Time to Next Treatment (TNNT)” 
with addition of separate subsections 
2. 
Addition of subsections 
“10.3.1 Objective” 
“10.3.2 Endpoint: Duration of response” 
“10.3.3 Censoring rules” 
“10.3.4 Main analysis” 
“10.3.5 Sensitivity analyses” 
with minor information from the previous 
SAP and addition of more details and 
analyses 
3. 
Detailed description for censoring and 
handling of missing response 
assessments 
4. 
Details regarding Duration of Best 
overall response are removed 
1. 
New structure provides a 
better overview of the 
endpoint 
2. 
Minor information from the 
previous SAP version 
remained unchanged. 
Essential details are provided 
now 
3. 
Details on censoring added. 
Details on missing response 
assessments added 
4. 
Replaced by details for 
duration of CR as sensitivity 
analysis 
10.4 Secondary 
objective 4 
1. 
Section “9.3.2.5 Overall Survival (OS)” 
from the previous SAP version renamed 
to “10.4 Secondary objective 4” with 
addition of separate subsections 
1. 
New structure provides a 
better overview of the 
endpoint 
2. 
Information from the previous 


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2. 
Addition of subsections 
“10.4.1 Objective” 
“10.4.2 Endpoint: Overall survival” 
“10.4.3 Censoring rules and imputation” 
“10.4.4 Main analysis” 
“10.4.5 Sensitivity analysis” 
with information from the previous SAP 
version and additional details and 
analyses 
3. 
Addition of handling of missing dates 
SAP version remained mainly 
unchanged with minor 
wording corrections. 
Additional details are provided 
for each subsection 
3. 
Information added to provide 
more details 
10.5 Secondary 
objective 5 and 
secondary objective 
11 
1. 
Section “9.3.2.3 time to Progression 
(TTP)” from the previous SAP version 
renamed to “10.5 Secondary objective 5 
and secondary objective 11” with 
addition of separate subsections 
2. 
Addition of subsections 
“10.5.1 Objectives” 
“10.5.2 Endpoint: Time to progression” 
“10.5.3 Main analyses” 
“10.5.4 Sensitivity analyses for 
Objective 5” 
with information from the previous SAP 
version and additional details and 
analyses 
3. 
Information regarding most recent 
therapy added 
1. 
New structure provides a 
better overview of the 
endpoint 
2. 
Information from the previous 
SAP version remained mainly 
unchanged with minor 
wording corrections. Definition 
for TTP expanded. Additional 
details are provides for each 
subsection 
3. 
Information added for more 
details 
10.6 Secondary 
objective 6 
1. 
Information is based on section “9.3.2.2 
Duration of Response (DoR), Duration 
of Best Response (DoBOR), and Time 
to Next Treatment (TTNT)” with addition 
of separate subsections 
2. 
Addition of subsections 
“10.6.1 Objective” 
“10.6.2 Endpoint: Time to next 
treatment” 
“10.6.3 Main analysis” 
“10.6.4 Sensitivity and subgroup 
analyses” 
with information from the previous SAP 
version and additional details and 
analyses 
3. 
Definition of TTNT expanded and 
includes the case of death as an event 
4. 
Analyses stratified by IPI groups 
removed 
1. 
New structure provides a 
better overview of the 
endpoint 
2. 
Additional details are 
provided. 
3. 
Information added for more 
details 
4. 
TTNT stratified by IPI is not 
essential for this endpoint 
10.7 Secondary 
objective 7 
1. 
Section “9.5 Safety Analysis” from the 
previous SAP version renamed to “10.7 
Secondary objective 7” with addition of 
separate subsections 
2. 
Addition of subsections 
“10.7.1 Objective” 
“10.7.2 Endpoint: Incidence, frequency 
and severity of treatment-emergent 
adverse events (AEs)” 
“10.7.3 Main analysis” 
3. 
Section “10.7.3.1 Overview” contains 
1. 
New structure provides a 
better overview of the 
endpoint 
2. 
Information from the previous 
SAP version remained 
unchanged 
3. 
In the previous SAP version 
different safety assessments 
were mentioned in different 
subsections, but are merged 
into one section for a better 


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categories for safety assessments 
given in the previous SAP version in 
different subsections 
4. 
Section “10.7.3.2 Adverse events” 
added with definition of an AE and rules 
for reporting AEs 
5. 
Section “10.7.3.3 Treatment-emergent 
adverse events” added with information 
from the previous SAP version and 
additional details 
6. 
Addition of subsections 
“10.7.3.4 Adverse events of special 
interest” 
“10.7.3.5 Relationship to study drug” 
“10.7.3.6 coding of adverse events” 
“10.7.3.7 Grading of adverse events” 
“10.7.3.8 Deaths” 
“10.7.3.9 General rule for reporting” 
7. 
Section “10.7.3.10 AE summaries” 
contains variables to be summarized 
from the previous SAP version with 
additional variables to be summarized 
overview 
4. 
Section added for more 
details 
5. 
Information on TEAE 
expanded. Additional details 
are provided 
6. 
Subsections added 
7. 
List of variables to be 
summarized expanded. 
Additional variables are 
provided with additional 
details 
10.8 Secondary 
objective 8 
1. 
Section “9.4.2 Immunogenictiy analysis” 
from the previous SAP version renamed 
to “10.8 Secondary objective 8” with 
addition of subsections 
2. 
Addition of the categorization of anti- 
MOR00208 antibody response 
3. 
Addition of the subsections 
“10.8.1 Objective” 
“10.8.2 Endpoint: Percentage of 
patients who develop anti-MOR00208 
antibodies as determined by a positive 
anti-MOR00208 antibody titre” 
“10.8.3 Main analysis” 
1. 
New structure provides a 
better overview of the 
endpoint 
2. 
The categorization added 
3. 
Information and details from 
the previous SAP version 
remained unchanged 
10.9 Secondary 
objective 9 
1. 
Section “9.4.1 Pharmacokinetic 
Analysis” from the previous SAP 
version renamed to “10.9 Secondary 
objective 9” with addition of subsections 
2. 
Addition of information on population 
PK analysis in subsection “10.9.3.3 
Population PK analysis” 
1. 
New structure provides a 
better overview of the 
endpoint. Information in the 
previous SAP remained 
unchanged with minor 
wording corrections 
2. 
Section added for more 
details 
10.10 Secondary 
objective 10 
Section with corresponding subsections and 
details added 
Section added for more details 
10.11 Secondary 
objective 11 
Section added with reference to section 
10.5.3.2 
Section added for more details 
10.12 Secondary 
objective 12 
1. 
Section “9.4.3 Exploratory Biomarker 
Analysis” from the previous SAP 
version renamed to “10.11 Secondary 
objective 11” with addition of 
subsections 
2. 
Addition of subsections 
“10.12.1 Objective” 
1. 
New structure provides a 
better overview of the 
endpoint. 
2. 
Information on the subgroups 
expanded. Additional details 
are provided 


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“10.12.2 Endpoint” 
“10.12.3 Main analysis” 
“10.12.4 Sensitivity analyses” 
with detailed description of subgroups, 
including new subgroups 
11 Exploratory 
efficacy analyses 
Section added with minor information on 
“time to response” from the previous SAP 
version 
Section added for more details 
12 Descriptive 
biomarker analyses 
Section added 
Section added for more details 
13 Additional Safety 
analyses 
1. 
Section “9.5.3 Vital Signs; body Weight 
and Height” from the previous SAP 
version renamed to “13.2.1 Vital signs 
variables” with minor changes in 
wording and additional variables 
2. 
Addition of subsection “13.2.2 Vital 
signs analysis” with details 
3. 
Section “9.5.2 Physical examination” 
from the previous SAP version renamed 
to “13.3 Physical examination” with 
some wording and editorial changes 
4. 
Section “9.5.4 Electrocardiograms (12- 
lead ECG)” from previous SAP 
renamed to “13.4 Electrocardiogram 
(ECG)” 
5. 
Section “13.4.1 ECG Variables” added 
6. 
Section “13.4.2 ECG Analysis” added 
with information on normal ranges for 
ECG variables from section “9.5.4 
Electrocardiograms (12-lead ECG)” 
from previous SAP version and 
additional details on analyses with 
detailed table on clinically notable ECG 
values 
7. 
Section “9.5.5 Clinical Laboratory 
Evaluations” from previous SAP version 
renamed to “13.5 Laboratory data” 
8. 
Section “13.5.1 Laboratory Variables” 
added with less laboratory parameters 
9. 
Section “13.5.2 Grading of Laboratory 
data” added 
10. Section “13.5.3 Laboratory Analysis” 
added 
11. Section “13.6 ECOG scores analyses” 
added 
12. Section “13.7 B-symptoms” added 
1. 
Some variables added 
2. 
Information added 
3. 
Information from the previous 
SAP version remained 
unchanged with minor 
wording changes 
4. 
New structure and numbering 
of section provides a better 
overview 
5. 
Section added for more 
details 
6. 
Information from previous 
SAP remains unchanged. 
Additional details provided, 
including table on clinically 
notable ECG values 
7. 
New structure and numbering 
of section provides a better 
overview 
8. 
Not all laboratory variables 
need to be analysed 
9. 
Section added for more 
details 
10. Section added for more 
details 
11. Information on ECOG 
expanded, additional 
information is provided 
12. Section added for more 
details 
14 General Guidance 
on reporting 
Section added 
To provide a consistent reporting 
15 Reference 
Standard Operating Procedure from 
 removed 
Not needed due to change of CRO 


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1. TABLE OF CONTENTS 
1. 
TABLE OF CONTENTS .................................................................................................................. xx 
2. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ..................................................... 29 
3. 
INTRODUCTION ........................................................................................................................... 33 
4. 
STUDY OBJECTIVES AND ENDPOINTS .................................................................................... 33 
5. 
STUDY DESIGN ............................................................................................................................ 36 
5.1 
General study design ...................................................................................................................... 36 
5.2 
Schedule of assessments .................................................................................................................. 38 
5.3 
Determination of sample size ......................................................................................................... 38 
5.4 
Timing of analyses ......................................................................................................................... 39 
5.4.1 
Safety run-in analysis ......................................................................................................... 39 
5.4.2 
Primary analysis ................................................................................................................. 39 
5.4.3 
Final analysis ...................................................................................................................... 40 
6. 
DEFINITIONS AND GENERAL METHODOLOGY .................................................................... 40 
6.1 
Enrolment date ............................................................................................................................... 40 
6.2 
Study drug and study treatment ...................................................................................................... 40 
6.3 
Study drug administration .............................................................................................................. 40 
6.3.1 
Date of first administration of study drug ........................................................................... 40 
6.3.2 
Date of last administration of study drug ............................................................................ 40 
6.3.3 
Date of first administration of study treatment ................................................................... 41 
6.3.4 
Date of last administration of study treatment .................................................................... 41 
6.4 
Reference start date and study day ................................................................................................. 41 
6.5 
Screening failure ............................................................................................................................ 42 
6.6 
Time unit ........................................................................................................................................ 42 
6.7 
Baseline .......................................................................................................................................... 42 
6.8 
On treatment assessment/event ....................................................................................................... 42 
6.9 
Start and end date for time to event variables ................................................................................. 43 
6.10 
Date of last contact ..................................................................................................................... 44 
6.11 
Analysis windows ....................................................................................................................... 44 
6.12 
Selection of data in the event of multiple records in a window .................................................. 44 
6.13 
Analysis populations .................................................................................................................. 45 
6.13.1 
All patients screened ...................................................................................................... 45 


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6.13.2 
Enrolled patients............................................................................................................. 45 
6.13.3 
Full analysis set (FAS) ................................................................................................... 45 
6.13.4 
Per protocol set (PPS) .................................................................................................... 45 
6.13.5 
Safety set (SAF) ............................................................................................................. 46 
6.13.6 
PK analysis set (PKAS) .................................................................................................. 46 
6.13.7 
Immunogenicity analysis set (IAS) ................................................................................. 46 
6.13.8 
Planned analyses for the different populations ............................................................... 46 
6.13.9 
Withdrawal of informed consent .................................................................................... 47 
6.14 
Efficacy Assessments ................................................................................................................. 48 
6.14.1 
Response criteria ............................................................................................................ 48 
6.14.2 
Disease progression ........................................................................................................ 49 
6.14.3 
Change in imaging modality ........................................................................................... 50 
7. 
STATISTICAL METHODOLOGY ................................................................................................ 50 
7.1 
General principles of statistical programming ................................................................................ 50 
7.2 
Variable types and descriptive statistics ......................................................................................... 50 
7.3 
Convention on missing data............................................................................................................ 51 
7.4 
Data included in the analysis and cut-off date ................................................................................ 51 
7.5 
Specifications and Analysis Database ............................................................................................. 52 
7.6 
Pooling of investigative sites .......................................................................................................... 52 
8. 
PATIENT DISPOSITION, BACKGROUND AND BASELINE CHARACTERISTICS ............... 52 
8.1 
Screened patients ............................................................................................................................ 53 
8.2 
Enrolled patients ............................................................................................................................ 53 
8.3 
Survival follow-up period and survival follow-up .......................................................................... 55 
8.3.1 
Summary statistics .............................................................................................................. 55 
8.3.2 
Duration of overall survival follow-up ............................................................................... 55 
8.4 
Protocol deviations ......................................................................................................................... 56 
8.5 
Baseline and demographic characteristics ...................................................................................... 56 
8.6 
Medical history and current medical conditions ............................................................................. 58 
8.6.1 
Coding and definitions ....................................................................................................... 58 
8.6.2 
DLBCL-specific medical history and diagnosis ................................................................. 58 
8.6.3 
Reason for ASCT ineligibility ............................................................................................ 61 
8.6.4 
History of indolent lymphoma ............................................................................................ 63 
8.7 
Prior and concomitant medications and non-drug treatments/procedures ....................................... 63 


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8.7.1 
Coding ................................................................................................................................ 63 
8.7.2 
Definitions .......................................................................................................................... 64 
8.7.3 
Data presentation ................................................................................................................ 64 
8.7.4 
DLBCL-specific prior therapies ......................................................................................... 65 
8.7.5 
Early vs. late relapse after DLBCL diagnosis ..................................................................... 71 
8.7.6 
Non-study anti-DLBCL treatment ....................................................................................... 72 
8.8 
Pre-Medication for MOR00208 infusion ....................................................................................... 72 
8.9 
Study treatment .............................................................................................................................. 72 
8.9.1 
Treatment cycles ................................................................................................................ 72 
8.9.2 
Exposure ............................................................................................................................ 73 
8.9.3 
Dose reduction ................................................................................................................... 74 
8.9.4 
Dose interruption ................................................................................................................ 74 
8.9.5 
Permanent discontinuations ................................................................................................ 75 
8.9.6 
Compliance ........................................................................................................................ 75 
9. 
PRIMARY OBJECTIVE ................................................................................................................. 79 
9.1 
Endpoint: Best objective response rate ........................................................................................... 79 
9.2 
Main analysis ................................................................................................................................. 79 
9.3 
Sensitivity analyses ........................................................................................................................ 80 
9.4 
Concordance between IRC and investigator (INV) assessment ...................................................... 80 
10. 
SECONDARY OBJECTIVES ......................................................................................................... 81 
10.1 
Secondary objective 1 ................................................................................................................ 81 
10.1.1 
Objective ........................................................................................................................ 81 
10.1.2 
Endpoint: Disease control rate ........................................................................................ 81 
10.1.3 
Main analysis .................................................................................................................. 81 
10.1.4 
Sensitivity analyses ........................................................................................................ 82 
10.2 
Secondary objective 2 ................................................................................................................ 82 
10.2.1 
Objective ........................................................................................................................ 82 
10.2.2 
Endpoint: Progression-free survival ............................................................................... 82 
10.2.3 
Disease assessments ....................................................................................................... 82 
10.2.4 
Censoring rules............................................................................................................... 83 
10.2.5 
Main analysis ................................................................................................................. 86 
10.2.6 
Sensitivity analyses ........................................................................................................ 87 
10.2.7 
Concordance between IRC and INV assessment of PFS events ..................................... 87 


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10.3 
Secondary objective 3 ................................................................................................................ 87 
10.3.1 
Objective ........................................................................................................................ 87 
10.3.2 
Endpoint: Duration of response ...................................................................................... 87 
10.3.3 
Censoring rules............................................................................................................... 88 
10.3.4 
Main analysis ................................................................................................................. 88 
10.3.5 
Sensitivity analyses ........................................................................................................ 89 
10.4 
Secondary objective 4 ................................................................................................................ 89 
10.4.1 
Objective ........................................................................................................................ 89 
10.4.2 
Endpoint: Overall survival ............................................................................................. 89 
10.4.3 
Censoring rules and imputation ...................................................................................... 89 
10.4.4 
Main analysis ................................................................................................................. 90 
10.4.5 
Sensitivity analyses ........................................................................................................ 90 
10.5 
Secondary objective 5 and secondary objective 11 .................................................................... 90 
10.5.1 
Objectives ...................................................................................................................... 90 
10.5.2 
Endpoint: Time to progression ....................................................................................... 90 
10.5.3 
Main analyses ................................................................................................................. 91 
10.5.4 
Sensitivity analyses ........................................................................................................ 91 
10.6 
Secondary objective 6 ................................................................................................................ 92 
10.6.1 
Objective ........................................................................................................................ 92 
10.6.2 
Endpoint: Time to next treatment ................................................................................... 92 
10.6.3 
Analysis ......................................................................................................................... 92 
10.7 
Secondary objective 7 ................................................................................................................ 92 
10.7.1 
Objective ........................................................................................................................ 92 
10.7.2 
Endpoint: Incidence, frequency and severity of treatment-emergent adverse events 
(AEs) 
93 
10.7.3 
Analysis ......................................................................................................................... 93 
10.8 
Secondary objective 8 .............................................................................................................. 103 
10.8.1 
Objective ...................................................................................................................... 103 
10.8.2 
Endpoint: Percentage of patients who develop anti-MOR00208 antibodies as 
determined by a positive anti-MOR00208 antibody titre ............................................................... 103 
10.8.3 
Analysis ....................................................................................................................... 104 
10.9 
Secondary objective 9 .............................................................................................................. 105 
10.9.1 
Objective ...................................................................................................................... 105 


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10.9.2 
Endpoint: MOR00208 plasma concentrations at sampling timepoints, accumulation 
ratios and trough concentrations .................................................................................................... 105 
10.9.3 
Analysis ....................................................................................................................... 105 
10.10 
Secondary objective 10 ............................................................................................................ 107 
10.10.1 
Endpoint ....................................................................................................................... 107 
10.10.2 
Main analysis ............................................................................................................... 107 
10.10.3 
Sensitivity analyses ...................................................................................................... 107 
10.11 
Secondary objective 11 ............................................................................................................ 107 
10.11.1 
Objective ...................................................................................................................... 107 
10.11.2 
End point and main analysis ......................................................................................... 107 
10.12 
Secondary objective 12 ............................................................................................................ 108 
10.12.1 
Objective ...................................................................................................................... 108 
10.12.2 
Endpoint ....................................................................................................................... 108 
10.12.3 
Main analysis ............................................................................................................... 108 
10.12.4 
Sensitivity analyses ...................................................................................................... 108 
11. 
EXPLORATORY EFFICACY ANALYSES .................................................................................. 109 
11.1 
Time to response and time to complete response ..................................................................... 109 
11.2 
PET-Confirmed Complete Responses ...................................................................................... 109 
11.3 
Tumor shrinkage over time: Assessment of indicator lesions ................................................... 109 
11.4 
Non-biomarker subgroup analyses ........................................................................................... 110 
12. 
DESCRIPTIVE BIOMARKER ANALYSES ................................................................................. 111 
13. 
ADDITIONAL SAFETY ANALYSES ......................................................................................... 113 
13.1 
Adverse events ......................................................................................................................... 113 
13.2 
Vital signs ................................................................................................................................ 113 
13.2.1 
Vital signs variables ..................................................................................................... 113 
13.2.2 
Vital signs analysis ....................................................................................................... 113 
13.3 
Physical examination ................................................................................................................ 114 
13.4 
Electrocardiogram (ECG) ........................................................................................................ 114 
13.4.1 
ECG variables .............................................................................................................. 114 
13.4.2 
ECG analysis ................................................................................................................ 114 
13.5 
Laboratory data ......................................................................................................................... 115 
13.5.1 
Laboratory variables ..................................................................................................... 115 
13.5.2 
Grading of laboratory data............................................................................................ 115 


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13.5.3 
Laboratory analysis ....................................................................................................... 116 
13.6 
ECOG scores analyses ............................................................................................................. 117 
13.7 
B-symptoms ............................................................................................................................. 117 
14. 
GENERAL GUIDANCE ON REPORTING ................................................................................. 118 
14.1 
Document headers and footers ................................................................................................. 118 
14.2 
Presentation of output numbering and titles within this document............................................ 118 
14.3 
Presentation of analysis sets ..................................................................................................... 119 
14.4 
General rules for presenting frequencies and percentages ........................................................ 119 
14.5 
General rule for tables/listings .................................................................................................. 120 
14.6 
Format of tables/listings and displays with no data................................................................... 120 
14.7 
Precision rules .......................................................................................................................... 121 
14.8 
General rules for presenting listings ......................................................................................... 122 
14.9 
Presentation of Dates................................................................................................................ 123 
15. 
REFERENCES .............................................................................................................................. 124 
16. 
ADDENDUM 1.0 .......................................................................................................................... 126 
16.1 
Compliance .............................................................................................................................. 126 
16.2 
Relative dose intensity ............................................................................................................. 126 
16.3 
Additional safety analyses ........................................................................................................ 126 
16.3.1 
TEAE by ‘search category’ .......................................................................................... 127 
16.3.2 
Time to first TEAE ....................................................................................................... 128 
16.3.3 
Tabulation of the most frequent TEAEs ....................................................................... 128 
16.3.4 
Reasons for temporary MOR00208 and LEN interruptions .......................................... 128 
16.4 
Additional efficacy analyses ..................................................................................................... 129 
16.4.1 
Time to PR and time to best response .......................................................................... 129 
16.4.2 
Event-free survival ....................................................................................................... 129 
16.5 
Subgroup analyses .................................................................................................................... 129 
16.5.1 
Patients who discontinued LEN treatment .................................................................... 129 
16.5.2 
Patients who reduced the daily prescribed LEN dose ................................................... 131 
16.5.3 
Evaluation of the influence of different CMC batches .................................................. 132 
16.5.4 
Efficacy by age category .............................................................................................. 133 
16.5.5 
Time to event analyses by best response category ........................................................ 133 
16.5.6 
Forest plots for biomarker and non-biomarker subgroups ............................................ 133 
16.5.7 
ASCT ineligibility subgroups ....................................................................................... 134 


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16.5.8 
NK cell numbers at baseline ......................................................................................... 136 
16.5.9 
Swimmers plot for responders ...................................................................................... 137 
17. 
SAP ADDENDUM 2.0 .................................................................................................................. 138 
17.1 
Efficacy in subgroups of BCL-2 expression levels determined by IHC .................................... 138 
17.2 
Efficacy in alternative age subgroups ....................................................................................... 138 
17.3 
Efficacy in different histological subgroups ............................................................................. 139 
17.4 
Identification of transformed lymphoma patients ..................................................................... 140 
17.5 
Swimmer plot for patients with transformed lymphoma ........................................................... 141 
17.6 
Deaths ...................................................................................................................................... 141 
17.7 
Lenalidomide dose intensity ..................................................................................................... 141 
17.8 
Categorization of reference diagnoses as per central pathology ............................................... 142 
18. 
SAP ADDENDUM 3.0 .................................................................................................................. 144 
18.1 
Forest plots for 24 month rates of Progression-free Survival, Duration of Response and Overall 
Survival 144 
19. 
SAP ADDENDUM 4.0 .................................................................................................................. 144 
20. 
SAP ADDENDUM 5.0 .................................................................................................................. 145 
20.1 
Exploratory biomarker analyses ............................................................................................... 145 
20.2 
Time since discontinuation of the last treatment....................................................................... 146 
20.3 
Time since disease progression in the last prior treatment (systemic anti-DLBCL medication)146 
20.4 
Post-L-MIND anti-DLBCL medications ................................................................................. 147 
20.4.1 
Summaries .................................................................................................................... 147 
20.4.2 
Swimmers plot .............................................................................................................. 148 
20.5 
Relationship between LEN dose intensity and efficacy ............................................................ 148 
20.5.1 
DoR and ORR in subgroups of varying relative cumulative LEN exposure ................. 148 
20.5.2 
Efficacy outcome for patients with defined LEN dose reductions ................................ 149 
20.5.3 
Other analyses related to LEN dose reduction .............................................................. 150 
20.6 
Efficacy analyses for the subgroup of patients confirmed as DLBCL by central pathology based 
on the FAS ............................................................................................................................................. 151 
20.6.1 
Efficacy analyses based on all patients centrally confirmed as DLBCL ....................... 151 
20.6.2 
Efficacy analyses for patient subgroups within the subgroup of patients classified as 
DLBCL as per central pathology ................................................................................................... 151 
20.7 
Additional subgroup analyses ................................................................................................... 153 
20.7.1 
Efficacy analyses in subgroups of patients enrolled at sites that enrolled ≤3 vs. >3 
patients 
153 


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20.7.2 
Efficacy analyses in subgroups of patients recruited at US sites vs. European sites ..... 154 
20.7.3 
Efficacy analyses for histological subgroups of NHL ................................................... 154 
20.7.4 
Listings displaying best response and DoR by NHL subtype ....................................... 154 
20.7.5 
Baseline characteristics of various patients subgroups ................................................. 155 
20.8 
Efficacy analyses based on the SAF ......................................................................................... 155 
20.8.1 
Summaries .................................................................................................................... 155 
20.8.2 
Forest plots ................................................................................................................... 156 
20.8.3 
Analyses for the subgroup of patients confirmed as DLBCL by central pathology based 
on the SAF ..................................................................................................................................... 157 
20.9 
PFS and DoR analyses applying alternative censoring rules .................................................... 158 
20.9.1 
Summaries / analyses of PFS ........................................................................................ 159 
20.9.2 
Summaries / analyses of DoR ....................................................................................... 160 
20.10 
First line treatment category ..................................................................................................... 160 
20.11 
Additional safety-related analyses ............................................................................................ 162 
20.11.1 
Listing of TEAEs summarized in as per Section 16.3.1 ............................................... 162 
20.11.2 
Opportunistic infections ............................................................................................... 162 
20.11.3 
TEAEs per patient years of exposure to MOR00208.................................................... 163 
20.12 
TEAEs leading to study drug modifications ............................................................................. 164 
20.13 
Time to onset of individual TEAEs, duration of individual TEAEs, and cumulative duration of 
TEAEs per cumulative exposure to tafasitamab ..................................................................................... 164 
21. 
SAP ADDENDUM 6.0 .................................................................................................................. 166 
21.1 
Post-L-MIND survival ............................................................................................................. 166 
21.2 
PD-related vs. non-PD-related deaths ...................................................................................... 167 
21.3 
Discontinuation of LEN treatment upon completion of Cycle 12 ............................................. 168 
22. 
SAP ADDENDUM 7.0 .................................................................................................................. 171 
22.1 
COVID-19 related missed visits and assessments .................................................................... 171 
APPENDIX: LIST OF CUSTOMIZED MEDDRA QUERIES ................................................................... 173 


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2. LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
ABC 
Activated B-cell 
ADCC 
Antibody-dependent cell-mediated cytotoxicity 
ADCP 
Antibody-dependent cell-mediated phagocytosis 
ASCT 
Autologous stem-cell transplantation 
AE 
Adverse event 
ANOVA 
Analysis of variance 
ATC 
Anatomical therapeutic chemical 
BCL-2/-6 
B-cell CLL/lymphoma 2/6 
BLQ 
Below the limit of quantification 
BMI 
Body mass index 
CD16/19/20 
Cluster of differentiation 16/19/20 
CHOP 
Cyclophosphamide, doxorubicin, vincristine, and prednisone 
CLL 
Chronic lymphocytic leukaemia 
CR 
Complete response 
CRF 
Case report form 
CRS 
Cytokine release syndrome 
CSR 
Clinical study report 
CT 
Computed tomography 
CTC(AE) 
Common Terminology Criteria (for Adverse Events) 
CV 
Coefficient of variation 
DCR 
Disease control rate 
DLBCL 
Diffuse large B-cell lymphoma 
DoR 
Duration of response 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EMA 
European medicines agency 


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EOT 
End of treatment 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
FU 
Follow up 
GCB 
Germinal center B -cell 
GEP 
Gene expression profiling 
HDC/HDT 
High-dose chemotherapy 
HR 
Heart rate 
IAS 
Immunogenicity analysis set 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IHC 
Immuno-histochemistry 
IND 
Investigational new drug 
INV 
Investigator 
IPI 
International prognostic index 
IRR 
Infusion-related reaction 
IRC 
Independent Radiology/Clinical Review Committee 
IV 
Intravenous 
IWG 
International Working Group 
LEN 
Lenalidomide 
mAb 
Monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic resonance imaging 
ms 
Millisecond 
NCI 
National Cancer Institute 
NCS 
Not clinically significant 
NHL 
Non-Hodgkin lymphoma 
NK 
Natural killer 


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ORR 
Objective response rate (complete response + partial response) 
OS 
Overall survival 
PD 
Progressive disease 
PE 
Physical examination 
PET 
Positron emission tomography 
PFS 
Progression-free survival 
PK 
Pharmacokinetics 
PKAS 
PK analysis set 
PPS 
Per-protocol set 
PR 
Partial response 
PR (ECG) 
PR interval 
PT 
Preferred term 
QC/QA 
Quality control/quality assurance 
QRS 
QRS interval 
QT 
QT interval 
QTc 
QT interval corrected 
QTcB 
QT interval, Bazett’s correction 
QTcF 
QT interval, Fridericia’s correction 
R-CHOP 
Rituximab plus cyclophosphamide, hydroxydaunorubicin (also referred 
to as doxorubicin or adriamycin), and oncovin (vincristine) plus 
prednisone or prednisolone 
RR (ECG) 
Relative rate 
R-R DLBCL 
Relapsed or refractory diffuse large B-cell lymphoma 
R-R NHL 
Relapsed or refractory non-Hodgkin lymphoma 
R-R CLL/SLL 
Relapsed or refractory chronic lymphocytic leukaemia/ small 
lymphocytic lymphoma 
RTX 
Rituximab 
SAE 
Serious adverse event 
SAF 
Safety analysis set 


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SAP 
Statistical analysis plan 
SD 
Stable disease 
SI 
System international 
SLL 
Small lymphocytic lymphoma 
SmPC 
Summary of product characteristics 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SPM 
Second primary malignancy 
StD 
Standard deviation 
TEAE 
Treatment-emergent adverse event 
TFR 
Tumour flare 
TLS 
Tumour lysis syndrome 
TTNT 
Time to next treatment 
TTP 
Time to progression 
US 
United States 
WHO-DDE 
World Health Organization–Drug Dictionary Enhanced 


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3. INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the planned analysis and reporting of data 
collected from MorphoSys protocol MOR208C203, Amendment 3.0, Version 6.0, dated 23- 
Oct-2017. Any amendments to the protocol which do not affect the statistical aspects of the 
trial will not necessitate an SAP update. 
 
 
This study is a single-arm, multicentre, open-label, phase IIa study of lenalidomide (LEN) 
combined with MOR00208 in adult patients with relapsed or refractory diffuse large B-cell 
lymphoma (R-R DLBCL). The structure and content of this SAP provides sufficient detail to 
meet the requirements identified by the Food and Drug Administration (FDA), European 
Medicines Agency (EMA), and International Conference on Harmonization (ICH) of Technical 
Requirements for Registration of Pharmaceuticals for Human Use: Guidance on Statistical 
Principles in Clinical Trials. All work planned and reported from this SAP will follow 
internationally accepted guidelines, published by the American Statistical Association and the 
Royal Statistical Society, for statistical practice. 
 
 
The planned analyses identified in this SAP may be included in clinical study report (CSRs) 
and/or in relevant summary report documents (e.g. regulatory submissions, or future 
manuscripts). Also, post-hoc exploratory analyses not necessarily identified in this SAP may be 
performed to further examine study data and will not require updating the final SAP. Any post-
hoc, or unplanned, exploratory analysis performed will be clearly identified as such and 
described in the final CSR. 
The following documents were reviewed in preparation of this SAP: 
• 
Clinical Research Protocol MOR208C203, Amendment 3; Version 6.0, dated 23-Oct-2017 
• 
Annotated electronic Case report forms (eCRFs), Version 6.0, dated 03-May-2018 
• 
ICH Guidance on Statistical Principles for Clinical Trials (E9) 
 
The reader of this SAP is encouraged to also read the clinical protocol, and other identified 
documents, for details on the planned conduct of this study. Operational aspects related to 
collection and timing of planned clinical assessments are not repeated in this SAP unless 
relevant to the planned analysis. 
 
 
4. STUDY OBJECTIVES AND ENDPOINTS 
An overview of the study objectives and endpoints is depicted in Table 1. 


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Table 1: Study objectives and endpoints 
 
Study objective 
Endpoint 
Analysis 
Primary objective: 
Primary endpoint: 
To determine the activity of a 
combination of LEN with 
MOR00208 
in 
terms 
of 
objective response rate (ORR 
= complete response (CR) + 
partial response (PR)) in 
adult patients with R-R DLBCL 
Best Objective Response Rate (ORR), defined 
as the proportion of responders whose best 
response at any time throughout treatment or 
follow-up is complete or partial (ORR=CR+PR) 
See 
9 
section 
Secondary objectives: 
Secondary endpoints: 
1. To determine the disease 
control rate (DCR = CR + PR + 
stable disease (SD) as best 
response) 
Disease Control Rate (DCR = CR+PR+SD as 
best response) 
See 
10.1 
section 
2. To determine progression- 
free survival (PFS) 
Progression-free Survival (PFS) 
See 
 
section 
3. To determine the duration 
of response (DoR) 
Duration of Response (DoR) 
See 
10.3 
section 
4. To determine the overall 
survival (OS) 
Overall Survival (OS) 
See 
10.4 
section 
5. To determine 
progression (TTP) 
time to 
TTP 
See 
10.5 
section 


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6. To determine the time to 
next treatment (TTNT) 
To deter
(TTNT) 
mine the time to next treatment 
See 
10.6 
section 
7. To determine the safety of 
LEN 
combined 
with 
MOR00208 
assessed 
according to the frequency 
and 
severity 
of 
adverse 
events (AEs) 
Incidence, 
frequency 
and 
severity 
of 
treatment-emergent AEs 
See 
10.7 
section 
8. To assess the potential 
immunogenicity 
of 
MOR00208 (anti-MOR00208 
antibodies) 
Anti-MOR00208 antibody formation (ADA): 
number and percentage of patients who 
develop anti-MOR00208 antibodies; Titer 
determination; Characterization of ADA- 
positive 
samples 
(neutralizing 
vs 
non- 
neutralizing) 
See 
10.8 
section 
9. 
To 
assess 
pharmacokinetics 
(PK) 
MOR00208 
the 
of 
Summary 
statistics 
for 
PK: 
plasma 
concentration-time profiles of MOR00208 
and appropriate individual PK parameters 
(e.g. accumulation ratios). 
See 
10.9 
section 
10. To make a preliminary 
evaluation of ORR, DCR, DoR, 
PFS, OS, TTP and TTNT in 
patients 
treated 
with 
a 
combination of LEN plus 
MOR00208 in cohorts with a 
“low risk”, “low-intermediate 
risk”, 
“high-intermediate 
risk” and “high risk” according
 
to 
the 
International 
Prognostic 
Index (IPI) 
ORR, DCR, DoR, PFS, OS, TTP, and TTNT 
stratified by: 
• 
four risk categories: “low risk”, “low- 
intermediate risk”, “high-intermediate 
risk” and “high risk” 
• 
2 risk categories: patients with “low risk” 
and “low-intermediate risk” vs. patients 
with “high-intermediate risk” and “high” 
risk 
See section 
10.10 
11. 
To 
compare 
each 
TTP in patients treated with LEN plus 
See section 
patient’s TTP on LEN plus 
MOR00208, and TTP in each individual´s 
10.11 
MOR00208 with the TTP of 
most recent prior treatment therapy. 
their 
most 
recent 
prior 
therapy 
12. 
To correlate 
efficacy 
parameters 
with 
certain 
Stratification of efficacy parameter according 
See section 


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biomarkers 
(e.g. 
baseline 
tumour 
CD19 
expression 
level, 
peripheral 
Natural 
Killer 
(NK) 
cell 
count, 
constitutional FcγRIIIa and 
FcγRIIa polymorphism status) 
to the following subgroups: 
• 
FcγRIIIa affinity (high affinity: FCGR3A- 
158V homozygosity vs. low affinity: 
FCGR3A-158F homozygosity, or FCGR3A- 
158F/V heterozygosity) 
• 
FcγRIIa affinity (high affinity: FCGR2A- 
131H homozygosity vs. low affinity: 
FCGR2A-131R homozygosity, or FCGR2A- 
131H/R heterozygosity) 
10.12 
• 
Cell-of-origin (determined by immuno- 
histochemistry/central 
pathology: 
Germinal center B-cell (GCB) vs. non- GCB) 
• 
Peripheral NK cell numbers at baseline (< 
median of NK cell numbers/µl vs. ≥ 
median of NK cell numbers/µl) 
 
5. STUDY DESIGN 
5.1 General study design 
This is a single-arm, multicentre, open-label phase II, study of LEN combined with MOR00208 
in adult patients with DLBCL who have relapsed after or are refractory to at least one, but no 
more than three previous systemic regimens administered for the treatment of their DLBCL 
and who are not candidates for high-dose chemotherapy (HDC) and subsequent autologous 
stem cell transplantation (ASCT) and are thus considered to have exhausted their therapeutic 
options for demonstrable clinical benefit. One prior therapy line must include an anti-CD20 
targeted therapy (e.g. rituximab (RTX)). 
Patients with primary refractory DLBCL, patients with known "double/triple hit" DLBCL 
genetics or those who have undergone previous allogenic stem cell transplantation are not 
eligible for study participation. Additionally, patients with a history of ASCT ≤3 months prior 
to the requirement to provide signed informed consent cannot be included in the study. 
This study will consist of two parts, which will be performed sequentially. During the course 
of the first part, six patients will be enrolled in the study and will complete the first cycle of 
study treatment. Once the sixth patient in the cohort has completed Cycle 1 Day 22 visit, a 
Safety Review Panel which consists of the sponsor, a representative of the participating 
investigators and two independent expert clinical haematologists will perform a clinical safety 
review based on the number and type of AEs occurring during the first cycle and on laboratory 
values (biochemistry and haematology). A LEN dose will be considered tolerated 


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or in need of reduction after discussion of these data between the sponsor’s Clinical Program 
Leader (or designee), the sponsor’s Drug Safety Officer (or designee), a representative of the 
participating investigators and two expert clinical haematologists who are not participating in 
the study. The second part of the study will only be opened for enrolment by the sponsor 
following the outcome of this discussion. 
Treatment consisting of LEN and MOR00208 combination will be administered up to twelve 
28-day cycles (Figure 1) at specified dose levels. 
 
 
MOR00208 dose: 12 mg/kg 
For the first three cycles (Cycles 1-3) of the study each cycle will consist of a MOR00208 
infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally, a loading dose will be 
administered on Day 4 of Cycle 1. Thereafter MOR00208 will be administered on a bi-weekly 
(every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. 
MOR00208 can be administered until disease progression, or unacceptable toxicity, or 
discontinuation for any other reason, whichever comes first. It is up to the investigator to 
decide according to the individual risk/benefit ratio if the patient should continue further 
treatment with MOR00208 in spite of disease progression. 
 
 
LEN: 
Patients will self-administer a starting dose of 25 mg oral LEN daily on Days 1–21 of each cycle. 
Treatment with LEN may be modified in a de-escalating fashion or discontinued based upon 
clinical and laboratory findings. Detailed dose modification guidelines to manage 
haematologic and/or other toxicities are provided in the respective sections of the protocol. 
LEN can be given for up to 12 cycles in total. Treatment with LEN will have to be stopped in 
the case of disease progression, or unacceptable toxicity, or discontinuation for any other 
reason, whichever comes first. 


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Figure 1: Study design 
 
 
 
Abbreviations: EOT=end of treatment; FU=follow-up; LEN=lenalidomide; R-R DLBCL=relapsed or refractory diffuse 
large B-cell lymphoma. 
 
 
Objective disease response assessments will be made according to the revised response 
criteria based on the guidelines of the International Working Group (IWG) reported by Cheson 
et al. (2007). The data used for the primary statistical analyses will be derived from a central 
independent review of the radiological + clinical disease assessments. A charter outlining the 
central imaging plus clinical assessment will be prepared. 
 
 
Approximately 80 patients with R-R DLBCL who meet the inclusion criteria and have none of 
the exclusion criteria will be enrolled in the study. This study will be conducted under a United 
States (US) Food and Drug Administration (FDA) Investigational New Drug (IND) application. 
 
 
5.2 Schedule of assessments 
For a detailed schedule of assessments, please refer to the Protocol Section 7. 
 
 
5.3 Determination of sample size 
Approximately 80 patients with R-R DLBCL who meet all of the inclusion criteria and have none 
of the exclusion criteria will be enrolled into the study. The study will be performed with an 
interim stop for the evaluation of the safety of the LEN dosage. No adjustment of sample size 
or adaptation of efficacy evaluations will be made at this point. As the primary purpose of this 
study is to evaluate the clinical efficacy of 25 mg daily oral LEN combined with 12 mg/kg 
MOR00208 administered by IV infusion in patients with R-R DLBCL, no formal statistical 
hypothesis testing will be performed. 


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For the determination of a suitable sample size, it is assumed that the combination treatment 
could improve the ORR of LEN from a value of 20% (under monotherapy) to 35% (under 
combination therapy). Applying an exact binomial test with a two-sided significance level of 
5% and a power of 85% the estimated sample size is 73 patients (calculation performed by 
nQuery Advisor® 7.0). According to this scenario an observed ORR of 32% would lead to the 
conclusion that the outcome is statistically superior to outcomes observed previously for the 
monotherapy. Assuming a drop-out rate of 10%, a total sample size of about 80 patients is 
estimated. 
The sample size determination has been conducted using various possible monotherapy and 
combination effect ORR rates and various power assumptions. Literature evaluation of study 
results concerning the ORR rates of LEN or comparable products (as mono- or combination 
therapy) as well as study results for MOR00208 ongoing studies were used to justify 
assumptions on response rates (Witzig et al., 2011; Wang et al., 2013). 
 
 
5.4 Timing of analyses 
5.4.1 Safety run-in analysis 
A Safety Review Panel consisting of the sponsor, a representative of the participating 
investigators and two independent expert clinical haematologists will perform a clinical safety 
review after the first six patients have been accrued based on the number and type of AEs 
occurring during the first cycle and on laboratory values (biochemistry and haematology). A 
total of six patients will be evaluated. A LEN dose will be considered tolerated or in need of 
reduction after discussion of these data between the sponsor’s Clinical Program Leader (or 
designee), the sponsor’s Drug Safety Officer (or designee), a representative of the 
participating investigators and two expert clinical haematologists who are not participating in 
the study. The second part of the study will only be opened for enrolment by the sponsor 
following the outcome of this discussion. 
 
 
5.4.2 Primary analysis 
The primary analysis will be conducted earliest after all patients have undergone at least one 
post-baseline response assessment (for those patients who did not discontinue before due to 
reasons such as death, adverse event, informed consent withdrawal etc.). The sponsor will 
decide when to perform the primary analysis (approximately 12 months after the last patient 
has been enrolled). All results of the primary analysis will be made available to MorphoSys AG 
prior to completion of the final CSR. 


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5.4.3 Final analysis 
The final analysis will be performed when all patients have performed their End of Treatment 
visit. The analyses will be conducted after database lock. All study results will be made 
available to MorphoSys AG prior to completion of the final CSR. 
MorphoSys may perform further exploratory analyses to investigate correlations between 
different biomarker and response variables. Any post-hoc, exploratory analyses completed to 
support planned study analyses, which were not identified in this SAP, will be documented 
and reported in appendices to the CSR, but will not necessitate an update of the final SAP. 
Any results from these unplanned analyses (post-hoc) will also be clearly identified in the text 
of the CSR. 
 
 
6. DEFINITIONS AND GENERAL METHODOLOGY 
6.1 Enrolment date 
The first date of administration of any study drug (i.e., MOR00208 or LEN). 
 
 
6.2 Study drug and study treatment 
Study treatment refers to MOR00208 in combination with LEN. Study drug refers to the 
individual drugs: MOR00208 or LEN. 
 
 
6.3 Study drug administration 
6.3.1 Date of first administration of study drug 
The date of first administration of study drug is the first date when a non-zero dose of study 
drug is administered and is referred as “start date of study drug”. Start date of study drug is 
defined for each drug which is part of study treatment. 
 
 
6.3.2 Date of last administration of study drug 
The date of last administration of study drug (“last date of study drug”) is the last date when 
a non-zero dose of study drug is administered. 
Last date of study drug is defined for each drug which is part of study treatment. 


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6.3.3 Date of first administration of study treatment 
The date of first administration of study treatment (“start date of study treatment”) is the 
first date when a non-zero dose of any component of study treatment is administered. 
For example: if the 1st dose of MOR00208 is taken on 03JAN2017, and 1st dose of LEN is 
taken on 05JAN2018, then the “Start date of study treatment” is 03JAN2017. 
 
 
6.3.4 Date of last administration of study treatment 
The date of last administration of study treatment (“last date of study treatment”) is the last 
date when a non-zero dose of any component of study treatment is administered. 
For example: if the last dose of MOR00208 is taken on 13APR2017, and last dose of LEN is 
taken on 20APR2018, then the “Last date of study treatment” is 20APR2018. 
 
 
6.4 Reference start date and study day 
The reference start date for all safety assessments (e.g. adverse event onset, laboratory 
abnormality occurrence, vital sign measurement, dose interruption etc.) will be the start date 
of study treatment. 
The reference start date for all efficacy assessments (e.g. tumour assessment, death, ECOG 
performance status) will be the start date of study treatment. 
For any non-safety screening assessments or events such as baseline disease characteristics 
or medical history (e.g., time since diagnosis of disease) that occurred prior to start date of 
study treatment the reference start date will be the start date of study treatment. 
The study day describes the day of the event or assessment date, relative to the reference 
start date (i.e., the study treatment). 
The reference start date is designated as Study Day 1. Study Day –1 is the day that precedes 
Study Day 1. Study Day 0 is not defined. 
The study day will be calculated as: 
o The date of the event (visit date, onset date of an event, assessment date etc.) minus 
reference start date + 1 if the event is on or after the reference start date. 
o The date of the event (visit date, onset date of an event, assessment date etc.) minus 
reference start date if the event precedes the reference start date. 
The study day will be displayed in the data listings. It will not be used for numerical 
computations for example calculating exposure. 


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6.5 Screening failure 
These patients are not treated. Screening failures are patients who have signed informed 
consent and failed screening criteria in a study. Patients who signed informed consent and 
fulfilled screening criteria, but have never received treatment are not considered as screening 
failures. 
 
 
6.6 Time unit 
A month-length is 30.4375 days (365.25 / 12). If duration is to be reported in months, duration 
in days is divided by 30.4375. If duration is to be reported in years, duration in days will be 
divided by 365.25. 
 
 
6.7 Baseline 
Baseline is the result of an investigation describing the “true” uninfluenced state of the 
patient, defined as the period from the date of signing any informed consent document to the 
start date of study treatment. Assessments, specified to be collected post-dose on the first 
date of treatment are not considered as baseline values. 
For efficacy evaluations, the last non-missing assessment, including unscheduled assessments 
on or before the start date of study treatment will be used as “baseline” value or “baseline” 
assessment. In the context of baseline definition, the efficacy evaluations also include the 
ECOG performance status. 
For safety evaluations, unless otherwise stated, the last available assessment, including 
unscheduled assessments on or before the start date of study treatment will be used as 
“baseline” value or ‘‘baseline” assessment. 
If patients have no value as defined above, the baseline result will be missing. 
 
 
6.8 On treatment assessment/event 
An on-treatment assessment/event is defined as any assessment/event happening after the 
start date of study treatment, i.e. assessments/events happening in the following time interval 
(including the lower and upper limits): start date of study treatment + 1; last date of study 
treatment + 30 days. 
Assessments collected post-dose on the start date of study treatment are on-treatment 
assessments. Data listings will include all assessments/events, flagging those which are not 
on-treatment assessments/events. 
A post-treatment assessment/event is defined as any assessment/event happening after the 
completion of on-treatment phase, that is assessments/events happening in the 


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following time interval (including the lower and upper limits): date of last administration of 
study treatment + 30 days + 1; Date of Study Discontinuation. 
 
 
6.9 Start and end date for time to event variables 
Assessment date 
For each assessment (i.e. evaluation number), the assessment date is calculated as the latest 
of all measurement dates (e.g. X-ray, CT-scan) if the overall response at that assessment is 
CR/PR/SD/UNK/NE. 
Otherwise - if overall response is progression – the assessment date is calculated as the 
earliest date of all measurement dates at that evaluation number. 
 
 
Start dates 
For all “time to event” variables, other than duration of response, the start date of study 
treatment will be used as the start date. 
For the calculation of duration of response the following start date should be used: 
Date of first documented response is the assessment date of the first overall response of CR 
or PR. 
 
 
End dates 
The end dates which are used to calculate ‘time to event’ variables are defined as follows: 
o Date of death (during treatment as recorded on the treatment completion page or during 
follow-up as recorded on the study evaluation completion page or the survival follow-up 
page). 
o Date of progression is the first assessment date at which the overall response was 
recorded as progressive disease. 
o When there is no documentation of radiologic evidence of progression, and the patient 
discontinued for ‘Disease progression’ due to documented clinical deterioration of 
disease, the date of discontinuation is used as date of progression. 
o If no post-baseline assessments are available (before an event or a censoring reason 
occurred) the start date of study treatment is used as the end date. 
 
 
Calculation of ‘time to event’ variables 
Time to event = End Date - Start date + 1 (in days). 


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When no post-baseline tumor assessments are available, the start date of study treatment 
will be used as end date (duration = 1 day). 
 
 
6.10 Date of last contact 
The date of last contact is derived for patients not known to have died at the analysis cut-off 
date (see section 7.4) based on the latest date among the following: 
• 
Actual assessment dates (Labs, vital signs, performance status, tumour imaging, EOT 
completion, PK sample collection dates). 
• 
Antineoplastic therapies administered after study drug discontinuation. 
• 
Adverse events dates. 
• 
“Date of contact” or “Last known date patient alive” collected on the “Survival Follow- 
up” eCRF page (if applicable). 
• 
Date of study completion or discontinuation from the “End of Survival Follow-up” eCRF 
page. 
• 
Study treatment start/end date. 
The date of last contact is defined as the latest date from the above list or the cut-off date 
whichever comes first. In case that a date is only partially complete the following rules will be 
applied. If month and year are present and only the day is missing the first day of the month 
will be used to impute the missing date. If day and month or year is missing the date will not 
be imputed. The date of last contact is used for censoring of patients in the analysis of overall 
survival and time to next treatment. 
 
 
6.11 Analysis windows 
For parameters that will be summarized by visit, the nominal visit as recorded in the eCRF will 
be used. There will be no additional analysis windowing done based on the assessment date. 
In order to summarize over time, parameters recorded at each visit (i.e. performance status, 
PK, vital signs), assessments (including unscheduled ones) will be time-slotted if indicated. 
 
 
6.12 Selection of data in the event of multiple records in a window 
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value per visit, 
whereas a time-to-event analysis would not require one value per analysis window but rather 
one value for the study. 
Unless otherwise noted throughout the rest of this document, when a single value is needed, 
the following rule(s) will be used: 


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• 
If more than one assessment occurs during the same nominal visit time window of the 
planned visit, select the record closest to the nominal day for that particular visit day. 
• 
If there are two assessments that are equidistant from the nominal planned visit day, 
the data of the assessment after the scheduled study day will be used. 
• 
The last measurement will be used if multiple measurements are all taken on the same 
day. 
 
 
6.13 Analysis populations 
The following analysis populations will be defined: 
 
 
6.13.1 All patients screened 
The All patients screened population consists of all patients who signed informed consent and 
completed the Informed Consent eCRF page. 
 
 
6.13.2 Enrolled patients 
The Enrolled patients population consists of all patients who received at least one dose of any 
study drug (MOR00208 or LEN). 
 
 
6.13.3 Full analysis set (FAS) 
The FAS includes all patients who received at least one dose of MOR00208 and one dose of 
LEN. This means that both study drugs must have been administered at least once. The FAS 
will be the primary population for the analysis of efficacy and baseline characteristics. 
A listing showing the patients who have been excluded from the efficacy analysis will be 
provided. 
 
 
6.13.4 Per protocol set (PPS) 
The PPS includes all patients in the FAS who do not have any major protocol deviations that 
could confound the interpretation of the primary analyses conducted on the FAS. The PPS 
includes all patients in the FAS who have received at least one dose of MOR00208 and LEN, 
and underwent at least one post-baseline response assessment. 
Those protocol deviations leading to exclusion from the PPS will be listed including the patient 
number 


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6.13.5 Safety set (SAF) 
The SAF includes all patients who received at least one dose of MOR00208 or LEN and had 
at least one post-baseline safety assessment. 
A valid safety assessment includes death. A “no adverse event” record is also considered as 
a valid safety assessment. 
Analyses using the SAF will be based on the treatment study drug actually received. 
 
 
6.13.6 PK analysis set (PKAS) 
The PKAS will include all patients who received at least one dose of MOR00208 and have at 
least one quantifiable serum MOR00208 concentration (PK parameters will be calculated as 
data permits). 
 
 
6.13.7 Immunogenicity analysis set (IAS) 
The IAS includes all patients who have at least one anti-MOR00208 antibody assessment. 
 
 
6.13.8 Planned analyses for the different populations 
The number of patients in each analysis set will be summarized. 
 
 
Table 2 gives an overview of the assessments performed on the different analysis sets. 
 
 
Table 2: Overview of the analyses performed on the different analysis populations 
 
Analysis 
All 
patients 
screened 
FAS 
PPS 
SAF 
PKAS 
IAS 
Patient disposition 
x 
Summary of baseline characteristics 
x 
x 
Overall response rate, disease control rate (central and 
local evaluation) 
x 
x 
PFS (central and local evaluation) 
x 
x 
Duration of response, duration of best overall response 
(central and local evaluation) 
x 
x 
Time to response (central and local evaluation) 
x 
x 


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Time to next treatment 
x 
x 
Time to progression (central and local evaluation) 
x 
x 
Overall survival 
x 
x 
Efficacy subgroup analyses 
x 
x 
ECOG performance status, B-symptoms 
x 
x 
Summary of drug exposure and compliance 
x 
x 
Summary of prior therapies 
x 
x 
Summary 
of 
pre-medication, 
prior medication, 
concomitant medication 
x 
x 
Summary of medical history and current medical 
condition 
x 
x 
Summary of vital signs, 12-lead ECG, laboratory safety 
evaluations, adverse events 
x 
Pharmacokinetic analyses 
x 
Immunogenicity analyses 
x 
Descriptive biomarker analyses 
x 
 
6.13.9 Withdrawal of informed consent 
Any data collected in the clinical database after a patient withdraws informed consent from 
all further participation in the trial, will not be included in the analysis data sets. The date on 
which a patient withdraws full consent is recorded in the eCRF (on the end of treatment eCRF 
page). Note: Patients who withdraw consent from treatment but consent to post- treatment 
follow up and/or survival follow up are not considered as having withdrawn full consent and 
no such withdrawal of consent date is recorded in the eCRF. Such post- treatment assessments 
will be included in the analysis data sets. 
Any data that is entered in the clinical database without the consent of the patient will be 
excluded from the analysis sets. Only exceptions are the information entered to close a page 
after the date of withdrawal of consent e.g. End of Treatment, End of post-treatment follow-
up. 
For OS, death events in some countries can be reported if the death event can be confirmed 
to be captured from public records. If confirmed, the events will be included in the analysis 
data sets. 
Third party data, e.g. PK, biomarker etc., collected in the clinical database without having 
obtained consent for collection will not be included in the analysis data sets. Data from such 
samples if collected prior to the date of consent withdrawal will be included in the analysis 
unless specific request is made by the patient not to analyze the sample. These data will be 
excluded by the presence of the appropriate protocol deviation criterion. 


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6.14 Efficacy Assessments 
6.14.1 Response criteria 
The efficacy variables / endpoints will be evaluated through central review by an Independent 
Radiology/Clinical Review Committee (IRC) that will apply the revised response assessment 
criteria based on the guidelines of the IWG reported by Cheson et al. (2007) (see Error! 
Reference source not found.). The review process will be defined in the IRC Charter. 
Local assessment of efficacy response (Cheson criteria) will be required in addition to central 
review at the beginning of Cycle 3, Cycle 5, Cycle 7, and Cycle 10, at the end of Cycle 12 (for 
decisions concerning the additional Cycle 13 through Cycle 24 MOR00208 treatment) and at 
the EOT Visit (to determine whether the disease has progressed). During the treatment phase 
from Cycle 13 onwards (MOR00208 monotherapy phase) tumour response assessments will 
be performed as follows: for Cycles 13 - 24 local assessments of response will be done 
approximately every 3 months ± 2 days from the previous scan. First assessment during this 
phase can be done directly 3 months after Cycle 12 Day 28 PET/CT assessment. Thus, the first 
response assessment after Cycle 12 is not needed at Cycle 13 Day 1. Moreover, the first 
assessment during the MOR00208 monotherapy phase can generally happen later than 3 
months after the Cycle 12 Day 28 assessment. From Cycle 25 onwards local assessments of 
response will be performed approximately once per year ± 2 weeks from the previous scan. 
Efficacy will be evaluated in terms of (best) ORR (primary endpoint), DCR, DoR, PFS, OS, TTP 
and TTNT (secondary endpoints) based on both INV and IRC response assessment. For 
definitions, see Sections 9 (primary endpoint) and 10 (secondary endpoints). 
 
 
Table 3: Definition of Response Criteria (Cheson et al., 2007) 
 
Response 
Definition 
Nodal masses 
Spleen, liver 
Bone marrow 
CR 
Disappearance of 
all evidence of 
disease 
a) FDG-avid or PET positive 
prior to therapy; mass of 
any size permitted if PET 
negative 
b) Variable FDG-avid or PET 
negative; regression to 
normal size on CT 
Not 
palpable, 
nodules 
disappeared 
Infiltrate cleared 
on 
repeat 
biopsy; 
 
if 
indeterminate 
by morphology, 
immunohisto- 
chemistry should 
be negative 
PR 
Regression 
of 
measurable 
disease and no 
new sites 
≥50% decrease in SPD of up 
to 
6 
largest 
dominant 
masses; no increase in size 
on CT 
a) FDG-avid or PET positive 
≥50% 
decrease 
in   SPD   of 
nodules 
(for 
single nodule in 
greatest 
Irrelevant 
if 
positive prior to 
therapy; 
cell 
type should be 
specified 


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prior to therapy; one or 
more PET positive at 
previously involved site 
b)Variable FDG-avid or PET 
negative; regression on 
CT 
transverse 
diameter); 
no 
increase in size 
of liver or spleen 
SD 
Failure to attain 
CR/PR or PD 
a) FDG-avid or PET positive 
prior to therapy; PET 
positive at prior sites of 
disease and no new sites 
on CT or PET 
b) Variable FDG-avid or PET 
negative; no change in 
size of previous lesions 
on CT 
Relapsed 
disease or 
PD 
Any new lesion or 
increase by ≥50% 
of 
previously 
involved 
sites 
from nadir 
a) Appearance of a new 
lesion(s) >1.5 cm in any 
axis, ≥50% increase in 
SPD of more than one 
node, or ≥50% increase 
in longest diameter of a 
previously 
identified 
node >1 cm in short axis 
b) Lesions PET positive if 
FDG-avid lymphoma or 
PET positive prior to 
therapy 
>50% 
increase 
from nadir in the 
SPD 
of 
any 
previous lesions 
New 
or 
recurrent 
involvement 
Abbreviations: CR = complete response; FDG = [18F]fluorodeoxyglucose; PET = positron emission 
tomography; CT = computed tomography; PR = partial response; SPD = sum of the product of the 
diameters; SD = stable disease; PD = progressive disease. 
 
 
6.14.2 Disease progression 
Only objective progressive disease (PD) according to the Cheson criteria as mentioned in Table 
3 is considered in all efficacy analyses. 
In particular, discontinuation due to PD (from the “End of Treatment Completion” eCRF page), 
without supporting objective evidence (as defined above), will not be considered as PD in the 
determination of best overall response rate (ORR) and in the analysis for progression-free 
survival (PFS). 


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6.14.3 Change in imaging modality 
Magnetic resonance imaging (MRI) may be used in lieu of CT, and PET/MRI in lieu of PET/CT 
for patients with contraindications to the administration of contrast agents, or due to other 
medical reasons, at the same time points as CT, or in addition to CT, at the discretion of the 
investigator (in this case, MRI may be performed as/when appropriate). The method used at 
baseline should be used throughout the study unless otherwise medically indicated. 
 
 
7. STATISTICAL METHODOLOGY 
7.1 General principles of statistical programming 
The statistical analysis will be performed on the analysis study database with appropriate 
software, SAS® Software version 9.4 or above (SAS Institute, Cary, N.C.). 
 
 
7.2 Variable types and descriptive statistics 
Descriptive statistics will be calculated using as reference the number of patients in the 
relevant analysis population (any exception will be specified) according to the nature of the 
data as follows: 
Continuous variables (e.g. age, body weight): number of non-missing observations, arithmetic 
mean, standard deviation (StD), minimum and maximum values, quartiles (median, Q1 and 
Q3). 
If there are less than 5 observations, only the number of non-missing observations, arithmetic 
mean, median, minimum and maximum will be presented. 
Descriptive statistics of plasma concentrations and PK parameters will include n, arithmetic 
mean, geometric mean, StD, median, coefficient of variation CV (%), geometric CV (%), 
minimum and maximum. Geometric mean and the geometric CV (%) will be derived from non-
zero values. For plasma concentrations, the number of non-zero values (m) will also be 
reported. 
Categorical variables: (e.g. ECOG, ethnicity) Number of non-missing observations, the number 
of missing and the relevant percentage on the analysis population, number and relative 
frequencies. If not defined otherwise, the percentage denominator will be the number of 
patients with non-missing information. 
In case of subcategories, the relative frequencies will be calculated on the basis of the patients 
in the respective category, in this case a footnote will be added explaining the different 
denominators. 


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Time variables (durations): Will be summarized using arithmetic mean, StD, minimum and 
maximum values, median and quartiles (Q1, Q3) and will be presented in months (unless 
otherwise stated). 
Time to event variables: (PFS, OS, etc.) Unless otherwise stated, Kaplan Meier estimates of 
Q1, Median, and Q3 along with their 95% Confidence Intervals will be presented. 
The majority of data obtained on the eCRF and entered into the database will be provided in 
separate data listings showing individual patient values. The planning and reporting of 
statistical analyses will be carried out as described in the 
standard operating procedures 
(SOPs). 
Any patient who withdraws from the study will be analyzed with the data available. 
Imputation of missing values will not be performed, unless specified in the relevant sections 
of the SAP. 
 
 
7.3 Convention on missing data 
For the statistical analysis, some particular data handling conventions (handling of missing 
data, pooling of centers) are planned. The details are present in the respective sections. 
 
 
7.4 Data included in the analysis and cut-off date 
All the analyses mentioned in Sections 8 to 16 will be performed using data collected in the 
database up to the data cut-off date. A cut-off date will be defined for each of these analyses 
and will be specified in the outputs. 
Of all the termination dates of the patients included in the final analysis, the last termination 
visit date will be defined as the cut-off date and will be specified in the outputs. 
Analyses will be based on the data collected for patients who did not fail screening, and for all 
patients treated prior to or on the cut-off date. 
Any data collected beyond the cut-off date will not be included in the analysis. Only data with 
an assessment date or event start date (e.g. vital sign assessment date or start date of an 
adverse event) prior to or on the cut-off date will be included in the analysis. For example, if 
the cut-off date is 15JUN2017 then an AE starting on 13JUN2017 will be reported, whereas 
an AE with start date on 17JUN2017 will not be reported. 
All events with an event start date either before or on the cut-off date and an event end date 
after the cut-off date will be reported as “continuing at the cut-off date”. The same rule will 
be applied to events starting either before or on the cut-off date and not having a documented 
end date. This approach applies, in particular, to adverse event and concomitant medication 
reports. For these events, the end date will not be imputed and therefore will appear as 
missing in listings. 


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If it is required to impute an end date to be able to perform a specific analysis (e.g. end date 
after the cut-off date) the cut-off date needs to be imputed as an end date. The imputed date 
will be displayed and flagged in the listings. 
Any data collected beyond a patient’s withdrawal of consent will not be included in the 
analysis; except for SAEs and the date of death provided confirmed by a public registry and 
patient status entered after the date of withdrawal of consent e.g. end of treatment, end of 
post-treatment follow-up. 
 
 
7.5 Specifications and Analysis Database 
Based on dataset in SDTM format provided by 
’s Clinical Data Services group analysis 
datasets adhering to CDISC ADaM standard will be generated with SAS ® software, version 
9.4 or above, based on the soft lock of data for the main analysis or hard lock study database 
for the full final statistical analysis (after all the patients discontinue the study) and according 
to agreed Analysis Dataset Specifications (ADS). 
 
 
7.6 Pooling of investigative sites 
Data will be pooled from all investigative sites for the analyses. The justification for this is 
based on the following: 
• 
The sites must implement one common protocol. 
• 
The sponsor must provide close monitoring of study procedures and compliance. 
• 
Several sites are expected to recruit a few patients only. 
• 
The study sites must use common data collection procedures. 
• 
For primary endpoint analysis the disease response assessments will be made 
centrally. 
Geographical region, however, may be included as a factor in supportive and/or exploratory 
analyses, as well as safety analyses. 
 
 
8. PATIENT DISPOSITION, BACKGROUND AND BASELINE 
CHARACTERISTICS 
The number of patients screened, treated, progressed/relapsed, died, and those included in 
each analysis population will be summarized. In addition, patients will be listed and 
summarized who discontinue treatment during the combination phase (cycles 1 to 12), 
antibody monotherapy treatment phase (> cycle 12), or are being treated despite 


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progression, along with reasons for discontinuation. The number of patients followed up for 
overall survival will be summarized. 
8.1 Screened patients 
The number (%) of patients who were 
• 
Screened 
• 
Screen failure 
• 
Enrolled 
will be summarized by country, center, and overall. Percentages will be calculated based on 
the number of patients screened. In a separate summary the reason for screen failures will be 
presented. 
 
 
8.2 Enrolled patients 
The following summaries will be provided: % based on the total number of Enrolled 
patients: 
• 
Number (%) of patients who were treated with study drug (split by MOR00208, LEN, and 
both study drugs). 
• 
Number (%) of patients who are still on-treatment with study drug split MOR00208, 
LEN, both drugs, or any drug (all Cycles considered; only for the primary analysis). 
• 
Number (%) of patients who are ongoing with combination treatment (Cycles 1-12). 
• 
Number (%) of patients who discontinued only one of the two study drugs (split by LEN 
only, MOR00208 only), or both study drugs during combination treatment (Cycle 1 to 12) 
including the primary reason for discontinuation. The discontinuation of LEN as per 
protocol after Cycle 12 will not be considered here. If drugs are sequentially discontinued, 
the reason for discontinuation of the later drug will be reported as reason for the 
discontinuation of both drugs. 
• 
Number (%) of patients who discontinued MOR00208 or LEN before completing 12 Cycles. 
All discontinuations are considered including both the discontinuation of MOR00208/LEN 
only or a sequential discontinuation of both drugs. The reason for discontinuation will also 
be reported. 
• 
Number (%) of patients who successfully completed combination treatment (Cycles 1- 12), 
i.e., patients who completed 12 Cycles on both drugs. 
• 
Number (%) of patients who reached Cycle 13 Day 1 on at least one study drug (split by 
both drugs, LEN only, MOR00208 only, any study drug). 


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• 
Number (%) of patients who are still ongoing with MOR00208 only, LEN only, or both drugs 
after completion of Cycle 12 (i.e., ongoing from Cycles 13 onwards; only for primary 
analysis). 
• 
Number (%) of patients who discontinued MOR00208 beyond Cycle 12 regardless of 
successful or unsuccessful completion of the combination treatment phase, including the 
reason for discontinuation. 
• 
Number (%) of patients who discontinued MOR00208 after successful completion of 
combination treatment phase (Cycle 1-12) including the reason for discontinuation. 
Successful completion means that the patient completed 12 Cycles on combination 
treatment. 
• 
Number (%) of patients who discontinued LEN after completion of the combination 
treatment (Cycle 1 to 12) including the reason for discontinuation (e.g., completion as per 
protocol). 
NOTES: 
o The following reasons for ‘End of Treatment’ as entered on the ‘End of Treatment’ 
eCRF page will be summarized under the term as “As per protocol”: 
 
▪ 
“CYCLE COMPLETED - LAST DOSE OF LENALIDOMIDE ON AUG, 20TH 2017” 
▪ 
“AS PER PROTOCOL” 
▪ 
“PER PROTOCOL” 
▪ 
“TREATMENT COMPLETED PER PROTOCOL” 
▪ 
„ACCORDING TO PROTOCOL“ 
▪ 
“IT WAS STOPPED AFTER 12 CYCLES PER PROTOCOL” 
▪ 
“PATIENT COMPLETED 12 CYCLES TREATMENT” 
▪ 
“COMPLETED” 
▪ 
“LEN TREATMENT COMPLETED" 
o Patients are only treated with LEN for 12 Cycles as per protocol. However, patients 
who reached Cycle 13, and who are still on treatment with MOR00208 are not 
depicted on the ‘End of Treatment’ page as only patients who have undergone an ‘End 
of Treatment Visit’ will be represented on this page. To also consider LEN 
discontinuations ‘as per protocol’ for patients who are still ongoing with MOR00208 
treatment the following strategy will be applied: 
Patients who reached Cycle 13 and who are not already represented on the ‘End of 
Treatment’ page will also be reported as having discontinued LEN. The reason for 
discontinuation will be reported as “As per protocol” if there is no evidence from 


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the recoded adverse events that a patient has discontinued LEN due to an adverse 
event, i.e. action taken with LEN for the respective event is recorded as ‘Study drug 
permanently discontinued due to this AE. In the latter case the reason for 
discontinuation will be reported as “Adverse Event”. 
• 
Number (%) of patients who discontinued LEN at any time during the study including the 
reason for discontinuation. 
• 
Number (%) of patients who discontinued MOR00208 at any time during the study 
including the reason for discontinuation. 
• 
Number (%) of patients who discontinued LEN at any time during the study without 
discontinuation of MOR00208 at the same time including the reason for discontinuation. 
• 
Number (%) of patients who discontinued MOR00208 at any time during the study 
without discontinuation of MOR00208 at the same time including the reason for 
discontinuation. 
 
 
Listings showing the reason for being eligible based on inclusion and exclusion criteria will 
be shown. Another listing depicting information on patient disposition will be prepared. 
 
 
8.3 Survival follow-up period and survival follow-up 
8.3.1 Summary statistics 
The following summaries will be provided (based on the total number of SAF patients): 
o Number (%) of patients who have entered the survival follow-up following the 30- 
day safety follow-up visit. 
o Number (%) of patients who have discontinued from the survival follow-up. 
o Reasons for discontinuation from the survival follow-up. 
 
8.3.2 Duration of overall survival follow-up 
• 
A summary table showing the duration of follow-up will be presented for the FAS 
population. Summary information regarding the follow-up of patients is displayed in order 
to describe the maturity of data and quality of follow-up. 
• 
Follow-up of the study will be summarized using the following metric to provide a 
comprehensive assessment of follow-up for patients: Follow-up time elapsed from study 
start reference date = (Date of event or censoring – study start reference date + 


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1) /30.4375 (months) regardless of censoring. Date of event or censoring is the same as 
the one defined in the section for overall survival analysis. 
 
 
8.4 Protocol deviations 
 
Key protocol deviation will be identified based on reviews of the data prior to database lock. 
Protocol deviations will be summarized overall and by center, and tabulated according to the 
following categories: 
 
• 
Prohibited concomitant medication 
• 
Informed consent form 
• 
Eligibility criteria 
• 
Laboratory assessments 
• 
Procedure or test 
• 
Study drug and treatment 
• 
Visit schedule 
• 
Other 
Only protocol deviations directly affecting the patient will be reported. Protocol deviations 
pertaining to the study centers will not be considered. The number (%) of patients in the SAF 
with at least one of the above protocol deviations will be tabulated. 
 
 
8.5 Baseline and demographic characteristics 
Descriptive statistics will be presented for continuous variables. The number and percentage 
(%) of patients in each category will be presented for categorical variables. All summaries will 
be presented for the FAS and the SAF. For categorical variables, the number and percentage 
of patients with missing data will be provided. Listings for demographic data will be produced 
for the SAF. 
The following continuous variables will summarized: 
• 
Age (as continuous variable [years]) 
• 
Height [cm] 
• 
Weight [kg] 
• 
Number of prior systemic treatment lines (DLBCL medications) as categorical variable 
• 
Number of patients with 1 vs. ≥ 2 prior anti-DLBCL medications 


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• 
BMI (calculated as weight[kg] / height[m]2 using weight at baseline) 
• 
Time since first DLBCL diagnosis [months] 
• 
Time since discontinuation of last prior anti-DLBCL medication or ASCT [months] 
The following categorical variables will be summarized: 
• 
Age as categorical variable: 
- 
with subgroups < 65 vs. ≥ 65 years of age 
- 
with subgroups < 60 vs. ≥ 60 years of age 
- 
with subgroups < 70 vs. ≥ 70 years of age 
• 
LDH levels at baseline (within reference range vs. beyond reference range) 
• 
Prior ASCT (yes vs. no) 
• 
Cell of origin (GCB vs. non-GCB based on immuno-histochemistry/central pathology) 
• 
Cell of origin (GCB vs. ABC based on gene expression profiling) 
• 
Rituximab refractoriness (yes vs. no) 
• 
Refractoriness to last prior therapy (yes vs. no) 
• 
Primary refractoriness (yes vs. no) 
• 
ECOG 
• 
Ann Arbor Disease Stage dichotomized (I and II vs. III and IV) 
• 
Sex 
• 
Race (Black or African American, American Indian or Alaskan native, Asian, Native 
Hawaiian or other Pacific Islander, White, Other) 
• 
IPI score dichotomized (score 0-2 vs. 3-5, i.e., “low risk” and “low-intermediate risk” vs. 
“intermediate-high risk” and “high risk”) 
• 
FcγRIIIa affinity (high affinity: FCGR3A-158V homozygosity vs. low affinity: FCGR3A-158F 
homozygosity, or FCGR3A-158F/V heterozygosity) 
• 
FcγRIIa affinity (high affinity: FCGR2A-131H homozygosity vs. low affinity: FCGR2A-131R 
homozygosity, or FCGR2A-131H/R heterozygosity) 
 
 
Note: the calculation of derived variables is described in the respective sections below. 


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8.6 Medical history and current medical conditions 
8.6.1 Coding and definitions 
Medical history and current medical conditions will be summarized by body system, preferred 
term and by toxicity grade. Coding will be performed using the current version of the Medical 
Dictionary for Regulatory Activities (MedDRA Version 21.0 or higher). Listings will also be 
provided for the SAF. 
Notes: 
• 
Toxicity grade will be coded according to National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) V4.03 or higher. 
• 
Medical history is defined as records in the “Medical History and Current Medical 
Conditions”- eCRF form which are not ongoing at Cycle 1 Day 1. 
• 
Current medical conditions are defined as records in the “Medical History and Current 
Medical Conditions”- eCRF form which are ongoing at Cycle 1 Day 1. 
 
 
8.6.2 DLBCL-specific medical history and diagnosis 
Data on the diagnosis of DLBCL will be presented in a summary table and in listings (SAF). 
The table will include a summary of the following: 
• 
Stage at screening and initial diagnosis. 
• 
Ann Arbor Disease Stage dichotomized (I and II vs. III and IV). 
• 
Disease risk (IPI) at screening by category (0, 1, 2, 3, 4, 5). 
• 
Disease risk (IPI) at screening (dichotomized: low risk and low-intermediate risk vs. 
intermediate-high risk and high risk). 
• 
Time since initial diagnosis of DLBCL. 
• 
Bulky disease (present vs. absent) at screening (defined as having a longest lesion 
diameter of ≥ 7.5 cm as assessed by central radiological assessment). 
• 
Time since first progression/relapse. 
• 
Time since last progression/relapse. 
• 
NHL subtype as per central pathology (DLBCL, Follicular Lymphoma, Mantle Cell 
Lymphoma etc.). 
• 
Lactate dehydrogenase (LDH) levels at baseline (elevated vs. not elevated). 
• 
Time since discontinuation of last prior anti-DLBCL medication or ASCT [months]. 


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• 
Relapse after initial diagnosis (relapse ≤12 months after initial DLBCL diagnosis vs. 
relapse >12 months after initial DLBCL diagnosis) 
The results of the central pathology have been reviewed by Morphosys and been classified 
for the tabulation into NHL subtypes. For the subgroup analysis based on dichotomized NHL 
pathology results the patients with the following diagnoses have been classified further as 
non-DLBCL patients: 
 
• 
MARGINAL ZONE LYMPHOMA 
• 
FOLLICULAR LYMPHOMA, GRADE 2 
• 
MANTLE CELL LYMPHOMA, CLASSIC TYPE 
• 
FOLLICULAR LYMPHOMA (GRADE 2 + 3A) 
 
The event times (in months) are defined as (for example): 
[(reference start date) – (date of initial diagnosis of DLBCL)]/30.4375 
A listing of the recorded diagnostic lymph node biopsy will also be presented depicting the 
information on the Diagnostic Lymph Node Biopsy eCRF page. Another listing will show 
information on NHL subtype as determined by central pathology (the pathological description 
of the sample as well as the NHL entity used for tabulation). 
Data on bone marrow aspiration and biopsies as recorded throughout the study will be 
summarized in a table and also listed. The data table will summarize the following information 
on: 
• 
Potential complete response. 
• 
Type of examination. 
• 
Percentage of lymphocytes. 
• 
Type of infiltration. 
• 
Identification of indolent lymphoma in the bone marrow. 
• 
Degree of lymphoma involvement. 
Disease involvement assessment of the spleen/liver may occur as part of the full or limited 
physical examinations throughout the study and recorded data will be presented in a listing. 


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1.1.1 
Handling of incomplete dates regarding DLBCL-specific medical 
history 
If the ‘Date of initial diagnosis of DLBCL’ is only partially completed, the ‘Time since first 
DLBCL diagnosis’ will be calculated based on the following imputation rules: 
 
 
Table 4: Imputation rules for the ‘Date of initial diagnosis of DLBCL’ 
 
Component of the Date 
Variable 
DD 
MMM 
YYYY 
Date of initial diagnosis of DLBCL 



No imputation 
x 


Day 15 of the month 
x 
x 

No imputation 
x 
x 
x 
 
If the ‘Date of initial diagnosis of DLBCL’ cannot be imputed, the ‘Time since first DLBCL 
diagnosis’ will be considered as ‘Unknown’. 
If the 'Date of progression/relapse’ is missing, the 'Time since first/last progression/relapse’ 
will be calculated based on the following imputation rules: 
 
Table 5: Imputation rules for the ‘Date of progression/relapse’ 
 
Component of the Date 
Variable 
DD 
MMM 
YYYY 
Date of progression/relapse 



No imputation 
x 


First day of the month 
x 
x 

No imputation 
x 
x 
x 
 
If the ‘Date of progression/relapse’ cannot be imputed, the ‘time since first/last 
progression/relapse’ will be considered as ‘Unknown’. 


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2.1.1 
Calculation of the International Prognostic Index (IPI): 
The IPI is being calculated from the following items based on the information collected on 
the eCRF page ‘Ann Arbor Disease Staging and Disease Risk Assessment’: 
• 
Age older than 60 years. 
• 
Lactate dehydrogenase level higher than upper limit of normal. 
• 
ECOG performance status score of 2 or greater. 
• 
Stage III or IV disease. 
• 
More than one involved extranodal disease site. 
 
The IPI gives one point for each of the above characteristics, for a total score ranging from 
zero to five correlating with the following risk groups: 
• 
Low risk: 0–1 point. 
• 
Low-intermediate risk: 2 points. 
• 
High-intermediate risk: 3 points. 
• 
High risk: 4–5 points. 
The categories above will also be collapsed into low risk (0–2 points) and high risk (3–5 
points). 
 
 
8.6.3 Reason for ASCT ineligibility 
The reason for ASCT ineligibility as collected in the eCRF will be listed using the SAF. 
Additionally, the following three categories will be defined for a table summarizing the 
number of patients who are ASCT ineligible due to the following reasons (see also Table 6): 
• 
Chemorefractory: 
o Chemorefractory patients as indicated on the eCRF page ‘ASCT Ineligibility 
Criteria’ (‘Failure to achieve PR or CR with salvage therapy’). 
o Patients who underwent a stem cell transplantation before as indicated on the 
eCRF page ‘Prior Cancer Therapies for DLBCL – Autologous Stem Cell Transplants’. 
o The presence or absence of any other reason such as comorbidities or high age 
will be ignored. 
• 
High age (in presence of absence of comorbidities): 


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o All patients who are ineligible due to high age as indicated on the eCRF page 
‘ASCT Ineligibility Criteria’ (‘Age > 70 years’). 
o Only those patients will be considered who are not already in the 
‘Chemorefractory’ group. 
o Presence or absence of other reasons such as comorbidities will be ignored. 
• 
Other reasons 
o All other patients who are not in the categories above will be considered as 
ASCT ineligible due to other reasons. 
 
Table 6: Reasons for ASCT Ineligibility 
 
Priority 
High level category 
Reason from eCRF 
1 
Chemo-refractory 
Failure to achieve PR or CR 
with salvage therapy 
Prior ASCT as indicated in 
eCRF page ‘Prior Cancer 
Therapies for DLBCL – 
Autologous Stem Cell 
Transplants’ 
2 
Age or Comorbidity 
Age >70 years 
Diffusion lung capacity for 
carbon monoxide <50% by 
pulmonary function test 
Left ventricular ejection 
fraction <50% by multiple 
gated acquisition 
echocardiogram 
Other organ dysfunction or 
comorbidities precluding the 
use of HDT/ASCT on the basis 
of unacceptable risk of 
treatment 
3 
Patient refusal or Other 
Patient refusal of HDT/ASCT 
Other Reason 


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8.6.4 History of indolent lymphoma 
A listing depicting patients with a history of indolent lymphoma will be generated for the SAF. 
Entries for ‘Condition’ on the eCRF page ‘Medical History and Current Medical Conditions’ will 
be searched for the following keywords: 
• 
Indolent lymphoma 
• 
Indolent non-hodgkin lymphoma 
• 
Indolent NHL 
• 
Other indolent lymphoma 
• 
Follicular lymphoma 
• 
Follicular non hodgkin’s lymphoma 
• 
Marginal zone lymphoma 
• 
Splenic marginal zone lymphoma 
• 
Extranodal marginal zone lymphoma 
• 
MALT 
• 
Mucosa associated lymphoid tissue lymphoma 
• 
Chronic lymphocytic leukemia 
• 
Small lymphocytic lymphoma 
• 
Waldenström macroglobulinemia 
The listing will show the verbatim term as entered in the eCRF, but also the MedDRA-coded 
NHL subtype. 
 
 
8.7 Prior and concomitant medications and non-drug treatments/procedures 
8.7.1 Coding 
Prior, concomitant and pre-medications will be recorded and coded using the current WHO 
Drug Dictionary Enhanced (WHO-DDE) and grouped by Anatomical Therapeutic Chemical 
(ATC) Level 2 and preferred name classes. Surgical and medical procedures will be coded using 
MedDRA and summarized by SOC and preferred term. 


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8.7.2 Definitions 
• 
Pre-medication: Medication given prior to MOR00208 infusion to mitigate potential 
infusion-related reactions. Pre-medication encompasses antipyretics, histamine receptor 
blockers, glucocorticosteroids, meperidine. 
• 
Prior medication/non-drug treatment: If the treatment start and stop dates are both 
before the start date of study treatment, the medication will be classified as prior 
medication. Patients will only be counted once for multiple drug use (by preferred drug 
name). 
• 
Concomitant medication/non-drug treatment: If the treatment start date is after start of 
study treatment the medication will be considered as concomitant medication. Patients 
will only be counted once for multiple drug use (by preferred drug name). If the 
medication stop date is incomplete, the following algorithm will apply to exclude the 
medication from the category concomitant medication: 
▪ 
If stop day is missing but month is complete, medication will only be excluded from 
concomitant medication if stop month is before month of treatment start. 
▪ 
If stop day and month are missing but year is complete, medication will only be 
excluded from concomitant medication if stop year is before year of treatment start. 
▪ 
If stop date is completely missing, medication will not be excluded. 
 
• 
Prior and concomitant medication/non-drug treatment: Medications with start date 
before start date of study treatment but ongoing or with stop date after the start of study 
treatment will be considered both as prior and as concomitant medications. Patients will 
only be counted once for multiple drug use (by preferred drug name). 
• 
Duration of response (DoR) to prior anti-DLBCL medication or ASCT (in months): 
(date of assessment of tumour progression – date of assessment of first documented 
response + 1) / 30.4375. 
• 
Time since last anti-DLBCL medication/radiation therapy/surgery (in months): 
(first date of study treatment – end of treatment date for last prior anti-DLBCL 
medication/radiation therapy/surgery) / 30.4375. 
• 
Time since last ASCT (in months): 
(first date of study treatment – date of procedure) / 30.4375. 
 
 
8.7.3 Data presentation 
Summary tables will be presented for: 


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• 
Prior medications. 
• 
Concomitant medications which started before start of study treatment. 
• 
Concomitant medications which started after start of study treatment. 
• 
Prior non-drug treatments and procedures. 
• 
Concomitant Non-Drug Treatments and Procedures Which Started Before Start of Study 
Treatment. 
• 
Concomitant Non-Drug Treatments and Procedures Which Started After Start of Study 
Treatment. 
All summaries will be conducted on both the FAS and SAF. Listings will be shown for pre- 
medication, prior medication, and concomitant medication, and listings for prior and 
concomitant non-drug treatments/procedures (for the SAF). 
 
 
8.7.4 DLBCL-specific prior therapies 
3.1.1 
Prior therapy procedures 
Prior anti-neoplastic therapies will be summarized: 
• Prior anti-DLBCL medications: 
- Patients with at least one prior anti-DLBCL medication. 
- Number of therapy lines (as categorical variable). 
- Time since last prior anti-DLBCL medication. 
- Number of patients with 1 vs. ≥ 2 prior anti-DLBCL medications 
• Prior radiation therapy: 
- 
Patients with at least one prior anti-cancer radiotherapy. 
• Prior surgery: 
- Patients with at least one prior anti-cancer Surgery. 
• Prior autologous stem cell transplantation (ASCT): 
- Patients with prior autologous stem cell transplantation. 
- Duration of response. 
• Duration of response to last prior systemic anti-DLBCL medication or ASCT: 
- The duration of response to the patients´ last prior anti-DLBCL medication (in case the 
last prior therapy was a medication) or ASCT (in case the last prior treatment was an ASCT) 
will be summarized. 


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Separate listings will be presented on prior anti-DLBCL medications, radiation therapies, 
surgeries, and ASCT. Listings on individual DLBCL-specific procedures will include information 
on: 
• 
The type and date of the initial response. 
• 
The type and date of the best overall response. 
• 
Date of progression. 
• 
Reason for therapy discontinuation. 
• 
Therapy start date. 
• 
Therapy end date. 
• 
The number of cycles. 
• 
Therapy type. 
• 
Medication name. 
• 
Number of the particular therapy line. 
• 
Duration of response (only for anti-DLBCL medication, and prior ASCT). 
 
4.1.1 
Handling of incomplete dates regarding prior therapies 
Handling of missing values for ‘Duration of Response (DoR)’ to prior therapies 
In case the date of initial response or progression is only partially completed the DoR as 
entered on the eCRF pages for ‘Prior Cancer Therapies for DLBCL-Autologous Stem Cell 
Transplants’ and ‘Prior Cancer Therapies for DLBCL Medications’ will be used. If the entry for 
DoR to previous therapy line is missing and the date of initial response or progression is only 
partially completed the following imputation rules will apply: 
 
Table 7: Imputation rules for the ‘Date of initial response’ and ‘Date of progression/relapse’ 
 
Component of the Date 
Variable 
DD 
MMM 
YYYY 
Date of initial 
response 
Date of progression/relapse 



No imputation 
No imputation 
x 


First day of the 
month 
Last day of the month 


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x 
x 

No imputation 
No imputation 
x 
x 
x 
 
The ‘Duration of Response’ to a particular prior therapy will be considered as ‘Unknown’ if 
the dates required for derivation cannot be imputed. 
 
 
Handling of missing values for the derived variables ‘Time since the last prior anti-DLBCL 
medication/radiation/surgery/ASCT’ 
A partial completion date for the completion of the last prior therapy will be imputed using 
the following algorithm for the last regimen: 
 
Table 8: Imputation rules for ‘End Date’ of last prior anti-DLBCL medication, the ‘Date of 
procedure’ (for surgery, radiation, ASCT) 
 
Component of the Date 
Variable 
DD 
MMM 
YYYY 
‘End Date’ of last 
prior anti-DLBCL 
medication 
Date of procedure 
(surgery, radiation, ASCT) 



No imputation 
No imputation 
x 


Day 15 of the month 
Day 15 of the month 
x 
x 

No imputation 
No imputation 
x 
x 
x 
The ‘Time since last prior anti-DLBCL medication/radiation/surgery/ASCT’ will be considered 
as ‘Unknown’ if the dates required for derivation cannot be imputed. 
 
 
5.1.1 
Refractoriness to prior therapies 
Three subgroups for treatment refractoriness in prior therapy lines will be defined using 
information on prior anti-DLBCL medications collected in the eCRF. 
- 
Primary refractoriness 
- 
Refractoriness to the last prior treatment line 
- 
Rituximab refractoriness 


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The number (%) of patients in each of these subgroups will be presented. The information will 
also be provided in listings (for the SAF). The refractoriness to prior therapies will be derived 
for the FAS only. 
 
 
8.7.4.1.1 Primary refractoriness 
Primary refractoriness is defined as disease progression in the course of the first line 
treatment, or showing a response of less than PR (i.e., PD or SD) as best response to the first 
line treatment, or disease progression within ≤ 6 months from the completion of first-line 
therapy (i.e., the ‘End Date’ for the first therapy line as entered on the eCRF page ‘Prior Cancer 
Therapies for DLBCL Medications’). 
• 
Only systemic anti-DLBCL medications as entered on the ‘Prior Cancer Therapies for DLBCL 
Medications’ eCRF page will considered as first line treatment 
• 
If the status for ‘Primary refractoriness’ cannot be determined the patient will be 
considered as having an “Unknown” status. 
 
 
8.7.4.1.2 Refractoriness to the last prior treatment line 
Refractoriness to the last prior treatment is defined as having less than a PR (i.e., SD or PD) as 
best overall response to the most recent therapy, progression during the course of treatment, 
or progression within ≤ 6 months from the completion of the most recent therapy line (i.e., 
the ‘End Date’ for the most recent therapy line as entered on the eCRF page ‘Prior Cancer 
Therapies for DLBCL Medications’). 
• 
Only systemic anti-DLBCL medications as entered on the ‘Prior Cancer Therapies for DLBCL 
Medications’ eCRF page will considered as last prior treatment. 
• 
If the status for ‘Refractoriness to the last prior treatment line’ cannot be determined the 
patient will be considered as having an “Unknown” status. 
 
 
 
8.7.4.1.3 Rituximab refractoriness 
Rituximab refractoriness is defined as having reached less than a partial response to any 
rituximab-containing treatment regimen, progression during the course of treatment, or 
progression within ≤ 6 months from the completion of any rituximab-containing (i.e., the ‘End 
Date’ for any rituximab-containing therapy line as entered on the eCRF page ‘Prior Cancer 
Therapies for DLBCL Medications’). If the status for ‘Rituximab refractoriness’ cannot be 
determined the patient will be considered as having and “Unknown” status. 


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8.7.4.1.4 Imputation of missing values required for defining refractoriness 
subgroups 
The ‘End Date’ for the first treatment line, or the last prior treatment line or any Rituximab- 
containing treatment line, will be imputed as follows: 
• 
In case day is missing but month and year are complete, the first day of the month or 
the starting date of the next treatment, whichever is later will be used. 
• 
In case day and month are missing but year is complete, the date will be considered as 
missing. 
• 
In case day, month and year are missing, the date will be considered as missing. 
 
The ‘Date of progression/relapse’ for a particular therapy line will be imputed as follows: 
• 
In case day is missing but month and year are complete, the last day of the month will 
be used. 
• 
In case day and month are missing but year is complete, the date will be considered as 
missing. 
• 
In case day, month and year are missing, the date will be considered as missing. 
• 
If the ‘Date of progression/relapse’ is completely missing or cannot be replaced by 
imputation, the following strategy will be used: 
o If the ‘Start Date’ of the subsequent therapy line is present, the ‘Start Date’ will be 
used as a surrogate for the ‘Date of progression/relapse’ for the previous line of 
treatment. If the day for the Start Date missing, the day will be imputed using the last 
day of the month. 
o If the ‘Start Date’ of the subsequent therapy line is missing, but the ‘End Date’ of the 
subsequent therapy line is present the ‘End Date’ will be used as a surrogate for the 
‘Date of progression/relapse’ for the treatment line of interest (the patient will be 
considered as ‘refractory’). If the day for the ‘End Date’ missing, the day will be 
imputed using the last day of the month. 
NOTE: The ‘End Date’ of the subsequent therapy will only be used as a surrogate if the 
time interval between the ‘End Date’ of the subsequent line and the ‘End Date’ of the 
previous line is ≤ 6 months (the patient will be considered ‘refractory’). Otherwise the 
refractory status will be considered as ‘Unknown’. 
o If L-MIND constitutes the immediate treatment line after the line of interest the 
‘Informed Consent’ date as entered on the ‘Informed Consent’ eCRF page will be used. 


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Table 9: Overview of imputation rules for ‘End Date’ and ‘Date of progression/relapse’ for the 
therapy line of interest 
 
Component of the Date 
Variable 
DD 
MMM 
YYYY 
‘End Date’ for the 
treatment line of 
interest 
‘Date of progression/relapse’ for the 
treatment line of interest 



No imputation 
No imputation 
x 


1st day of the month 
Last day of the month 
x 
x 

No imputation 
1. 
‘Start Date’ of the subsequent 
treatment (a partially completed 
date can be imputed as outlined in 
2. 
Table 10) 
3. 
‘Stop Date’ of the subsequent 
treatment if the ‘Stop Date’ is ≤ 6 
months after the ‘End Date’ of the 
therapy line of interest (a partially 
completed date can be imputed as 
outlined in 
4. 
Table 10) 
5. 
‘Informed Consent’ date for L- 
MIND study participation if the 
subsequent treatment is L-MIND 
x 
x 
x 
 
 
Table 10: Overview of imputation rules for a partially completed ‘Start Date’ or ‘End Date’ 
for the therapy line subsequent to the therapy line of interest (if the ‘Date of 
progression/relapse’ for the therapy line of interest has to be imputed) 
 
Component of the Date 
Variable 
DD 
MMM 
YYYY 
‘Start Date’ 
‘End Date’ 



No imputation 
No imputation 
x 


Last day of the month 
Last day of the month 


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x 
x 

No imputation 
No imputation 
x 
x 
X 
8.7.5 Early vs. late relapse after DLBCL diagnosis 
Patients having an ‘early relapse’ or ‘late relapse’ after their initial DLBCL diagnosis will be 
summarized. The following definitions will apply: 
• 
Early relapse after initial DLBCL diagnosis: relapse ≤12 months after initial DLBCL 
diagnosis. 
• 
Late relapse after initial DLBCL diagnosis: relapse >12 months after initial DLBCL 
diagnosis. 
The ‘Date of initial diagnosis of DLBCL’ and the ‘Date of first progression/relapse’ can be 
found on the ‘Diagnosis of DLBCL’ eCRF page. 
The following imputation rules will be applied in the situation of partially completed dates: 
 
Table 11: Imputation rules for the ‘Date of initial diagnosis of DLBCL’ and the ‘Date of first 
progression/relapse’ 
 
Component of the Date 
Variable 
DD 
MMM 
YYYY 
Date of initial 
diagnosis of DLBCL 
Date of first progression/relapse 



No imputation 
No Imputation 
x 


1st day of the month 
Last day of the month 
x 
x 

No imputation 
No imputation 
x 
x 
x 
 
• 
If day and month are missing, but only the year is present for one or both variables 
required the patient will be assigned to the category ‘Late relapse after initial DLBCL 
diagnosis’ if the difference between the year for the ‘Date of initial diagnosis of DLBCL’ 
and the year for the ‘Date of first progression/relapse’ is two years or higher. In case the 
difference for the years is only one year the relapse category after initial DLBCL diagnosis 
will be considered as ‘Unknown’. In case the year is the same for both variables the patient 
will be assigned to the category ‘Early relapse after initial DLBCL diagnosis’ 
• 
If the relapse category cannot be determined, the patient will be considered as ‘Unknown’. 


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8.7.6 Non-study anti-DLBCL treatment 
Data on non-study anti-DLBCL treatments will be provided for patients who are still on any 
study drug, and for patients who have already discontinued the treatment (based on the 
‘Other Anti-Neoplastic Therapies after end of Study Drug Treatment’ and “Concurrent Anti- 
Neoplastic Therapies Medications” eCRF pages). The following summaries will be presented 
for both the FAS and the SAF: 
• 
The number (%) of patients who received non-study cancer treatment prior to study 
treatment discontinuation. 
• 
The number (%) of patients who received non-study cancer treatment after study 
treatment discontinuation. 
• 
The number (%) of patients who received non-study cancer treatment without a 
documented radiological progression as per CHESON Criteria. 
• 
The type of anti-cancer treatment received by ATC level 2 class and preferred name. 
• 
Time to start of non-study anti-cancer treatment. 
• 
Therapy line of non-study anti-cancer treatment. 
• 
Reason for stopping non-study anti-cancer treatment. 
Time to start of anti-cancer therapy is defined as (start date of anti-cancer treatment – date 
of last dose of study treatment + 1). In case the anti-cancer therapy started before the last 
dose of study treatment the time will be set to zero. If the start date of anti-cancer treatment 
is missing, then the time to start of anti-cancer treatment for that patient will be missing. 
Listings on other non-study cancer treatments will be presented for the SAF. 
 
 
8.8 Pre-Medication for MOR00208 infusion 
Due to the occurrence of infusion related reactions (IRRs), patients may receive pre- 
medications administered prior to MOR00208 infusions. These may include antipyretics, 
histamines, glucocorticosteroids, and meperidine. Pre-medications and their doses will be 
listed for all patients who received either LEN or MOR00208 (SAF population). 
 
 
8.9 Study treatment 
8.9.1 Treatment cycles 
The patients will be administered study treatment according to cycles. Each Treatment cycle 
will consist of 28 days. The duration of exposure for each study treatment drug is defined 
according to regimen as outlined below. 
MOR00208: 


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The planned administration of MOR00208 is as follows: 
• 
Cycle 1: Day 1, Day 4 (loading dose), Day 8, Day 15, Day 22. 
• 
Cycle 2: Day 1, Day 8, Day 15, Day 22. 
• 
Cycle 3: Day 1, Day 8, Day 15, Day 22. 
• 
Cycle 4 onwards: Day 1 and Day 15. 
MOR00208 will be administered at a dose of 12.0 mg/kg IV. Dose reductions of MOR00208 
are not allowed during the course of the study. Unless contraindicated the MOR00208 
treatment should continue, even if the patient discontinues LEN treatment. 
LEN: 
The planned administration of LEN is as follows: 
• 
Cycle 1 to Cycle 12: 25 mg oral LEN daily on days 1-21 of the respective cycle. 
• 
Reduced LEN doses after reduction of the total daily dose (see Section 8.9.3) will also be 
administered on days 1-21 until Cycle 12. 
 
 
8.9.2 Exposure 
6.1.1 
Duration of exposure to study drug 
Exposure to study treatment and each study drug will be summarized for the FAS and the 
SAF. 
Duration of exposure (days) = (last date of exposure to study drug) – (date of first 
administration of study drug) + 1. 
Taking into account the period of rest between infusions, the last date of exposure is defined 
as follows: 
• 
For MOR00208: When the study drug is administered over several regular doses with 
regular time intervals, the last date of exposure is identified according to the planned dose 
schedule of the cycle. If no rest period is included in the cycle then the last date of 
exposure is: (last date of administration of the study drug) + (length of time interval-1). 
Length of time interval: 7 days in Cycle 1-3 and 14 days from Cycle 4 onwards. In case a 
patient dies before the end of the time interval the date of death will be used to truncate 
the time interval, i.e., in this case the last date of exposure will be set as the date of death. 
• 
For LEN, the last date of exposure will be defined as the last date of administration. Thus, 
planned dose interruptions between days 22 to 28 of each cycle, as per protocol, will not 
be considered. That is, only day 1 to 21 will be considered as being exposed to LEN. 


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7.1.1 
Duration of exposure to study treatment 
Duration of exposure (days) = (last date of exposure of all the study drugs) – (date of first 
administration of study treatment) + 1. 
The definition of exposure is specified in the section duration of exposure to study drug. 
8.1.1 
The duration of exposure to study treatment / drug will be 
calculated in months. 
 
 
9.1.1 
Exposure analysis 
• The number of patients completing each cycle will be summarized. A patient is considered 
to have completed a cycle for MOR00208 if he/she was compliant for all MOR00208 
infusions during the cycle. A patient is considered to have completed a cycle for LEN if 
he/she was compliant (see Section 8.9.6) for LEN administration during the cycle. 
• Summary statistics will be displayed. The duration of exposure will also be summarized 
according to the following categories: Month 1-2, 3-4, 5-6, 7-8, etc. 
• Number of infusions with MOR00208 will be summarized as follows: 
o The total number of MOR00208 infusions will be summarized 
o The number (%) of patients belonging to the following categories will be derived: 
0-2 infusions, 3-4 infusions, 5-6 infusions, 7-8 infusions, etc. 
 
8.9.3 Dose reduction 
Dose reductions are only possible for LEN, but not for MOR00208. The number (%) of patients 
with any dose reduction will be summarized for LEN. The number (%) of patients with a 
reduction to a minimum of 20 mg, 15 mg, 10 mg, or 5 mg without having completely 
discontinued treatment will be shown. Moreover, the number (%) of patients who had no 
reduction at all or only a reduction to 20 mg (but not lower) will be summarized. 
 
 
8.9.4 Dose interruption 
The number (%) of patients with temporary interruptions and the associated reasons will be 
summarized for both study drugs. 


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8.9.5 Permanent discontinuations 
A summary of patients who discontinued permanently will be provided for both study drugs. 
The reasons for permanent discontinuation from the study drug will be summarized for each 
study drug. 
 
 
8.9.6 Compliance 
10.1.1   MOR00208 
Compliance for MOR00208 will be calculated by taking the actual MOR00208 infusion dose 
divided with the planned MOR00208 infusion dose. Compliance will be summarized per single 
infusion and per cycle: 
• 
MOR00208 compliance per single infusion: if the MOR00208 dose administered is ≥80% 
and ≤120% of the planned dosage. 
• 
MOR00208 compliance per cycle: if this quantity is ≥80% and ≤120% of the planned 
dosage for the cycle, then the patient will be considered compliant for that cycle. 
 
 
11.1.1   LEN 
LEN is taken for the first 21 days of each cycle. Patients experiencing a transient treatment 
interruption, e.g., due to toxicities, or patients undergoing treatment discontinuation may 
take LEN for less than 21 days, which would not be considered as non-compliance. Similarly, 
a planned reduction of the Total Daily Dose will not be considered as non-compliance. 
For some patients and Cycles the Total Daily Dose will be reached by combining tablets of two 
different Dose Strengths. Compliance will be calculated as follows: 
If (total used dose)/(total planned dose) is between 80% and 120%, both inclusive, of the 
assigned dosage during a particular cycle, then the patient is considered compliant for LEN 
during that particular cycle. The Total Planned Dose and the Total Used Dose will be derived 
as follows: 
 
 
For patients who did not experience a dose change or treatment interruption (as indicated 
on the eCRF page ‘Lenalidomide Dosing Record’): 
• 
The Total Planned Dose will be calculated as follows: 
21 x Total Daily Dose (as entered on the eCRF page ‘Lenalidomide Dosing Record’). 
• 
The Total Used Dose will be calculated as follows: 
o For patients and cycles in which the Total Daily Dose is reached by taking one 
capsule only: 


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Total Used Dose = (Number of Capsules Dispensed - Number of Capsules 
Returned) x Dose Strength. 
For patients and cycles in which the Total Daily Dose is reached by combining 
two or more capsules of different Dose Strengths (e.g., Dose Strength 1 and 
Dose Strength 2): 
 
Total Used Dose = [(Number of Capsules of Dose Strength 1 Dispensed -Number 
of Capsules of Dose Strength 1 Returned) x Dose Strength 1] + [(Number of 
Capsules of Dose Strength 2 Dispensed - Number of Capsules of Dose Strength 2 
Returned) x Dose Strength 2]. 
 
 
For patients who experienced a dose change, treatment interruption or treatment 
discontinuation (as indicated on the eCRF page ‘Lenalidomide Dosing Record’): 
• 
The Total Planned Dose will be calculated as follows: 
o Patients who required a dose change or interruption and did not start LEN 
treatment (with same or changed dose) before completion of that particular 
Cycle the dose change/interruption happened: 
Min[21, (Dosing Stop Date – Dosing Start Date + 1)] x Total Daily Dose (as 
entered on the eCRF page ‘Lenalidomide Dosing Record’). 
Note: Separate log lines on the eCRF page ‘Lenalidomide Dosing Record’ may 
exist for patients who reach the Total Daily Dose by combining capsules of 
different dose strengths. In this case, Total Daily Dose, Dosing Start Date and 
Dosing Stop Date are identical across the different eCRF log lines and only 
information from one log line will be used. In rare cases it may happen that 
actually Dosing Stop Date – Dosing Start Date + 1 is > 21, in this case the 
planned dose is calculated with 21 days only. 
o Patients who required a dose change / treatment interruption, and started the 
new Total Daily Dose / re-initiated treatment (in case of interruption) before 
completion of that particular Cycle the dose change/interruption happened: 
E.g., for one dose reduction, or one interruption: 
[(Dosing Stop Date for Total Daily Dose 1 – Dosing Start Date for Total Daily 
Dose 1 + 1 Day) x Total Daily Dose 1] + [(Dosing Stop Date for Total Daily Dose 2 
– Dosing Start Date for Total Daily Dose 2 + 1 Day) x Total Daily Dose 2]. 
Notes: 


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- Separate log lines on the eCRF page ‘Lenalidomide Dosing Record’ will show 
the Total Daily Dose before and after dose change, or before and after 
treatment interruption, respectively. 
- In case of treatment interruption Total Daily Dose 1 and Total Daily Dose 2 (in 
case of only one interruption) will be identical. 
- Separate log lines may exist showing the identical information on Dosing Start 
Date, Dosing Stop Date, and Total Daily Dose in case the Total Daily Dose is 
reached by combining different Dose Strengths. In this situation, only the 
information from one eCRF log line will be used. 
 
 
• 
The Total Used Dose will be calculated as follows: 
o Patients who required a dose change or treatment interruption, and did not 
start LEN treatment (with same or changed dose) before completion of that 
particular Cycle the dose change/interruption happened: 
▪ 
For patients and Cycles in which the Total Daily Dose (as entered in the eCRF 
page ‘Lenalidomide Dosing Record’) is reached by taking one capsule only: 
Total Used Dose = (Number of Capsules Dispensed - Number of Capsules 
Returned) x Dose Strength. 
Note: Only one log line on the eCRF page ‘Lenalidomide Dosing Record’ will 
exist for this situation. 
▪ 
For patients and cycles in which the Total Daily Dose (as entered in the eCRF 
page ‘Lenalidomide Dosing Record’) is reached by combining capsules of 
different Dose Strengths: 
E.g., Dose Strength 1 and Dose Strength 2: 
Total Used Dose = [(Number of Capsules of Dose Strength 1 Dispensed - 
Number of Capsules of Dose Strength 1 Returned) x Dose Strength 1] + 
[(Number of Capsules of Dose Strength 2 Dispensed - Number of Capsules of 
Dose Strength 2 Returned) x Dose Strength 2]. 
Note: Several log lines with the same Dosing Start Date on the eCRF page 
‘Lenalidomide Dosing Record’ exist for this situation (representing the 
different dose strengths). 
o Patients who required a dose change / treatment interruption, and started the 
new Total Daily Dose / re-initiated treatment (in case of interruption) before 
completion of that particular Cycle the dose change/interruption happened: 
▪ 
Change of the Total Daily Dose within a particular Cycle: 


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Capsules of only one dose strength or a combination of several dose 
strengths might be used before or after dose change to reach the targeted 
Total Daily Dose. The Total Used Dose will be calculated as follows: 
 
E.g., for capsules of two different dose strengths before and after dose 
change: 
 
Total Used Dose = [(Number of Capsules of Dose Strength 1 Dispensed 
before dose change - Number of Capsules of Dose Strength 1 Returned 
before dose change) x Dose Strength 1] + [(Number of Capsules of Dose 
Strength 2 Dispensed before dose change - Number of Capsules of Dose 
Strength 2 Returned before dose change) x Dose Strength 2] + 
[(Number of Capsules of Dose Strength 1 Dispensed after dose change - 
Number of Capsules of Dose Strength 1 Returned after dose change) x Dose 
Strength 1] + [(Number of Capsules of Dose Strength 2 Dispensed after dose 
change - Number of Capsules of Dose Strength 2 Returned after dose 
change) x Dose Strength 2]. 
 
Note: In case only one dose strength is being used before or after changing 
the Total Daily Dose, one of the summands (e.g., the terms for Dose 
Strength 2) will become 0. 
 
 
▪ 
Interruption and re-initiation of treatment within a particular Cycle: 
Capsules of only one dose strength or a combination of several dose 
strengths might be used to reach the targeted Total Daily Dose. The Total 
Used Dose will be calculated as follows (e.g., for capsules of two different 
dose strengths): 
 
Total Used Dose = [Number of Capsules of Dose Strength 1 Dispensed 
before dose change x Dose Strength 1] + [Number of Capsules of Dose 
Strength 2 Dispensed before dose change x Dose Strength 2] + 
[Number of Capsules of Dose Strength 1 Returned after dose change x Dose 
Strength 1] + [Number of Capsules of Dose Strength 2 Returned after dose 
change x Dose Strength 2]. 
 
Notes: The Total Daily Dose before and after interruption in a particular 
Cycle is represented in separate log lines on the eCRF page ‘Lenalidomide 
Dosing Record’. 
 
• 
The following applies if the Total Planned Dose is 0 for an entire Cycle: 


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o If the Total Used Dose is 0 for the Cycle, the patient will be considered as 
compliant for that particular Cycle. 
o If the Total Used Dose is not 0, the patient will be considered as non-compliant 
for that particular Cycle. 
 
Listings showing eCRF entries on LEN dosing records, MOR00208 dosing administration, and 
MOR00208 infusion details will be produced (for the SAF). A listing will be generated showing 
the compliance per cycle for each individual for both LEN and MOR00208 (for the SAF). 
 
 
9. PRIMARY OBJECTIVE 
The primary objective is to determine the activity of a combination of LEN with MOR00208 in 
terms of best objective response rate (ORR = rate of patients with complete response [CR] or 
partial response [PR]) in adult patients with R-R DLBCL. 
 
 
9.1 Endpoint: Best objective response rate 
The best ORR is defined as the proportion of patients with CR or PR as best response achieved 
at any time during the study. The denominator will be the total number of patients included 
in the analysis population. 
 
 
9.2 Main analysis 
The number and percentage of patients classified as having best overall response of CR or PR 
as well as 95% confidence limits (using the Clopper-Pearson exact method) will be presented. 
The number and percentage of patients with CR, and the number and percentage of patients 
with PR as best response will be shown. The main analysis will be conducted on the FAS for 
both the IRC response assessment, and the local, i.e., investigator (INV) response assessment. 
 
 
For the main analysis of best ORR: 
• 
The tumour assessments will be derived according to the IWG treatment response criteria 
for malignant lymphoma (Cheson et al., 2007; see Section 6.14), by an Independent 
Radiology/Clinical Review Committee (IRC). The review process will be defined in the IRC 
Charter. 
• 
Patients with no post-baseline assessment of response will be included as non- 
responders. 


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• 
Patients with a best response of “Not Evaluable” will be summarized by reason for 
having unknown status. The following reasons will be used: 
o No valid post-baseline assessment available. 
o All post-baseline assessments have overall response “Unknown” or “Not 
evaluable” or “Indeterminate”. 
o New anti-cancer therapy started before first post-baseline assessment. 
• 
No formal hypothesis testing will be conducted. 
The main analysis will be performed using the FAS. 
 
9.3 Sensitivity analyses 
• 
The main analysis as described in Section 9.2 will be conducted based on the INV 
assessment. 
• 
The main analysis as described in Section 9.2 will be conducted using the PPS (based on 
INV and IRC assessment). 
• 
The analysis as described in Section 9.2 will be performed excluding the patients with no 
post-baseline assessment of response or with all post-baseline assessments categorized 
as “Unknown”. The analysis will be performed using the FAS based in both IRC and INV 
assessment. 
• 
The number (%) of patients will be descriptively tabulated by categories of individual best 
outcome in tumor response assessments (CR, PR, SD, PD, Not Evaluable). Listings will be 
generated for both central and local response assessments (for the SAF). 
 
 
9.4 Concordance between IRC and investigator (INV) assessment 
The concordance rate in terms of response assessment represents the agreement in the best 
overall outcome (CR, PR, SD, PD, Not Evaluable, and Not Available) in tumour response 
assessments between the IRC and INV assessment. The concordance rate is the number of 
patients that are concordant over the total number of patients assessed, and will be calculated 
across all response categories. A contingency table will be generated. The concordance rate is 
calculated by adding the diagonal counts and dividing by the total number of patients 
assessed. Moreover, the agreement (%) of the INV assessment by the IRC in terms of best 
ORR will be calculated (i.e., the proportion of patients with a best response of CR or PR by 
investigator assessment that have a confirmed best response of CR or PR by the IRC 
assessment). 
Patients who have been evaluated by investigator assessment, but not by central review 
assessment will be excluded from the concordance analysis. 


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The proportion (%) of patients who had at least one central review among the total number 
of patients who underwent at least one INV assessment will be calculated. Moreover, the 
proportion (%) of the total number of central reviews among the total number of INV 
assessments will be derived (i.e., the total number of central reviews across all visits and all 
patients divided with the total number of investigator response assessments across all visits 
and all patients multiplied by 100). The analysis will be conducted using the FAS. 
 
 
10. SECONDARY OBJECTIVES 
10.1 Secondary objective 1 
10.1.1 Objective 
To determine the activity of a combination of LEN with MOR00208 in terms of disease control 
rate (DCR = complete response (CR) + partial response (PR) + stable disease (SD) as best 
objective response) in adult patients with R-R DLBCL. 
 
 
10.1.2 Endpoint: Disease control rate 
DCR is defined as the proportion of patients having CR, PR or SD based on the best objective 
response achieved at any time during the study. The denominator will be the total number of 
patients included in the analysis population. 
 
 
10.1.3 Main analysis 
The number and percentage of patients classified as having best overall response of CR or PR 
or SD as well as 95% confidence limits (using Clopper-Pearson exact method) will be 
presented. The number and percentage of patients with CR, the number and percentage of 
patients with PR and the number and percentage of patients with SD as best response will be 
presented. The main analysis will be conducted on the FAS for the both IRC and INV response 
assessments. 
For the main analysis of DCR: 
• 
The tumour assessments will be derived according to the IWG treatment response criteria 
for malignant lymphoma (Cheson et al., 2007; see Appendix), by an Independent 
Radiology/Clinical Review Committee (IRC). The review process will be defined in the IRC 
Charter. 
• 
Patients with no post-baseline assessment of response will be included as non- 
responders. 
• 
Patients with a DCR of “unknown” will be summarized by reason for having unknown 
status. The following reasons will be used: 


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- 
No valid post-baseline assessment. 
- 
All post-baseline assessments have overall response “Unknown” or “Not evaluable”. 
- 
New anti-cancer therapy started before first post-baseline assessment. 
• 
No formal hypothesis testing will be conducted. 
 
10.1.4 Sensitivity analyses 
• 
The main analysis as described in Section 10.1.3 will be conducted based on the INV 
assessment. 
• 
The analysis mentioned in Section 10.1.3 will be performed excluding the patients with no 
post-baseline assessment of response or with all post-baseline assessments categorized 
as “Unknown”. The analysis will be performed using the FAS based in both IRC and INV 
assessment. 
 
 
10.2 Secondary objective 2 
10.2.1 Objective 
To determine the activity of a combination of LEN with MOR00208 in terms of progression- 
free survival (PFS). 
 
 
10.2.2 Endpoint: Progression-free survival 
PFS will be defined as the time (in months) from the date of the first administration of any 
study drug to the date of tumour progression or death from any cause (see Independent 
Review Charter version 4.3, 10-JUL-2018). The date of progression will be the first date for 
which progressive disease was assessed as the objective response. The tumour assessments 
will be derived according to the IWG treatment response criteria for malignant lymphoma 
(Cheson et al., 2007; see section 6.14), by an Independent Radiology/Clinical Review 
Committee (IRC). The review process will be defined in the IRC Charter. 
 
 
10.2.3 Disease assessments 
Disease assessments will be performed with either PET/CT scans or CT/MRI scans as per the 
schedule in Table 12. 


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Table 12: Schedule of Tumour Assessments 
 
Evaluation 
Screen- 
ing 
C3 
D1 
C5 
D1 
C7 
D1 
C10 
D1 
C12 
D28 
C13 
D1 
Every 
3 
month 
s 
From 
C25 
D1 on- 
ward 
once 
per 
year 
EOT 
visit 
Disease 
response 
assessment 
(PET/CT or 
PET/MRI) 
X 
X 
X$ 
X 
CT or MRI 
scan for 
tumour 
measureme 
nt and 
disease 
response 
assessment 
X 
X 
X 
X 
X* 
X 
X 
*Can be done approx. 3 months after C12D28 PET/CT or PET/MRI assessment. 
$Only if deemed necessary and not more frequently than once per year. A window of ± 2 weeks 
is allowed by the protocol for these assessments. Tumour assessments will continue until 
disease progression, death or study discontinuation (whichever occurs first). 
 
 
10.2.4 Censoring rules 
12.1.1 
Censoring situations 
If a patient is alive and progression-free at the date of the analysis (i.e., cut-off date), the 
patient will be censored, and the reason for censoring will be provided as per Table 13. 
 
The date of last adequate tumor assessment is the date of the last tumor assessment with 
overall lesion response of CR, PR or SD before an event or a censoring reason occurred. In this 
case the last tumor evaluation date at that assessment is used. If no post-baseline assessments 
are available (before an event or a censoring reason occurred) the date of start date of 
treatment is used. 


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Table 13: Censoring Rules 
 
Situation 
Date of Progression 
or Censoring 
Outcome 
Censoring reason 
Ongoing and No event 
until data cut-off 
Date of last adequate 
tumour assessment 
Censored 
Ongoing 
Discontinued the study 
with no event 
Date of last adequate 
tumour assessment 
Censored 
Discontinued 
without event 
No baseline tumour 
assessment 
Date of C1D1 
Censored 
No baseline 
tumour 
assessment 
Lost to follow-up 
Date of last IRC 
tumour assessment 
(or C1D1 in case of 
study discontinuation 
w/o progression 
before any post- 
baseline assessment) 
Censored 
Lost to follow-up 
Patient received non- 
study anti-DLBCL 
treatment before 
disease progression 
Date of last adequate 
tumour assessment 
before start of non- 
study cancer 
treatment 
Censored 
New anti-cancer 
therapy started 
Clinical Progression* 
Date of last adequate 
tumour assessment 
Censored for 
Analysis based on 
Investigator 
assessment only 
Clinical 
Progression not 
validated by 
Cheson Criteria 
PD by modality not 
including PET Scan is 
not confirmed by 
modality including PET 
Scan**. 
Date of last adequate 
tumour assessment 
Censored for 
Analysis based on 
Investigator 
assessment only 
Non-PET PD not 
confirmed by 
PET. 
Death before any date 
of PD assessment 
Date of death 
Progressed 
Death between 
adequate assessments 
Date of death 
Progressed 
Death or progression 
after two or more 
Date of last adequate 
Censored 
Event 
documented 


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Situation 
Date of Progression 
or Censoring 
Outcome 
Censoring reason 
missed visits 
tumour assessment 
after two or 
more missing 
tumor 
assessments 
EOT after two or more 
missed assessments 
without disease 
progression 
Date of Last adequate 
Tumour Assessment 
Censored 
Adequate 
assessment no 
longer available 
Abbreviations: EOT = End of Treatment; IRC = Independent Review Committee; PD = 
progressive disease; CT = Computed tomography; PET = Positron emission tomography. 
*Progression as per Investigator’s assessment and without meeting PD criteria according to 
Response Criteria for Malignant Lymphoma (Cheson et al., 2007). **The rule only applies in 
case a PET-including modality is performed after a non-PET including modality. 
 
 
13.1.1   Identification of two or more missing tumour assessments 
If death or progression happens after two or more missed Tumour Assessments (TA), then the 
event is censored. 
o An event occurring after two or more missing assessments or non-adequate tumour 
assessments will be censored on the date of last adequate tumour assessment. 
o In one of the sensitivity analyses for PFS, an event occurring after two or more missing 
assessments is back-dated to the date of next scheduled assessment. The date of next 
scheduled assessment is the date of the last adequate tumour assessment plus the 
protocol specified time interval for assessments. 
o If the patient has an EOT after two missed assessments without an event, then the patient 
will be censored for PFS at the last assessment and the censoring reason will be ‘Adequate 
assessment no longer available’. 
o Table 14 shows the maximum time [days] that can elapse between two response 
assessments without resulting in censoring. 
 
 
Table 14: Time windows for missing response assessments 
 
Missed tumor assessments 
No tumor assessment 
between 
Censored at 
C3D1, C5D1 
C1D1, C1D1 + 114 days (4 x 
28 + 2) 
C1D1 
C5D1, C7D1 
C3D1, C3D1 + 115 days (4 x 
C3D1 


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28 + 1 + 2) 
C7D1, C10D1 
C5D1, C5D1 + 144 days (5 x 
28 + 2 + 2) 
C5D1 
C10D1, C12D28 
C7D1, C7D1 + 173 days (6 x 
28 + 2 + 4 - 1) 
C7D1 
C12D28, C15D1/C16D1 
C10D1, C10D1 + 186 days (6 
x 28 + 2 + 2 + 14) 
C10D1 
C15D1/C16D1, 
C18D1/C19D1 
C12D28, C12D28 + 184 days 
(6 x 28 + 14 + 2) 
C12D28 
C18D1/C19D1, 
C21D1/C22D1 
C15D1/C16D1 + 172 days (6 
x 28 + 4) 
C15D1/C16D1 
C21D1/C22D1, 
C24D1/C25D1 
C18D1/C19D1 + 172 days (6 
x 28 + 4) 
C18D1/C19D1 
C24D1/C25D1 
C21D1/C22D1 + 451 days (3 
x 28 + 2 + 365) 
C21D1/C22D1 
Tumor assessments in Year 3 
and Year 4 after treatment 
initiation* 
C24D1/C25D1 + 730 days (2 
x 365) 
C24D1/C25D1 
*Apply this interval also for assessments after C24D1/C25D1 
 
 
10.2.5 Main analysis 
o The tumour assessments will be derived according to the IWG treatment response criteria 
for malignant lymphoma (Cheson et al., 2007), by an Independent Radiology/Clinical 
Review Committee (IRC). The review process will be defined in the IRC Charter. 
o The distribution of PFS will be estimated using the Kaplan-Meier (K-M) method. The 
median PFS time along with 95% confidence intervals will be presented (Brookmeyer and 
Crowley 1982). 25th and 75th percentiles will be considered as well. 
o The PFS probabilities at specific time points (1 month, 3 months, 6 months, 12 months, 18 
months, 24 months, 30 months), and the associated 95% CIs (Greenwood formula) will be 
summarized. 
o PFS events will be described according to the type of event (death, documented tumour 
progression). 
o The reason for censoring will be tabulated. 
o A plot of the Kaplan-Meier curve for PFS will be provided. 
o The median follow-up time for PFS including a 95% confidence interval (Brookmeyer and 
Crowley 1982) will be calculated using the reverse Kaplan-Meier method. 
o No formal hypothesis testing will be conducted. 
o The main analysis will be conducted on the FAS for both the IRC and INV response 
assessment. 


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10.2.6 Sensitivity analyses 
o The main analysis as described in Section 10.2.5 will be conducted on the PPS. 
o The main analysis as described in Section 10.2.5 will be conducted based on the INV 
response assessment as entered on the ‘Lymphoma Tumour Assessment’ eCRF page. The 
same censoring rules will apply as for the analysis based on the IRC assessment. If the 
response assessment is not based on radiological examination the date when the 
diagnosis of relapse or progression was made by the investigator is considered as the date 
of progression. The analysis will be conducted using both the FAS and the PPS. 
o Patients having more than one missed visit, but having an available death date, will be 
included in the time-to-event analysis and considered as having a PFS event. The analysis 
will be performed on the FAS for both IRC and INV response assessment. 
 
 
10.2.7 Concordance between IRC and INV assessment of PFS events 
The concordance rate in terms of PFS events represents the agreement (PFS event, No PFS 
event) regarding the definition of these events based on the IRC and INV tumour response 
assessment, respectively. A contingency table will be generated and the concordance rate is 
calculated by adding the diagonal counts and dividing by the total number of patients. This 
concordance analysis will be performed on the FAS. 
 
 
10.3 Secondary objective 3 
10.3.1 Objective 
To determine the duration of response (DoR). 
 
 
10.3.2 Endpoint: Duration of response 
DoR is defined as the elapsed time between the date of first documented response (CR or 
PR) and the following date of event defined as the first documented progression or death: 
DoR [days] = date of assessment of tumour progression or death – date of assessment of 
first documented response of (CR or PR) + 1. 
The DoR will be reported in months. 


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10.3.3 Censoring rules 
14.1.1 
Censoring situations 
If a patient is alive and progression-free at the date of the analysis (i.e., at the cut-off date), 
the patient will be censored, and the reason for censoring will be provided as per Table 13. 
 
 
15.1.1   Identification of two or more missing response assessments 
If death or progression happens after two or more missed Tumour Assessments (TA), then the 
event is censored. 
o An event occurring after two or more missing assessments or non-adequate tumour 
assessments will be censored on the date of last adequate tumour assessment. 
o In one of the sensitivity analyses for PFS, an event occurring after two or more missing 
assessments is back-dated to the date of next scheduled assessment. The date of next 
scheduled assessment is the date of the last adequate tumour assessment plus the 
protocol specified time interval for assessments. 
o If the patient has an EOT after two missed assessments without an event, then the patient 
will be censored for PFS at the last assessment and the censoring reason will be ‘Adequate 
assessment no longer available‘. 
The maximum time [days] that can elapse between two response assessments without 
resulting in censoring is the same as for PFS and is shown in Table 14. 
 
 
10.3.4 Main analysis 
o The tumour assessments will be derived according to the IWG treatment response criteria 
for malignant lymphoma (Cheson et al., 2007), by an Independent Radiology/Clinical 
Review Committee (IRC). The review process will be defined in the IRC Charter. 
o The distribution of DoR will be estimated using the Kaplan-Meier (K-M) method. The 
median DoR along with 95% confidence interval will be presented. 25th and 75th 
percentiles will also be shown. 
o A plot of the Kaplan-Meier curve for DoR will be provided. 
o The DoR probabilities at specific time points (1 month, 3 months, 6 months, 12 months, 
18 months, 24 months, 30 months), and the associated 95% CIs (Greenwood formula) will 
be summarized. 
o No formal hypothesis testing will be conducted. 
o The main analysis will be conducted on the FAS based on the IRC response assessment. 


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10.3.5 Sensitivity analyses 
o The main analysis as described in Section 10.3.4 will be conducted based on the INV 
response assessment as entered on the ‘Lymphoma Tumour Assessment’ eCRF page. The 
same censoring rules will apply as for the analysis based on the IRC assessment. The 
analysis will be conducted using the FAS. 
o DoR stratified by best overall response: The DoR will be stratified by patients who reached 
PR as best overall response, and patients who reached CR as best overall response: 
▪ 
The stratified DoR will be tabulated according to both INV and IRC response 
assessment (for the FAS): 
o Kaplan-Meier methods will be used to derive median, Q1, Q3, and 95% 
confidence intervals (for the FAS). 
o Kaplan-Meier curves will be presented. The graph will include the following 
strata: DoR for patients with PR as best response, CR as best response, and 
one group representing the DoR for all responders (for the FAS). 
o Duration of CR: 
The duration of CR (in days) is defined as follows: (date of assessment of tumour progression 
or death – date of assessment of tumour response [CR] + 1). The duration of CR will be 
reported in months and tabulated according to both local and IRC radiological assessments. 
The duration of CR will be analysed using Kaplan-Meier methods (median, Q1, Q3, 95% 
confidence intervals). A Kaplan-Meier curve will be shown. The analysis will be performed on 
the FAS for both IRC and INV response assessment. 
 
 
10.4 Secondary objective 4 
10.4.1 Objective 
To determine the overall survival (OS). 
 
 
10.4.2 Endpoint: Overall survival 
Overall survival (OS) is defined as the time from the date of the first administration of any 
study drug until death from any cause (documented by the date of death). 
 
 
10.4.3 Censoring rules and imputation 
Patients who are alive or who drop out early for any reason will be censored at date of last 
contact. 


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If for a patient’s death month and year are provided but the day is missing, the day will set to 
the first day of the month, unless other qualifying study data support survival until a later date 
during the same month. If day and month or year is missing, no imputation will be done and 
the date of death will be censored at the date of last contact. A listing showing the information 
on eCRF pages for survival follow-up and end of survival follow-up will be presented (for the 
SAF). 
 
 
10.4.4 Main analysis 
o The distribution of OS will be estimated using the Kaplan-Meier (K-M) method. The 
median OS time along with 95% confidence intervals will be presented (Brookmeyer and 
Crowley 1982). 25th and 75th percentiles will be considered as well. 
o The OS probabilities at specific time points (1 month, 3 months, 6 months, 12 months, 18 
months, 24 months, 36 months, 48 months), and the associate 95% CIs (Greenwood 
formula) will be summarized. 
o A plot of the Kaplan-Meier curve for OS will be provided. 
o The median follow-up for OS will be calculated using the reverse Kaplan-Meier method. 
o No formal hypothesis testing will be conducted. 
o The main analysis will be conducted on the FAS. 
 
10.4.5 Sensitivity analyses 
o The main analysis as described in Section 10.4.4 will be conducted on the PPS. 
 
10.5 Secondary objective 5 and secondary objective 11 
10.5.1 Objectives 
o Objective 5: To determine the time to progression (TTP). 
o Objective 11: To compare each patient’s TTP on LEN plus MOR00208 with the TTP of 
their most recent prior therapy. 
 
 
10.5.2 Endpoint: Time to progression 
TTP is defined as the time from the first administration of any study drug until documented 
DLBCL progression or death as a result of lymphoma. Death from other causes than lymphoma 
will not be considered in relation to the TTP evaluation. 
If a patient does not have an event, TTP will be censored on the date of the last tumour 
assessment before the data analysis cut-off date or the anti-neoplastic therapy start date if 
the patient started any new anti-neoplastic therapy or the date of death for death from other 
causes than lymphoma. 


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10.5.3 Main analyses 
16.1.1   Main analysis for Objective 5 
o The tumour assessments will be derived according to the IWG treatment response criteria 
for malignant lymphoma (Cheson et al., 2007), by an Independent Radiology/Clinical 
Review Committee (IRC). The review process will be defined in the IRC Charter. 
o The distribution of TTP will be estimated using the Kaplan-Meier (K-M) method. The 
median TTP along with 95% confidence intervals will be presented (Brookmeyer and 
Crowley 1982). 25th and 75th percentiles will be considered as well. 
o The TTP probabilities at specific time points (1 month, 3 months, 6 months, 12 months, 
18 months, 24 months), and the associate 95% CIs (Greenwood formula) will be 
summarized. 
o TTP events will be described according to the type of events (death due to lymphoma, 
documented tumour progression). 
o A plot of the Kaplan-Meier curve for TTP will be provided. 
o No formal hypothesis testing will be conducted. 
 
17.1.1   Analysis for Objective 11 
TTP will be compared with TTP of each patient’s most recent therapy via tabulating descriptive 
statistics for TTP of patient’s most recent therapy. A graph showing the Kaplan- Meier curve 
for patients´ last prior treatment will be generated for the FAS. 
The following therapies will be considered as most recent therapy: 
• 
Last prior systemic anti-DLBCL medication (taken from the eCRF page: Prior Cancer 
Therapies for DLBCL-Medications) 
• 
ASCT in case the last prior treatment was ASCT (taken from the eCRF page: Prior Cancer 
Therapies for DLBCL-Autologous Stem Cell Transplants) 
 
 
10.5.4 Sensitivity analyses 
18.1.1   Sensitivity analyses for Objective 5 
o The analyses will be conducted based on the INV response assessment as entered on the 
‘Lymphoma Tumour Assessment’ eCRF page. The same censoring rules will apply as for 
the analysis based on IRC assessments. 
o Patients lost to follow-up or having an event after more than one missed visit, but having 
an available death date, will be included in the time-to-event analysis and considered as 
having a TTP event. 


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19.1.1 
Sensitivity analyses for Objective 11 
No sensitivity analyses will be conducted. 
10.6 Secondary objective 6 
10.6.1 Objective 
To determine the time to next treatment (TTNT). 
 
 
10.6.2 Endpoint: Time to next treatment 
Time to next treatment (TTNT) is defined as the time from the first administration of any study 
drug to the institution of next anti-neoplastic therapy (for any reason including disease 
progression, treatment toxicity and patient preference) or death due to any cause, whatever 
comes first. 
Patients without documented institution of a new anti-neoplastic therapy will be censored at 
the date of last contact. 
 
 
10.6.3 Analysis 
o The distribution of TTNT will be estimated using the Kaplan-Meier (K-M) method. The 
median TTNT along with 95% confidence intervals will be presented (Brookmeyer and 
Crowley 1982). 25th and 75th percentiles will be considered as well. 
o The TTNT probabilities at specific time points (1 month, 3 months, 6 months, 12 months, 
18 months, 24 months), and the associate 95% CIs (Greenwood formula) will be 
summarized. 
o A plot of the Kaplan-Meier curves for TTNT will be provided. 
o No formal hypothesis testing will be conducted. 
o The main analysis will be conducted on the FAS. 
 
10.7 Secondary objective 7 
10.7.1 Objective 
To determine the safety of LEN combined with MOR00208 assessed according to the 
frequency and severity of adverse events (AEs). 


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10.7.2 Endpoint: Incidence, frequency and severity of treatment-emergent 
adverse events (AEs) 
 
 
10.7.3 Analysis 
With the exception of the Listing on pre-treatment AEs emerging in patients who have never 
been exposed to any drug, all safety analyses including the analysis on AEs will be conducted 
using the Safety Set (SAF). The pre-treatment AEs emerging in patients who have never been 
exposed to any drug will be reported on the population of “All screened patients”. 
 
 
20.1.1 
Overview 
The analysis of safety assessments in this trial will include summaries of the following 
categories of safety and tolerability: 
1. Adverse Events (AEs, number and severity) 
▪ 
Treatment-emergent AEs (TEAEs) 
▪ 
Treatment-emergent Serious AEs (SAEs) 
▪ 
TEAEs by maximum toxicity grade 
▪ 
TEAEs by intensity 
▪ 
TEAE suspected to be related to a study drug 
▪ 
TEAEs leading to study discontinuation and AEs leading to death 
▪ 
AEs of special interest (AESI) 
2. Vital signs: systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate 
3. Physical Examination 
4. 12-lead ECG parameters: PR, QRS, RR and QT interval values 
5. Laboratory safety evaluations (blood chemistry, haematology, coagulation, urinalysis, anti- 
MOR00208 antibodies) 
6. ECOG Performance Status 
7. B-Symptoms 
 
 
21.1.1   Adverse events 
An AE is defined as any untoward medical occurrence in a patient or participant in a clinical 
trial administered a medicinal product, which does not necessarily have a causal relationship 
to this treatment. 


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An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a study drug, 
whether or not it is considered related to that study drug. AEs include any clinically significant 
deterioration of a patient’s medical status after the signing of the informed consent form (ICF). 
Also, an increase in the frequency or intensity of a pre-existing event or conditions and events 
resulting from protocol mandated procedures (e.g., invasive procedures) fall under the 
definition of AEs. 
In addition, overdoses exceeding the planned infusion dose by 20% should be recorded as AEs. 
Please note that in the context of this protocol symptoms that are clearly associated to the 
progression of underlying malignancy (DLBCL) do not fall under the definition of AEs. 
Each AE will be reported to determine the following: 
o Relationship to the study drug(s) (suspected/not-suspected) 
o Duration (start and end date, or if continuing at end of study) 
o NCI-CTCAE Grade (see below) 
o Intensity: the intensity of all AEs will be graded as mild, moderate, or severe using the 
following definitions: 
▪ 
mild: tolerable 
▪ 
moderate: interferes with normal activity 
▪ 
severe: incapacitating (causes inability to perform usual activities or work 
o Outcome 
o Action taken with study drug(s) 
▪ 
no action taken 
▪ 
study drug temporarily interrupted 
▪ 
study drug permanently discontinued due to this AE 
o Other action taken (medication taken; non-drug therapy given; hospitalisation/ 
prolonged hospitalisation) 
o Seriousness: whether it is serious, where an SAE is defined as one that: 
▪ 
results in death 
▪ 
is life-threatening 
▪ 
requires inpatient hospitalisation or prolongation of existing hospitalisation 
(hospitalisation signifies that the patient was an inpatient for at least one overnight 
stay) unless hospitalisation is for: 
o Routine treatment or monitoring of the studied indication, not associated 
with deterioration of symptoms related to DLBCL. 


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o Elective or pre-planned treatment for a pre-existing condition that is 
unrelated to DLBCL and has not worsened since signing of the ICF. 
o Social reason and respite care in the absence of any deterioration in the 
patient’s general condition. 
▪ 
Results in persistent or significant disability or incapacity. 
▪ 
Is a congenital anomaly or birth defect. 
▪ 
Is medically significant, i.e., defined as an event that jeopardizes the patient or may 
require medical intervention to prevent one of the outcomes listed previously. 
 
 
22.1.1   Treatment-emergent adverse events 
An on-treatment adverse event (or Treatment-emergent Adverse Event – TEAE) is defined 
as any adverse event reported in the following time interval (including the lower and upper 
limits): date of first administration of any study drug; date of last administration of any study 
drug + 30 days. 
If the last date of study drug administration is missing, on-treatment assessments/events 
include any assessment/event recorded in the database and which occur after the start date 
of study treatment. Safety summary tables including summaries of on-treatment deaths will 
be based only on on-treatment assessments/events. 
An adverse event present prior to study drug administration but increased in severity after 
treatment start, will also be included as TEAE. 
Events with missing onset dates will be included as TEAE if the end date is not before the start 
date of treatment. 
Adverse events occurring or worsening later than 30 days after the date of last study drug 
administration or the date of completion/discontinuation of the study are defined as TEAE if 
these are considered to be related to the study drug. 
If the start date and time of an AE are partially or completely missing, the AE will be assumed 
to be a TEAE if it cannot be definitely shown that the AE did not occur or worsen during the 
treatment-emergent period (worst case approach). Missing dates and times will not be 
replaced. 
Thus, the following approach will be taken: 
o If the start time of an AE is missing but the start date is complete, an AE will only be 
excluded from TEAE if start day is before day of first treatment or start day is after end 
day of treatment-emergent period. 
o If start time and day are missing but the start month is complete, an AE will only be 
excluded from TEAE if start month is before month of first treatment or start month is 


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after end month of treatment-emergent period or if stop date/time is before start of first 
treatment. 
o If start day and months are missing but the start year is complete, an AE will only be 
excluded from TEAE if start year is before year of first treatment or if start year is after 
end year of treatment-emergent period or if stop date/time is before start of first 
treatment. 
o If start date is completely missing, an AE will not be excluded from TEAE unless the stop 
date/time is before start of first treatment. 
 
 
If the last date of study treatment is missing, on-treatment assessments/events include any 
assessment/event recorded in the database and which occur after the start date of study 
treatment. 
The incidence of treatment-emergent AEs will be summarized in incidence tables. If a patient 
experiences more than one occurrence of the same AE, the occurrence with the greatest 
severity and the closest association with the study drug will be counted in the summary tables. 
All AEs will be listed by patient, along with information regarding onset, duration, relationship 
to study drug, intensity, toxicity grade, action taken with study drug, treatment of event, and 
outcomes. 
 
 
23.1.1 
Adverse events of special interest 
Adverse events of special interest (AESI) are: 
- 
Tumour flare (TFR) 
- 
Tumour lysis syndrome (TLS), 
- 
Second primary malignancy (SPM) 
- 
Infusion-related reactions (IRRs) ≥ grade 3 
- 
Allergic reactions to study drug ≥ grade 3 
- 
Cytokine release syndrome 
- 
Overdoses 
Unlike routine safety assessments, SAEs and AESI are monitored continuously and have 
special reporting requirements. 
 
 
24.1.1   Relationship to study drug 
The Investigator should determine the causality (relationship to the study drug) based on 
his/her clinical experience, on Summary of Product Characteristics (SmPC) and Prescribing 
Information, and on the information given in the Investigator’s Brochure (IB) for MOR00208 
and the SmPC/prescribing information for LEN. The causal relationship of all AEs to the study 
drug will be judged as either suspected or not suspected. A suspected causal 


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relationship means at least a reasonable possibility that the event is caused by the study drug. 
If no relationship has been provided by the Investigator, the event will be considered as 
related to the study drug. 
 
 
25.1.1   Coding of adverse events 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA) and will be reported by primary system organ class (SOC) and preferred term (PT). 
The MedDRA version used for reporting the study will be the version used for coding the trial 
and will be specified in the clinical study report and as a footnote in the related outputs (if 
possible). 
 
 
26.1.1   Grading of adverse events 
Toxicity grade: determined according to the National Cancer Institute- Common Terminology 
Criteria for Adverse Events (NCI-CTCAE) version 4.03 of June 14, 2010 (or higher), using the 
following definitions: 
o Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
o Grade 2: moderate; minimal, local or noninvasive intervention indicated; limiting age- 
appropriate instrumental activities of daily living (refers to preparing meals, shopping for 
groceries or clothes, using the telephone, managing money, etc.) 
o Grade 3: severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self-care 
activities of daily living 
o Grade 4: life-threatening consequences; urgent intervention indicated 
o Grade 5: death related to AE 
 
The CTCAE represents a comprehensive grading system for reporting the acute and late effects 
of cancer treatments. CTCAE grading is by definition a 5-point scale generally corresponding 
to mild, moderate, severe, life threatening, and death. This grading system inherently places 
a value on the importance of an event although there is not necessarily proportionality among 
grades (a grade 2 is not twice as bad as a grade 1). 
 
 
27.1.1   Deaths 
All deaths including those that occurred on-treatment and post-treatment, will be listed (SAF), 
post treatment deaths will be flagged. In addition to the on-treatment deaths and additional 
summary of all deaths (on-treatment + post-treatment) will be provided. 


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28.1.1   General rules for reporting 
10.7.3.1.1 AE tables 
i. 
All safety analyses will be done using the Safety Set (SAF). The incidence of treatment- 
emergent AEs will be summarised in incidence tables. 
ii. AEs will be summarised by SOC and PT using the Medical Dictionary for Regulatory Activities 
(MedDRA) version 21.0 and will be updated to the most current version at the end of the 
trial. The SOCs and PTs will be used for tabulation. 
iii. AE frequency tables will display the number of events (incidence), number of patients 
experiencing an event and the percentage of patients with the event by System Organ 
Class (SOC) and Preferred Term (PT). 
iv. If a patient experiences more than one occurrence of the same AE, the occurrence with the 
greatest severity and the closest association with the study drug will be counted in the 
summary tables. 
v. If a patient reported more than one AE with the same preferred term, the AE with the 
maximum toxicity grade will be presented. 
vi. If a patient reported more than one AE within the same primary system organ class, the 
patient will be counted only once with the maximum toxicity grade at the system organ 
class level, where applicable. 
vii. The most common AEs reported (≥10 % for each preferred term) will be presented in 
descending frequency according to its incidence starting from the most common event. 
 
10.7.3.1.2 AE listings 
i. 
All AEs will be listed by patient, along with information regarding onset, duration, relationship 
to study drugs, intensity, toxicity grade, action taken with study drug, treatment of event, 
and outcomes. This listing will be generated for all patients in the SAF. 
ii. In the AE listings, AEs that started prior to the administration of any study drug will be flagged 
as pre-treatment AEs. AEs that start 30 days after the last study treatment and which are 
not related to one of the study drugs will be flagged as post-treatment AEs. 
iii. Special AE listings displaying details of the event(s) captured on the eCRF in a compact format 
will be provided for: 
• 
Serious Adverse Events. 
• 
TEAEs of toxicity grade 3 or grade 4. 
• 
AEs leading to discontinuation of treatment (split by MOR00208, LEN and overall). 
• 
TEAEs of special interest. 
• 
TEAEs suspected to be related to study drug 


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• 
Treatment-emergent SAEs 
• 
TEAEs pertaining to the SOC ‘infections and infestations’ 
• 
AEs leading to death. 
• 
Pre-treatment adverse events (i.e., adverse events that happened before administration 
of any study drug). This listing will be generated for all patients successfully screened but 
never treated. The pre-treatment AEs will be determined using the analysis population of 
‘All screened patients’. 
 
 
29.1.1   AE summaries 
10.7.3.1.3 TEAEs (serious and non-serious) 
The following summaries will be provided: 
i. 
All TEAEs regardless of study treatment relationship by primary SOC, PT, grade. 
ii. All TEAEs regardless of study treatment relationship by primary SOC, PT, intensity. 
iii. Most frequent TEAEs (at least in 10% of the patients), regardless of study treatment 
relationship by SOC, PT and grade. 
iv. TEAEs regardless of study treatment relationship ≥ grade 3 by primary SOC, PT and grade. 
v. TEAEs regardless of study treatment relationship of grade 3 or grade 4 by primary SOC, PT and 
grade. 
vi. TEAEs suspected to be related to the study drug by primary SOC, PT, and grade (according to 
NCI-CTC toxicity criteria) (split by MOR00208, LEN, both drugs at the same time, and any 
study drug). 
vii. TEAEs suspected to be related to the study drug by primary SOC, PT, and intensity (according 
to NCI-CTC toxicity criteria) (split by MOR00208, LEN, both drugs at the same time, and 
any study drug). 
viii. TEAEs suspected to be related to the study drug of ≥ grade 3 by primary SOC, PT and grade 
(split by MOR00208, LEN, both drugs at the same time, and any study drug). 
ix. TEAEs suspected to be related to the study drug of grade 3 or grade 4 by primary SOC, PT and 
grade (split by MOR00208, LEN, both drugs at the same time, and any study drug). 
x. Most frequent TEAEs suspected to be related to the study drug (at least in 10% of the patients) 
by primary SOC, PT and grade (split by MOR00208, LEN, both drugs at the same time, and 
any study drug). 
xi. TEAEs leading to any action on MOR00208, on LEN, or either on MOR00208 or on LEN 
regardless of study treatment relationship, by primary SOC, PT and grade. 
Note: Any Action = Dose reduction/Dose interruption/Permanent discontinuation. 


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xii. TEAEs leading to discontinuation of treatment (split by MOR00208, LEN, both drugs at the 
same time, and overall) regardless of study treatment relationship by primary SOC, PT and 
grade. 
xiii. Most frequent Non-serious TEAEs, regardless of study treatment relationship by primary SOC, 
PT and grade (at least 5% incidence). 
 
10.7.3.1.4 Treatment-emergent SAEs 
The following summaries on treatment-emergent SAEs will be produced: 
i. 
Treatment-emergent SAEs regardless of study treatment relationship, by primary SOC, PT, 
grade. 
ii. Most frequent treatment-emergent SAEs (at least in 2% of the patients), regardless of study 
treatment relationship, PT and grade. 
iii. Treatment-emergent SAEs regardless of study treatment relationship ≥ grade 3 by primary 
SOC, PT, and grade. 
iv. Treatment-emergent SAEs of grade 3 or grade 4 regardless of study treatment relationship by 
primary SOC, PT, and grade. 
v. Treatment-emergent SAEs suspected to be related to the study drug by primary SOC, PT, grade 
(split by MOR00208, LEN, both drugs at the same time, and any study drug). 
vi. Treatment-emergent SAEs suspected to be related to study drug ≥ grade 3 by primary SOC, 
PT, and grade (split by MOR00208, LEN, both drugs at the same time, and any study drug). 
vii. Treatment-emergent SAEs suspected to be related to the study drug of grade 3 or grade 4 by 
primary SOC, PT, and grade (split by MOR00208, LEN, both drugs at the same time, and any 
study drug). 
viii. Most frequent treatment-emergent SAEs suspected to be related to the study drug (at least 
in 2% of the patients) by SOC, PT and grade (split by MOR00208, LEN, both drugs at the same 
time, and any study drug). 
ix. Treatment-emergent SAEs of grade 5 by primary SOC and PT. 
 
 
10.7.3.1.5 AESIs 
AEs of special interest will be presented by primary SOC, PT and grade. 
 
 
10.7.3.1.6 Deaths 
Deaths will be summarized as follows: 


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• 
Treatment-emergent deaths (deaths observed within 30 days after last administration of 
study treatment) in total and grouped by: 
o Deaths related to disease progression as indicated on the eCRF pages for ‘End of 
Survival Follow-up’ or ‘End of Treatment’: all reasons/causes for death containing the 
phrases: 
- ‘PROGRESSIVE DISEASE’ 
- ‘PROGRESSION DISEASE’ 
- ‘PROGRESSION OF DISEASE’ 
- ‘LYMPHOMA’ 
- ‘MULTIPLE RELAPSING AND REFRACTORY DLBCL’ 
- ‘DLBCL DISEASE PROGRESSION’ 
- ‘LYMPHOMA’ 
- ‘DISEASE PROGRESSION’ 
- ‘PROGRESSIVE DESEASE’ 
- ‘PROGRESSION DESEASE’ 
- ‘RELAPSE’ 
- ‘IMMEDIATE CAUSE OF DEATH: PARALYTIC ILEUS, DUE TO ABDOMINAL 
LYMPHOMA PROGRESS’ 
- ‘PROGRESIVE DISEASE’ 
- ‘PD’ 
- ‘RECURRENCE OF LARGE CELL LYMPHOMA’ 
will be considered as related to disease progression. 
o Deaths unrelated to disease progression: All on-treatment deaths not considered as 
related to disease progression will be considered as unrelated to disease progression. 
 
 
• 
Post-treatment deaths (deaths observed after 30 days after last administration of study 
treatment) overall and grouped by: 
o Deaths related to disease progression as indicated on the eCRF page for ‘End of 
Survival Follow-up ‘: all reasons for death containing the phrases: 
- ‘PROGRESSIVE DISEASE’ 
- ‘PROGRESSION DISEASE’ 
- ‘PROGRESSION OF DISEASE’ 
- ‘LYMPHOMA’ 
- ‘MULTIPLE RELAPSING AND REFRACTORY DLBCL’ 
- ‘DLBCL DISEASE PROGRESSION’ 
- ‘DISEASE PROGRESSION’ 
- ‘PROGRESSIVE DESEASE’ 


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- ‘PROGRESSION DESEASE’ 
- ‘RELAPSE’ 
- ‘IMMEDIATE CAUSE OF DEATH: PARALYTIC ILEUS, DUE TO ABDOMINAL 
LYMPHOMA PROGRESS’ 
- ‘PROGRESIVE DISEASE’ 
- ‘PD’ 
- ‘RECURRENCE OF LARGE CELL LYMPHOMA’ 
will be considered as related to disease progression. 
o Deaths unrelated to disease progression: all post-treatment deaths not considered as 
related to disease progression will be considered as unrelated to disease progression. 
 
• 
Total number of deaths (All deaths (on-treatment + post treatment) are included) overall 
and grouped by: 
o Deaths related to disease progression as indicated on the eCRF pages for ‘End of 
Survival Follow-up’ or ‘End of Treatment’: all reasons/causes for death containing the 
phrases: 
- ‘PROGRESSIVE DISEASE’ 
- ‘PROGRESSION DISEASE’ 
- ‘PROGRESSION OF DISEASE’ 
- ‘LYMPHOMA’ 
- ‘MULTIPLE RELAPSING AND REFRACTORY DLBCL’ 
- ‘DLBCL DISEASE PROGRESSION’ 
- ‘DISEASE PROGRESSION’ 
- ‘PROGRESSIVE DESEASE’ 
- ‘PROGRESSION DESEASE’ 
- ‘RELAPSE’ 
- ‘IMMEDIATE CAUSE OF DEATH: PARALYTIC ILEUS, DUE TO ABDOMINAL LYMPHOMA 
PROGRESS’ 
- ‘PROGRESIVE DISEASE’ 
- ‘PD’ 
- ‘RECURRENCE OF LARGE CELL LYMPHOMA’ 
will be considered as related to disease progression. 
o Deaths unrelated to disease progression: All deaths not considered as related to 
disease progression will be considered as unrelated to disease progression. 
 
 
A listing on the deaths based on the ‘all patients screened’ population will be produced 
indicating if a death is PD-related, and if the death happened on treatment, pre-treatment, or 
post-treatment. 


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10.7.3.1.7 Overall Summary of AEs 
In addition, an Overall AE summary table will be presented showing the incidence and 
number of patients with at least one of the events: 
• 
At least one TEAE. 
• 
At least one treatment-emergent SAE. 
• 
On-treatment deaths. 
• 
Post-treatment deaths. 
• 
At least one treatment-emergent SAE suspected to be related to the study drug (split by 
MOR00208, LEN, MOR00208 and LEN, and any study drug). 
• 
At least one TEAE suspected to be related to the study drug (split by MOR00208, LEN, 
MOR00208 and LEN, and any study drug). 
• 
At least one drug-related TEAE with grade 3 or grade 4 (split by MOR00208, LEN, 
MOR00208 and LEN, and overall). 
• 
At least one drug-related TEAE by intensity (split by MOR00208, LEN, MOR00208 and 
LEN, and overall). 
• 
At least one AESI. 
• 
At least one TEAE leading to any action on MOR00208, on LEN, on MOR00208 and LEN, 
or on any study drug 
• 
TEAEs leading to discontinuation of treatment (split by MOR00208, LEN, MOR00208 and 
LEN, and overall). 
• 
Treatment-emergent SAEs of grade 5. 
• 
At least one TEAE of PT ‘Infusion-related reactions (IRRs) ’ ≥ grade 3 
 
Additional safety-related analyses on vital signs, physical examinations, electrocardiogram, 
and laboratory data are being described in Section 13. 
 
 
10.8 Secondary objective 8 
10.8.1 Objective 
To assess the potential immunogenicity of MOR00208 (anti-MOR00208 antibodies). 
 
 
10.8.2 Endpoint: Percentage of patients who develop anti-MOR00208 antibodies 
as determined by a positive anti-MOR00208 antibody titre. 


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10.8.3 Analysis 
Assessment of immunogenicity will be performed using the immunogenicity analysis 
population (IAS). 
 
 
1. The results of the anti-MOR00208 antibody assessment will be listed for each anti- 
MOR00208 sample analysed, including a categorization if the anti-MOR00208 antibody 
response is neutralizing or non-neutralizing. 
 
 
Note: For 2. and 3. below, “negative” is defined as a sample reported negative in the screening 
assay OR confirmatory assay. “Positive” is defined as a sample being reported positive in the 
confirmatory assay. 
 
 
2. The absolute number and percentage of the following categories will be tabulated by visit: 
 
 
Patient has positive anti-MOR00208 antibodies (yes/no/missing) by visit: 
• 
Yes, if a titre is available. 
• 
No, if result is reported as negative. 
• 
Missing, if anti-MOR00208 measurement is not available. 
 
3. In addition, the absolute number and percentage of patients who develop anti- MOR00208 
antibodies will be tabulated using the following categories: 
 
 
Patient has developed positive anti-MOR00208 antibodies during study (yes/no/not 
evaluable/missing): 
• 
Yes, if the patient has at least one positive post-baseline sample containing positive anti- 
MOR00208 antibodies, baseline sample has to be tested negative. 
• 
No, if baseline as well as all post-baseline results are negative. 
• 
Not evaluable, if the baseline sample of the respective patient was tested positive. 
• 
Missing, if no post-baseline anti-MOR00208 measurement is available. 


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4. Results (n, mean, median, StD, minimum, maximum) of semi-quantitative anti MOR00208 
antibody titre determinations of confirmed positive sample assessments will be tabulated by 
visit. 
 
 
10.9 Secondary objective 9 
10.9.1 Objective 
To assess the pharmacokinetics (PK) of MOR00208. 
 
 
10.9.2 Endpoint: MOR00208 plasma concentrations at sampling timepoints, 
accumulation ratios and trough concentrations 
 
10.9.3 Analysis 
The main analysis will be conducted on the PKAS. Individual plasma samples for the analysis 
of MOR00208 PK will be collected on various study days. For evaluation of PK metrics, a patient 
subsample will be considered consisting of those patients who have at least one quantifiable 
MOR00208 serum concentration (the PK analysis set, PKAS). 
 
 
30.1.1   Bioanalytical assessment of pharmacokinetic serum samples 
MOR00208 concentration values for each serum sample are to be determined using a 
validated Ligand Binding Assay. A separate bioanalytical phase plan and report will be 
generated that provide details on samples handling and processing, methods used for sample 
analysis, statements on quality control/quality assurance (QC/QA) and results of the each 
individual sample analyzed for each patient by the bioanalytical labs. 
 
 
31.1.1   Data analysis 
MOR00208 serum concentrations will be summarized based on nominal (scheduled) sampling 
times. Serum concentrations below the limit of quantification or missing data will be labelled 
as such in the concentration data listings. Analyte concentrations that are below the limit of 
quantification (BLQ) will be assigned a value of zero when they precede the first quantifiable 
sample. All other BLQ samples will be treated as missing data. Summary statistics for 
MOR00208 serum concentrations will include n, arithmetic mean, StD, geometric mean, 
coefficient of variation (CV), median, minimum and maximum. The CV will be expressed as a 
percentage and calculated as follows: 


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• 
CV of the arithmetic mean (%) = StD/mean*100. 
• 
CV of the geometric mean (%) = sqrt(exp(variance for log transformed data)–1)*100. 
 
Concentration figures (linear and log y-axis) of mean concentrations +/- StD will be presented. 
Individual MOR00208 serum concentrations may be excluded from summary statistics and 
concentration figures (mean) if the actual collection time/date of the sample exceeds 
allowable windows relative to the scheduled collection time/date. 
 
 
• 
For samples collected 1h after the end of MOR00208 infusion, results will be excluded 
from summary statistics if the deviation of the actual collection time is larger than ± 15 
min from the scheduled collection time. 
• 
Results of PK samples collected outside of the allowed window of ± 1 day relative to the 
scheduled collection day will be excluded from summary statistics. Each 28 day cycle will 
be considered separately. 
 
 
Irrespective of exclusion of data points from summary statistics, each obtained MOR00208 
serum concentration will be listed and reported. 
 
 
Accumulation of MOR00208 will be investigated by comparing the average concentration of 
pre-dose and 1 hour post-dose of Cycle 3 Day 1 (i.e. the 10th dose) with the corresponding 
mean from the previous visit for which MOR00208 concentration data is available using 
ANOVA (α = 0.05). If no significant difference is found, Cycle 3 Day 1 will be compared to 
previous visit for which MOR00208 concentration data is available and so forth until two 
consecutive times a significant difference is found. 
 
 
32.1.1    Population PK analysis 
A population PK analysis of MOR00208 will be conducted. The planned meta-analysis will 
encompass PK data from study MOR208C203 and other clinical trials with MOR00208. The 
analysis will provide an understanding of the population PK of MOR00208 and determine the 
influence of intrinsic and extrinsic factors (such as but not limited to age, gender, race, level 
of hepatic or renal function and presence of anti-drug antibodies) that may influence PK 
variability. Details of the intended population PK analysis will be described in a separate 
population PK protocol and the results will be described in a separate population PK study 
report. 


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10.10 Secondary objective 10 
To make a preliminary evaluation of ORR, DCR, DoR, PFS, OS, TTP and TTNT in patients treated 
with a combination of LEN plus MOR00208 in cohorts with a “low risk”, “low- intermediate”, 
“high-intermediate” and “high” International Prognostic Index (IPI). 
 
 
10.10.1 Endpoint 
ORR, DCR, DoR, PFS, OS, TTP, and TTNT stratified by: 
• 
four risk categories: “low risk”, “low-intermediate risk”, “high-intermediate risk” and 
“high risk”. 
• 
two risk categories: “low risk” and “low-intermediate risk” vs. “high-intermediate risk” 
and “high risk”. 
 
 
10.10.2 Main analysis 
• 
The main analyses are described above in the respective sections addressing ORR, DCR, 
DoR, PFS, OS, TTP, and TTNT (see Sections 9.2, 10.1.3, 10.3.4, 10.2.5, 10.4.4, 10.5.3, 
10.6.3). 
• 
For the analysis comprising two risk categories: An estimate of the hazard ratio and 
corresponding 95% CI will be calculated for PFS and OS analyses using a Cox proportional 
hazard model with only one covariate in the model. 
 
 
10.10.3 Sensitivity analyses 
The main analyses as described in Section 10.10.2 will be conducted based on the INV 
response assessment (see sections 9.3, 10.1.4, 10.3.5, 10.2.6, 10.4.5, and 10.5.4). 
 
 
10.11 Secondary objective 11 
10.11.1 Objective 
To compare each patient’s TTP on LEN plus MOR00208 with the TTP of their most recent 
prior therapy. 
 
 
10.11.2 End point and main analysis 
End point analyses are described in detail above in section 10.5.3. 


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10.12 Secondary objective 12 
10.12.1 Objective 
To correlate efficacy parameters with certain biomarkers (e.g. peripheral NK cell count, 
constitutional FcγRIIIa and FcγRIIa polymorphism status). 
 
 
10.12.2 Endpoint 
PFS, DoR, ORR, OS will be analyzed in the following subgroups: 
• 
FcγRIIIa affinity (high affinity: FCGR3A-158V homozygosity vs. low affinity: FCGR3A-158F 
homozygosity, or FCGR3A-158F/V heterozygosity). 
• 
FcγRIIa affinity (high affinity: FCGR2A-131H homozygosity vs. low affinity: FCGR2A-131R 
homozygosity, or FCGR2A-131H/R heterozygosity). 
• 
Peripheral NK cell numbers at baseline (< median of NK cell numbers/µl vs. >= median of 
NK cell numbers/µl). 
• 
Cell of origin determined by immuno-histochemistry (IHC) (i.e., central pathology) 
assessment: germinal center B cell (GCB) phenotype vs. non-GCB phenotype. 
• 
Cell 
of 
origin 
determined 
by 
gene 
expression 
profiling 
(GEP): 
GCB phenotype vs. activated B cell (ABC) phenotype vs. unclassified phenotype. 
 
 
10.12.3 Main analysis 
The following analyses will be conducted on the FAS: 
• 
The main analyses pertaining to the biomarker subgroup analyses are being described in 
the respective sections above addressing ORR, PFS, DoR, and OS (Sections 9.2, 10.1.3, 
10.2.5, 10.3.4, and 10.4.4). 
• 
PFS, DoR and OS will be compared between subgroups by a log-rank test. 
• 
For PFS and OS analyses, the estimate of the hazard ratio and corresponding 95% CI will 
be calculated using a Cox proportional hazards model with only one covariate (i.e., the 
biomarker in question) in the model. 
 
 
10.12.4 Sensitivity analyses 
The main analysis as described in Section 10.12.3 will be conducted based on the INV 
response assessment using the FAS. 
 
 
A comprehensive analysis of all biomarker assessments will be described in a separate 
biomarker-specific Statistical Analysis Plan, and summarized in a separate report. 


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11. EXPLORATORY EFFICACY ANALYSES 
11.1 Time to response and time to complete response 
The time to response will be calculated and tabulated for patients achieving response (PR of 
CR). The time to response [months] is defined as follows: 
((date of assessment of first documented response of (CR or PR)) – (date of first 
administration of any study drug) + 1) / 30.4375. 
Moreover, the time to complete response [months] will be calculated and tabulated for 
patients achieving complete response. The time to complete response is defined as follows: 
((date of assessment of first documented complete response (CR)) – (date of first 
administration of any study drug) + 1) / 30.4375. 
The time to response will be calculated using the FAS for both the INV and IRC assessment. 
 
 
11.2 PET-Confirmed Complete Responses 
Number (%) of patients with a PET-confirmed CR at any point in time will be presented for the 
IRC response assessment. The device used for imaging for a particular Visit can be found on 
the ‘Lymphoma Tumour Assessment’ eCRF page. The following devices will be considered as 
PET modality: 
• 
PET/CT 
• 
PET/MRI 
• 
PET 
A separate listing will show those patients who reached a PET-confirmed CR (SAF). 
 
 
11.3 Tumor shrinkage over time: Assessment of indicator lesions 
Data on lesion size will be presented by descriptive statistics and individual data listings (for 
the SAF). The sum of the product of the longest perpendicular diameters (SPD) reflecting the 
lesion area will be used for the analysis (based on the IRC assessment). Data will be presented 
separately for the two central reviewers. 
The area of indicator lesions will be examined as follows: 
1. Analysis across all points in time: 
• 
Absolute values and both absolute and the individual relative changes (from baseline) for 
each patient will be summarized for each visit. 


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• 
A graph showing the individual relative changes over time will be generated separately for 
both central readers. The best overall response of each individual will be indicated by 
colour coding (CR, PR, SD, PD, NE=not evaluable). 
 
2. Analysis comparing baseline and nadir: 
• 
The area of indicator lesions will be reported at baseline and at the nadir. The absolute 
value and both the absolute and relative difference between baseline and nadir will be 
reported. 
• 
A “waterfall plot” indicating the best change (%) for indicator lesions will be generated 
separately for both central readers. 
3. Correlation between radiologists. 
The SPD as determined by radiologist 1 at screening and nadir will be correlated with the SPD 
at screening and nadir as determined by radiologist 2. The Pearson Correlation Coefficient will 
be derived for both assessments, i.e., at screening and nadir. 
Listings showing individual lesion sizes over time will be produced. 
 
 
11.4 Non-biomarker subgroup analyses 
PFS, ORR, DoR, and OS will be reported for the following subgroups. All analyses will be 
conducted using the FAS based on both IRC and INV response assessment. Kaplan-Meier 
curves will be provided for PFS, DoR, and OS. For PFS and OS analyses, the estimate of the 
hazard ratio and corresponding 95% CI will be calculated using a Cox proportional hazards 
model with only one covariate in the model. 
• 
Gender (Male vs. Female) 
• 
RTX refractoriness (yes vs. no; see section 8.7.4.1.3) 
• 
Refractoriness to last prior treatment line (yes vs. no; see section 8.7.4.1.2) 
• 
Primary refractoriness (yes vs. no; see section 8.7.4.1.1) 
• 
Prior autologous stem cell transplantation (yes vs. no) 
• 
NHL subtype as per central pathology (dichotomized, i.e., DLBCL patients vs. non-DLBCL 
patients) 
• 
Number of prior treatment lines (1 vs. >= 2) 
• 
Number of prior treatment lines (1 vs. 2 vs. 3 vs. 4) 
• 
Reason for ASCT ineligibility: 
o Chemorefractory 


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o High age or Comorbidites 
o Other 
 
12. DESCRIPTIVE BIOMARKER ANALYSES 
Biomarker assessments will be tabulated by descriptive statistics. Summaries will be 
provided for the following variables: 
• 
CD16 molecules on CD16+CD56+ NK cells (continuous variable) 
• 
Percentage specific killing (ADCC assay) (continuous variable) 
• 
FcγRIIIa affinity (categorical variable): 
o 2 subgroups (high affinity: FCGR3A-158V homozygosity vs. low affinity: FCGR3A- 
158F homozygosity, or FCGR3A-158F/V heterozygosity). 
o 3 subgroups (FCGR3A-158V homozygosity vs. FCGR3A-158F homozygosity vs. 
FCGR3A-158F/V heterozygosity). 
• 
FcγRIIa affinity (categorical variable): 
o 2 subgroups (high affinity: FCGR2A-131H homozygosity vs. low affinity: FCGR2A- 
131R homozygosity, or FCGR2A-131H/R heterozygosity). 
o 3 subgroups (FCGR2A-131H homozygosity vs. FCGR2A-131R homozygosity vs. 
FCGR2A-131H/R heterozygosity). 
• 
NK cell numbers at baseline (continuous and categorical variable): 
o NK cell numbers/µl at baseline (continuous variable). 
o Baseline and demographics characteristics as described in Section 8.5 will be 
shown for both subgroups defined by NK cell numbers/µl at baseline less than the 
median and above or equal to the median. 
• 
Longitudinal analyses will be conducted for: Peripheral numbers of NK cells, B cells, and T 
cells (analysed separately): 
o Summary statistics per visit (a 95% confidence interval for the median will be 
derived by bootstrapping) 
o Relative change from baseline (a 95% confidence interval for the median will be 
derived by bootstrapping). 
o Graphical illustration showing individual values for both absolute values and 
separately relative change from baseline. The median across all patients (without 
confidence interval) will be shown. 


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o Graphical illustration showing the median and its 95% confidence interval (via 
bootstrapping) for both absolute values and relative change per visit across all 
patients assessed. 
o Graphical illustration showing boxplots for both absolute values and relative 
change per visit across all patients assessed. 
• 
Cell of origin (categorical variable): 
o Cell of origin determined by immuno-histochemistry (IHC) assessment (i.e., 
central pathology): germinal center B cell (GCB) phenotype vs. non-GCB 
phenotype. 
o Cell  of  origin  determined  by  gene  expression  profiling  (GEP): 
GCB phenotype vs. activated B cell (ABC) phenotype vs. unclassified phenotype. 
• 
A Listing will provided showing the information on double hit status (genetic lesions in 
BCL-2 and MYC as assessed by FISH), and triple hit status (genetic lesions in BCL-2, MYC, 
and BCL-6 as assessed by FISH). Only those patients will be listed who have been assessed. 
 
 
Concordance between cell-of-origin determination by gene expression profiling and 
immuno-histochemistry 
The concordance rate represents the agreement regarding the cell-of-origin as determined by 
gene expression profiling (GEP) and immuno-histochemistry (IHC). The concordance rate is 
the number of patients that are concordant over the total number of patients assessed, and 
will be calculated across all cell-of-origin categories. The concordance rate will be calculated 
using the following categories: 
Analysis 1: ABC (GEP) and GCB (GEP) vs. Non-GCB (IHC) and GCB (IHC). 
Analysis 2: (ABC (GEP) + Unclassified (GEP)) and GCB (GEP) vs. Non-GCB (IHC) and GCB (IHC). 
A confusion matrix (i.e., a contingency table with GEP cell-of origin as rows and IHC cell-of- 
origin as columns) will be generated. The concordance rate will be calculated by adding the 
diagonal counts and dividing by the total number of patients assessed. 
As only a fraction of patients have undergone GEP and IHC analysis, only those patients will 
be considered for the concordance analysis who have been evaluated by both assessments 
(i.e., GEP and IHC). Considered for the concordance analysis are only patients from the FAS. 
Listings will be provided for all biomarkers (both baseline values and, if applicable, results of 
subsequent assessments). 
All descriptive analysis of biomarkers will be performed using the FAS. Listings will be 
generated showing individual data on the biomarkers. 


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13. ADDITIONAL SAFETY ANALYSES 
13.1 Adverse events 
The analysis of adverse events is comprehensively described in Section 10.7. 
 
 
13.2 Vital signs 
13.2.1 Vital signs variables 
The Vital Signs captured in the eCRF for each patient at each visit are the following: 
- 
Weight (all visits) 
- 
Height (only Screening Visit) 
- 
Systolic Blood Pressure (all visits) 
- 
Diastolic Blood Pressure (all visits) 
- 
Heart Rate (all visits) 
- 
Respiratory Rate (all visits) 
- 
Temperature (all visits) 
- 
Overall interpretation of Vital Signs (all visits) 
 
13.2.2 Vital signs analysis 
The following analysis will be performed on these variables: 
i. 
These variables will be summarized by visit by means of descriptive statistics of actual values 
and change from baseline. 
ii. Overall interpretation of Vital Signs will be tabulated to present the corresponding 
frequency count and percentage at each visit. 
iii. The normal ranges for the vital sign variables are: 
- 
Systolic blood pressure: 70-149 mm Hg 
- 
Diastolic blood pressure: 60-90 mm Hg 
- 
Heart rate: 55-110 beats per minute 
- 
Respiratory rate: 10-24 breaths per minute 
- 
Body temperature: 36.1-37.8 C (97.0-100.0 °F) 
 
Vital Signs will be listed by visit for the SAF and an abnormal value will be flagged to 
show whether it is a value below or above the normal limit. 
 
The analysis will be performed on the SAF. 


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13.3 Physical examination 
Baseline and End of Treatment full physical examinations will be summarized by body system. 
New and worsening abnormal physical examination findings during the study will be entered 
as AEs and analysed within the AE tables. The analysis will be performed on the SAF. Listings 
on full physical examination will be shown (for the SAF). 
 
 
13.4 Electrocardiogram (ECG) 
13.4.1 ECG variables 
The Electrocardiogram variables captured in the eCRF for each patient at each visit are the 
following: 
- 
QRS Interval 
- 
RR Interval 
- 
PR Interval 
- 
QT Interval 
- 
QTcB: Bazett’s correction for QT given by 
, where RR=60/heart rate. 
- 
QTcF: Fridericia’s correction for QT given by 
, where RR=60/heart rate. 
- 
Overall Interpretation of 12 Lead ECG tracing 
 
The variables listed above are not derived by programming, but will be used as entered in 
the eCRF. 
 
13.4.2 ECG analysis 
The following analyses will be performed on these variables: 
i. Overall interpretation of 12 Lead ECG tracing will be tabulated to present the corresponding 
frequency count and percentage at each visit. 
ii. ECG variables will be summarized by visit by means of descriptive statistics of actual values 
and change from baseline. 
iii. The normal ranges for the ECG variables are: 
- 
PR interval: 110-220 ms 
- 
QRS interval: 60-120 ms 
- 
RR interval: 600-1200 ms 
- 
QT interval (also corrected): ≤400 ms 
iv. As recommended in the FDA guidance E14 on Clinical Evaluation of QT/QTc interval 
prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs (October 2015), 
the number and percentage of patients having notable ECG interval values will be as 
follows in Table 15. 


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Table 15: Clinically notable ECG values 
 
ECG parameter (unit) 
Clinically notable criteria 
QTcF (ms) 
New > 450 ms 
New > 480 ms 
New > 500 ms 
Increase from Baseline > 30 ms 
Increase from Baseline > 60 ms 
PR duration (ms) 
Increase > 25% from Baseline and to PR duration > 200 ms 
QRS duration (ms) 
Increase > 25% from Baseline and to QRS duration > 110 ms 
 
v. All assessments will be listed and those collected outside of the treatment window will be 
flagged. 
The summaries will include only assessments on treatment. The analysis will be performed on 
the SAF. Listings on ECG interpretation and ECG intervals will be shown. 
 
 
13.5 Laboratory data 
13.5.1 Laboratory variables 
Laboratory parameters measured in the central laboratory can be separated into 
• 
Blood parameters (haematology, serum chemistry, coagulation). 
• 
Urine parameters (urinalysis). 
 
13.5.2 Grading of laboratory data 
Laboratory data grades of severity will be derived according to the Common Terminology 
Criteria for Adverse Events (CTCAE) v4.03. A severity grade of 0 will be assigned when the 
value is within normal limits. In the case a local laboratory normal range overlaps into the 
higher (i.e. non-zero) CTCAE grade, the CTCAE grade will be taken. Lab values having hyper or 
hypo shifts will be classified as a particular CTCAE grade irrespective of the shift direction (no 
differentiation between CTCAE grades resulting from increased or decreased lab values). The 
laboratory values for which CTCAE grades are defined for only one direction of deviation (e.g., 
platelet count) will be assigned grade 0 in case a laboratory value is outside the reference 
range, but in a direction for which CTCAE grading is not defined. 
Laboratory test results will also be shown by the low/normal/high classifications based on 
laboratory normal ranges. 


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For duplicate laboratory measurements taken at the last assessment date on or before the 
start date of study treatment, the value of lower CTCAE grade will be considered as the 
baseline value. 
For non-gradable labs with duplicate laboratory measurements taken at the last assessment 
date on or before the start date of study treatment: 
• 
If both within normal range: take average value. 
• 
If one within normal range and the other outside: take the one within normal range. 
• 
If both outside normal range: take the one closest to the normal range. 
Laboratory values with missing units or normal range may not be able to be graded or included 
in laboratory tables. 
 
 
13.5.3 Laboratory analysis 
Laboratory data that are continuous in nature but are less than the lower limit of quantitation 
or above the upper limit of quantitation will be imputed. The limit of quantitation will be used 
for calculation of descriptive statistics if the data is reported in the form of “≤ x” or “< x” or “≥ 
x” (x is considered as the limit of quantitation). 
The following analysis on laboratory parameters will be performed: 
i. 
Laboratory parameters will be summarized. Descriptive summaries of actual (absolute) 
values and change-from-baseline values will be presented for haematology and serum 
chemistry for the SAF by visit. SI units will be used in the generation of these descriptive 
summaries. The assessment of categorical urinalysis variables will be tabulated by time 
point for each categorical urine parameter. 
ii. Abnormal values will be flagged in the listings (SAF population) to indicate whether the 
value is below or above the reference range and whether the investigator assessed the 
abnormal value as clinically significant. A clinically significant result can be commented 
with “Adverse Event”, “Due to primary disease”, “Pre-existing condition” or free text. 
iii. The assessment of the clinical significance of laboratory variables will be tabulated by time 
point for each clinical laboratory analyte. 
iv. For each laboratory parameter, shifts in assessments from baseline to worst-post baseline 
will be presented. 
v. If NCI-CTCAE grades are available for a clinical laboratory analyte, they will be derived 
according to NCI CTCAE, Version 4.03, and used to present additional frequency and shift 
tables based on NCI-CTCAE grades. 
The following summary will be produced for the laboratory data (by laboratory 
parameter): 


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• 
 
Number (%) of patients with worst post-baseline CTCAE grade (regardless 
of the baseline status). Each patient will be counted only for the worst grade 
observed on-treatment 
• 
 
Shift tables to compare baseline to the worst post-baseline value will be 
produced for hematology and biochemistry laboratory parameters using: 
o CTCAE grades for laboratory parameters where CTCAE grades are defined. 
o The classifications relative to the laboratory reference ranges 
(low/normal/high) for laboratory parameters where CTCAE grades are not 
defined. 
vi. 
The following listing will be produced: 
• 
Listing of patients with laboratory values outside the normal ranges with 
values flagged to show the corresponding CTCAE grade and the classifications 
relative to the laboratory reference ranges. 
 
The summaries will include only assessments on treatment. The analysis will be performed 
on the SAF. 
 
 
13.6 ECOG scores analyses 
The analysis of ECOG scores will be performed on FAS and SAF. 
The following analyses will be performed on ECOG scores: 
• The ECOG performance status will be summarized categorically in a frequency table by 
visit. 
• Shift Tables in ECOG status from baseline to worst post-baseline will be presented. 
• The ECOG status will be listed (for the SAF). 
 
13.7 B-symptoms 
B-symptoms are defined as any one or more of the following disease-related symptoms or 
signs: 
• 
Unintentional weight loss of ≥ 10% within the preceding 6 months or less. 
• 
Drenching night sweats without signs of infection. 
• 
Recurrent, unexplained fever with temperatures above 38 °C without signs of infection. 
 
The presence of B-symptoms will be summarized categorically in a frequency table by visit. 
The analysis will be performed on FAS and SAF. Data listings will be presented (for the SAF). 


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14. GENERAL GUIDANCE ON REPORTING 
14.1 Document headers and footers 
The following header will be used for all tables, listings and figures outlined in this 
document: MOR208C203 – reporting event (Cut-off date ddMONyyyy). 
The following labels of reporting event will be used for all outputs: 
• 
PA for Primary Analysis 
• 
FA for Final Analysis 
The following display will be used for outputs: 
• 
footnote 1 
• 
footnote 2 
• 
footnote 3 
program source, date and version information. 
For example: 
MOR208C203- PA (Cut-off date: 06JUN2014) 
“/report/pgm_saf/program.sas 07MAY14:15” 
 
 
In the applicable outputs, the MedDRA version and WHO-DDE version used for reporting the 
study will be specified as a footnote. 
- MedDRA Version <xx.x> has been used for the reporting 
- WHO-DDE Version <xx.x> has been used for the reporting 
The latest available version of dictionaries at the time of reporting will be used. 
 
 
14.2 Presentation of output numbering and titles within this document 
In practice, the numbering and title for all tables, figures and listings in sections 14 and 16 
defined in this document will be formatted as follows, respectively: 
 
 
Table XX.X-X.X 
Title Title Title Title Title Title 
Population 


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Listing XX.X-X.X 
Title Title Title Title Title Title 
Population 
 
14.3 Presentation of analysis sets 
The outputs to be produced based on this document will use ‘Screened Patients’, ‘Enrolled 
Patients’, ‘FAS’, “PPS’, “SAF’, “PKAS’, ‘IAS” in the table/figure/listing titles. 
 
 
14.4 General rules for presenting frequencies and percentages 
If a summary table displays only categorical variables then the convention illustrated in the 
following example will be used: 
 
Preferred Term 
N=xx 
n (%) 
 
 
Total 
xx (xx.x) 
 
 
Fatigue 
xx (xx.x) 
Nausea 
xx (xx.x) 
Anemia 
xx (xx.x) 
 
 
However, if a summary table displays both continuous and categorical variables then the 
convention illustrated in the following example will be used: 


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Sex, n (%) 
All patients 
N=xx 
Male 
xx (xx.x) 
Female 
xx (xx.x) 
 
 
Age (Years) 
n 
xx 
Mean 
xx.x 
StD 
xx.xx 
Median 
xx.x 
Minimum 
xx.x 
Maximum 
xx.x 
 
 
 
 
14.5 General rule for tables/listings 
All other data as documented in the eCRF will be listed and/or tabulated using descriptive 
statistics or counts/percentages depending on the nature of data. All the data collected and 
derived in the trial will be presented in patient data listings. 
 
 
14.6 Format of tables/listings and displays with no data 
Where a listing or table has been planned, but no data meet the criteria, then a single line 
stating ‘No data meeting the criteria are present’ will be provided in the output. The default 
tables, listings and figures (TLF) layout will be as follows. 


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Orientation 
Landscape 
Paper Size 
A4 
Margins 
Top: 2 cm 
Bottom: 2 cm 
Left: 2 cm 
Right: 2 cm 
Header: 1.27 cm 
Footer: 1.27cm 
Font 
Courier New 8pt 
Headers 
Protocol number – Type of Analysis (Cut-off date) (Left); 
Page X of Y (Right) 
TLF Number and Title 
Footers 
SAS program name 
Source Data 
File name 
Extract date 
Date, Time TLF generated 
 
The font size may be reduced as necessary to allow additional columns to be presented, but 
not at the expense of clarity. Also the orientation may be changed to portrait if appropriate. 
 
 
14.7 Precision rules 
For continuous variables, minimum and maximum will be presented to the same precision as 
the raw data. Mean, median, 25th and 75th percentiles will be presented to one more decimal 
place and standard deviation to two more decimal places than the raw data. An exception will 
be made for biomarker representing counts where mean and median will be presented 
without a decimal place. Geometric mean will be presented to one more decimal place than 
the raw data. CV of mean and CV of geometric mean will be shown to one decimal place. 
For concentrations and PK parameters 3 significant digits apply for mean, geometric mean, 
median, StD, min and max. Elapsed time and Tmax should have 2 decimal places in the listings. 
For categorical variables, the number (n) and percentage (%) of patients per category will be 
presented. If the count is zero in a cell, then only ‘0’ count will be presented and not ‘0.0 (0.0)’. 
The number of missing values will be presented as a “Missing” category. Percentage 


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values are to be rounded and presented to one decimal place. If percentages are equal to 100, 
then no decimal places will be presented ‘xx (100)’. 
The confidence intervals of a percentage will be presented to the same precision as the 
percentage. The p-values will be presented with three decimals. P-values below 0.001 will be 
denoted as <0.001. Hazard ratios and respective confidence intervals will be presented to two 
decimal places. 
 
 
14.8 General rules for presenting listings 
The following general rules for presenting listings should be applied by default for all listings. 
For listings, the default sorting order is by patient number and event/assessment date unless 
otherwise stated. 
The first column of the listing will always be “Patient identifier” field. 
Where a listing or table has been planned, but no data meet the criteria, then a single line 
stating ‘No data meeting the criteria are present’ will be provided in the output. 
The study day will always be displayed in the listings if applicable. It will be printed under the 
label ‘Study Day’ in all listings. The definition of study day is: 
The reference start date for all safety assessments (e.g. adverse event onset, laboratory 
abnormality occurrence, vital sign measurement, dose interruption, etc.) will be the start date 
of study treatment. The following footnote will be added in all safety listings: “Study Day is 
relative to the first date of study treatment (Day 1)”. 
The reference start date for all efficacy assessments (e.g. tumor assessment, death, disease 
progression, tumor response, performance status) will be the start date of study treatment. 
The following footnote will be added in all efficacy listings: “Study Day is relative to the first 
date of study treatment (Day 1)”. 
For data collected at the visit level: ‘Visit’ column will be displayed in the listings. Unscheduled 
visits will appear as “Unsch” (or similar) in all the listings, if any. 
For all laboratory parameters, SI units are used as default. 
When a variable collected in the eCRF is linked to another variable, one or both variables will 
be presented in the same column of the listing or in adjacent columns if space permits this. 
For example: 
• 
‘Setting’=’OTHER’ and ‘Other, specify’=’Lung’ 
“OTHER: Lung” will be displayed in the column as ‘Setting’. 
• 
‘Dose’=’120’ and Dose unit =’mg’ 
‘120 mg’ will be displayed in the column as ‘dose (unit)’. 


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• 
Date = “2012-05-12” and Study day =”5”. 
• 
“12MAY2012 / 5” will be displayed in the column as ‘Date / Study Day’. 
• 
(1) End date = “2012-05-22” and Study day =”15” or 
(2) End date = “ ” and ongoing is ticked: 
(1) “22MAY2012 / 15” will be displayed in the column as ‘End date / Study Day’ 
(2) “Ongoing” will be displayed in the column as ‘End date / Study Day’. 
 
 
14.9 Presentation of Dates 
Calendar dates and times (optional) in all the listings will be displayed in the format: 
DDMMMYYYY/hh:mm e.g. 2011-01-15/00:20. 
Note: If time is not collected, calendar dates will be displayed as: DDMMMYYYY. 


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3. Awan FT, Lapalombella R, Trotta R, et al. CD19 targeting of chronic lymphocytic leukemia 
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Overcomes Negative Prognostic Impact of Non-Germinal Center B-Cell Phenotype in 
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20. Woyach JA, Awan F, Flinn IW, et al. A Phase I Trial of the Fc Engineered CD19 Antibody 
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21. Zinzani PL, Pellegrini C, Gandolfi L, et al. Combination of lenalidomide and rituximab in 
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22. Zinzani PL, Rigacci L, Cox MC, et al. Lenalidomide monotherapy in heavily pretreated 
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with  non-Hodgkin 
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retrospective 
study 
in 
daily  clinical 
practice. 
Leuk  Lymphoma. 
2014 
(doi: 
10.3109/10428194.2014.964702). 


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16. ADDENDUM 1.0 
16.1 Compliance 
The compliance for MOR00208 and LEN as outlined in Section 8.9.6 is summarized by Cycle. 
Boxplots showing the distribution of compliance within the patient population will be 
produced. The analyses will be performed for both the FAS. 
 
 
16.2 Relative dose intensity 
The dose intensity of LEN and MOR00208 as defined below will be summarized by Cycle. 
Boxplots will be generated showing the distribution of the relative dose intensity. The analyses 
will be conducted using the FAS. 
The relative dose intensity for LEN is derived as follows: 
• 
„Planned dose“ for each Cycle: 25 mg x 21 days = 525 mg per Cycle (ignoring dose 
change, interruptions, discontinuations) 
• 
„Used dose“ for each Cycle: X mg total daily dose x number of pills taken in that Cycle 
(pills returned – pills dispensed will be used as surrogate for pills taken) 
• 
Relative Dose Intensity by Cycle: „Used dose“ / „Planned dose“ x 100 
• 
A boxplot showing the distribution of the Relative Dose Intensity by Cycle will be 
generated 
The relative dose intensity for MOR00208 is derived as follows: 
• 
„Planned dose“ for a particular Cycle: 250 ml x planned number of infusions for a 
particular Cycle (varies depending on the Cycle) 
• 
Infusion interruptions and skipped doses will be ignored when determining the „planned 
dose“ 
• 
„Used dose“ for a particular Cycle: sum of actual volume administered across all 
infusions of a Cycle 
• 
Relative Dose Intensity by Cycle: „Used dose“ / „planned dose“ x 100 
• 
A boxplot showing the distribution of the Relative Dose Intensity by Cycle will be 
generated 
 
 
16.3 Additional safety analyses 
For all additional safety analyses specified in the SAP Addendum the general approach for 
reporting the incidence and frequency of adverse events is used as detailed in Section 10.7. 


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16.3.1 TEAE by ‘search category’ 
The incidence of TEAEs will be summarized by ‘search category’, PT, and NCI-CTCAE Grade. 
The following search categories are defined: 
1) Search Category: ‘Infective pneumonias’ 
All AEs belonging to Standardised MedDRA Query (SMQ) “Infective pneumonias” will be 
displayed in a combined fashion. For instance, the following terms will be pooled: 
• 
PT pneumonia 
• 
PT lung infection 
 
2) Search Category: Sepsis 
All AEs with PTs including the term “Sepsis” (in MedDRA: 54 terms) will be displayed in a 
combined fashion. For instance, the following terms will be pooled: 
• 
PT sepsis 
• 
PT neutropenic sepsis 
• 
PT streptococcal sepsis 
• 
PT Klebsiella sepsis 
 
3) Search Category: Urinary tract infections 
All AEs with PTs including the term “Urinary tract infection” (in MedDRA: 42 terms) plus all 
AEs belonging to MedDRA HLT “Urinary tract infections” will be displayed in a combined 
fashion, for instance, the following terms will be pooled: 
• 
PT urinary tract infection 
• 
PT urinary tract infection bacterial 
• 
PT Escherichia urinary tract infection 
• 
PT urinary tract infection enterococcal 
 
4) Search Category: Rashes 
All AEs belonging to MedDRA HLGT “Epidermal and dermal conditions” will be displayed in a 
combined fashion, for instance, the following terms will be pooled: 
• 
PT rash 


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• 
PT rash maculo-papular 
• 
PT rash erythematous 
• 
PT rash pruritic 
• 
PT dermatitis allergic 
 
16.3.2 Time to first TEAE 
The time to the first TEAE will be summarized for the following TEAEs: 
• 
Neutropenia ≥ G3 (PT ‘neutropenia‘) 
• 
Thrombocytopenia ≥ G3 (PT ‘thrombocytopenia‘) 
• 
Infections and infestations ≥ G3 (SOC ‘infections and infestations’) 
• 
Infective pneumonia ≥ G3 (SMQ code 20000231, narrow scope 
• 
Urinary tract infection ≥ G3 (CMQ as defined in the SAP Appendix) 
• 
Sepsis ≥ G3 (CMQ as defined in the SAP Appendix) 
• 
Febrile neutropenia (PT ‘febrile neutropenia‘) 
• 
Thromboembolic events of all CTCAE Grades (SMQ code 20000081) 
• 
Thromboembolic events ≥ G3 (SMQ code 20000081) 
 
16.3.3 Tabulation of the most frequent TEAEs 
Most frequent TEAEs, regardless of study drug relationship, will be tabulated by SOC, PT and 
NCI-CTCAE Grade. An incidence of 5% will be used as cut-off (i.e., TEAEs that happened in at 
least 5% of the patients are displayed). 
 
 
16.3.4 Reasons for temporary MOR00208 and LEN interruptions 
The following will be displayed by study drug: 
• 
Number (%) of patients who experienced at least one interruption of dosing. 
• 
The total number of interruptions 
Temporary interruptions of MOR00208 include skipped visits and infusion interruptions. 
Temporary interruptions of LEN include any cases where the full number of 21 capsules was 
not taken during a cycle due to one or several TEAEs, or if LEN intake stopped within a cycle 
due to a TEAE, and restarted in the same cycle. This includes cases with or without dose 


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reduction of LEN. Permanent treatment discontinuations of LEN are not considered in this 
summary. 
Of note, a patient can have more than one reason for a temporary interruption of study drug, 
and also experience multiple sequential interruptions. Percentages will be based on the 
number of patients who had at least one temporary interruption of MOR00208 or LEN, 
respectively. 
 
 
16.4 Additional efficacy analyses 
16.4.1 Time to PR and time to best response 
The time to PR and the time to best response will be summarized for the FAS. 
 
 
16.4.2 Event-free survival 
A Kaplan-Meier analysis for event-free survival (EFS) will be performed using the FAS based on 
the IRC response assessment. The same rules definitions and analysis rules as defined in 
Section 10.2 will be applied, with the following exception: 
The initiation of a new anti-DLBCL therapy (medication, radiation, surgery) will be considered 
as an EFS event, instead of leading to censoring. 
A Kaplan-Meier curve will be produced for illustration. 
 
 
16.5 Subgroup analyses 
16.5.1 Patients who discontinued LEN treatment 
Efficacy assessment 
A Kaplan-Meier analysis on PFS and OS will be conducted as described in Sections 10.2 and 
10.4 for those patients who discontinued LEN treatment at any point in time. That is, 
regardless whether the discontinuation is due to an adverse event, or as per protocol after 
Cycle 12. The analysis will start from the moment of LEN discontinuation (zero time elapsed). 
Both Tables and Kaplan-Meier curves will be produced based on the FAS. 
 
 
Safety assessment 
Incidence and frequency of adverse events will be displayed separately for the periods before 
LEN discontinuation, and after LEN discontinuation. All discontinuations of LEN treatment are 
considered, regardless of the reason for discontinuation (per protocol, or due to AE). 


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TEAEs are considered for the pre-LEN discontinuation period if they are observed in the 
following interval (including the lower and upper limits): date of first administration of study 
treatment to date of last administration of LEN + 7 days (or if they are suspected to be related 
to LEN). 
TEAEs are considered for the post-LEN discontinuation period if they are observed in the 
following interval (including the lower and upper limits): date of last administration of LEN + 
8 days to date of last administration of MOR00208 + 30 days (if they are not suspected to be 
related to LEN). 
For both periods following will be summarized by SOC, PT, and NCI-CTCAE Grade for the SAF: 
• 
All TEAEs 
• 
TEAEs by ‚Search Category‘ (see Section 16.3.1) 
• 
SAEs 
• 
AESIs 
• 
G3 vs. G4 TEAEs 
Moreover, a Table summarizing fatal TEAEs (i.e., Grade 5 SAEs) will be produced. 
 
 
A barplot will be produced illustrating the TEAEs that happened with an incidence of ≥10% of 
patients in the SAF. Each bar will represent a particular PT, and for each bar the fraction of 
patients with Grade 1, 2, 3, 4, 5 will be indicated by color-coding or shading. 
Exposure as described in Section 8.9.2 will be calculated for both the pre-LEN discontinuation 
period (exposure to LEN or the combination LEN/MOR00208), and the post- LEN 
discontinuation period (exposure to MOR00208). The exposure to LEN or the combination for 
the pre-LEN discontinuation period is starting from the first date of LEN dosing. The exposure 
to MOR00208 only for the post-LEN discontinuation period is starting from the first 
administration of MOR00208 after the discontinuation of LEN. 
 
 
The Tables displaying the TEAEs and exposure, and the also the barplot will be additionally be 
produced for an alternative definition of the pre- and post-LEN discontinuation period. 
TEAEs are considered for the pre-LEN discontinuation period if they are observed in the 
following interval (including the lower and upper limits): date of first administration of study 
treatment to date of last administration of LEN+ 30 days (or if they are suspected to be related 
to LEN). 
TEAEs are considered for the post-LEN discontinuation period if they are observed in the 
following interval (including the lower and upper limits): date of last administration of LEN + 


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31 days to date of last administration of MOR00208 + 30 days (if they are not suspected to 
be related to LEN). 
 
 
16.5.2 Patients who reduced the daily prescribed LEN dose 
Incidence and frequency of TEAEs by the degree of LEN dose reduction 
TEAEs will be tabulated by SOC, PT, and NCI-CTCAE Grade as described in Section 10.7 for 
the following subgroups of patients: 
• 
Patients with no reduction of LEN. 
• 
Patients with a minimum LEN dose of 20 mg/day: for this category, all TEAEs that occurred 
before exceeding the threshold of 20 mg/day are considered. The calculation of incidence 
rates is based on the number of patients in the SAF. 
• 
Patients with a minimum LEN dose of <20 mg/day but ≥5mg/day: for this category, all 
TEAEs are considered that happened after exceeding the threshold of 20 mg/day. The 
calculation of incidence rates is based on the number of patients who had a reduction to 
<20 mg/day but ≥5mg/day. 
 
 
Duration of TEAEs of interest 
The duration of various TEAEs of interest will be summarized for the following dose 
categories: 
• 
Patients who are treated with 25 mg LEN per day 
• 
Patients who are treated with 20 or 15 or 10 or 5 mg LEN per day 
• 
Patients who are treated with 15 or 10 or 5 mg LEN per day 
 
For each category only those TEAEs are considered that happen during the period of treatment 
with the particular dose or dose range defining the categories above (e.g., only those TEAEs 
are considered that happen during while the patient is on 15 or 10 or 5 mg LEN per day). The 
duration of a particular TEAE is summarized for the following TEAEs: 
• 
Neutropenia ≥G3 (PT ‘neutropenia‘) 
• 
Thrombocytopenia ≥G3 (PT ‘thrombocytopenia‘) 
• 
Infections and infestations ≥G3 (SOC ‘infections and infestations’) 
• 
Infective pneumonia ≥G3 (SMQ code 20000231, narrow scope) 
• 
Urinary tract infection ≥G3 (CMQ as defined in the SAP Appendix) 


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• 
Sepsis ≥G3 (CMQ as defined in the SAP Appendix) 
• 
Febrile neutropenia (PT ‘febrile neutropenia‘) 
• 
Thromboembolic events of all CTCAE Grades (SMQ code 20000081) 
• 
Thromboembolic events ≥G3 (SMQ code 20000081) 
 
16.5.3 Evaluation of the influence of different CMC batches 
In L-MIND patients were treated with different production batches of the material patients 
were treated with (denoted with CMC2 and CMC4 material). A summary will be produced 
showing the number of patients who were treated with: 
• 
CMC2 only 
• 
CMC4 only 
• 
Both CMC2 and CMC4 material 
For those patients who were first treated with CMC2 and later with CMC4 the ‘time to switch’ 
will be displayed in a histogram. The time to switch will be summarized. 
 
 
Evaluation of the influence on safety 
Incidence of TEAEs by SOC, PT, Grade pre-switch vs. post-switch: 
• 
TEAEs 
• 
SAEs 
• 
AESIs 
• 
Fatal TEAEs 
• 
G3 vs. G4 TEAEs 
 
The exposure as defined in Section 8.9.2 will be determined for both the CMC2 and CMC4 
material. 
 
 
Evaluation of the influence on efficacy 
Based on the investigator response assessment (INV) the following quantities will be 
summarized: 
• 
Median time to censoring post-switch due to data cut-off (considering only censored 
patients; no Kaplan-Meier methodology) 


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• 
Median time to PFS event post-switch (considering only patients with PFS event; no 
Kaplan-Meier methodology) 
• 
Median follow-up time after the switch (applying the reverse Kaplan-Meier method) 
 
Based on the investigator response assessment, a swimmers plot will be produced for the 
patients who switched from CMC2 to CMC4, indicating: 
• 
The bar length will represent the time to event / censoring 
• 
Point in time when the CMC switch happened 
• 
Point in time when PR or CR were detected first 
• 
Patients without PFS event who are censored due to data cut-off (arrow head on top of 
bar) 
• 
Patients who experienced a PFS event, or patients who were censored due to other 
reasons than data cut-off (blunt bar end); patients who are treated despite progression 
will have a blunt end at the time the PD was detected 
 
 
16.5.4 Efficacy by age category 
Based on the FAS, PFS, OS, ORR, and DoR will be derived for the following subgroups as 
detailed in the respective SAP sections for both the INV and IRC response assessment. For 
time-to-event endpoints both Figures and Tables will be produced. The following categories 
are considered: 
• 
Patients ≤70 years of age 
• 
Patients >70 years of age 
 
16.5.5 Time to event analyses by best response category 
OS will be summarized for the following categories based on the FAS: 
• 
Patients having a CR as best response (as determined by IRC) 
• 
Patients having a PR as best response (as determined by IRC) 
A Kaplan-Meier curve for the two subgroups will be produced. 
 
16.5.6 Forest plots for biomarker and non-biomarker subgroups 
Forest plots for the ORR, the CR rate, and the hazard ratio between the subgroups of a 
particular subgroup factor (determined from a univariable Cox regression model) will be 


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produced for the biomarker and non-biomarker subgroups as defined in Sections 10.12, 10.10, 
and 11.4. The plots will be based on the FAS and generated separately for both the IRC and 
INV response assessment. 
 
 
16.5.7 ASCT ineligibility subgroups 
Subgroup analyses 
In addition to the ASCT ineligibility subgroups as defined in Section 8.6.3, the following four 
mutually exclusive categories will be defined: 
• 
Chemorefractory patients: 
o Chemorefractory patients as indicated on the eCRF page ‘ASCT Ineligibility Criteria’ 
(‘Failure to achieve PR or CR with salvage therapy’). 
o Patients who underwent a stem cell transplantation before as indicated on the eCRF 
page ‘Prior Cancer Therapies for DLBCL – Autologous Stem Cell Transplants’. 
o The presence or absence of any other reason such as comorbidities or high age will 
be ignored. 
• 
Co-morbid patients 
o Only those patients will be considered who are not already in the ‘Chemorefractory’ 
group. 
o Co-morbid as indicated on the ‘ASCT Ineligibility Criteria’ page 
o Presence or absence of other reasons such as high age will be ignored. 
• 
Patients of high age 
o Only those patients will be considered who are not already in the ‘Chemorefractory’ 
or ‘co-morbid’ category. 
o All patients who are ineligible due to high age as indicated on the eCRF page ‘ASCT 
Ineligibility Criteria’ (‘Age > 70 years’). Other reasons for ASCT ineligibility like ‘Refusal’ 
or ‘Other reasons’ will be ignored. 
• 
Refusal 
o Only those patients 
will be considered 
who are not already in the 
‘Chemorefractory’, ‘Co-morbid’, or ‘High age’ category. 
o All patients who are ineligible due to the patients´ refusal to undergo ASCT as 
indicated on the eCRF page ‘ASCT Ineligibility Criteria’. 
• 
Other reasons 


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o All other patients who are not in the categories above will be considered as ASCT 
ineligible due to other reasons. 
 
Table 16: Reasons for ASCT Ineligibility 
 
Priority 
High level category 
Reason from eCRF 
1 
Chemorefractory 
Failure to achieve PR or CR 
with salvage therapy 
Prior ASCT as indicated in 
eCRF page ‘Prior Cancer 
Therapies for DLBCL – 
Autologous Stem Cell 
Transplants’ 
2 
Comorbidity 
Diffusion lung capacity for 
carbon monoxide <50% by 
pulmonary function test 
Left ventricular ejection 
fraction <50% by multiple 
gated acquisition 
echocardiogram 
Other organ dysfunction or 
comorbidities precluding the 
use of HDT/ASCT on the basis 
of unacceptable risk of 
treatment 
3 
Age 
Age >70 years 
4 
Refusal 
Patient refusal of HDT/ASCT 
5 
Other 
Other Reason 
 
The reasons for being ASCT ineligible will be summarized for the FAS. The following subgroup 
analyses in terms of efficacy will be conducted based on both the INV and IRC response 
assessment (using the FAS): 
• 
PFS 
• 
OS 
• 
DoR 


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• 
ORR 
Both Tables and Kaplan-Meier curves for time-to-event analyses will be produced as described 
in the respective sections that detail the analysis of the listed endpoints. If less than three 
patients are included in the ‘Other’ category this subgroup will not be analyzed or displayed 
in the graphs. 
 
 
Contingency table for displaying the reasons for ASCT ineligibility 
The five reasons for being ASCT ineligible as defined above are presented in a cross-table. The 
table will show the number of patients who are characterized by a particular combination of 
two different ASCT ineligibility reasons. For this summary the reasons for ASCT ineligibility are 
not defined as mutually exclusive, i.e, a patient can have more than one reason for being 
ASCT ineligible, resulting in the fact that patients can generally be represented multiple times 
in the table. Percentages are calculated row-wise and are based on the number of patients in 
FAS with reason for ASCT ineligibility as displayed in the first column. 
The contingency table will be produced for: 
• 
The FAS 
• 
The subgroup of patients with only one prior treatment line (on the FAS) 
• 
The subgroup of patients with two prior treatment lines (on the FAS) 
• 
The subgroup of patients with three or four prior treatment lines (on the FAS) 
 
16.5.8 NK cell numbers at baseline 
In analogy to the subgroup analysis specified in Section 10.12 the NK cell categories are 
additionally defined using a cut-off of 100 NK cells/µl (<100 cells/µl vs. ≥100 cells/µl). The 
following efficacy analyses will be conducted based on the FAS: 
• 
PFS (based on IRC only) 
• 
OS 
• 
ORR (based on IRC only) 
• 
DoR (based on IRC only) 
Kaplan-Meier curves will be produced for time-to-event endpoints. 
Baseline characteristics in the NK count subgroups defined by the cut-off of 100 NK cells/µl 
will be tabulated as described in Section 8.5. 


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16.5.9 Swimmers plot for responders 
A swimmers plot will be produced for the responders in the FAS. The bar length will indicate 
the time on treatment defined as follows: (date end of treatment – date of first dosing with 
any study drug) + 1. Different landmarks will be indicated in the plot: 
• 
Arrow heads: indicate if a patient is still ongoing on treatment at data cut-off. 
• 
Patients who have discontinued treatment are indicated by a blunt end of the bar. 
• 
Time to partial response and time to complete response is indicated by different 
symbols. 
• 
A symbol at the start of the bar will indicate if a patient is primary refractory. 
• 
A symbol at the end of the bar will indicate if a patient has already progressed. 


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17. SAP ADDENDUM 2.0 
17.1 Efficacy in subgroups of BCL-2 expression levels determined by IHC 
Three complementary subgroups of patients will be defined: 
• 
Patients with high BCL-2 expression: ≥50% BCL-2-positive cells and BCL-2 staining 
intensity ≥2 
• 
Patients with low BCL-2 expression: 
- 
<50% BCL-2-positive cells and BCL-2 staining intensity <2 
- 
<50% BCL-2-positive cells, and BCL-2 staining intensity ≥2 or unknown 
staining intensity 
- 
BCL-2 staining intensity <2, and ≥50% BCL-2-positive cells or unknown 
percentage of positive cells 
• 
Patients with unknown status regarding BCL-2 expression: 
- 
≥50% BCL-2-positive cells and unknown BCL-2 staining intensity 
- 
BCL-2 staining intensity ≥2 and unknown percentage of BCL-2 positive cells 
- 
Unknown percentage of BCL-2 positive cells, and unknown BCL-2 staining 
intensity 
The following endpoints will be summarized for the BCL-2 subgroups based on the FAS: 
• 
ORR (based on IRC only) 
• 
PFS (based on IRC only) 
• 
DoR (based on IRC only) 
• 
OS 
The methodology for summarizing the endpoints are described in Sections 9, 10.2, 10.3, and 
10.4. Kaplan-Meier plots will be presented for the time-to-event endpoints. 
 
 
17.2 Efficacy in alternative age subgroups 
In addition to the subgroup analysis specified in Section 16.5.4, selected efficacy endpoints 
will also be analyzed for the following subgroups: 
• 
Patients of ≤65 years of age 
• 
Patients of >65 years of age 
The following endpoints will be summarized for the alternative age subgroups based on the 
FAS: 


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• 
ORR (based on IRC only) 
• 
PFS (based on IRC only) 
• 
DoR (based on IRC only) 
• 
OS 
The methodology for summarizing the endpoints are described in Sections 9, 10.2, 10.3, and 
10.4. Kaplan-Meier plots will be presented for the time-to-event endpoints. 
 
 
17.3 Efficacy in different histological subgroups 
Selected endpoints will be reported for patients belonging to different pathological subgroups 
as per central pathology are depicted in Table 17. Pathological subgroups will be identified as 
outlined in Section 17.8. Moreover, the duration of being progression-free will be visualized 
in a swimmer plot. Summaries will be generated based on the FAS. 
 
Table 17: Analyses for various NHL subgroups as per central pathology 
 
Histology 
Outputs 
DLBCL, no further specification 
ORR, (CR rate, PR rate) 
DoR 
PFS 
OS 
Swimmer plot 
Composite Lymphoma with DLBCL Component 
ORR, (CR rate, PR rate) 
DoR 
PFS 
OS 
Swimmer plot 
Any high grade lymphoma with double or triple hit 
ORR, (CR rate, PR rate) 
Swimmer plot 
EBV positive DLBCL + T cell histiocyte-rich large B cell 
lymphoma 
ORR, (CR rate, PR rate) 
Swimmer plot 
Follicular Lymphoma Grade 2 + Grade 3A 
ORR, (CR rate, PR rate) 
Swimmer plot 
Mantle Cell Lymphoma 
ORR, (CR rate, PR rate) 
Swimmer plot 
Marginal Zone Lymphoma 
ORR, (CR rate, PR rate) 
DoR 
Swimmer plot 


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Histological transformation to DLBCL from indolent 
NHL 
ORR, (CR rate, PR rate) 
Swimmers plot 
Unknown / missing 
ORR, (CR rate, PR rate) 
Swimmers plot 
 
The methodology for summarizing the endpoints ORR, DoR, PFS, and OS are described in 
Sections 9, 10.2, 10.3, and 10.4. 
The swimmer plot will be designed as follows: 
• 
the length of the bar will indicate the time of being progression free in months. 
• 
a blunt end indicates progression 
• 
an arrow head will indicate that the patient is still progression-free: color-coding for 
the arrow head will be used to indicate if the patient is still ongoing on PFS-follow- up, 
or has been censored due to other reasons 
• 
bars will be color-coded to differentiate between patients with PR and CR as best 
response 
• 
the patient ID will be shown for each bar, together with the number of prior treatment 
lines 
• 
symbols will be used to indicate the point in time (relative to first dosing with any 
study drug) when the first PR and first CR was detected 
• 
symbols on the right of the bars will be used to indicate if a patient is primary 
refractory and/or refractory to his/her last prior treatment lineBest response and 
progression free survival will be based on the IRC evaluation. 
 
 
17.4 Identification of transformed lymphoma patients 
Section 8.6.4 describes how patients with previous indolent lymphoma (i.e., patients who 
transformed to high-grade lymphoma) are identified. The algorithm will be modified as 
follows: 
• 
“Presumed INHL” will be added to the list of search terms. 
• 
Patients who developed a secondary indolent lymphoma after the diagnosis of DLBCL 
(or other high-grade lymphoma as specified in the protocol) will not be considered. 
• 
Patients who have the reference diagnosis “HISTOLOGICAL TRANSFORMATION TO 
DLBCL FROM INDOLENT NHL” per central pathology assessment will also be 
considered. 


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17.5 Swimmer plot for patients with transformed lymphoma 
A swimmer plot for patients with transformed lymphoma will be produced. The strategy to 
identify patients with previously indolent lymphoma that had transformed to a high-grade 
lymphoma is outlined in Sections 8.6.4 and 17.4. 
The swimmer plot will be produced as described in Section 17.3 
17.6 Deaths 
Section 10.7.3.1.6 describes how deaths will be summarized according to the following 
categories: PD-related vs. non-PD-related. The list of terms determining that a death is PD- 
related will be extended by the terms “Progression”, “Study disease” and “Progression of the 
disease”. The following terms will lead to a classification into the new “Unknown” category in 
terms of PD-relatedness: 
• 
“End stage marrow failure” 
• 
“Unkown” 
In case that for a patient more than one cause of death is reported in different sections of the 
eCRF, the patients’s death will be categorized as PD-related if at least one of the causes of 
death is classified as PD-related. 
 
 
17.7 Lenalidomide dose intensity 
The dose intensity is calculated as average daily dose of treatment. 
 
 
 
While considering treatment duration, discontinuation for any reason (disease progression, 
AE, Investigator’s decision, etc) will be taken into account. 
A total daily dose will be multiplied with the difference between the “dosing stop study day” 
and the “dosing start study day” + 1 for each cycle. Days where no Lenalidomide capsule is 
taken are counted as days with a dose of 0 mg. The difference in number of capsules dispensed 
and returned will not be considered. 
Exemplified calculation: 
 
Dosing start day 
Dosing end day 
Total daily dose (mg) 
Total dose (mg) 
1 
21 
25 
25 x 21 = 525 


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30 
50 
25 
25 x 21 = 525 
59 
79 
20 
20 x 21 = 420 
87 
91 
10 
10 x 5 = 50 
Dose intensity = (525 + 525 + 420 + 50) / 91 = 16.7 mg 
 
Dose intensity of Lenalidomide will be summarized based on the FAS. 
 
 
17.8 Categorization of reference diagnoses as per central pathology 
For reporting, the diagnosis as per central pathology will be coded as follows: 
 
 
Reference diagnosis as 
per central pathology 
Diagnosis findings as 
reported by central 
pathology 
Diagnosis for 
reporting in 
Tables, Listings, 
Figures 
Non-Hodgkin 
lymphoma category 
• Not available 
• DLBCL. GCB-TYPE 
DLBCL; NOT 
OTHERWISE SPECIFIED 
• I AGREE WITH THE 
DIAGNOSIS OF 
DLBCL, GCB-TYPE IN 
BOTH SPECIMENS. 
ANALYSIS WAS 
DONE ON 28020/14 
DLBCL 
DLBCL 
• LIKELY DLBCL, VERY 
LIMITED MATERIAL; 
IMPORTANT STAINS 
(E.G. EBV) MISSING 
DLBCL; NOT 
OTHERWISE SPECIFIED 
HIGH-GRADE B-CELL 
LYMPHOMA, WITH 
MYC AND BCL2 AND 
BCL6 
TRANSLOCATIONS 
(`TRIPLE HIT 
LYMPHOMA') 
DLBCL (Triple Hit 
Lymphoma) 
DLBCL 
DLBCL; NOT 
UPDATE WHO: HIGH 
DLBCL (Double 
DLBCL 


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OTHERWISE SPECIFIED 
GRADE B-CELL 
LYMPHOMA WITH 
MYC AND BCL2 
TRANSLOCATION 
("DOUBLE HIT") 
Hit Lymphoma) 
T-CELL HISTIOCYTE 
RICH LARGE B-CELL 
LYMPHOMA 
• Not available 
• T-CELL HISTIOCYTE 
RICH LARGE B-CELL 
LYMPHOMA 
T cell histiocyte 
rich large B cell 
lymphoma 
DLBCL 
DIAGNOSIS NOT 
CONFIRMED 
MARGINAL ZONE 
LYMPHOMA 
Marginal zone 
lymphoma 
Non-DLBCL 
COMPOSITE 
LYMPHOMA WITH A 
DLBCL COMPONENT 
• 
Not available 
or 
• 
Pathological 
specifications 
Composite 
lymphoma with 
a DLBCL 
component 
DLBCL 
EPSTEIN-BARR VIRUS 
(EBV) POSITIVE DLBCL 
OF THE ELDERLY 
Not available 
EBV-positive 
DLBCL 
DLBCL 
DLBCL; NOT 
OTHERWISE SPECIFIED 
PARTIAL EBV+ 
EBV-positive 
DLBCL 
DLBCL 
DIAGNOSIS NOT 
CONFIRMED 
FOLLICULAR 
LYMPHOMA GRADE 2 
Follicular 
Lymphoma 
Grade 2 
Non-DLBCL 
DIAGNOSIS NOT 
CONFIRMED 
Not available 
Unknown 
Unknown 
DIAGNOSIS NOT 
CONFIRMED 
MANTLE CELL 
LYMPHOMA, CLASSIC 
TYPE 
Mantle cell 
lymphoma, 
classic type 
Non-DLBCL 
DIAGNOSIS NOT 
CONFIRMED 
FOLLICULAR 
LYMPHOMA (GRADE 2 
+ 3A) 
Follicular 
lymphoma 
(Grade 2 + 3A) 
Non-DLBCL 
HISTOLOGICAL 
TRANSFORMATION TO 
DLBCL FROM 
INDOLENT NHL 
DLBCL, TRANSFORMED 
FROM MZL 
Histological 
transformation 
to DLBCL from 
indolent NHL 
DLBCL 


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18. SAP ADDENDUM 3.0 
18.1 Forest plots for 24 month rates of Progression-free Survival, Duration of 
Response and Overall Survival 
Forest plots for the 24 month rates of PFS, DoR and OS will be generated for selected non- 
biomarker subgroups as defined in Section 11.4. The plots will be based on the FAS and will 
be generated for the IRC response assessment for PFS and DoR. Estimation of the 24 month 
rates and the pertaining confidence intervals will be based on the Kaplan-Meier method. 
 
 
19. SAP ADDENDUM 4.0 
For the subgroup of centrally confirmed DLBCL patients (see Section 17.8, Non-Hodgkin 
lymphoma category of DLBCL), the following Table will be created: 
• 
Baseline characteristics: tabulation as described in Section 8.5. 
 
The Table will be created based on both the FAS and the SAF. 


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20. SAP ADDENDUM 5.0 
20.1 Exploratory biomarker analyses 
Longitudinal analyses will be conducted for: Peripheral numbers of NK cells and B cells 
(analysed separately): 
Tabulations (for NK cells, B cells; based on FAS): 
• 
Summary statistics per visit (a 95% confidence interval for the median will be 
derived by bootstrapping) by response status (responders vs. non-responders) 
• 
Absolute change from baseline (a 95% confidence interval for the median will be 
derived by bootstrapping) by response status (responders vs. non-responders) 
• 
Relative change from baseline (a 95% confidence interval for the median will be 
derived by bootstrapping) by response status (responders vs. non-responders) 
Graphical illustrations (for B cells and NK cells; based on FAS): 
• 
Median and its 95% confidence interval (via bootstrapping) for absolute values, 
absolute change from baseline and relative change per visit across all patients 
assessed by response status (responders vs. non-responders). The median over time 
for responders and non-responders will be depicted in parallel in one graph. 
• 
Spaghetti plots displaying the absolute values, absolute change from baseline, and 
relative change from baseline by visit (i.e., three individual plots for each cell type). 
The point in time when the PFS event (based on IRC) happened will be indicated in 
each plot. Each spaghetti plot will only display the subgroup of patients who 
o have a best response PR or CR (at any point in time) and 
o have experienced a PFS event (based on IRC) within 12 months after 
treatment start with any study drug 
• 
Spaghetti plots displaying the absolute values, absolute change from baseline, and 
relative change from baseline by visit (i.e., three individual plots for each cell type). 
Each spaghetti plot will only display the subgroup of patients who 
o have a best response PR or CR (at any point in time) and 
o have NOT experienced a PFS event (based on IRC) within 12 months after 
treatment start with any study drug 
 
 
 
Listing (for B cells and NK cells; based on the SAF) 


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A Listing will be provided for patients who: 
o have a best response PR or CR (at any point in time) and 
o have experienced a PFS event (based on IRC) within 12 months after 
treatment start with any study drug 
The Listing will show the following by Visit: 
a) absolute count of B cells and NK cells 
b) absolute change from baseline 
c) percent change from baseline 
d) response category by IRC (if available) 
The nominal Visit and the date of the Visit should be indicated for each assessment. 
20.2 Time since discontinuation of the last treatment 
Based on the FAS, the time since discontinuation of the last anti-DLBCL medication before 
receiving any study drug in L-MIND will be summarized for the following patient subgroups: 
• 
Patients with one prior treatment line 
• 
Patients with two prior treatment lines 
• 
Patients with three or four prior treatment lines 
A Listing (based on the SAF) will be provided indicating the time since discontinuation of the 
last treatment for each patient including the number of previous treatment lines. 
 
 
20.3 Time since disease progression in the last prior treatment (systemic anti- 
DLBCL medication) 
Based on the FAS, the time since disease progression in the last anti-DLBCL medication 
before receiving any study drug in L-MIND will be summarized for the following patient 
subgroups: 
• 
Patients with one prior treatment line 
• 
Patients with two prior treatment lines 
• 
Patients with three or four prior treatment lines 
A Listing (based on the SAF) will be provided indicating the time since disease progression in 
the last treatment for each patient including the number of previous treatment lines. 


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20.4 Post-L-MIND anti-DLBCL medications 
20.4.1 Summaries 
Tabulations of anti-neoplastic therapies after discontinuation of MOR00208+LEN 
A Table based on the FAS will be provided summarizing anti-neoplastic therapies after 
discontinuation of all study drugs. The anti-neoplastic therapies will be displayed for the 
following categories: 
• 
First line after L-MIND 
• 
Second line after L-MIND 
• 
Third line after L-MIND 
• 
Line 4 or higher after L-MIND 
Summary statistics for the number of post-L-MIND anti-neoplastic therapies will be 
provided. 
Summary / analysis of OS 
A Kaplan-Meier analysis for OS will be conducted focusing only on the period after the end 
of treatment of both MOR00208 and LEN. The following four patient subgroups will be 
defined: 
 
Subgroup 
Treatment status 
PFS Event / Censoring 
status (based on IRC) 
Post-L-MIND anti- 
DLBCL medication 
1 
Both MOR00208 and LEN 
discontinued 
PFS Event (deaths not 
considered) 
Experienced (at 
least one line) 
2 
Both MOR00208 and LEN 
discontinued 
PFS Event (deaths not 
considered) 
No post-L-MIND 
anti-DLBCL 
medication at all 
3 
Both MOR00208 and LEN 
discontinued 
Censored for PFS 
follow-up 
Experienced (at 
least one line) 
4 
Both MOR00208 and LEN 
discontinued 
Censored for PFS 
follow-up 
No post-L-MIND 
anti-DLBCL 
medication at all 
 
Baseline for the OS analysis is the earliest point in time when both requirements are met: 
a) Both study drugs discontinued 
b) PFS event / censoring happened 
A Kaplan-Meier plot will also be generated displaying the four subgroups. 


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A Table showing the censorings reasons (ongoing at data cut-off, lost to follow-up, ICF 
withdrawal etc.) for each subgroup will be produced. 
A Listing will be provided showing all post-L-MIND anti-DLBCL medications by treatment 
line, survival status at the data cut-off date, and date of death. 
20.4.2 Swimmers plot 
Based on the FAS, four swimmers plots will be generated for the four patient subgroups 
above. The following will be displayed: 
• 
Bar length: [(Date of death or date censoring of OS follow-up) – (Date of PFS event 
or date of PFS censoring) + 1]. 
• 
An arrow head at the end of the bar will indicate if OS follow-up is still ongoing at 
data cut-off, or the point in time when a patient was censored for OS follow-up. A 
blunt end will indicate that the patient has died. 
• 
Symbols will be used to indicate the initiation every new treatment line after the 
treatment with MOR00208 + LEN. 
 
 
20.5 Relationship between LEN dose intensity and efficacy 
20.5.1 DoR and ORR in subgroups of varying relative cumulative LEN exposure 
Patients will be categorized according to their relative cumulative LEN dose, which will be 
derived as follows: 
Relative cumulative LEN dose intensity = (cumulative total used dose / reference 
cumulative dose) x 100. 
• 
The reference cumulative dose represents the cumulative LEN dose a patient is 
supposed take until he/she progresses per IRC (for summaries of DoR; see below) or 
until he/she reaches a CR or PR (for summaries of ORR; see below): 
o Example 1 for a summary of DoR: a patient who only progresses later than Cycle 
12 experiences the following reference cumulative dose: 12 months x 21 days x 
25 mg LEN per day = 6300 mg LEN 
o Example 2 for a summary of DoR: a patient who progresses on Cycle 7, Day 10 
experiences the following reference cumulative dose: (6 months x 21 days x 25 
mg LEN per day) + (10 days x 25 mg LEN per day) = 3400 mg LEN 
o Example 3 for a summary of ORR: a patient who reaches a CR at Cycle 3 Day 25 
experiences the following reference cumulative dose: 3 months x 21 days = 
1575 mg LEN 
• 
The cumulative total used dose represents the cumulative LEN dose a patient has 
actually ingested until he/she progresses per IRC (for summaries of DoR) or until he/she 


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reaches a CR or PR (for summaries of ORR). The derivation of the total used dose for 
LEN is described in Section 8.9.6. 
 
 
Based on the relative cumulative LEN dose intensity, the following patient subgroups will be 
defined: 
• 
Patients with relative cumulative LEN dose intensity of <50% 
• 
Patients with relative cumulative LEN dose intensity of 50%-80% (inclusive) 
• 
Patients with relative cumulative LEN dose intensity of >80% 
 
The following will be analyzed for the subgroups defined above: 
• 
Summary of DoR including a Kaplan-Meier plot (see Section 10.3) 
• 
Best objective response rate and rates for best response of CR/PR/SD/PD/not evaluable 
assessment (see Section 9) 
 
 
20.5.2 Efficacy outcome for patients with defined LEN dose reductions 
The following subgroups will be defined: 
• 
Patients with no LEN dose reduction 
• 
Patients with one LEN dose reduction to 20 mg/day 
• 
Patients with two or more LEN dose reductions (i.e., to a maximum reduction to 15, 
10, or 5 mg LEN) 
• 
Patients who permanently discontinued LEN (directly, or after having reduced the 
daily LEN dose before) 
Patient subgroups 1-3 are mutually exclusive and the total number of patients in the 
subgroups should sum up to the total number of patients in the FAS. 
 
 
Based on the FAS, the following will be summarized / analyzed for each subgroup: 
• 
Baseline characteristics as described in Section 8.5 
• 
Best objective response rate and rates for best response of CR/PR/SD/PD/not 
evaluable assessment (by IRC) as described in Section 9 
• 
DoR (by IRC) as described in Section 10.3 
• 
PFS (by IRC) as described in Section 10.2 


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• 
OS as described in Section 10.4 
 
For the endpoints DoR, PFS, and OS, Kaplan-Meier plots will be presented. 
A swimmers plot will be created for all patients with at least one LEN dose reduction at any 
point in time. The following will apply: 
• 
The bar length will indicate the time on treatment with any study drug (MOR00208 
only, LEN only, or both drugs at the same time) 
• 
An arrow head at the top of the bar will indicate whether the patient is still ongoing 
on any study drug at data cut-off 
• 
Using different symbols and colors/shadings for the symbols, the following will be 
indicated for each patient: 
o Point in time (relative from baseline) and quality of the initial response (CR 
or PR) 
o Point in time (relative from baseline) and quality of the best response (CR or 
PR) 
o Point in time (relative from baseline) of LEN discontinuation 
o Point in time (relative from baseline) of progression by IRC 
o Point in time (relative from baseline) of death 
o Point in time of LEN dose reductions /LEN discontinuations (each reduction 
will be symbol-/color-coded individually) 
 
 
20.5.3 Other analyses related to LEN dose reduction 
The following will be summarized (FAS): 
• 
Time from baseline until first/second/third/fourth LEN dose reduction or LEN 
discontinuation 
• 
Number (%) of patients who experienced at least one “deepening of response” 
(transition from PR to CR or SD to PR or SD to CR by IRC) after having experienced at 
least one dose reduction 
The permanent discontinuation of LEN as per protocol will be ignored (i.e., not be 
considered in the analysis as dose reduction or discontinuation). 


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A Listing will be provided for the patients in the SAF who have discontinued both MOR00208 
and LEN at the same time (i.e., sequential discontinuations will not be considered). The 
Listing based on the SAF will display the following: 
• 
Point in time when the TEAE happened that led to the discontinuation of treatment 
• 
The Preferred Term that led to the discontinuation of treatment 
• 
Point in time (relative from baseline) when individual LEN dose reductions / LEN 
discontinuation happened 
• 
The response status (CR, PR, SD, PD, not evaluable; based on IRC) at the point in 
time when the discontinuation happened 
• 
The overall outcome (based on the integrated overall clinical assessment) of all 
central tumor response assessments 
 
 
20.6 Efficacy analyses for the subgroup of patients confirmed as DLBCL by central 
pathology based on the FAS 
Patients with a Non-Hodgkin Lymphoma category of “DLBCL” by central pathology as 
defined in Section 17.8 will be considered. All analyse will be based on the FAS. 
 
 
20.6.1 Efficacy analyses based on all patients centrally confirmed as DLBCL 
The following will be summarized / analyzed based on the IRC: 
• 
Disease control rate (see Section 10.1) 
• 
Time to progression including a Kaplan-Meier plot (see Section 10.5) 
 
20.6.2 Efficacy analyses for patient subgroups within the subgroup of patients 
classified as DLBCL as per central pathology 
IPI subgroups (low risk + low-intermediate risk vs. intermediate-high + high risk) 
• 
ORR and rates for best response categories (CR/PR/SD/PD/not evaluable) by IRC 
(see Section 9) 
• 
PFS by IRC (see Section 10.2) 
• 
OS (see Section 10.4) 
For the endpoints PFS and OS, Kaplan-Meier curves will be provided. 
 
 
Prior treatment lines subgroups (1 prior treatment line vs. ≥2 prior treatment lines) 


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• 
ORR and rates for best response categories (CR/PR/SD/PD/not evaluable) by IRC 
(see Section 9) 
 
 
Primary refractoriness subgroups (refractory vs. non-refractory) 
• 
PFS by IRC (see Section 10.2) 
• 
OS (see Section 10.4) 
Kaplan-Meier plots will be presented. 
 
 
Last line refractoriness subgroups (refractory vs. non-refractory) 
• 
PFS by IRC (see Section 10.2) 
• 
OS (see Section 10.4) 
Kaplan-Meier plots will be presented. 
 
 
Rituximab refractoriness subgroups (refractory vs. non-refractory) 
• 
PFS by IRC (see Section 10.2) 
• 
OS (see Section 10.4) 
Kaplan-Meier plots will be presented. 
 
 
Age subgroups (≤70 vs. >70 years of age) 
• 
PFS by IRC (see Section 10.2) 
A Kaplan-Meier plot will be presented. 
 
Forest plot 
Forest plots for various endpoints will be generated, displaying the following biomarker and 
non-biomarker subgroups in one and the same illustration: 
• 
Non-biomarker subgroups: 
o IPI subgroups dichotomized: low and low-intermediate vs. high- 
intermediate and high 
o Gender: female vs. male 
o Rituximab refractoriness: yes vs. no 


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o Refractoriness to last prior treatment line: yes vs. no 
o Primary refractoriness: yes vs. no 
o Prior autologous stem cell transplantation: yes vs. no 
o Number of prior treatment lines dichotomized: 1 vs. ≥2 
o Age dichotomized: ≤70 years vs. >70 years of age 
• 
Biomarker subgroups: 
o NK cell numbers at baseline: <100 vs. ≥100 cells/µl 
o Cell of origin by IHC: GCB vs. non-GCB vs. unknown 
 
The following Forest plots displaying an estimate for the expectation together with 95% 
confidence intervals will be generated: 
• 
Forest plot for ORR (by IRC) 
• 
Forest plot for CR rate (by IRC) 
• 
24-month PFS rate (by IRC) 
• 
24-month DoR rate (by IRC) 
• 
24-month OS rate 
• 
30-month PFS rate (by IRC) 
• 
30-month DoR rate (by IRC) 
• 
30-month OS rate (by IRC) 
 
20.7 Additional subgroup analyses 
20.7.1 Efficacy analyses in subgroups of patients enrolled at sites that enrolled ≤3 
vs. >3 patients 
The following subgroups will be defined: 
• 
Sites recruiting ≤3 patients 
• 
Sites recruiting >3 patients 
 
The following will be summarized / analyzed by subgroup based on the FAS: 
• 
ORR and rates for best response categories (CR/PR/SD/PD/not evaluable) by IRC 
(see Section 9) 


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• 
OS (see Section 10.4) 
• 
Duration of CR (by IRC; Section 10.3.5) 
For the endpoints OS and Duration of CR, a Kaplan-Meier plots will be presented. 
 
 
ORR by site 
An analysis on ORR as specified in Section 9 will be also conducted for individual sites that 
had recruited at least one patient. 
 
 
20.7.2 Efficacy analyses in subgroups of patients recruited at US sites vs. 
European sites 
The following subgroups will be defined: 
• 
Patients recruited at sites in the USA (US sites) 
• 
Patients recruited at European sites 
 
The following will be analyzed / summarized based on the FAS: 
• 
ORR and rates for best response categories (CR/PR/SD/PD/not evaluable) by IRC 
(see Section 10.1) 
• 
OS (Section 10.4) 
• 
Duration of CR (by IRC; Section 10.3.5) 
For the endpoints OS and duration of CR, Kaplan-Meier plots will be produced. 
 
 
20.7.3 Efficacy analyses for histological subgroups of NHL 
Section 17.3 specifies the analyses of ORR, DoR, OS, and PFS for the NHL subtypes DLBCL- NOS 
(=DLBCL, not further specified) and Composite Lymphoma as determined by central 
pathology. The following will be added: 
• 
All analyses will be additionally be produced based on the SAF 
• 
Kaplan-Meier plots will be produced for endpoints DoR, OS, PFS for both FAS and 
SAF 
 
 
20.7.4 Listings displaying best response and DoR by NHL subtype 
Based on the SAF, a Listing will be produced displaying the following: 


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• 
Best response by IRC 
• 
DoR per IRC including the following: 
o Information whether the DoR follow-up has discontinued due to PD 
o Information whether the patient has been censored including the reason for 
censoring 
• 
Best response by INV 
• 
DoR per INV including the following: 
o Information whether the DoR follow-up has discontinued due to PD 
o Information whether the patient has been censored including the reason for 
censoring 
 
 
Based on the SAF, another Listing will be produced displaying the following: 
• 
PFS time and the information if the patient was censored or had a PFS event by IRC 
• 
PFS time and the information if the patient was censored or had a PFS event by INV 
• 
OS time and the information if the patient was censored or had an OS event 
 
20.7.5 Baseline characteristics of various patients subgroups 
The baseline characteristics as outlined in Section 8.5 will be summarized for the following 
subgroups: 
• 
Patients ≤70 years of age: based on the FAS 
• 
Patients >70 years of age: based on the FAS 
• 
Patients confirmed as DLBCL as per central pathology (i.e., patients with a Non- 
Hodgkin Lymphoma category of “DLBCL” by central pathology as defined in Section 
17.8 will be considered): based on the FAS 
• 
Patients confirmed as DLBCL as per central pathology (i.e., patients with a Non- 
Hodgkin Lymphoma category of “DLBCL” by central pathology as defined in Section 
17.8 will be considered): based on the SAF 
 
 
20.8 Efficacy analyses based on the SAF 
20.8.1 Summaries 
The following endpoints will be analysed / summarized: 


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• 
ORR and rates for best response categories (CR/PR/SD/PD/not evaluable) by IRC 
(see Section 10.1) 
• 
DoR (by IRC; see Section 10.3) 
• 
DoR (by IRC) by best response (by IRC) 
• 
PFS (by IRC; Section 10.2) 
• 
OS (Section 10.4) 
For the endpoints DoR, DoR by best response, PFS, and OS, Kaplan-Meier plots will be 
generated. 
 
 
20.8.2 Forest plots 
Forest plots for various endpoints will be generated, displaying the following biomarker and 
non-biomarker subgroups in one and the same illustration: 
• 
Non-biomarker subgroups: 
o IPI subgroups dichotomized: low and low-intermediate vs. high- 
intermediate and high 
o Gender: female vs. male 
o Rituximab refractoriness: yes vs. no 
o Refractoriness to last prior treatment line: yes vs. no 
o Primary refractoriness: yes vs. no 
o Prior autologous stem cell transplantation: yes vs. no 
o Number of prior treatment lines dichotomized: 1 vs. ≥2 
o Age dichotomized: ≤70 years vs. >70 years of age 
• 
Biomarker subgroups: 
o NK cell numbers at baseline: <100 vs. ≥100 cells/µl 
o Cell of origin by IHC: GCB vs. non-GCB vs. unknown 
 
The following Forest plots displaying an estimate for the expectation together with 95% 
confidence intervals will be generated: 
• 
Forest plot for ORR (by IRC) 
• 
Forest plot for CR rate (by IRC) 
• 
24-month PFS rate (by IRC) 


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• 
24-month DoR rate (by IRC) 
• 
24-month OS rate 
• 
30-month PFS rate (by IRC) 
• 
30-month DoR rate (by IRC) 
• 
30-month OS rate (by IRC) 
 
20.8.3 Analyses for the subgroup of patients confirmed as DLBCL by central 
pathology based on the SAF 
Patients with a Non-Hodgkin Lymphoma category of “DLBCL” by central pathology as 
defined in Section 17.8 will be considered. 
Summaries 
The following endpoints will be analysed / summarized: 
• 
ORR and rates for best response categories (CR/PR/SD/PD/not evaluable) by IRC 
(see Section 9.1) 
• 
DoR (by IRC; Section 10.3) 
• 
DoR (by IRC) by best response (by IRC) 
• 
PFS (by IRC; Section 10.2) 
• 
OS (Section 10.4) 
For the endpoints DoR, DoR by best response, PFS, and OS, Kaplan-Meier plots will be 
generated. 
 
 
Summaries for the subgroup of primary refractory patients within the subpopulation of 
DLBCL 
• 
ORR and rates for best response categories (CR/PR/SD/PD/not evaluable) by IRC 
(see Section 9.1) 
• 
DoR (by IRC; Section 10.3) 
For DoR, a Kaplan-Meier graph will be produced. 
 
 
Forest plots 
Forest plots for various endpoints will be generated, displaying the following biomarker and 
non-biomarker subgroups in one and the same illustration: 


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• 
Non-biomarker subgroups: 
o IPI subgroups dichotomized: low and low-intermediate vs. high- 
intermediate and high 
o Gender: female vs. male 
o Rituximab refractoriness: yes vs. no 
o Refractoriness to last prior treatment line: yes vs. no 
o Primary refractoriness: yes vs. no 
o Prior autologous stem cell transplantation: yes vs. no 
o Number of prior treatment lines dichotomized: 1 vs. ≥2 
o Age dichotomized: ≤70 years vs. >70 years of age 
• 
Biomarker subgroups: 
o NK cell numbers at baseline: <100 vs. ≥100 cells/µl 
o Cell of origin by IHC: GCB vs. non-GCB vs. unknown 
 
The following Forest plots displaying an estimate for the expectation together with 95% 
confidence intervals will be generated: 
• 
Forest plot for ORR (by IRC) 
• 
Forest plot for CR rate (by IRC) 
• 
24-month PFS rate (by IRC) 
• 
24-month DoR rate (by IRC) 
• 
24-month OS rate 
 
20.9 PFS and DoR analyses applying alternative censoring rules 
Analyses for the endpoints PFS and DoR will be performed using alternative censorings 
rules, i.e., three scenarios that led to censoring as per Table 13 will be considered as a PFS 
event. 
 
Situation 
Outcome as 
per main 
analysis (see 
Table 13) 
Censoring date as 
per main analysis 
(see Table 13 
Outcome as per 
alternative 
censoring rules 
Date of 
progression as 
per alternative 
censoring rules 
Discontinued the 
Censored 
Date of last 
Event 
Date of 


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Situation 
Outcome as 
per main 
analysis (see 
Table 13) 
Censoring date as 
per main analysis 
(see Table 13 
Outcome as per 
alternative 
censoring rules 
Date of 
progression as 
per alternative 
censoring rules 
study with no 
event 
adequate tumour 
assessment 
discontinuation 
of the study 
drug that was 
discontinued 
latest* 
Patient received 
non-study anti- 
DLBCL treatment 
before disease 
progression 
Censored 
Date of last 
adequate tumour 
assessment 
before start of 
non-study cancer 
treatment 
Event 
Date of 
initiation of 
non-study anti- 
DLBCL 
treatment 
Death or 
progression after 
two or more 
missed visits 
Censored 
Date of last 
adequate tumour 
assessment 
Event 
Date of the 
first missed 
tumour 
assessment 
(i.e., the 
planned date 
of the 
assessment 
that was 
missed) 
*Note: in L-MIND, PFS follow-up stops with treatment discontinuation (a post-treatment PFS 
follow-up is not conducted in L-MIND). 
The censoring strategy for the remaining scenarios described in Table 13 will still apply. 
The following analyses applying the alternative censoring rules will be conducted: 
20.9.1 Summaries / analyses of PFS 
• 
Based on the FAS and IRC 
• 
Based on the FAS and the investigator tumor response assessment (INV) 
• 
Based on the ITT and IRC 


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• 
Based on the ITT and the investigator tumor response assessment (INV) 
Kaplan-Meier graphs will be produced for each combination. 
20.9.2 Summaries / analyses of DoR 
• 
Based on the FAS and IRC 
• 
Based on the FAS and the investigator tumor response assessment (INV) 
• 
Based on the ITT and IRC 
• 
Based on the ITT and the investigator tumor response assessment (INV) 
Kaplan-Meier graphs will be produced for all summary Tables. 
 
 
 
20.10 First line treatment category 
Summary 
The number (%) of patients who received a first-line treatment belonging to the following 
categories will tabulated: 
• 
Number (%) of patients treated with R-CHOP 
• 
Number (%) of patients treated with R-CHOP equivalent regimens 
• 
Number (%) of patients treated with non-R-CHOP regimens 
Based on the ‘prior cancer therapies for DLBCL medication’ eCRF page, the following 
strategy will be applied to find out whether a first-line treatment belongs to one of the 
categories mentioned above. The information on the first line treatment can be reported in 
the eCRF in several ways: 
• 
One acronym in a single eCRF log line (e.g., “R-CHOP”) 
• 
Individual components of a regimen entered in a single eCRF log line (e.g., one log 
line with entry: “rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, 
prednisone”) 
• 
Individual components of a regimen entered across multiple eCRF log lines 
The case (small or capital letter) will be ignored during screening. In case a regimen is 
reported as individual components, the regimen will only be considered as R-CHOP or R- 
CHOP equivalent if all components belonging to the regimen are present (regardless of any 
additional drugs that have been co-administered). Multiple search terms for a particular 
drug will be applied to cover generic and grand names. Both the verbatim terms as entered 
by the investigator as well as the coded terms will be screened. The following search terms 
will be used 


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Treatment category 
assignment 
Search terms used to 
identify regimens belonging 
to the treatment category 
of interest 
Search terms used to 
identify regimen 
components indicating a 
particular treatment 
category (R-CHOP vs. R- 
CHOP equivalent vs. Other) 
R-CHOP 
• 
“R-CHOP” or “RCHOP” 
or “R CHOP” 
(“rituximab” or “rtx”) and 
“cyclophos” and 
• 
“R-mini-CHOP” or “R 
mini-CHOP” 
“prednis” and 
• 
“R-CHOP14” or 
“RCHOP14” or “R 
CHOP14” 
“vincris” or “leurocris” or 
“vcr”) 
OR: 
• 
“Pola-R-CHP” 
“CHOP” and 
(“rituximab” or “rtx”) 
OR: 
“CHP” and 
(“pola” or “polivy” or 
“CD79” and 
(“rtx” or “rituximab”) 
OR: 
“RCHP or R-CHP” and 
(“pola” or “polivy” or 
“CD79”) 
R-CHOP equivalent 
• 
“R-ACVBP” or “RACVBP” 
or “R ACVBP” 
(“rtx” or “rituximab” or 
“obinu” or “GA101” or 
“polivy” or “pola” or 
“CD79”) and “ACVBP” 
OR 
(“rtx” or “rituximab” or 
“obinu” or “GA101” or 
“polivy” or “pola” or 
“CD79”) and (CHOEP or 
CHOP) 
• 
“R-CHOEP” or “RCHOEP” 
or “R CHOEP” 
• 
“R-EPOCH” or “REPOCH” 
or “R EPOCH” 
• 
“R-HyperCVAD” or “R 
HyperCVAD” 
• 
“DA-R-EPOCH” or “R- 


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EPOCH” or “R-DA- 
EPOCH” or “R 
DAEPOCH” or “R 
EPOCH” 
(“rtx” or “rituximab” or 
“obinu” or “GA101” or 
“polivy” or “pola” or 
“CD79”) and EPOCH 
• 
“G-CHOP” or “GCHOP” 
or “G CHOP” 
• 
“G-mini-CHOP” or “G 
mini-CHOP” 
• 
“GA101-CHOP” or 
“GA101 CHOP” 
 
If a patient cannot be classified as having been treated with an R-CHOP or R-CHOP equivalent 
regimen, the patient will be classified as having received a non-R-CHOP treatment. 
Listing 
A Listing will be provided showing the first line treatment by the following categories: 
• 
Number (%) of patients treated with R-CHOP 
• 
Number (%) of patients treated with R-CHOP equivalent regimens 
• 
Number (%) of patients treated with non-R-CHOP regimens 
The Listing will display the following: 
• 
All components of the first-line regimen as reported verbatim in the eCRF 
• 
The coded terms of the regimen / components 
• 
The start date for all regimen components 
• 
The stop date for all regimen components 
 
20.11 Additional safety-related analyses 
20.11.1 Listing of TEAEs summarized in as per Section 16.3.1 
Listing for summaries outlined in 16.3.1 
 
 
20.11.2 Opportunistic infections 
TEAEs pertaining to the MedDRA CMQ “Opportunistic Infections” will be summarized by 
Primary SOC, HLT, PT and NCI-CTCAE Grade regardless of study treatment relationship 


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(based on the SAF). The PTs used to define the CMQ “Opportunistic Infections” are outlined 
in the APPENDIX. 
A Listing will be provided displaying the TEAEs of the CMQ “Opportunistic infections” (based 
on the SAF). 
 
20.11.3 TEAEs per patient years of exposure to MOR00208 
Summary across both treatment phases: 
Based on the SAF, the absolute number of TEAEs (i.e., the actual number of events) by patient 
years of exposure will be summarized by SOC, PT and NCI-CTCAE Grade. For the summary, 
patient years of exposure will be defined as follows: 
[(end date of the MOR00208) – (start date of MOR00208) + 1] / 365.25. 
The TEAEs per patient years of exposure will be reported with three decimal places. 
 
Summary by treatment phase: 
Based on the SAF, the number of TEAEs (i.e., the actual number of events) by patient years of 
exposure to combination treatment vs. MOR00208 monotherapy treatment will be 
summarized by SOC, PT and NCI-CTCAE Grade. Summaries will be provided separately for the 
combination treatment (MOR00208 + LEN) and MOR00208 monotherapy phase. 
• 
Exposure to the combination treatment is defined as follows: 
[(Latest date when at least one of either study drug has been discontinued) - (earliest date 
when the patient is treated with both study drugs) + 1] / 365.25. 
Due to the fact that patients may discontinue LEN before reaching Cycle 12 Day 21 (i.e., 
the time when LEN is discontinued as per protocol), combination treatment may stop 
before completing 12 Cycles of LEN. 
• 
Exposure to MOR00208 monotherapy treatment is defined as follows: 
[(Discontinuation date of MOR00208) - (earliest date of MOR00208 infusion after LEN has 
been permanently discontinued) + 1] / 365.25. 
Due to the fact that patients may discontinue LEN before reaching Cycle 12 Day 21 (i.e., the time when 
LEN is discontinued as per protocol), MOR00208 monotherapy treatment may start before reaching Cycle 
13 Day 1.The TEAEs per patient years of exposure will be reported with three decimal places. 


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20.12 TEAEs leading to study drug modifications 
Based on the SAF, TEAEs leading to any Study Drug Modification of MOR00208 or LEN 
regardless of any study drug relationship by Primary SOC, PT and NCI-CTCAE Grade will be 
tabulated. TEAEs leading to the following modifications will be reported separately by 
modification category: 
• 
Any modification (interruption or dose reduction) 
• 
Interruptions 
• 
Dose reductions (only applicable for LEN) 
The TEAEs leading to the modifications mentioned above will be reported separately for: 
• 
MOR00208 
• 
LEN 
• 
Any study drug 
 
A Listing will be provided displaying TEAEs leading to study drug modifications (SAF). 
 
 
20.13 Time to onset of individual TEAEs, duration of individual TEAEs, and 
cumulative duration of TEAEs per cumulative exposure to tafasitamab 
For the categories listed below in this section, the following will be summarized based on 
the SAF: 
• 
Time to TEAE onset [in days] 
• 
TEAE duration [in days] 
• 
Cumulative duration of TEAEs per cumulative exposure to MOR00208 [in months] 
o The cumulative duration of TEAEs will be reported in months 
o The cumulative exposure to MOR00208 will be calculated in years: 
[(end date of the MOR00208) – (start date of MOR00208) + 1] / 365.25. 
 
 
The summaries will be provided for the following categories: 
• 
PT Neutropenia (all Grades) 
• 
PT Neutropenia (>= Grade 3) 
• 
PT Thrombocytopenia (all Grades) 
• 
PT Thrombocytopenia (>= Grade 3) 


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• 
SOC Infections and infestations (all Grades) 
• 
SOC Infections and infestations (>= Grade 3) 
• 
SMQ "Infective pneumonia" (all Grades) 
• 
SMQ "Infective pneumonia" (>= Grade 3) 
• 
CMQ "Urinary tract infection" (all Grades) 
• 
CMQ "Urinary tract infection" (>= Grade 3) 
• 
CMQ "Sepsis" (all Grades) 
• 
CMQ "Sepsis" (>= Grade 3) 
• 
CMQ "Opportunistic infections" (all Grades) 
• 
CMQ "Opportunistic infections" (>= Grade 3) 
• 
PT Fatigue + PT Asthenia (all Grades) 
• 
All PTs including the verbatim Diarrhoea (all Grades) 
• 
PT Nausea + PT Vomiting (all Grades) 
• 
PT Febrile neutropenia (all Grades) 
• 
SMQ Thromboembolic event (all Grades) 
• 
SMQ Thromboembolic event (>= Grade 3) 


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21. SAP ADDENDUM 6.0 
21.1 Post-L-MIND survival 
Summary / analysis of OS 
A Kaplan-Meier analysis for OS will be conducted focusing only on the period after the end 
of treatment of both MOR00208 and LEN. The following four patient subgroups will be 
defined: 
 
Subgroup 
Treatment status 
PFS Event / Censoring 
status (based on INV) 
Post-L-MIND anti- 
DLBCL medication 
1 
Both MOR00208 and LEN 
discontinued 
PFS Event 
Experienced (at 
least one further 
treatment) 
2 
Both MOR00208 and LEN 
discontinued 
PFS Event 
No post-L-MIND 
anti-DLBCL 
medication at all 
3 
Both MOR00208 and LEN 
discontinued 
Censored for PFS 
follow-up 
Experienced (at 
least one further 
treatment) 
4 
Both MOR00208 and LEN 
discontinued 
Censored for PFS 
follow-up 
No post-L-MIND 
anti-DLBCL 
medication at all 
 
Baseline for the OS analysis is the earliest point in time when both requirements are met: 
a) Both study drugs discontinued 
b) PFS event / censoring happened 
A Kaplan-Meier plot will also be generated displaying the four subgroups. 
A Table showing the censorings reasons (ongoing at data cut-off, lost to follow-up, ICF 
withdrawal etc.) for each subgroup will be produced. 
A Listing will be provided showing all post-L-MIND anti-DLBCL medications by treatment 
line, survival status at the data cut-off date, and date of death. 
Swimmers plot 
Based on the FAS, four swimmers plots will be generated for the four patient subgroups 
above. The following will be displayed: 
• 
Bar length: [(Date of death or date censoring of OS follow-up) – (Date of end of 
treatment) + 1]. 


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• 
An arrow head at the end of the bar will indicate if OS follow-up is still ongoing at 
data cut-off, or the point in time when a patient was censored for OS follow-up. A 
blunt end will indicate that the patient has died. 
• 
Symbols will be used to indicate the initiation every new treatment line after the 
treatment with MOR00208 + LEN. 
 
 
21.2 PD-related vs. non-PD-related deaths 
The categorization of deaths as outlined in Section 10.7.3.1.6 will be extended. Deaths will 
be categorized as follows using reasons of death as reported in the eCRF by the investigator: 
 
Reason of death as per investigator 
Death category 
CONGESTIVE HEART FAILURE 
non-PD-related 
SUBJECT DEVELOPED SECONDARY MDS/AML AND WAS 
GETTING TREATMENT. HOWEVER, SUBJECT WAS UNABLE TO 
GET ASCT. SUBJECT DIED OF COMPLICATIONS OF AML - 
MULTI SYSTEM ORGAN FAILURE - SECONDARY TO PAST 
CHEMO. 
non-PD-related 
AUTOPSY REVEALED CAUSE OF DEATH AS PROGRESSIVE 
MULTIFOCAL LEUKOENCEPHALOPATHY 
non-PD-related 
INTRACEREBRAL HAEMORRHAGE 
non-PD-related 
LUNG EDEMA DUE TO CARDIAC DEFICIT 
non-PD-related 
PNEUMONIA 
non-PD-related 
RESPIRATORY FAILURE 
non-PD-related 
STROKE 
non-PD-related 
SUDDEN DEATH 
non-PD-related 
END STAGE MARROW FAILURE 
non-PD-related 
UNKNOWN 
Unknown 
DIFFUSE LARGE B CELL LYMPHOMA 
PD-related 
DISEASE PROGRESSION 
PD-related 
DLBCL DISEASE PROGRESSION 
PD-related 
IMMEDIATE CAUSE OF DEATH: PARALYTIC ILEUS, DUE TO 
ABDOMINAL LYMPHOMA PROGRESS 
PD-related 
LYMPHOMA 
PD-related 


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MULTIPLE RELAPSING AND REFRACTORY DLBCL 
PD-related 
PROGRESIVE DISEASE 
PD-related 
PROGRESSION 
PD-related 
PROGRESSION DESEASE 
PD-related 
PROGRESSION DISEASE 
PD-related 
PROGRESSION OF DISEASE 
PD-related 
PROGRESSION OF THE DISEASE 
PD-related 
PROGRESSIVE DESEASE 
PD-related 
PROGRESSIVE DISEASE 
PD-related 
RELAPSE 
PD-related 
STUDY DISEASE 
PD-related 
 
 
 
21.3 Discontinuation of LEN treatment upon completion of Cycle 12 
The identification of patients who discontinued LEN as per protocol is described in Section 
8.2. The algorithm used to identify patients who completed LEN treatment after 12 Cycles as 
per protocol will be extended. The following terms/phrases will be used to find patients who 
discontinued after 12 Cycles: 
OTHER: CYCLE COMPLETED - LAST DOSE OF LENALIDOMIDE ON AUG, 20TH 
2017 
OTHER: AS PER PROTOCOL 
OTHER: PER PROTOCOL 
OTHER: TREATMENT COMPLETED PER PROTOCOL 
OTHER: ACCORDING TO PROTOCOL 
OTHER: IT WAS STOPPED AFTER 12 CYCLES PER PROTOCOL 
OTHER: COMPLETED 
OTHER: LEN TREATMENT COMPLETED 
OTHER: LENALIDOMIDE TERMINATED PER PROTOCOLE 
OTHER: PATIENT FINISHED THE TREATMENT WITH LENALIDOMIDE BUT IS 
STILL ONGOING WITH MOR00208 
OTHER: PLANNED BY STUDY 


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OTHER: THIS STUDY DRUG WAS FOR ONLY THE FIRST 12 CYCLES AND WAS 
COMPLETED IN SEPT 2018 
OTHER: TREATMENT COMPLETED 
OTHER: TREATMENT COMPLETED AS PER PROTOCOL 
OTHER: TREATMENT COMPLETION 
OTHER: TREATMENT PHASE (LEN) 


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22. SAP ADDENDUM 7.0 
22.1 COVID-19 related missed visits and assessments 
The following will be tabulated for the SAF: 
• 
Number of visits completely missed due to the SARS pandemic 
• 
Number of visits with at least one missed assessment due to the SARS pandemic 
• 
Number of missed assessments (for partially completed visits) 
• 
Number of missed assessments by category 
 
A Listing will be provided showing missed visits or assessments. 
 
23. SAP ADDENDUM 8.0 
23.1.1 
TEAEs per patient years of exposure to MOR00208 and LEN 
Summary across both treatment phases: 
Based on the SAF, the absolute number of TEAEs (i.e., the actual number of events) by patient 
years of exposure will be summarized by SOC, PT and NCI-CTCAE Grade. For the summary, 
patient years of exposure will be defined as follows: 
Exposure to the treatment phase is defined as per section 8.9.2 and all TEAEs are counted.  
The TEAEs per patient years of exposure will be reported with two decimal places. 
 
Summary by treatment phase: 
Based on the SAF, the number of TEAEs (i.e., the actual number of events) by patient years of 
exposure to combination treatment vs. MOR00208 monotherapy treatment will be 
summarized by SOC, PT and NCI-CTCAE Grade. Summaries will be provided separately for the 
combination treatment (MOR00208 + LEN) and MOR00208 monotherapy phase. 
• 
Exposure to the combination treatment is defined as per section 8.9.2: 
However, for the counts of TEAE the period considered is the earliest date when the 
patient is treated with both study drugs till the latest date when LEN has been 
discontinued. 
Because patients may discontinue LEN before reaching Cycle 12 Day 21 (i.e., the time 
when LEN is discontinued as per protocol), combination treatment may stop before 
completing 12 Cycles of LEN. The definition of TEAE still applies when AE occurs beyond 
the discontinuation of LEN for the next 30 day follow up period. For patients who do not 
continue to monotherapy, any TEAE beyond 30 day follow up and related to either of the 
drugs will be considered in the combined therapy only. For the others who continue on to 
monotherapy the TEAEs beyond 30-day period are included in the monotherapy phase. 


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• 
Exposure to MOR00208 monotherapy treatment is defined as per section 8.9.2: 
However, for the counts of TEAE the period considered is 1 day after LEN has been 
permanently discontinued till the discontinuation date of MOR00208.  
Because patients may discontinue LEN before reaching Cycle 12 Day 21 (i.e., the time 
when LEN is discontinued as per protocol) or they have not received any dose of LEN, 
MOR00208 monotherapy treatment may start before reaching end of Cycle 12. The 
definition of TEAE still applies when AE occurs beyond the discontinuation of MOR00208 
for the next 30 day follow up period. Any TEAE which still occurs beyond the 30 day follow 
up period will only be included if the AE is related to MOR00208. 
 
The TEAEs per patient years of exposure will be reported with two decimal places. Additionally, there 
would be an overlap of the 30 days at the end of combined therapy and monotherapy and hence some 
of the TEAEs will be included in both treatment phases to not have an underestimation of the TEAE rates. 
The rates of TEAE by treatment phase is overestimated in this summary outcome compared to the true 
estimate. 
 
23.1.2 Forest plots 
Forest plots for various endpoints will be generated, displaying the following biomarker and 
non-biomarker subgroups in one and the same illustration: 
• 
Non-biomarker subgroups: 
o IPI subgroups dichotomized: low and low-intermediate vs. high- 
intermediate and high 
o Gender: female vs. male 
o Rituximab refractoriness: yes vs. no 
o Refractoriness to last prior treatment line: yes vs. no 
o Primary refractoriness: yes vs. no 
o Prior autologous stem cell transplantation: yes vs. no 
o Number of prior treatment lines dichotomized: 1 vs. ≥2 
o Age dichotomized: ≤70 years vs. >70 years of age 
• 
Biomarker subgroups: 
o NK cell numbers at baseline: <100 vs. ≥100 cells/µl 
o Cell of origin by IHC: GCB vs. non-GCB vs. unknown 
 
The following Forest plots displaying an estimate for the expectation together with 95% 
confidence intervals will be generated: 


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• 
Forest plot for ORR (by IRC) 
• 
Forest plot for CR rate (by IRC) 
• 
48-month PFS rate (by IRC) 


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• 
48-month DoR rate (by IRC) 
• 
48-month OS rate 
• 
Forest plot for ORR (by IRC for Patients with Centrally Confirmed DLBCL at Baseline) 
• 
Forest plot for CR rate (by IRC for Patients with Centrally Confirmed DLBCL at Baseline) 
• 
48-month PFS rate (by IRC for Patients with Centrally Confirmed DLBCL at Baseline) 
• 
48-month DoR rate (by IRC for Patients with Centrally Confirmed DLBCL at Baseline) 
• 
48-month OS rate (for Patients with Centrally Confirmed DLBCL at Baseline) 
 


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APPENDIX: LIST OF CUSTOMIZED MEDDRA QUERIES 
 
 
Sepsis (CMQ) 
PT 
PTCD 
Escherichia sepsis 
10015296 
Meningococcal sepsis 
10027280 
Postpartum sepsis 
10036422 
Sepsis 
10040047 
Sepsis neonatal 
10040049 
Sepsis pasteurella 
10040051 
Umbilical sepsis 
10045470 
Urosepsis 
10048709 
Streptococcal sepsis 
10048960 
Neutropenic sepsis 
10049151 
Pulmonary sepsis 
10051739 
Candida sepsis 
10053166 
Group B streptococcus neonatal sepsis 
10053588 
Bacterial sepsis 
10053840 
Sepsis syndrome 
10053879 
Pneumococcal sepsis 
10054047 
Stenotrophomonas sepsis 
10054137 
Klebsiella sepsis 
10054160 
Micrococcal sepsis 
10054162 
Brucella sepsis 
10054210 
Citrobacter sepsis 
10054213 
Enterobacter sepsis 
10054219 
Enterococcal sepsis 
10054221 
Helicobacter sepsis 
10054264 


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Staphylococcal sepsis 
10056430 
Corynebacterium sepsis 
10057767 
Biliary sepsis 
10057847 
Abdominal sepsis 
10058040 
Wound sepsis 
10058041 
Fungal sepsis 
10058872 
Anthrax sepsis 
10058873 
Haemophilus sepsis 
10058875 
Herpes sepsis 
10058876 
Pseudomonal sepsis 
10058877 
Salmonella sepsis 
10058878 
Serratia sepsis 
10058879 
Plague sepsis 
10058889 
Pseudallescheria sepsis 
10058973 
Pelvic sepsis 
10059070 
Listeria sepsis 
10063085 
Nocardia sepsis 
10064952 
Pseudosepsis 
10064991 
Post procedural sepsis 
10066593 
Burkholderia cepacia complex sepsis 
10069684 
Device related sepsis 
10069802 
Campylobacter sepsis 
10070681 
Viral sepsis 
10071362 
Yersinia sepsis 
10072902 
Herpes simplex sepsis 
10074246 
Shigella sepsis 
10074481 
Intestinal sepsis 
10075622 
Clostridial sepsis 
10078496 


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Erysipelothrix sepsis 
10080432 
Actinomycotic sepsis 
10080434 
 
 
 
Urinary Tract Infections 
(CMQ) 
PT 
PTCD 
Urinary tract infection 
10046571 
Urinary tract infection enterococcal 
10046572 
Urinary tract infection neonatal 
10046573 
Urinary tract infection fungal 
10049059 
Cytomegalovirus urinary tract infection 
10051350 
Escherichia urinary tract infection 
10052238 
Urinary tract infection bacterial 
10054088 
Genitourinary tract infection 
10061182 
Urinary tract infection pseudomonal 
10062279 
Urinary tract infection staphylococcal 
10062280 
Urinary tract infection viral 
10064825 
Prophylaxis urinary tract infection 
10066700 
Streptococcal urinary tract infection 
10070300 
HLT 
HLTCD 
Urinary tract infections 
10046577 


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Opportunistic infections (CMQ) 
PT 
PTCD 
Gastroenteritis salmonella 
10017914 
Gastroenteritis shigella 
10017915 
Shigella infection 
10054178 
Gastroenteritis Escherichia coli 
10017903 
Clostridium colitis 
10058305 
Clostridium difficile colitis 
10009657 
Clostridium difficile infection 
10054236 
Bartonellosis 
10004145 
Anal candidiasis 
10002140 
Balanitis candida 
10004074 
Proctitis monilial 
10036781 
Candida nappy rash 
10007135 
Bladder candidiasis 
10058523 
Candida osteomyelitis 
10064699 
Endocarditis candida 
10014669 
Gastrointestinal candidiasis 
10017938 
Genital candidiasis 
10018143 
Meningitis candida 
10027205 
Mucocutaneous candidiasis 
10028080 


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Nail candida 
10028688 
Neonatal candida infection 
10028924 
Oesophageal candidiasis 
10030154 
Oral candidiasis 
10030963 
Otitis externa candida 
10033076 
Respiratory moniliasis 
10038705 
Systemic candida 
10042938 
Vulvovaginal candidiasis 
10047784 
Hepatic candidiasis 
10049653 
Nasal candidiasis 
10050345 
Oropharyngeal candidiasis 
10050346 
Hepatosplenic candidiasis 
10051590 
Splenic candidiasis 
10051725 
Candida pneumonia 
10053158 
Candida sepsis 
10053166 
Skin candida 
10054152 
Peritoneal candidiasis 
10056562 
Stoma site candida 
10059052 
Candida endophthalmitis 
10059449 
Candidiasis of trachea 
10064459 
Candida retinitis 
10068612 
Candida cervicitis 
10071209 
Candida infection 
10074170 
Cerebral candidiasis 
10078126 
Denture stomatitis 
10080528 
Candida urethritis 
10081262 
Urinary tract candidiasis 
10083162 
American trypanosomiasis 
10001935 


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Coccidioidomycosis 
10009825 
Disseminated cryptococcosis 
10013439 
Neurocryptococcosis 
10068368 
Osseous cryptococcosis 
10080483 
Cryptosporidiosis infection 
10011502 
Congenital 
cytomegalovirus 
infection 
10010430 
Cytomegalovirus hepatitis 
10011830 
Cytomegalovirus infection 
10011831 
Cytomegalovirus mononucleosis 
10011834 
Encephalitis cytomegalovirus 
10014586 
Pneumonia cytomegaloviral 
10035676 
Cytomegalovirus chorioretinitis 
10048843 
Cytomegalovirus colitis 
10048983 
Cytomegalovirus duodenitis 
10049014 
Cytomegalovirus enterocolitis 
10049015 
Cytomegalovirus gastritis 
10049016 
Cytomegalovirus oesophagitis 
10049018 
Cytomegalovirus enteritis 
10049074 
Disseminated 
cytomegaloviral 
infection 
10049075 
Cytomegalovirus pancreatitis 
10049566 
Cytomegalovirus gastroenteritis 
10051349 
Cytomegalovirus 
urinary 
tract 
infection 
10051350 
Cytomegalovirus gastrointestinal 
infection 
10052817 
Cytomegalovirus myocarditis 
10056261 
Cytomegalovirus syndrome 
10056262 
Cytomegalovirus pericarditis 
10056721 


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Cytomegalovirus viraemia 
10058854 
Cytomegalovirus mucocutaneous 
ulcer 
10065036 
Cytomegalovirus 
myelomeningoradiculitis 
10065621 
Cytomegalovirus gastrointestinal 
ulcer 
10075619 
Cytomegalovirus nephritis 
10079095 
Congenital hepatitis B infection 
10010496 
Hepatitis B 
10019731 
Hepatitis B reactivation 
10058827 
Acute hepatitis B 
10059193 
Asymptomatic viral hepatitis 
10063838 
Perinatal HBV infection 
10075233 
Gianotti-Crosti syndrome 
10053842 
Hepatitis C 
10019744 
Hepatitis non-A non-B 
10019786 
Congenital varicella infection 
10010668 
Eczema herpeticum 
10014197 
Exanthema subitum 
10015586 
Genital herpes 
10018150 
Herpes simplex 
10019948 
Congenital 
herpes 
simplex 
infection 
10019949 
Herpes simplex encephalitis 
10019953 
Herpes simplex meningitis 
10019956 
Herpes simplex otitis externa 
10019959 
Herpes simplex visceral 
10019963 
Herpes virus infection 
10019973 
Herpes zoster 
10019974 


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Human herpesvirus 6 infection 
10020431 
Herpes simplex cervicitis 
10077449 
Meningitis herpes 
10027242 
Meningoencephalitis herpetic 
10027285 
Ophthalmic herpes zoster 
10030865 
Herpes 
simplex 
virus 
conjunctivitis neonatal 
10049458 
Varicella keratitis 
10077496 
Pneumonia herpes viral 
10035703 
Herpes zoster oticus 
10063491 
Varicella 
10046980 
Gastritis herpes 
10051784 
Herpes simplex gastritis 
10074240 
Varicella zoster gastritis 
10074241 
Herpes simplex colitis 
10074239 
Herpes simplex oesophagitis 
10074242 
Varicella zoster oesophagitis 
10074243 
Colitis herpes 
10051782 
Herpes oesophagitis 
10052330 
Meningoencephalitis 
herpes 
simplex neonatal 
10053586 
Neonatal mucocutaneous herpes 
simplex 
10053587 
Haemorrhagic 
varicella 
syndrome 
10078873 
Herpes simplex hepatitis 
10067389 
Herpes sepsis 
10058876 
Herpes 
zoster 
infection 
neurological 
10061208 
Herpes ophthalmic 
10062004 


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Herpes dermatitis 
10062639 
Varicella post vaccine 
10063522 
Human herpesvirus 7 infection 
10063571 
Herpes zoster disseminated 
10065038 
Herpes simplex pneumonia 
10065046 
Necrotising herpetic retinopathy 
10065119 
Human herpesvirus 8 infection 
10066435 
Herpes pharyngitis 
10066888 
Oral herpes 
10067152 
Genital herpes zoster 
10072210 
Genital herpes simplex 
10073931 
Ophthalmic herpes simplex 
10073938 
Herpes simplex pharyngitis 
10074244 
Herpes zoster pharyngitis 
10074245 
Herpes simplex sepsis 
10074246 
Herpes 
simplex 
meningoencephalitis 
10074247 
Herpes 
zoster 
meningoencephalitis 
10074248 
Meningomyelitis herpes 
10074249 
Herpes simplex meningomyelitis 
10074250 
Herpes zoster meningomyelitis 
10074251 
Herpes 
simplex 
necrotising 
retinopathy 
10074252 
Herpes 
zoster 
necrotising 
retinopathy 
10074253 
Varicella zoster pneumonia 
10074254 
Herpes zoster meningitis 
10074259 
Herpes 
zoster 
cutaneous 
disseminated 
10074297 


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Nasal herpes 
10074936 
Varicella zoster virus infection 
10075611 
Disseminated 
varicella 
zoster 
vaccine virus infection 
10076667 
Lower respiratory tract herpes 
infection 
10077390 
Herpes zoster meningoradiculitis 
10079327 
Herpes simplex viraemia 
10080365 
Human 
herpesvirus 
6 
encephalitis 
10081897 
Proctitis herpes 
10036780 
Acute pulmonary histoplasmosis 
10001027 
Chronic 
pulmonary 
histoplasmosis 
10009115 
Endocarditis histoplasma 
10014676 
Histoplasmosis 
10020141 
Histoplasmosis disseminated 
10020144 
Meningitis histoplasma 
10027243 
Pericarditis histoplasma 
10034489 
Retinitis histoplasma 
10038912 
Histoplasmosis cutaneous 
10049142 
Presumed ocular histoplasmosis 
syndrome 
10063664 
Anogenital warts 
10059313 
Anorectal human papilloma virus 
infection 
10073941 
Laryngeal papilloma 
10023849 
Cervicitis human papilloma virus 
10051800 
Cervix warts 
10063815 
Penile wart 
10034325 


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Respiratory papilloma 
10038707 
Skin papilloma 
10040907 
Urethral papilloma 
10046462 
Vulvovaginal warts 
10047793 
Epidermodysplasia verruciformis 
10052339 
Buschke-Lowenstein's tumour 
10059427 
Blepharal papilloma 
10057885 
Vulvovaginal human papilloma 
virus infection 
10066416 
Papilloma viral infection 
10061331 
Oral papilloma 
10068322 
Congenital condyloma 
10066944 
Tracheal papilloma 
10067203 
Sinonasal papilloma 
10071665 
Focal epithelial hyperplasia 
10076576 
Viral acanthoma 
10077282 
Cutaneous leishmaniasis 
10011668 
Leishmaniasis 
10024198 
Visceral leishmaniasis 
10047505 
Mucocutaneous leishmaniasis 
10054165 
Congenital malaria 
10010538 
Malaria 
10025487 
Plasmodium falciparum infection 
10035500 
Plasmodium malariae infection 
10035501 
Plasmodium ovale infection 
10035502 
Plasmodium vivax infection 
10035503 
Plasmodium knowlesi infection 
10079602 
Cerebral malaria 
10063094 
Malarial myocarditis 
10054123 


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Microsporidia infection 
10053982 
Mycobacterium avium complex 
infection 
10058806 
Pneumonia legionella 
10035718 
Pneumonia chlamydial 
10035673 
Pneumocystis 
jirovecii 
pneumonia 
10073755 
Pneumonia pseudomonal 
10035731 
Pneumonia fungal 
10061354 
Progressive 
multifocal 
leukoencephalopathy 
10036807 
JC virus infection 
10023163 
Adenopathy syphilitic 
10001242 
Alopecia syphilitic 
10001765 
Aortic aneurysm syphilitic 
10002887 
Aortitis syphilitic 
10002923 
Cardiovascular syphilis 
10007658 
Cerebral 
aneurysm 
ruptured 
syphilitic 
10008076 
Congenital syphilis 
10010641 
Congenital syphilitic encephalitis 
10010643 
Congenital syphilitic meningitis 
10010644 
Endocarditis syphilitic 
10014685 
Eye infection syphilitic 
10015938 
Hepatitis syphilitic 
10019794 
Myocarditis syphilitic 
10028616 
Neurosyphilis 
10029339 
Pericarditis syphilitic 
10034497 
Peritonitis syphilitic 
10034684 
Pinta 
10035068 


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Pulmonary syphilis 
10037434 
Renal syphilis 
10038530 
Syphilis anal 
10042877 
Syphilis genital 
10042880 
Syphilis musculoskeletal 
10042881 
Syphilitic endocarditis of heart 
valve 
10042907 
Yaws 
10048234 
Yaws of bone 
10048235 
Yaws of skin 
10048236 
Endemic syphilis 
10053025 
Congenital 
syphilitic 
osteochondritis 
10054002 
Malignant syphilis 
10054118 
Tertiary syphilis 
10056873 
Secondary syphilis 
10056883 
Primary syphilis 
10056884 
Spirochaetal infection 
10061370 
Syphilis 
10062120 
Condyloma latum 
10062317 
Latent syphilis 
10070738 
Brachyspira infection 
10077447 
Penicillium infection 
10078580 
Cerebral toxoplasmosis 
10057854 
 

Prot_001.pdf: 
Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 1 of 110 
 
 
CLINICAL STUDY PROTOCOL 
 
 
 
AMENDMENT NO. 5 
 
A Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the 
Safety and Efficacy of Lenalidomide Combined with MOR00208 in Patients 
with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL) 
Brief Description of 
Study: 
Open-label study to evaluate the safety and clinical efficacy of 
lenalidomide combined with MOR00208 in adult patients with 
R-R DLBCL (L-MIND) 
Study Type: 
Phase II 
Sponsor: 
MorphoSys AG 
Sponsor's Address: 
Semmelweisstr. 7 
82152 Planegg 
Germany 
Study Protocol Number: 
MOR208C203 
IND No.: 
EudraCT No.: 
114,856 
2014-004688-19 
Date of Protocol: 
18 March 2015 
Amendment No. 5: 
Final v8.0, 24 February 2021  
 
 
Confidentiality Statement 
This confidential document is the property of MorphoSys AG. No unpublished information in 
this document may be disclosed without prior written approval of MorphoSys AG. 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 2 of 110 
SIGNATURES 
Amendment No. 5: 
Final v8.0, 24 February 2021 
 
Approved/Authorised By: 
 
 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 3 of 110 
Country Coordinating Investigator’s Signature (in countries where 
required) 
 
 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 4 of 110 
Signature of Principal Investigator 
 
I have read the entire clinical study protocol. I agree that this protocol version contains all 
the information required to conduct this study. I agree to conduct the study as outlined in the 
study protocol and to comply with all the terms and conditions set out therein. I confirm that 
I will conduct the study in accordance with ICH GCP guidelines and the principles which 
have their origin in the Declaration of Helsinki; copies of both documents have been given 
to me by the sponsor. I will also ensure that co-investigator(s) and other relevant members 
of my staff have access to copies of this protocol, the ICH GCP guidelines and the 
Declaration of Helsinki, to enable them to work in accordance with the provisions of these 
documents. 
Investigator: 
 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 5 of 110 
Contact Details of Key Study Personnel 
Sponsor's Clinical 
Programme Leader 
Sponsor’s Clinical Project 
Manager 
Contact for Serious 
Adverse Events (SAEs): 
Medical Monitor 
(24/7 Medical Coverage) 
 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 6 of 110 
PROTOCOL SYNOPSIS 
Title of Study 
A Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the 
Safety and Efficacy of Lenalidomide Combined with MOR00208 in 
Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-
R DLBCL) 
 
Investigational Drugs 
MOR00208 (an Fc-engineered, humanised, monoclonal antibody 
targeting the B-cell surface antigen CD19) and Lenalidomide (LEN: 
Revlimid®) 
 
Protocol Number 
MOR208C203 
IND Number 
114,856 
EudraCT Number 
2014-004688-19 
Sponsor and CRO 
Sponsor: 
MorphoSys AG 
Semmelweisstr. 7 
82152 Planegg 
Germany 
 
 
 
 
 
 
Study Phase 
Phase II 
Background/Study 
Purpose and Rationale  
Diffuse large B-cell lymphoma (DLBCL) represents approximately 40% 
of all non-Hodgkin lymphomas (NHLs), with a rate of incidence which 
continues to increase and a median age at diagnosis of 64 years.  
 
The addition of the CD20 monoclonal antibody (mAb) rituximab (RTX) 
to standard CHOP (cyclophosphamide, doxorubicin, vincristine, and 
prednisone) chemotherapy (R-CHOP) has been shown to improve the 
outcome compared with CHOP alone in untreated patients with DLBCL. 
Despite advances in first-line treatment, 30–40% of such patients relapse. 
Patients progressing or relapsing after first-line treatment may be offered 
salvage chemotherapy followed by high-dose chemotherapy (HDC) with, 
if the disease is still chemosensitive, autologous stem-cell transplantation 
(ASCT). Several second-line combination therapies are used with variable 
success. However, a substantial percentage of patients will either fail to 
respond to salvage therapy and subsequently not be eligible for ASCT, or 
will progress after ASCT.  
 
Additionally, the use of HDC with stem cell support in patients with R-R 
DLBCL may not be appropriate for those with comorbidities or advanced 
age, restricting the benefit of this aggressive approach to a relatively small 
fraction of patients. 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 7 of 110 
R-CHOP-like regimens have become standard first-line treatment in 
patients with DLBCL. Those patients who have received prior RTX are 
less likely to respond to RTX-containing salvage treatment and therefore 
effective and well-tolerated new treatment modalities with manageable 
toxicities are needed to ameliorate prognosis in R-R DLBCL. Rational 
combinations of effective compounds have been shown to be active and 
often lead to better clinical outcomes in DLBCL than single-agent therapy. 
 
The B-lymphocyte lineage specific surface antigen CD19 is the earliest 
and most broadly expressed of the selective B-cell markers, and is highly 
expressed in the tumour cells of most patients with B-cell NHL. Because 
of this expression pattern, a CD19 antibody may have clinical utility as a 
new therapeutic approach to NHL treatment.  
 
MOR00208 is an Fc-engineered, humanised, mAb with significantly 
enhanced antibody-dependent cell-mediated cytotoxicity (ADCC), 
antibody-dependent cell-mediated phagocytosis (ADCP) and direct 
cytotoxic effects (apoptosis) compared with the parental murine antibody. 
 
Monotherapy with MOR00208 has shown preliminary signs of clinical 
efficacy and acceptable toxicity in a phase I study in R-R chronic 
lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) and a 
phase IIa study in R-R NHL. Additionally, MOR00208 is currently being 
studied as single-agent therapy in a phase IIa study in R-R B-cell acute 
lymphoblastic leukaemia (B-ALL). 
 
Lenalidomide (LEN) belongs to a class of immunomodulating agents 
(immunomodulatory drugs [IMiDs®]), which have demonstrated direct 
tumouricidal 
and 
immunomodulatory 
actions. 
LEN 
has 
both 
antiproliferative and antiangiogenic activities, modulating the tumour cell 
microenvironment and stimulating the activity of effector cells such as 
cytotoxic T-cells and natural killer (NK) cells. LEN demonstrated 
manageable toxicity when administered as monotherapy and in 
combination, as well as a synergistic effect with RTX, administered alone 
or as a part of an immunochemotherapeutic regimen. 
 
Preclinical data suggest that the combination of LEN with MOR00208 
may increase NK cell-mediated ADCC, making this combination of 
interest for further study in patients with R-R DLBCL. This patient 
population is particularly relevant for the current study as they can usually 
achieve a rapid and complete lymphoma regression with second-line 
therapy, but invariably experience relapse, which is the principal 
unfavourable prognostic factor. 
 
Combining two agents with probable synergistic mechanisms of action 
and acceptable safety profiles could potentially contribute to significantly 
prolonging time to progression, and possibly overall survival (OS), in this 
patient population. Therefore, this open label, single-arm, prospective 
phase II study is designed to confirm the activity of MOR00208 combined 
with LEN in patients with R-R DLBCL who have had at least one, but no 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 8 of 110 
more than three prior systemic regimens and who are not eligible for HDC 
with ASCT at the time of study entry. 
 
Study Objectives (Key 
Primary and Secondary) 
PRIMARY OBJECTIVE: 
To determine the activity of a combination of LEN with MOR00208 in 
terms of objective response rate (ORR = complete response [CR] + partial 
response [PR]) in adult patients with R-R DLBCL. 
 
SECONDARY OBJECTIVES: 
1. To determine the disease control rate (DCR = CR + PR + 
stable disease [SD])  
2. To determine the duration of response (DoR)  
3. To determine the activity of a combination of LEN with 
MOR00208 in terms of progression-free survival (PFS) 
4. To determine the overall survival (OS)  
5. To determine time to progression (TTP) 
6. To determine the time to next treatment (TTNT)  
7. To determine the safety of LEN combined with MOR00208 
assessed according to the frequency and severity of adverse 
events (AEs) 
8. To assess the potential immunogenicity of MOR00208 
9. To assess the pharmacokinetics (PK) of MOR00208 
10. To make a preliminary evaluation of ORR, DCR, DoR, PFS, 
OS, TTP and TTNT in patients treated with a combination of 
LEN plus MOR00208 in cohorts with a “low risk”, “low-
intermediate”, “high-intermediate” and “high” International 
Prognostic Index (IPI) 
11. To compare each patient’s TTP on LEN plus MOR00208 with 
the TTP of their most recent prior therapy 
12. To correlate efficacy parameters with certain biomarkers 
(e.g., baseline tumour CD19 expression level, peripheral NK 
cell 
count, 
constitutional 
FcγRIIIa 
and 
FcγRIIa 
polymorphism status). 
 
Study Endpoints (Key 
Primary and Secondary) 
PRIMARY ENDPOINT: 
1. ORR, defined as the proportion of complete and partial 
responders (ORR = CR + PR) 
 
SECONDARY ENDPOINTS:  
2. DCR, DoR, PFS, OS, TTP and TTNT  
3. Incidence and severity of AEs 
4. Determination and characterisation of a potential anti-
MOR00208 antibody formation 
5. PK analysis of MOR00208 
6. Absolute and percentage change from baseline in 
measurements of B-, T- and NK cell populations 
7. Analysis of exploratory and diagnostic biomarkers (e.g., 
CD19, CD20, BCL2, and BCL6 expression, CD16 expression 
on NK cells, ADCC capacity), gene expression profiling for 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Page 9 of 110 
cell of origin subtyping and evaluation of AEs and ORR 
stratified by FcγRIIIa and FcγRIIa polymorphism) are 
planned to be investigated during the course of the study. 
 
Design and 
Methodology/Patient 
Population 
This is a single-arm, multicentre, open-label, phase II study of LEN 
combined with MOR00208 in adult patients with DLBCL who have 
relapsed after or are refractory to at least one, but no more than three prior 
systemic therapies and who are not candidates for HDC and ASCT, and 
are thus considered to have exhausted their therapeutic options for 
demonstrable clinical benefit. One prior therapy line must have included 
a CD20-targeted therapy (e.g., RTX). 
 
Histological confirmation of the diagnosis of DLBCL will be performed 
by a central pathologist, retrospectively after enrolment. Objective disease 
response assessments will be made by central radiology and clinical 
reviewers. Details will be provided in an imaging charter, outlining 
functions and processes. 
 
This study will consist of two parts, which will be performed sequentially, 
where the first part (safety run-in) will conclude with an evaluation of the 
safety data after six patients have completed the first cycle of treatment. 
The second part will commence pending the outcome of this evaluation. 
 
Approximately 80 patients will be enrolled in the study. 
 
Key Inclusion/Exclusion 
Criteria 
INCLUSION CRITERIA: 
Diagnosis/Study Population 
1. 
Age >18 years 
2. 
Histologically confirmed diagnosis of DLBCL not otherwise 
specified (NOS); T cell/histiocyte rich large B-cell lymphoma 
(THRLBCL); Epstein-Barr virus (EBV) positive DLBCL of 
the elderly (EBV-positive DLBCL), Grade 3b Follicular 
Lymphoma, Composite lymphoma with a DLBCL component 
with a subsequent DLBCL relapse, according to the Revised 
European American Lymphoma/World Health Organization 
(REAL/WHO) classification. Additionally, patients with the 
evidence of histological transformation to DLBCL from an 
earlier diagnosis of low grade lymphoma (i.e., an indolent 
pathology such as follicular lymphoma, marginal zone 
lymphoma, chronic lymphocytic leukaemia) into DLBCL 
with a subsequent DLBCL relapse are also eligible. 
3. 
Fresh tumour tissue for central pathology review and 
correlative studies must be provided as an adjunct to 
participation in this study. Should it not be possible to obtain 
a fresh tumour tissue sample from the patient, archival paraffin 
embedded tumour tissue acquired ≤3 years prior to screening 
for this protocol must be available for this purpose. 
4. 
Patients must have: 
a) relapsed and/or refractory disease as defined in the 
protocol (Section 5.1.15.1.1) 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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b) at least one bidimensionally measurable disease site. The 
lesion must have a greatest transverse diameter of 
≥1.5 cm and greatest perpendicular diameter of ≥1.0 cm 
at baseline. The lesion must be positive on PET scan (for 
definition see Juweid et al., 2007) 
c) received at least one, but no more than three previous 
systemic regimens for the treatment of DLBCL and one 
therapy line must have included a CD20-targeted therapy 
(e.g., RTX) 
d) an Eastern Cooperative Oncology Group (ECOG) 
performance status of 0 to 2 
5. 
Patients not considered in the opinion of the investigator 
eligible, or patients unwilling to undergo intensive salvage 
therapy including ASCT because of, but not limited to, 
advanced age, comorbidities, impossibility or, refusal to 
perform ASCT. Documentation of the reason for a patient’s 
ineligibility must be provided in the patient’s source data. 
 
Laboratory Values 
6. 
Patients must meet the following laboratory criteria at 
screening: 
a) absolute neutrophil count (ANC) ≥1.5 × 109/L (unless 
secondary to bone marrow involvement by DLBCL as 
demonstrated by recent bone marrow aspiration and bone 
marrow biopsy) 
b) platelet count ≥90 × 109/L (unless secondary to bone 
marrow involvement by DLBCL as demonstrated by 
recent bone marrow aspiration and bone marrow biopsy) 
c) total serum bilirubin ≤2.5 × upper limit of normal (ULN) 
unless secondary to Gilbert’s syndrome or documented 
liver involvement by lymphoma. Patients with Gilbert’s 
syndrome 
or 
documented 
liver 
involvement 
by 
lymphoma may be included if their total bilirubin is 
≤5 × ULN (see exclusion criterion 5g) 
d) alanine transaminase (ALT), aspartate aminotransferase 
(AST) and alkaline phosphatase (AP) ≤3 × ULN or 
<5 × ULN in cases of documented liver involvement 
e) serum creatinine clearance must be ≥60 mL/minute either 
measured or calculated using a standard Cockcroft and 
Gault formula (Cockroft and Gault, 1976; see 
Appendix_A) 
 
General Provisions 
7. 
Females of childbearing potential (FCBP) must: 
a) not be pregnant as confirmed by a negative serum 
pregnancy test at screening and a medically supervised 
urine pregnancy test prior to starting study therapy 
b) refrain from breastfeeding and donating blood or oocytes 
during the course of the study and for 3 months after the 
last dose of study medication. Restrictions concerning 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Page 11 of 110 
blood donation apply as well to females who are not of 
childbearing potential 
c) agree to ongoing pregnancy testing during the course of 
the study, and after study therapy has ended. This applies 
even if the patient practices complete and continued 
sexual abstinence 
d) commit to continued abstinence from heterosexual 
intercourse if it is in accordance with her lifestyle (which 
must be reviewed on a monthly basis) or agree to use and 
be able to comply with the use of effective contraception 
without interruption during the study and for 3 months 
after the last dose of study medication 
8. 
Males must use an effective barrier method of contraception 
without interruption, refrain from donating blood or sperm 
during the study participation and for 3 months after the last 
dose of study medication if the patient is sexually active with 
a FCBP 
9. 
In the opinion of the investigator, the patients must: 
a) be able and willing to receive adequate prophylaxis 
and/or therapy for thromboembolic events  
b) be able to understand, give written informed consent, and 
comply with all study-related procedures, medication use, 
and evaluations  
c) not have a history of noncompliance in relation to medical 
regimens or be considered potentially unreliable and/or 
uncooperative 
d) be able to understand the reason for complying with the 
special conditions of the pregnancy prevention risk 
management plan and give written acknowledgement of 
this. 
 
EXCLUSION CRITERIA: 
Exclusionary Diagnosis 
1. Patients who have: 
a) any other histological type of lymphoma including 
primary mediastinal (thymic) large B-cell (PMBL) or 
Burkitt lymphoma 
b) primary refractory DLBCL (see Section 5.1.1 for 
definitions) 
c) a history of "double/triple hit" genetics DLBCL 
characterised by simultaneous detection of MYC with 
BCL2 
and/or 
BCL6 
translocation(s) 
defined 
by 
fluorescence in situ hybridisation. MYC, BCL2, BCL6 
testing prior to study enrolment is not required 
 
Exclusionary Previous and Current Treatment 
2. Patients who have, within 14 days prior to Day 1 dosing: 
a) 
not discontinued CD20-targeted therapy, chemotherapy, 
radiotherapy, investigational anticancer therapy or other 
lymphoma-specific therapy 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Page 12 of 110 
b) 
undergone major surgery or suffered from significant 
traumatic injury 
c) 
received live vaccines (see Section 6.7 for details) 
d) required parenteral antimicrobial therapy for active, 
intercurrent infections 
3. Patients who: 
a) have, in the opinion of the investigator, not recovered 
sufficiently from the adverse toxic effects of prior 
therapies 
b) were previously treated with CD19-targeted therapy or 
IMiDs® (e.g., thalidomide, LEN) 
c) have a history of hypersensitivity to compounds of similar 
biological or chemical composition to MOR00208, 
IMiDs® and/or the excipients contained in the study drug 
formulations 
d) have undergone ASCT within the period ≤ 3 months prior 
to signing the informed consent form. Patients who have 
a more distant history of ASCT must exhibit full 
haematological recovery before enrolment into the study  
e) have 
undergone 
previous 
allogenic 
stem 
cell 
transplantation 
f) have a history of deep venous thrombosis/embolism, 
threatening thromboembolism or known thrombophilia or 
are at high risk for a thromboembolic event in the opinion 
of the investigator and who are not willing/able to take 
venous thromboembolic event prophylaxis during the 
entire treatment period 
g) concurrently use other anticancer or experimental 
treatments 
 
Exclusionary Patient’s Medical History 
4. Prior history of malignancies other than DLBCL, unless the 
patient has been free of the disease for ≥5 years prior to 
screening. Exceptions to the ≥5 year time limit include a 
history of the following: 
a) basal cell carcinoma of the skin 
b) squamous cell carcinoma of the skin 
c) carcinoma in situ of the cervix 
d) carcinoma in situ of the breast 
e) carcinoma in situ of the bladder 
f) incidental histological finding of prostate cancer 
(Tumour/Node/Metastasis [TNM] stage of T1a or T1b) 
5. Patients with: 
a) positive hepatitis B and/or C serology (see Section 
7.2.13.2 for details) 
b) known seropositivity for or history of active viral 
infection with human immunodeficiency virus (HIV) 
c) CNS lymphoma involvement – present or past medical 
history 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Page 13 of 110 
d) history or evidence of clinically significant 
cardiovascular, CNS and/or other systemic disease that 
would in the investigator’s opinion preclude 
participation in the study or compromise the patient’s 
ability to give informed consent 
e) history or evidence of rare hereditary problems of 
galactose intolerance, the Lapp lactase deficiency or 
glucose-galactose malabsorption 
f) gastrointestinal abnormalities including the inability to 
take oral medication, requiring intravenous alimentation, 
or prior surgical procedure affecting absorption 
g) history or evidence of severe hepatic impairment (total 
serum bilirubin > 3mg/dL), jaundice unless secondary to 
Gilbert’s syndrome or documented liver involvement by 
lymphoma (see inclusion criterion 6c) 
 
Investigational Drug(s) 
(Name, Description)  
MOR00208 and LEN (Revlimid®) 
Dose, Route of 
Administration, 
Treatment Regimen 
Treatment consisting of LEN and MOR00208 combination will be 
administered up to twelve 28-day cycles at specified dose levels, as 
scheduled, until disease progression, unacceptable toxicity, or 
discontinuation for any other reason, whichever comes first.  
 
MOR00208 Dose: 12 mg/kg 
For the first three cycles of the study, each cycle (Cycles 1-3) will consist 
of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the 
cycle. Additionally a loading dose will be administered on Day 4 of Cycle 
1.  
Thereafter MOR00208 will be administered on a bi-weekly (every 
fourteen days) basis with infusions on Days 1 and 15 of each 28-day cycle 
until disease progression, or unacceptable toxicity, or discontinuation for 
any other reason, whichever comes first. 
 
 
LEN: 
Patients will self-administer a starting dose of 25 mg oral LEN daily on 
Days 1–21 of each cycle. Treatment with LEN may be modified in a de-
escalating fashion or discontinued based upon clinical and laboratory 
findings. Detailed dose modification guidelines to manage haematologic 
and/or other toxicities are provided in the relevant sections of the protocol. 
 
LEN can be given for up to a total of 12 cycles. MOR00208 can be 
administered until disease progression, or unacceptable toxicity, or 
discontinuation for any other reason, whichever comes first. 
 
It is up to the investigator to decide according to the individual risk/benefit 
ratio if the patient should continue further MOR00208 therapy in the case 
of disease progression. 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Page 14 of 110 
Supply, Preparation and 
Administration 
MOR00208 DP is a lyophilisate supplied in single-use 20 mL glass vials. 
Each vial contains 200 mg of MOR00208 for reconstitution with 5 mL of 
water for injection (WFI). Reconstitution yields 40 mg/mL MOR00208 in 
25 mM sodium 
citrate, 
200 mM 
trehalose 
and 
0.02% 
(w/v) 
polysorbate 20 at pH 6.0. Each product vial is intended to deliver 200 mg 
of MOR00208 in 5 ml of reconstituted solution. MOR00208 will be 
diluted into a 250 mL infusion bag containing 0.9% (w/v) sodium chloride 
for injection.  
 
LEN will be sourced from commercially available drug suppliers 
(Revlimid®). 
 
Efficacy Assessments 
Disease response assessments will be made according to the revised 
response criteria for malignant lymphoma based on the guidelines of the 
International Working Group (IWG, as reported by Cheson et al. (2007) 
and will be based on a central review (radiological + clinical) of the 
disease assessments. Efficacy will be evaluated in terms of ORR, DCR, 
DoR, PFS, OS, TTP and TTNT. Results of local disease response 
assessments will also be available. 
 
Safety Assessments 
The safety and tolerability of study drug treatments will be evaluated by 
means of AE reports (number and severity), performance status, physical 
examinations, 12-lead resting electrocardiograms (ECGs), and laboratory 
safety evaluations. 
 
Laboratory and AE toxicities will be graded according to National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE), version 4.0. 
 
Pharmacokinetics 
The PK of MOR00208 will be investigated during the course of the study. 
 
Biomarker Assessments  Blood and tumour specimens for the analysis of exploratory biomarkers 
will be collected throughout the study and will be characterised for 
markers which are important in the mechanism of action of, or could 
predict response to, the study drugs. Exploratory and diagnostic 
biomarkers (e.g., CD19, CD20, BCL2, BCL6), CD16 expression on NK 
cells, B-, T- and NK cell counts, ADCC capacity and gene expression 
profiling for cell of origin subtyping are planned to be investigated during 
the course of the study. 
 
Statistical Methods and 
Data Analysis 
The primary purpose of this study is to evaluate the clinical efficacy of 
oral LEN combined with MOR00208 administered by IV infusion in 
patients with R-R DLBCL. No formal statistical hypothesis testing will be 
performed. 
 
For the sample size determination it is assumed that the combination 
treatment could improve the ORR from a value of 20% (corresponding to 
monotherapy) to one of 35% which is achievable under combination 
treatment. Sample size estimation using a one-sample exact binomial test 
with a two-sided significance level of 5% and a power of 85% delivers a 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 15 of 110 
sample size of 73 patients. According to this scenario an observed ORR 
of 32% would lead to a statistically significant study outcome. Allowing 
for a drop-out rate of 10% the total required sample size comes to 
approximately 80 patients. 
 
All data will be summarised using appropriate statistics (counts/ 
percentages for discrete variables, mean, median, standard deviation, 
minimum, maximum, number of valid observations for continuous 
variables) for tabulation purposes. For specific variables, p-values and 
95% confidence limits will be presented. 
 
Overall baseline and demographic data will be summarised using 
appropriate statistics. Patient disposition and status at the end of the study 
will be tabulated presenting the number of patients and frequencies. 
General medical history and history of DLBCL, including prior cancer 
therapies, will be tabulated using coding systems (e.g., MedDRA, WHO-
DDE), where appropriate. 
 
PRIMARY OBJECTIVE: 
 
Primary efficacy endpoint: Objective response rate (ORR) 
The ORR will be the percentage of patients who have met the ORR 
definition up until progression based on the central (independent) 
radiological and clinical evaluations. The denominator for calculating the 
rate will be based upon the total number of patients in the full analysis set 
(FAS) population. As a sensitivity analysis, patients without any post-
baseline assessment of response will be included in the denominator for 
ORR calculation. Number of patients being a responder and the respective 
rates, as well as 95% confidence limits, will be presented. 
 
SECONDARY OBJECTIVES: 
 
Disease control rate (DCR) 
The DCR will be evaluated like ORR. 
 
Duration of response (DoR) and Time to next treatment (TTNT) 
Response duration by the local assessment and by the central radiological 
+ clinical assessments will be tabulated with descriptive statistics. Time to 
next treatment will be descriptively analysed. 
 
Progression-free survival (PFS), overall survival (OS) and time to 
progression (TTP) 
Kaplan-Meier methodology will be used to evaluate median survival, 
presenting corresponding statistical parameters and 95% confidence limits 
and Kaplan-Meier survival curves. 
 
Incidence and severity of adverse events 
MedDRA coded adverse events will be used to show the incidence of all 
AEs by specific organ class (SOC), preferred term (PT), relationship to 
treatment, severity and seriousness. An AE summary table will present the 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 16 of 110 
 
number of events, number of patients and the percentage of patients 
having treatment-emergent AEs (TEAEs), serious AEs, adverse drug 
reactions, and TEAEs that led to study discontinuation. 
AE frequency tables will display event and patient counts/frequency by 
MedDRA SOC and PT, distinguishing also by severity/toxicity, 
relationship to study drug, seriousness and outcome. 
 
Concomitant medications taken, starting on the day of the screening visit 
and through the followup- period, will be coded using appropriate coding 
systems and tabulated by each code system. 
 
Extent of exposure, clinical laboratory assessments, vital sign 
measurements, physical examination and results of ECGs will be 
summarised with appropriate descriptive statistics. 
 
Immunogenicity 
The absolute number and percentage of patients who develop anti-
MOR00208 antibodies, and the results of semi-quantitative anti-
MOR00208 antibody titre determinations of confirmed positive samples 
assessments, will be tabulated. 
 
Pharmacokinetics 
Appropriate PK parameters for MOR00208 will be computed based on 
non-compartmental data analysis and summarised using descriptive 
statistics. Mean concentrations will be visualised by figures. 
 
Biomarkers 
Blood and protein biomarkers which are important in the mechanism of 
action of, or could predict response to, the study drugs will be 
descriptively tabulated, presenting absolute and change to baseline values, 
if applicable. 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 17 of 110 
TABLE OF CONTENTS 
Overall Table of Contents 
PROTOCOL SYNOPSIS ........................................................................................................................ 6 
TABLE OF CONTENTS ....................................................................................................................... 17 
Overall Table of Contents ..............................................................................................................17 
List of Tables ...................................................................................................................................20 
List of Figures .................................................................................................................................20 
LIST OF ABBREVIATIONS ................................................................................................................ 21 
1 
INTRODUCTION ................................................................................................................ 25 
1.1 
Overview of Non-Hodgkin Lymphomas.............................................................................25 
1.2 
Treatment of DLBCL...........................................................................................................25 
1.3 
Lenalidomide in Haematological Malignancies .................................................................26 
 
LEN as a Single Agent in Relapsed DLBCL .......................................................27 
 
LEN and DLBCL Subtype ...................................................................................27 
 
LEN in Combination with RTX in R-R DLBCL .................................................28 
 
LEN in Combination with R-CHOP or R-ICE in DLBCL...................................28 
1.4 
Overview of MOR00208 ......................................................................................................29 
 
Clinical Experience with MOR00208 ..................................................................30 
1.4.1.1 
Protocol No. XmAb®5574-01 ..............................................................................30 
1.4.1.2 
Ongoing Studies ...................................................................................................32 
 
Safety of MOR00208 ...........................................................................................33 
2 
STUDY PURPOSE/RATIONALE ..................................................................................... 34 
3 
STUDY OBJECTIVES ........................................................................................................ 35 
3.1 
Primary Objective ................................................................................................................35 
3.2 
Secondary Objectives ...........................................................................................................35 
4 
STUDY ENDPOINTS .......................................................................................................... 36 
4.1 
Primary Endpoint: ...............................................................................................................36 
4.2 
Secondary Endpoints: ..........................................................................................................36 
5 
INVESTIGATIONAL PLAN .............................................................................................. 37 
5.1 
Study Design .........................................................................................................................37 
 
Protocol-specific definitions ................................................................................37 
 
Description of study design ..................................................................................37 
5.2 
Safety Run-in ........................................................................................................................39 
5.3 
Study Duration .....................................................................................................................39 
 
Study Conduct ......................................................................................................39 
 
End of Study .........................................................................................................40 
5.4 
Patient Selection Criteria .....................................................................................................40 
 
Inclusion Criteria ..................................................................................................40 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Page 18 of 110 
 
Exclusion Criteria .................................................................................................42 
 
Definition of Female of Childbearing Potential ...................................................43 
5.5 
Re-screening Procedures .....................................................................................................43 
6 
STUDY TREATMENTS AND CONCOMITANT DRUGS............................................. 44 
6.1 
MOR00208 ............................................................................................................................44 
6.2 
Lenalidomide (LEN) ............................................................................................................46 
6.3 
Treatment with Study Drugs ...............................................................................................46 
6.4 
Pre-Medication for MOR00208 Infusions ..........................................................................47 
6.5 
Patient Monitoring During MOR00208 Infusion ..............................................................47 
6.6 
Criteria for Dose Modifications and Drug Discontinuation .............................................47 
 
Management of MOR00208 Infusion-Related Reactions (IRRs) ........................47 
6.6.1.1 
Grade 2 IRRs ........................................................................................................49 
6.6.1.2 
Grade 3 IRRs ........................................................................................................49 
6.6.1.3 
Grade 4 IRRs ........................................................................................................49 
 
Management of Toxicities ....................................................................................50 
6.6.2.1 
Haematological and Other Toxicities ...................................................................50 
6.6.2.2 
LEN Dose Reduction Guidelines .........................................................................53 
6.6.2.3 
Tumour Flare with LEN .......................................................................................54 
6.6.2.4 
Tumour Lysis Syndrome ......................................................................................54 
6.6.2.5 
Thromboembolism ...............................................................................................54 
6.7 
Prior and Concomitant Therapy ........................................................................................55 
6.8 
Treatment Compliance ........................................................................................................58 
6.9 
Withdrawal from Study Treatment or Study/Site Termination ......................................58 
 
Withdrawal Criteria ..............................................................................................58 
 
Study or Site Termination ....................................................................................60 
7 
VISIT ASSESSMENTS AND PROCEDURES ................................................................. 60 
7.1 
Visit Schedule .......................................................................................................................60 
7.2 
Procedures ............................................................................................................................69 
 
Screening followed by Enrolment (Start of IMP) ................................................69 
 
End of Treatment (EOT) Visit .............................................................................70 
 
MOR00208 Administration Despite Disease Progression ...................................70 
 
Safety Follow-up Visit .........................................................................................71 
 
Survival Follow-up ...............................................................................................71 
 
Diagnostic Biopsy ................................................................................................71 
 
Demographic Data/Relevant Medical History and Current Medical 
Conditions/Baseline Stage and Prognostic Classification ....................................72 
 
Vital Signs ............................................................................................................73 
 
Physical Examination (PE) ...................................................................................73 
7.2.9.1 
Full PE ..................................................................................................................73 
7.2.9.2 
Limited PE ...........................................................................................................73 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Page 19 of 110 
7.2.9.3 
Body Weight and Height Measurements..............................................................74 
7.2.9.4 
B-Symptoms .........................................................................................................74 
 
Electrocardiogram ................................................................................................74 
 
Adverse Event Monitoring ...................................................................................74 
 
Monitoring of Second Primary Malignancies ......................................................74 
 
Laboratory Assessments .......................................................................................75 
7.2.13.1 
Safety and Haematology Laboratory Testing .......................................................75 
7.2.13.2 
Hepatitis Virus Serology ......................................................................................78 
7.2.13.3 
Pregnancy Testing ................................................................................................79 
7.2.13.4 
PK Assessments ...................................................................................................79 
7.2.13.5 
Immunogenicity ...................................................................................................80 
7.2.13.6 
Other Laboratory Evaluations ..............................................................................80 
 
Efficacy Assessments ...........................................................................................80 
7.2.14.1 
Tumour Imaging Assessment ...............................................................................81 
7.2.14.2 
Bone Marrow .......................................................................................................82 
8 
SAFETY MONITORING .................................................................................................... 82 
8.1 
Definition of Adverse Events, Serious Adverse Events, Adverse Events of Special 
Interest ..................................................................................................................................83 
8.2 
Adverse Event and Serious Adverse Event Recording and Reporting ...........................85 
8.3 
Pregnancies ...........................................................................................................................87 
9 
DATA HANDLING AND ARCHIVING ........................................................................... 88 
9.1 
Completing and Signing Case Report Forms ....................................................................88 
9.2 
Clinical Data Management ..................................................................................................88 
9.3 
Archiving and Filing ............................................................................................................88 
10 
STATISTICAL METHODS AND PLANNED ANALYSIS............................................. 89 
10.1 Populations for Analysis ......................................................................................................89 
10.2 Primary Endpoint ................................................................................................................89 
10.3 Secondary Endpoints ...........................................................................................................89 
10.4 General Statistical Methods ................................................................................................89 
10.5 Patient Disposition................................................................................................................90 
10.6 Analysis of Efficacy Data .....................................................................................................90 
 
Primary Efficacy Endpoint ORR ..........................................................................90 
 
Secondary Endpoints ............................................................................................91 
10.6.2.1 
Disease Control Rate (DCR) ................................................................................91 
10.6.2.2 
Duration of Response (DoR) and Time to Next Treatment (TTNT) ....................91 
10.6.2.3 
Time to Event Variables: Progression-Free Survival (PFS), Overall 
Survival (OS), and Time to Progression (TTP) ....................................................91 
10.6.2.4 
Immunogenicity Analysis ....................................................................................92 
10.6.2.5 
Pharmacokinetic Analysis ....................................................................................92 
10.6.2.6 
Biomarkers ...........................................................................................................92 
10.7 Analysis of Safety Data ........................................................................................................93 


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Adverse Events .....................................................................................................93 
 
Clinical Laboratory Evaluations ...........................................................................93 
 
Physical Examination, Vital Signs and Electrocardiogram (12-lead ECG) .........93 
10.8 Sample Size Determination .................................................................................................93 
10.9 Safety Run-In ........................................................................................................................94 
11 
SPECIAL REQUIREMENTS AND PROCEDURES ....................................................... 94 
11.1 Charters 94 
11.2 Protocol Amendments and Other Changes in Study Conduct .........................................94 
11.3 Regulatory and Ethical Considerations, Including the Informed Consent Process .......95 
11.4 Quality Control (Study Monitoring)...................................................................................95 
11.5 Quality Assurance ................................................................................................................96 
11.6 Insurance 96 
11.7 Publication Policy .................................................................................................................96 
12 
REFERENCES ..................................................................................................................... 98 
13 
APPENDICES .................................................................................................................... 102 
Appendix A: ..................................................................................................................................103 
Appendix B: ..................................................................................................................................104 
Appendix C: ..................................................................................................................................105 
Appendix D: ..................................................................................................................................106 
Appendix E: ..................................................................................................................................107 
Appendix F: ...................................................................................................................................108 
Appendix G: ..................................................................................................................................109 
 
List of Tables 
(Excluding those in the appendix) 
 
Table 1 
Definition of Infusion-Related Reaction ...................................................................... 48 
Table 2 
Haematological and Other Toxicities ........................................................................... 51 
Table 3 
Other Toxicities Judged to be Related to LEN ............................................................. 52 
Table 4 
LEN Dose Reduction Guidelines ................................................................................. 53 
Table 5 
Schedule of Assessments .............................................................................................. 61 
Table 6 
Laboratory Evaluations ................................................................................................ 77 
 
List of Figures 
Figure 1 Study design ............................................................................................................................. 38 
 


Product Name: MOR00208 
 
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LIST OF ABBREVIATIONS 
ABC 
Activated B-cell type 
ADCC 
Antibodydependent- cell-mediated cytotoxicity 
ADCP 
Antibody-dependent cell-mediated phagocytosis 
AE 
Adverse event 
ALC 
Absolute lymphocyte count 
ALL 
Acute lymphoblastic leukaemia 
ALT 
Alanine transaminase 
ANC 
Absolute neutrophil count 
Anti-Hbc 
Hepatitis B core antibody 
Anti-HBs 
Hepatitis B surface antibody 
Anti-HCV 
Hepatitis C virus antibody 
AP 
Alkaline phosphatase 
ASCT 
Autologous stem-cell transplantation 
AST 
Aspartate aminotransferase 
B-ALL 
B-cell acute lymphoblastic leukaemia 
BCL-2/6 
B-cell leukaemia/lymphoma protein-2/6 
BEN 
Bendamustine 
bpm 
Beats per minute (heart rate) 
BSC 
Best supportive care 
CBC 
Complete blood count 
CD19 
Cluster of differentiation 19 
CDC 
Complement-dependent cytotoxicity 
CHOP 
Cyclophosphamide, hydroxydaunorubicin (also referred to as doxorubicin or 
adriamycin), and oncovin (vincristine) plus prednisone or prednisolone 
CLL 
Chronic lymphocytic leukaemia 
CML 
Chronic myeloid leukaemia 
CNS 
Central nervous system  
COPD 
Chronic obstructive pulmonary disease 
CR 
Complete response 
CRF 
Case report form 
CRO 
Contract research organisation 
CSF 
Cerebrospinal fluid 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DHAP 
Cisplatin, cytarabine, dexamethasone 
DCR 
Disease control rate 
DLBCL 
Diffuse large B-cell lymphoma 
DLT 
Dose-limiting toxicity 
DNA 
Deoxyribonucleic acid 
DoR 
Duration of response 
DP 
Drug product 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDTA 
Ethylenediaminetetraacetic acid 
EMA 
European Medicines Agency  
EOT 
End of treatment 


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ESHAP 
Etoposide, methylprednisone, cytarabine, cisplatin 
FAS 
Full analysis set 
FCBP 
Female(s) of childbearing potential 
FDG 
[18]-Fluordesoxyglucose 
FcγR 
Fc gamma receptor 
FDA 
Food and Drug Administration 
FL(-3) 
Follicular (grade 3) lymphoma 
GCB 
Germinal centre B-cell 
GCP 
Good clinical practice 
G-CSF 
Granulocyte colony-stimulating factor 
GEP 
Gene expression profiling 
GGT 
Gamma-glutamyltransferase 
GLP 
Good laboratory practice 
HbsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCL 
Hairy cell leukaemia 
HCV 
Hepatitis C virus 
HDC 
High-dose chemotherapy 
HIV 
Human immunodeficiency virus 
IB 
Investigator’s brochure 
ICE 
Ifosfamide, carboplatin, etoposide 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Independent ethics committee 
Ig 
Immunoglobulin 
IHC 
Immunohistochemistry 
IIT 
Investigator initiated trial 
IL-2 
Interleukin-2  
IMiD® 
Immunomodulatory drug 
IMP 
Investigational medicinal product 
IND 
Investigational new drug 
iNHL 
Indolent non-Hodgkin lymphoma 
IPI 
International Prognostic Index 
IRB 
Institutional/independent review board 
IRR 
Infusion-related reaction 
IV 
Intravenous 
IWG 
International Working Group 
LDH 
Lactate dehydrogenase 
LEN 
Lenalidomide 
mAb 
Monoclonal antibody 
MALT 
Mucosa-associated lymphoid tissue lymphoma 
MCL 
Mantle cell lymphoma 
MedDRA 
Medical Dictionary for Regulatory Activities 
MM 
Multiple myeloma 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
MYC 
v-myc avian myelocytomatosis viral oncogene homolog 
MZL 
Marginal zone lymphoma 


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NCI 
National Cancer Institute 
NHL 
Non-Hodgkin lymphoma 
NK 
Natural killer 
NOAKs 
New oral anticoagulants 
NOS 
Not otherwise specified 
NSAIDs 
Non-steroidal anti-inflammatory drugs  
NYHA 
New York Heart Association 
ORR 
Objective response rate (complete response + partial response) 
OS 
Overall survival 
PD 
Pharmacodynamics 
PE 
Physical examination 
PET 
Positron emission tomography 
PFS 
Progression-free survival 
PK 
Pharmacokinetic 
PLL 
Prolymphocytic leukaemia 
PMBL 
Primary mediastinal (thymic) large B-cell lymphoma 
p.o. 
By mouth 
PPS 
Per-protocol set 
PR 
Partial response 
PR (ECG) 
PR interval 
PT 
Preferred term 
QRS 
QRS interval 
QT 
QT interval 
RBC 
Red blood cell 
R-CHOP 
Rituximab plus cyclophosphamide, hydroxydaunorubicin (also referred to as 
doxorubicin or adriamycin), and oncovin (vincristine) plus prednisone or 
prednisolone  
REAL/WHO 
Revised European American Lymphoma/World Health Organization 
R-EPOCH 
Rituximab plus etoposide, prednisone or prednisolone, oncovin, 
cyclophosphamide, and hydroxydaunorubicin 
R-ICE 
Rituximab plus ifosfamide, carboplatin, etoposide 
RNA 
Ribonucleic acid 
rpm 
Respirations per minute (respiration rate) 
RR (ECG) 
RR interval 
R-R 
Relapsed or refractory 
R-R CLL/SLL 
Relapsed or refractory chronic lymphocytic leukaemia/small lymphocytic 
lymphoma 
R-R DLBCL 
Relapsed or refractory diffuse large B-cell lymphoma 
R-R NHL 
Relapsed or refractory non-Hodgkin lymphoma 
RTX 
Rituximab 
SAE 
Serious adverse event 
SAF 
Safety analysis set 
SAP 
Statistical analysis plan 
SCID 
Severe combined immunodeficiency 
SD 
Stable disease  
SLL 
Small lymphocytic lymphoma 
SOC 
System organ class 
SOP 
Standard operating procedure 
SPC 
Summary of Product Characteristics 


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SPD 
Sum of Product Diameter 
SPM 
Second primary malignancy 
TEAE 
Treatment emergent adverse event 
Th1 
T (thymus) helper cell 1 
TL 
Transformed lymphoma 
TLS 
Tumour Lysis Syndrome 
TFR 
Tumour flare 
TNM 
Tumour/Node/Metastasis 
TTNT 
Time to next treatment 
TTP 
Time to progression 
ULN 
Upper limit of normal 
US 
United States 
VIM 
Etoposide, ifosfamide, methotrexate 
VTE 
Venous thromboembolic event 
WBC 
White blood cell 
WFI 
Water for injection 
WHO-DDE 
World Health Organization–Drug Dictionary Enhanced 
β-HCG 
Beta-human chorionic gonadotropin 


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1 INTRODUCTION 
 
1.1 Overview of Non-Hodgkin Lymphomas 
Non-Hodgkin lymphomas (NHLs) account for approximately 5% of all new cancer cases and 
comprise a heterogeneous group of lymphoproliferative malignancies, which in 90% of cases 
are derived from B-cells. 
 
Diffuse large B-cell lymphoma (DLBCL), the most common high-grade NHL, accounts for 
approximately 40% of NHLs (Armitage and Weisenbuger, 1998; Swerdlow et al., 2008) and 
comprises 60% of all new lymphomas in the elderly population (Thieblemont and Coiffier, 
2007). The median age at the diagnosis of DLBCL is 64 years and the majority of patients present 
with advanced disease. There were an estimated 386,000 new cases of NHL worldwide in 2012, 
including 93,500 new cases in Europe and 70,400 in North America (Ferlay et al., 2014). 
 
DLBCL is a heterogeneous disorder with two major molecular subtypes identified by gene 
expression profiling (GEP): germinal centre B-cell type (GCB) and activated B-cell type (ABC). 
The latter group is often included in non-GCB type in immunohistochemistry (IHC)-based 
algorithms. The ABC (non-GCB subtype) has been associated with worse outcome.  
 
Other NHLs include mantle cell lymphoma (MCL), follicular lymphoma (FL) and other indolent 
NHLs (iNHL) such as marginal zone lymphoma (MZL), mucosa-associated and lymphoid tissue 
lymphoma (MALT). 
 
1.2 Treatment of DLBCL 
DLBCL is considered to be a chemosensitive neoplasm. Originally, CHOP (cyclophosphamide, 
doxorubicin, vincristine, and prednisone) chemotherapy was the standard first-line treatment. 
However the addition of rituximab (RTX) into CHOP-like (R-CHOP-like), anthracycline-based 
regimens has significantly improved the clinical results in patients with DLBCL, becoming the 
standard of care (Feugier et al., 2005; Habermann et al., 2006; Coiffier et al., 2002). 
 
Nevertheless, even with the availability of R-CHOP-like treatment regimens, approximately 30–
40% of patients will ultimately relapse or progress. In patients progressing or relapsing after 
first-line treatment the ultimate therapeutic goal is to be able to offer salvage chemotherapy such 
as DHAP (cisplatin, cytarabine, dexamethasone), VIM (etoposide, ifosfamide, methotrexate), 
ICE (ifosfamide, carboplatin, etoposide), or ESHAP (etoposide, methylprednisone, cytarabine, 
cisplatin), followed by high-dose chemotherapy (HDC) with autologous stem cell transplantation 
(ASCT) if the disease is still chemosensitive. HDC with ASCT is a potentially curative treatment, 
significantly improving disease-free survival and overall survival (OS) in patients with relapsed 
DLBCL (Philip et al., 1995). 
 
However, the use of HDC with stem cell support may not be appropriate, especially for patients 
with comorbidities or older age, restricting the benefit of this aggressive approach to a relatively 
small percentage of patients. For the remaining patient population, several second-line 
combination therapies are used with variable success, but the median survival for patients who 


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have relapsed after second-line therapy is less than one year, and the median survival for those 
not responding to second-line therapy is less than 6 months. 
 
Monoclonal antibody (mAb) therapy may have the potential to improve objective response rates 
(ORRs) and OS without increasing haematological toxicity. This is supported by data from 
studies investigating other CD19 mAbs, including MDX-1342, SAR3419 and MEDI-551 
(Ribrag et al., 2014; Matlawska-Wasowska et al., 2013; Younes et al., 2012; Bargou et al., 2008; 
Viardot et al., 2011). 
 
1.3  Lenalidomide in Haematological Malignancies 
Lenalidomide (LEN [Revlimid®]) belongs to the class of pharmaceutical compounds known as 
immunomodulatory drugs (IMiDs®). Although the mechanism(s) of LEN activity remain(s) 
unclear, in vitro and in vivo preclinical studies show that IMiDs® demonstrate a variety of 
biological effects (Haslett et al., 2003; Galustian et al., 2009; Pan et al., 2012; Saloura and Grivas, 
2010; Wiernik, 2013). Specifically, they: 
 inhibit the proliferation and increase the proapoptosis of NHL cells 
 costimulate CD4+ and CD8+ T-cells, thereby enhancing Th1-type cellular immunity. 
IMiDs® may inhibit T-regulatory cells which are known to suppress CD4+ T-cell activity 
in NHL 
o T-cell costimulation leads to interleukin-2 (IL-2) mediated enhanced natural 
killer (NK) effector function leading to enhanced tumour cell recognition and 
killing and increased potential for antibody dependent cell-mediated cytotoxicity 
(ADCC) 
 inhibit regulatory T-cells that are known to suppress CD4+ and CD8+ T-cell activity in 
NHL 
 exert antiangiogenic effects in the tumour microenvironment, and reduce endothelial cell 
migration. 
 
LEN has been approved by multiple health authorities: 
a. for the treatment of patients with transfusion dependent anaemia due to low- or 
intermediate-1-risk myelodysplastic syndrome (MDS) associated with the cytogenetic 
abnormality, deletion 5q, with or without additional cytogenetic abnormalities 
b. for use in combination with dexamethasone for patients with previously treated multiple 
myeloma (MM) based on significant antitumour activity 
c. for the treatment of patients with MCL whose disease has relapsed or progressed after 
two prior therapies including bortezomib. 
 
LEN has also shown activity in R-R chronic lymphocytic leukaemia (CLL)/small lymphocytic 
lymphoma (SLL) (Chanan-Khan et al., 2006). Additionally, LEN is being investigated as a 
treatment for various oncological indications, including MM, NHL and solid tumours. Studies 
have also been conducted in non-oncological indications. 
 


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Protocol Number: MOR208C203 
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 LEN as a Single Agent in Relapsed DLBCL 
It has been demonstrated that LEN has single-agent activity in R-R DLBCL. Wiernik et al. 
(2008) evaluated the safety and efficacy of 25 mg LEN administered orally, daily, for 52 weeks, 
until disease progression or intolerance as monotherapy in patients with R-R aggressive NHL. 
The primary endpoint was ORR; secondary endpoints included duration of response (DoR), 
progression-free survival (PFS), and safety. Forty-nine patients with a median age of 65 years 
received LEN in this study. The most common histology was DLBCL, established in 53% of 
patients, and patients had received a median of four prior treatment regimens for NHL. The ORR 
was 35% including a 12% complete response (CR)/unconfirmed CR rate. Of patients with stable 
disease (SD) or partial response (PR) at first assessment, 25% improved with continued 
treatment. Estimated median DoR was 6.2 months, and median PFS was 4.0 months. The most 
common grade 4 adverse events (AEs) were neutropenia (8.2%) and thrombocytopenia (8.2%). 
 
Similarly, in a phase II study of LEN in patients with R-R DLBCL, MCL, follicular grade 3 
lymphoma (FL-3), or transformed lymphoma (TL) patients received oral LEN 25 mg on days 1–
21 every 28 days as tolerated or until progression (Witzig et al., 2011). Two hundred and 
seventeen patients were enrolled and received LEN. The ORR was 35% (77/217), with 13% 
(29/217) of patients achieving CRs, 22% (48/217) PRs, and 21% (45/217) with SD. The ORR 
for DLBCL was 28% (30/108). Median PFS for all 217 patients was 3.7 months. For 
77 responders, the median DoR was 10.6 months. The most common AE was myelosuppression, 
with grade 4 neutropenia and thrombocytopenia in 17% and 6% of patients, respectively. 
 
Zinzani et al. (2014) have shown in a retrospective, multicentre study that LEN monotherapy is 
effective and safe for heavily pretreated patients with R-R NHL. The ORR in 64 evaluable 
patients was 42.2% and was similar among patients receiving 10, 15 or 25 mg/day LEN. ORR 
in patients with MCL, DLBCL and FL were 45.5%, 42.1% and 20%, respectively. Mean DoR 
in patients receiving any LEN dose was 10.5 months; 1-year PFS and OS rates were 50.3% and 
82.6%, respectively. 
 
Additionally it has been shown that single agent LEN was active in heavily pretreated patients 
with aggressive, R-R NHL subsequent to a prior ASCT (Vose et al., 2013). 
 
 LEN and DLBCL Subtype 
A retrospective analysis of the outcomes of patients with GCB vs non-GCB DLBCL treated with 
LEN was performed by Hernandez-Ilizaliturri et al. (2011). Forty patients with R-R DLBCL 
were included (24 men; 16 women; median age, 66 years; median of four prior treatments, 
including RTX-containing chemotherapy). Patients were classified as having GCB (n=23) or 
non-GCB (n=17) DLBCL. This analysis showed that patients with R-R DLBCL with a non-GCB 
phenotype had a higher ORR and CR rate and longer PFS when treated with LEN than those 
with a GCB phenotype, despite similarities in terms of disease stage, International Prognostic 
Index (IPI) score, number of prior treatments, and RTX resistance. 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
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IND Number: 114,856 
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 LEN in Combination with RTX in R-R DLBCL 
The combination of LEN with RTX has been shown to be active and well tolerated with a 
manageable toxicity profile in heavily pretreated patients with R-R DLBCL. Zinzani et al. (2011) 
conducted a phase II study in heavily pretreated, elderly patients with R-R DLBCL. The 
induction treatment with oral LEN (20 mg/day for 21 days of each 28-day cycle) combined with 
RTX followed by LEN maintenance therapy resulted in a 35% CR rate at a median follow-up of 
16 months. LEN maintenance in responding patients led to continuation of their initial response. 
The most common AEs included neutropenia and thrombocytopenia. 
 
Wang et al. (2013) assessed the clinical activity of oral LEN and RTX in 45 patients with R-R 
DLBCL (n=32), transformed large cell lymphoma (n=9) or FL-3 (n=4) who had received 
1-4 prior lines of treatment. Patients were given 20 mg oral LEN on Days 1–21 of each 28-day 
cycle, and RTX. The ORR was 33%; median DoR was 10.2 months. Median PFS and OS were 
3.7 and 10.7 months, respectively. Grade 3/4 haematological toxicities included neutropenia 
(53%), lymphopenia (40%), thrombocytopenia (33%), leukopenia (27%) and anaemia (18%). 
 
Ivanov et al. (2014) analysed clinical outcomes in 17 patients with R-R DLBCL treated with 
LEN at a dose of 25 mg/day for 21/28 days and RTX for a maximum of 12 months. The ORR 
was 41.2% with 35.3% of patients achieving a CR, while the median DoR was 26.5 months at a 
median follow-up of 24.9 months. The estimated 24-month OS and PFS rates were 45% and 
38%, respectively. The most common AEs were thrombocytopenia and neutropenia. 
 
 LEN in Combination with R-CHOP or R-ICE in DLBCL  
A phase I study established the maximum tolerated dose (MTD) of LEN that could be combined 
with R-CHOP chemotherapy for adults with newly diagnosed aggressive B-cell NHL 
(Nowakowski et al., 2011). Eligible patients were those with newly diagnosed, untreated CD20-
positive DLBCL or FL-3. Patients received oral LEN on Days 1–10 with standard dose R-CHOP 
administered over 21 days. All patients received pegfilgrastim on Day 2 of the cycle and aspirin 
prophylaxis. The LEN dose levels tested were 15, 20 and 25 mg. Twenty-four patients were 
enrolled. The median age was 65 (range 35–82) years and 54% (13/24) were over 60 years. Three 
patients received 15 mg, 3 received 20 mg and 18 received 25 mg of LEN. No dose-limiting 
toxicity (DLT) was found. LEN dose escalation beyond 25 mg Days 1–10 was not performed 
and LEN 25 mg Days 1–10 was the recommended dose for phase II studies. The incidence of 
grade 4 neutropenia and thrombocytopenia was 67% and 21%, respectively. The incidence of 
febrile neutropenia requiring hospitalisation was 4% and there were no bleeding or toxicity 
related deaths. There were no delays in chemotherapy due to cytopenias. The ORR was 100% 
with a CR rate of 77%. It was shown that the combination of LEN with the R-CHOP regimen 
was safe and effective for the treatment of aggressive lymphomas including DLBCL. In a 
subsequent phase II study, Nowakowski et al. (2015) have not only confirmed their initial 
observation concerning clinical efficacy, but also established that the addition of LEN to R-
CHOP mitigates the negative impact of the non-GCB phenotype on patient outcome. 
 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
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IND Number: 114,856 
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Additionally, studies conducted by Fondazione Italian Linfomi have shown that combining 
15 mg oral LEN on Days 1–14 of 21-day cycles with standard doses of R-CHOP chemotherapy 
is an effective and safe treatment modality in untreated, elderly patients with DLBCL (Chiapella 
et al., 2013; Vitolo et al., 2014). 
 
Feldman et al. (2014) showed that combining LEN (at doses up to 25 mg daily) with RTX in 
combination with ICE (R-ICE) was associated with promising clinical activity, with no 
additional toxicological burden, in patients with R-R DLBCL. 
 
1.4  Overview of MOR00208 
MOR00208 (synonym: XmAb®5574) is an Fc-engineered mAb that binds to the human B-cell 
surface antigen CD19. MOR00208 possesses significantly increased tumour cytotoxicity when 
compared with the parental, non-engineered, murine 4G7 CD19 antibody. The increased binding 
of MOR00208 to Fc gamma receptors (FcγR), due to the engineered mutations, significantly 
enhances in vitro ADCC, antibody-dependent cell-mediated phagocytosis (ADCP), and its direct 
cytotoxic effects (apoptosis) on the tumour cells compared with the non-engineered parental 
murine antibody. MOR00208 has not been shown to mediate complement-dependent 
cytotoxicity (CDC). 
 
More specifically, in preclinical studies, MOR00208 has been shown to significantly enhance in 
vitro ADCC, ADCP, and direct cytotoxic effects (apoptosis) on CD19+ tumour cell lines 
spanning a broad range of human lymphomas and leukaemias (Burkitt lymphoma, CLL, hairy 
cell leukaemia [HCL], CD19+ chronic myeloid leukaemia [CML], DLBCL and acute 
lymphoblastic leukaemia [ALL]), expressing levels of CD19 antigen ranging from 15,000 to 
105,000 molecules/cell. Similar effects were also noted in relation to freshly isolated patient CLL 
or ALL cells and are also expected to translate to primary NHL cells since the expression range 
reported for ALL and CLL B-cells covers the range observed for NHL B-cells (Ginaldi et al., 
1998; Olejniczak et al., 2006). MOR00208 has also shown superior efficacy to its non-
engineered parental antibody in relation to its ability to induce a marked reduction in tumour 
growth, inhibit tumour growth rate and increase survival in vivo in xenograft models of human 
lymphoma in severe combined immunodeficiency (SCID) mice (Investigator’s Brochure [IB]). 
 
The pharmacodynamic (PD) interactions of MOR00208 in combination with two standard-of-
care drugs fludarabine and bendamustine (BEN), and one investigational drug, LEN used in the 
treatment of patients with CLL and NHL, were investigated in a human intravenous (IV) 
lymphoma model in SCID mice (see IB). In this orthotopic model for disseminated B-cell 
malignancies, the median survival was superior for all of the groups receiving MOR00208 
combination therapy (with fludarabine, BEN or lenalidomide) when compared with the groups 
receiving MOR00208 monotherapy. The LEN xenograft study showed a clear potentiation of 
the efficacy benefit of MOR00208 (3 mg/kg) and LEN (100/200 mg/kg) combination therapy 
compared with the respective monotherapies (1.5 x increase in median lifespan). 
 
Tissue cross-reactivity studies have shown that the pattern and distribution of MOR00208 
binding to cynomolgus monkey tissues closely parallels those of human tissues. Flow cytometry 
experiments show MOR00208 binding to human and cynomolgus monkey B-cells, but not to the 
B-cells of other common laboratory species (such as rat, mouse, rabbit and dog). Therefore, 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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pharmacology studies were restricted to human and cynomolgus monkey cell-based in vitro 
systems, CD19+ human B-cell tumour xenograft models in SCID mice, and cynomolgus 
monkeys in vivo. In in vivo studies in cynomolgus monkeys, MOR00208 was shown to induce 
B-lymphocyte depletion in peripheral blood, bone marrow, spleen and inguinal lymph nodes. 
Cynomolgus monkeys were also judged to be the only relevant common laboratory species for 
toxicity studies. 
 
The results of studies evaluating the pharmacokinetics (PK), PD and toxicity of MOR00208 in 
cynomolgus monkeys, are provided in the IB. The findings in four preclinical studies were 
limited to the expected pharmacological effects of MOR00208, with no reports of unanticipated 
toxicity. 
 
The four studies, all conducted in cynomolgus monkeys included: a 26-week single 10.0 mg/kg 
dose, PK, PD and toxicity study; a 28-day single IV dose, dose-ranging (0.3, 1.0 and 3.0 mg/kg) 
PK/PD study; a 29-day, single-dose (3.0 mg/kg) study comparing MOR00208 with two other 
CD19 antibodies with different Fc regions; and an 8-week toxicity study in which MOR00208 
was administered IV every 2 weeks at a dose of 2.0, 10.0 or 50.0 mg/kg for 8 consecutive weeks 
with a 90-day recovery period. The aim of the latter Good Laboratory Practice (GLP)-compliant, 
multiple-dose toxicology study was to support the use of MOR00208 in human clinical studies. 
Other than the expected dose-related decreases in B-lymphocyte levels and cellularity in spleen 
tissues, there were no MOR00208-related changes identified in ‘clinical observations’, food 
consumption, body weight, electrocardiography, ophthalmology, urinalysis, coagulation, serum 
chemistry, and gross anatomic pathology at doses up to 50.0 mg/kg. In addition, GLP-compliant 
tissue cross-reactivity studies were performed on normal tissue panels from human and 
cynomolgus monkey donors. No specific staining of structures other than the expected 
mononuclear leucocytes, lymphocytes and haematopoietic precursor cells was observed. 
 
 Clinical Experience with MOR00208 
1.4.1.1 Protocol No. XmAb®5574-01 
A Phase 1 Study of mAb®5574 to Evaluate the Safety, Tolerability, and Pharmacokinetics 
in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia 
 
The first study in humans was a phase I study (now completed) exploring the use of MOR00208 
(also known as XmAb®5574) in adult patients diagnosed according to International Workshop 
on CLL guidelines (Hallek et al., 2008) with active, treatment-requiring, R-R CLL/SLL. The 
results of the study were reported by Woyach et al. (2014). 
 
A total of 27 patients were treated with MOR00208 IV in 6 dose cohorts: 0.3 mg/kg (n=1), 
1.0 mg/kg (n=1), 3.0 mg/kg (n=3), 6.0 mg/kg (n=3), 9.0 mg/kg (n=3) and 12.0 mg/kg (n=16) on 
a weekly schedule for 8 weeks (2 cycles), with an extra dose administered on Day 4 of Cycle 1. 
Patients received MOR00208 via IV infusion over a period of 2 hours on Days 1, 4, 8, 15 and 
22 of Cycle 1 and Days 1, 8, 15 and 22 of Cycle 2 for a total of 9 doses. Patients were evaluated 
at weeks 4, 8 and 12 following completion of Cycle 2 for safety and preliminary antitumour 
activity. Patients enrolled in the expansion phase of cohort 6 (12.0 mg/kg) received an additional 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Page 31 of 110 
four monthly doses of MOR00208 after completing the initial two 28-day cycles of therapy, if 
there was no evidence of disease progression or intolerable drug-related toxicity. 
 
All 27 enrolled patients received at least one dose of MOR00208, with 22 patients receiving all 
nine of the planned initial doses. Of the five patients who did not receive all nine doses, two 
experienced disease progression, one experienced a DLT (grade 4 neutropenia lasting at least 
7 days), one was omitted from the study by the treating physician, and one completed the study 
but missed a dose due to an AE (grade 3 thrombocytopenia). No patients had dose reductions 
during the study. Five patients had at least one dose delayed due to an AE. Eighteen patients had 
their infusion paused at least once due to an infusion-related reaction (IRR). Eight patients were 
included in a maintenance cohort. One patient received only three additional infusions and the 
other seven patients received all four planned additional infusions. 
 
All 27 patients treated with MOR00208 experienced treatment-emergent AEs (TEAEs) and 
24 patients experienced TEAEs that were assessed by the investigator to be possibly or probably 
related to MOR00208. No patient deaths were reported either on study or during the 12-week 
follow-up phase of the study. One DLT, grade 4 neutropenia lasting at least 7 days, was observed 
during the study in one of 16 patients treated at the maximum-administered 12.0 mg/kg dose 
level. Eight treatment-emergent serious AEs (SAEs) were reported in six patients; one at the 0.3 
mg/kg dose level and seven at the 12.0 mg/kg dose-level. Only two were considered to be related 
to the study drug: one of grade 3 febrile neutropenia in the same patient who experienced the 
DLT and one of grade 3 tumour lysis syndrome (TLS) in a patient receiving his first dose of 
study drug at 12.0 mg/kg. In the latter case, after resolution of the SAE, the patient continued to 
receive additional doses of MOR00208 without further complications. The six unrelated SAEs 
were two cases of pneumonia, sinusitis, acute otitis media and bacterial infection, all of them of 
grade 3 in severity and one grade 1 rash. With a data cut-off date of 28 March 2013, the most 
common TEAEs were IRRs in 66.7% of patients, diarrhoea, neutropenia, thrombocytopenia 
(29.6% of patients each), anaemia, increased alanine transaminase (ALT), hypoalbuminaemia, 
hypocalcaemia, insomnia and muscle spasms (22.2% of patients each) and increased aspartate 
aminotransferase (AST), headache, hyperglycaemia, pyrexia, rash and upper respiratory tract 
infection (18.5% of patients each). 
 
Twenty seven patients were evaluable for response. Blood disease cleared in the majority of 
patients, with a median reduction in absolute lymphocyte count (ALC) from baseline of 90.8% 
and a decrease in CLL cell count. Based upon physical examination and laboratory studies alone, 
18 patients (66.7%) achieved a PR, while the remaining nine (33.3%) achieved stable disease 
(SD). Using computed tomography (CT) criteria alongside examination and laboratory data, 
eight patients (29.6%) achieved a PR while an additional 16 patients (59.3%) achieved SD. Two 
patients had progressive disease according to CT criteria. 
 
Considering only those 16 patients who received the 12 mg/kg dose, 12 (75%) achieved a PR 
according to physical examination criteria while six (37.5%) achieved a PR according to CT 
criteria. Patients who responded according to physical examination criteria tended to do so 
quickly, with 14 of 18 patients achieving a PR by the first response evaluation (Cycle 2, Day 1). 
Patient responses according to CT criteria were slower, with three of eight patients achieving a 
PR by Cycle 2 (Day 28), three by the 4-week follow-up time point, and two patients in the 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 32 of 110 
expansion cohort by Cycle 5 and Cycle 7, respectively. Across all treatment groups eight (29.6%) 
and sixteen patients (59.3%) had a PR and SD, respectively. In the 12.0 mg/kg treatment group 
only, six (37.5%) and nine of 16 (56.3%) had best responses of PR and SD, respectively. The 
disease control rate was 88.9% (8 PR, 16 SD) across all cohorts, and 93.8% (6 PR, 9 SD) in the 
12 mg/kg cohort. 
 
At evaluation, 12 weeks post-Cycle 2 (Day 28), five patients (18.5%) had progressed according 
to CT criteria and eight (29.6%) according to physical examination criteria. No patient died 
during the observation period. PFS for all patients, including those in the extended treatment 
cohort, was 199 days (95% CI, 168–299) and for patients in the extended treatment cohort alone, 
PFS was 420 days (95% CI, 168–not reached). 
 
The results of the first clinical study showed MOR00208 to have an acceptable safety profile as 
well as providing preliminary evidence of antitumour activity in patients with high-risk, heavily 
pretreated CLL. Although IRRs were common, they were limited to grade 1/2. Since the MTD 
for MOR00208 was not established, due to the occurrence of only one DLT in the 12.0 mg/kg 
dose cohort, this dose of MOR00208 was selected for use in subsequent clinical studies. 
Promising antitumour activity of MOR00208, combined with the absence of safety signal, 
justified movement to phase II. 
 
Protocol MOR208C202 
A Phase IIa, Single-Arm, Open-Label Study of MOR00208, a Humanised Fc-Engineered Anti-
CD19 Antibody, in Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukaemia 
(B-ALL) 
This study is completed (study was terminated prematurely due to slow recruitment after 22 out 
of planned 30 patients were enrolled). For details, please refer to the MOR00208 IB. 
 
1.4.1.2 Ongoing Studies 
The following studies are ongoing and indicate a positive risk-benefit ratio for the patients so 
far. Details of safety and efficacy data will be reported on an ongoing basis in the IB. The studies 
are: 
 
Protocol MOR208C201 
A Phase IIa, Open-Label, Multicentre Study of Single-Agent MOR00208, an Fc-Optimised Anti-
CD19 Antibody, in Patients with Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma. 
 
Protocol OSU-13031 
A Phase II Study of MOR00208 in combination with LEN for Patients with Relapsed or 
Refractory Chronic Lymphocytic Leukaemia (CLL)/Small Lymphocytic Lymphoma 
(SLL)/Prolymphocytic Leukaemia (PLL) or Patients with untreated CLL/SLL/PLL Investigator 
Initiated Trial (IIT). 
 
Protocol MOR208C204 
A Phase II/III, Randomised, Multicentre Study of MOR00208 with Bendamustine versus 
Rituximab with Bendamustine in Patients with Relapsed or Refractory Diffuse Large B-Cell 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 33 of 110 
Lymphoma (R-R DLBCL) Who Are Not Eligible for High-Dose Chemotherapy (HDC) and 
Autologous Stem-Cell Transplantation (ASCT). 
 
Protocol MOR208C205 
A Phase II, Two-Cohort, Open-Label, Multicenter Study to Evaluate the Safety and Preliminary 
Efficacy of MOR00208 Combined with Idelalisib or Venetoclax in Patients with Relapsed or 
Refractory CLL/SLL Previously Treated with Bruton’s Tyrosine Kinase (BTK) Inhibitor. 
 
 Safety of MOR00208  
MOR00208 has a novel mechanism of action that may have the potential to add to the care of 
patients with NHL. Based on the available data from the completed clinical study of MOR00208 
(Protocol XmAb®5574-01), the preliminary data from the ongoing MOR208C201 clinical study, 
nonclinical studies and experiments, and literature data on CD19, the sponsor is of the opinion 
that the potential benefit of MOR00208 outweighs the potential risks. It is expected that the 
potential risks will be adequately controlled by the design of this study (e.g., by the inclusion 
and exclusion criteria) and by frequent monitoring of potential adverse drug reactions throughout 
the entire study. Based on the results of the phase I clinical study of MOR00208 in patients with 
CLL/SLL (Woyach et al., 2014), and the preliminary results of the MOR208C201 and 
MOR208202 studies, the anticipated possible risks associated with administration of MOR00208 
to patients include the following AEs (incidence > 4%) with a suspected relationship to 
MOR00208 treatment: 
 IRRs (mostly Grade ½) 
 Febrile neutropenia 
 Neutropenia 
 Thrombocytopenia 
 Tumour lysis syndrome 
 Upper respiratory tract infections 
 Fatigue 
 Chills 
 Pyrexia 
 Nausea 
 Diarrhoea 
 Headache 
 Rash 
 Aspartate aminotransferase (AST) and alanine transaminase (ALT) increases. 
 
Since a major pharmacological effect of MOR00208 is B-cell depletion, the risks associated with 
the use of approved B-cell depleting therapeutics based on the labelling of other agents with 
similar effects should be considered. The anticipated possible risks include: B-cell depletion, 
ALC reduction, IRRs, TLS, neutropenia/thrombocytopenia, hepatitis B reactivation, progressive 
multifocal leukoencephalopathy, mucocutaneous reactions and infections. 
 
The possible risks associated with the administration of MOR00208 are described in detail in the 
MOR00208 IB. 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 34 of 110 
2 STUDY PURPOSE/RATIONALE 
Despite recent improvements in the management of DLBCL, approximately 30–40% of patients 
with DLBCL treated with R-CHOP relapse following initial immunochemotherapy (Coiffier et 
al., 2002; Feugier et al., 2005; Sehn et al., 2005; Habermann et al., 2006; Pfreundschuh et al., 
2006). Although a significant number of patients with R-R aggressive NHL can be salvaged with 
HDC and subsequent ASCT, the majority will succumb to the disease. Thus, the development of 
a more effective initial therapy in aggressive NHL is essential to improve long-term outcomes. 
 
LEN has been shown to have significant activity in relapsed aggressive B-cell NHL either alone 
or in combination with immunochemotherapeutic regimens. The mechanism of action of LEN is 
complex and involves 
immune modulation, 
antiangiogenesis, modulation of the 
microenvironment and direct antitumour activity (Hasslet et al., 2003; Zhang et al., 2005). 
 
As stated previously, the effects of MOR00208 appear to involve ADCC, ADCP, and direct 
cytotoxic activity (apoptosis). The B-lymphocyte lineage-specific surface antigen CD19 is the 
earliest and most broadly expressed of the selective B-cell markers, and is highly expressed on 
the malignant cells of most patients with B-cell NHL. As a consequence, it can be envisaged that 
a CD19 antibody may have clinical utility as a new therapeutic approach for the treatment of 
patients with B-cell malignancies. This hypothesis is supported by the preliminary results of 
ongoing clinical studies involving various CD19-targeting mAbs (Topp el al., 2012; Raufi et al., 
2013; Goswami et al., 2012) and the approval of blinatumomab for the treatment of patients with 
Philadelphia chromosome-negative, R-R B-cell ALL. 
 
As RTX-based regimens have become standard first-line treatment in DLBCL, the efficacy of 
RTX combined with chemotherapy in the second-line setting has decreased and there is a need 
for new therapies in patients progressing or relapsing after first- or second-line RTX-based 
treatment. It is anticipated that by using MOR00208 instead of RTX, it might be possible to 
partially overcome the RTX resistance in R-R NHL, improving ORRs and OS. Data from a phase 
I study in patients with R-R CLL/SLL (Woyach et al., 2014) and an ongoing phase IIa study in 
patients with R-R B-cell NHL previously treated with RTX demonstrate that MOR00208 is well-
tolerated, with a potential clinical benefit in patients with R-R DLBCL (Blum et al., 2014). 
 
MOR00208 and LEN, both as single agents and in combination show antileukaemic and 
antilymphoma activity in vivo and in vitro. The pattern of AEs is different. Recent data 
demonstrate that the modulation of immunoeffector cells by LEN enhances the NK-mediated 
ADCC exerted by MOR00208, increasing cancer cell killing compared with that seen with the 
single drugs (Awan et al., 2010). It seems justified to assume that this effect may be especially 
evident during chronic administration of LEN. 
 
Since the MTD for MOR00208 was not established during the course of the previous studies the 
12.0 mg/kg dose of MOR00208 was selected for use in subsequent clinical studies. 
 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 35 of 110 
The LEN starting dose is primarily based on a review of published data and the recommendations 
of expert clinicians. The published studies indicate a consistent, manageable and comparable 
(between studies) toxicity profile for patients with DLBCL beginning treatment with LEN, 25 
mg daily (Wiernik et al., 2008; Witzig et al., 2011), or a combination of 20–25 mg LEN with 
RTX (Zinzani et al., 2011; Wang et al., 2013; Ivanov et al., 2014) or R-CHOP (Nowakowski et 
al., 2011; Nowakowski et al., 2015; Vitolo et al., 2013). In the light of the available evidence, 
expert clinicians who were consulted thought an efficacious dose of LEN to be in the range of 
20–25 mg in patients with R-R DLBCL. 
 
As a result, MorphoSys designed MOR208C203 as an open-label, single-arm prospective phase 
II study investigating the safety, antitumour activity and preliminary efficacy of LEN in 
combination with MOR00208 in adult patients with R-R DLBCL who are not candidates for 
ASCT. The study will consist of two parts, which will be performed sequentially. The first part 
of the study (safety run-in) will conclude with an evaluation of safety data. The outcome of this 
evaluation will provide a recommendation for the LEN starting dose to be used in the following 
part of the study. The starting dose is 25 mg LEN daily on Days 1–21 of each 28-day cycle 
followed by a step-wise dose de-escalation if not tolerated. 
 
In this study, several correlative analyses may be conducted; for example, biomarkers that could 
be predictive of response to this therapeutic combination may be assessed. These markers may 
be genetic in nature, cellular, or protein-based and a range of laboratory methodologies may be 
used for their evaluation and possible quantitation. When relevant, the markers can be evaluated 
in the context of PK and clinical response analyses. 
 
 
3 STUDY OBJECTIVES 
 
3.1 Primary Objective 
To determine the activity of a combination of LEN with MOR00208 in terms of objective 
response rate (ORR = CR + PR) in adult patients with R-R DLBCL. 
 
3.2 Secondary Objectives 
1. To determine the disease control rate (DCR = CR + PR + SD) 
2. To determine the duration of response (DoR) 
3. To determine the activity of a combination of LEN with MOR00208 in terms of 
progression-free survival (PFS) 
4. To determine the overall survival (OS) 
5. To determine time to progression (TTP) 
6. To determine the time to next treatment (TTNT) 
7. To determine the safety of LEN combined with MOR00208 assessed according to 
the frequency and severity of adverse events (AEs) 
8. To assess the potential immunogenicity of MOR00208 
9. To assess the PK of MOR00208 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Page 36 of 110 
10. To make a preliminary evaluation of ORR, DCR, DoR, PFS, OS, TTP and TTNT in 
patients treated with a combination of LEN plus MOR00208 in cohorts with a “low 
risk”, “low-intermediate”, “high-intermediate” and “high” International Prognostic 
Index (IPI) (see Appendix B) 
11. To compare each patient’s TTP on LEN plus MOR00208 with the TTP of their most 
recent prior therapy 
12. To correlate efficacy parameters with certain biomarkers (e.g., baseline tumour CD19 
expression level, peripheral NK cell count, constitutional FcγRIIIa and FcγRIIa 
polymorphism status). 
 
 
4 STUDY ENDPOINTS 
 
4.1 Primary Endpoint: 
1. ORR, defined as the proportion of complete and partial responders (ORR = CR + 
PR). 
 
4.2 Secondary Endpoints: 
2. DCR, defined as the proportion of patients having CR or PR or stable disease (SD) 
(DCR = ORR + SD); DoR, defined as the time between the initial time point of 
tumour response and the first time point where a change in response is detailed 
(specifically, the duration of CRs or PRs until progression or relapse will be 
evaluated); PFS, defined as the time between first IMP dosing and tumour 
progression or death from any cause, whichever occurs first; TTP, defined as the time 
from first IMP dosing until time of progression (the only events of interest are limited 
to disease progression and death from lymphoma - death from other causes will not 
be considered in relation to the TTP evaluation); OS, defined as time from first IMP 
dosing to the date of death; time to next treatment (TTNT) 
3. Incidence and severity of AEs 
4. Determination and characterisation of a potential anti-MOR00208 antibody 
formation 
5. PK analysis of MOR00208 
6. Absolute and percentage change from baseline in measurements of B-, T- and NK 
cell populations  
7. Analysis of exploratory and diagnostic biomarkers from blood and tumour tissue 
(e.g., CD19, CD20, BCL-2, and BCL-6 expression, CD16 expression on NK cells, 
ADCC capacity), gene expression profiling for cell of origin subtyping and evaluation 
of AEs and ORR stratified by FcγRIIIa and FcγRIIa polymorphism, are planned to 
be investigated during the course of the study. 
 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 37 of 110 
5 INVESTIGATIONAL PLAN 
 
5.1 Study Design 
 Protocol-specific definitions 
For the purposes of this protocol, primary refractory disease is defined as a disease progressing 
in the course of the first line treatment as per International Working Group response criteria 
(Cheson et al., 2007), and / or, showing a response of less than a PR to first-line treatment or 
disease recurrence/progression within < 6 months from the completion of first-line therapy. 
 
Disease refractory to last treatment is defined as having had less than a partial response to the 
most recently administered systemic therapy. 
 
Relapsed/progressive/recurrent disease reflects the appearance of any new lesions or increase 
by ≥50% of previously involved sites from nadir according to the International Working Group 
response criteria (Cheson et al., 2007) after the most recent systemic therapy. 
 
 Description of study design 
This is a single-arm, multicentre, open-label phase II, study of LEN combined with MOR00208 
in adult patients with DLBCL who have relapsed after or are refractory to at least one, but no 
more than three previous systemic regimens administered for the treatment of their DLBCL and 
who are not candidates for HDC and subsequent ASCT and are thus considered to have 
exhausted their therapeutic options for demonstrable clinical benefit. One prior therapy line must 
include an anti-CD20 targeted therapy (e.g., RTX). 
 
Patients with primary refractory DLBCL or, patients with known "double/triple hit" DLBCL 
genetics or those who have undergone previous allogenic stem cell transplantation are not 
eligible for study participation. Additionally patients with a history of ASCT ≤3 months prior to 
the requirement to provide signed informed consent cannot be included in the study. 
 
This study will consist of two parts, which will be performed sequentially. During the course of 
the first part, six patients will be enrolled in the study and will complete the first cycle of study 
treatment. Once the sixth patient in the cohort has completed Cycle 1 Day 22 visit, a Safety 
Review Panel which consists of the sponsor, a representative of the participating investigators 
and two independent expert clinical haematologist will perform a clinical safety review based on 
the number and type of AEs occurring during the first cycle and on laboratory values 
(biochemistry and haematology). A LEN dose will be considered tolerated or in need of 
reduction after discussion of these data between the sponsor’s Clinical Program Leader (or 
designee), the sponsor’s Drug Safety Officer (or designee), a representative of the participating 
investigators and two expert clinical haematologists who are not participating in the study. The 
second part of the study will only be opened for enrolment by the sponsor following the outcome 
of this discussion. 
 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 38 of 110 
Treatment consisting of LEN and MOR00208 combination will be administered up to twelve 
28-day cycles (Figure 1) at specified dose levels. 
 
 
Figure 1 Study design 
 
Abbreviations: EOT=end of treatment; FU=follow-up; LEN=lenalidomide; R-R DLBCL=relapsed or refractory diffuse large B-
cell lymphoma; SD=stable disease. 
 
 
MOR00208 dose: 12 mg/kg 
For the first 3 cycles (Cycles 1-3) of the study each cycle will consist of a MOR00208 infusion 
on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally a loading dose will be 
administered on Day 4 of Cycle 1. Thereafter MOR00208 will be administered on a bi-weekly 
(every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle. 
 
MOR00208 can be administered until disease progression, or unacceptable toxicity or 
discontinuation for any other reason, whichever comes first. It is up to the investigator to decide, 
according to the individual risk/benefit ratio, if the patient should continue on MOR00208 in 
spite of disease progression (refer to Section 7.2.3). 
 
LEN: 
Patients will self-administer a starting dose of 25 mg oral LEN daily on Days 1–21 of each cycle. 
Treatment with LEN may be modified in a de-escalating fashion or discontinued based upon 
clinical and laboratory findings. Detailed dose modification guidelines to manage haematologic 
and/or other toxicities are provided in the respective sections of the protocol. 
 
LEN can be given for up to 12 cycles in total. 
 
Treatment with LEN will have to be stopped in case of disease progression, or unacceptable 
toxicity, or discontinuation for any other reason, whichever comes first. 
 
Objective disease response assessments will be made according to the revised response criteria 
based on the guidelines of the International Working Group (IWG) reported by Cheson et al. 
(2007). The data used for the primary statistical analyses will be derived from a central 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 39 of 110 
independent review of the radiological + clinical disease assessments. A charter outlining the 
central imaging plus clinical assessment will be prepared. 
 
Approximately 80 patients with R-R DLBCL who meet the inclusion criteria and have none of 
the exclusion criteria will be enrolled in the study. This study will be conducted under a United 
States (US) Food and Drug Administration (FDA) Investigational New Drug (IND) application. 
 
5.2 Safety Run-in 
As the combination of MOR00208 with LEN has not previously been evaluated in a clinical 
study, an evaluation of safety data will occur after the first 6 patients have been accrued at the 
starting dose level of 25 mg LEN daily and 12 mg/kg MOR00208 Days 1, 8, 15 and 22 with an 
additional loading dose on Day 4 of Cycle 1. 
 
To enable the assessment of individual safety parameters by the investigators these patients will 
be enrolled sequentially with a 48 hours lag period between enrolment (same as start of treatment 
with study drugs, or Cycle 1 Day 1 Visit) of two consecutive patients. Accrual will be held until 
all patients have been followed for one treatment cycle. Once the sixth patient in the cohort has 
completed the Cycle 1 Day 22 visit, an evaluation based on the number and type of AEs occurring 
during the first cycle and laboratory values (biochemistry and haematology) will be performed 
by the sponsor’s Clinical Program Leader (or designee), the sponsor’s Drug Safety Officer (or 
designee), a representative of the participating investigators, and two expert clinical 
haematologists who are not participating in the study. The second part of the study will only be 
opened for enrolment by the sponsor following the outcome of this discussion. 
 
The outcome of this safety run-in evaluation will provide a recommendation on the starting dose 
of LEN to be used in the following part of the study. Patients involved in the safety run-in will 
continue the study as per protocol. 
 
5.3 Study Duration 
 Study Conduct 
The study duration per patient will be at least 5 years including periods of screening (up to 28 
days from signature of the Informed Consent Form (ICF), the treatment period (maximum 12 
cycles for LEN + MOR00208 followed by MOR00208 monotherapy thereafter) and the survival 
follow-up phase. MOR00208 can be administered until disease progression as described in 
Section 5.1.2.  
 
The survival follow-up phase begins with the End of Treatment (EOT) Visit (Section 7.2.2). 
Patients will have an on-site safety evaluation visit 30-days after last administration of study 
treatment (LEN + MOR208 combination or either LEN or MOR208 if one of these two drugs 
was discontinued earlier) (30-Day Follow-up Visit). All patients discontinued for any reason 
other than withdrawal of consent, or death, will be contacted every 90 days by phone from the 
date of the 30-Day (Safety) Follow-up Visit until end of study, or until withdrawal of consent, 
or death, whichever comes first. 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 40 of 110 
 End of Study 
The end of the study is defined as the date of the last visit of the last patient completing 5 years 
study duration.  If any patient is on treatment at the end of the study and MOR00208 is not yet 
commercially available, patients will be switched to alternative methods of supply with 
MOR00208, upon assessment of a clinical benefit of continued treatment by the investigator, 
and in accordance with the local regulatory guidance. Upon study closure, MorphoSys will notify 
the applicable regulatory agencies in accordance with local requirements. 
 
 
 
5.4 Patient Selection Criteria 
 Inclusion Criteria 
Patients must satisfy the following criteria to be enrolled in the study: 
 
Diagnosis/Study Population 
1. Age > 18 years 
2. Histologically confirmed diagnosis of DLBCL not otherwise specified (NOS); 
T cell/histiocyte rich large B-cell lymphoma (THRLBCL); Epstein-Barr virus (EBV) 
positive DLBCL of the elderly (EBV-positive DLBCL), Grade 3b Follicular 
Lymphoma, Composite lymphoma with a DLBCL component with a subsequent 
DLBCL relapse, according to the Revised European American Lymphoma/World 
Health Organization (REAL/WHO) classification. Additionally, patients with the 
evidence of histological transformation to DLBCL from an earlier diagnosis of low 
grade lymphoma (i.e., an indolent pathology such as follicular lymphoma, marginal 
zone lymphoma, chronic lymphocytic leukaemia) into DLBCL with a subsequent 
DLBCL relapse are also eligible.  
3. Fresh tumour tissue for central pathology review and correlative studies must be 
provided as an adjunct to participation in this study. Should it not be possible to obtain 
a fresh tumour tissue sample from the patient, archival paraffin embedded tumour 
tissue acquired ≤3 years prior to screening for this protocol must be available for this 
purpose.  
4. Patients must have: 
a) relapsed and/or refractory disease as defined in the protocol (Section 5.1) 
b) at least one bidimensionally measurable disease site. The lesion must have a 
greatest transverse diameter of ≥1.5 cm and greatest perpendicular diameter of 
≥1.0 cm at baseline. The lesion must be positive on PET scan (for definition see 
Juweid et al., 2007) 
c) received at least one, but no more than three previous systemic regimens for the 
treatment of DLBCL and one therapy line must have included a CD20-targeted 
therapy (e.g., RTX) 
d) an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 
5. Patients not considered in the opinion of the investigator eligible or patients unwilling 
to undergo intensive salvage therapy including ASCT because of, but not limited to, 
advanced age, co-morbidities, impossibility or, refusal to perform ASCT. 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Documentation of the reason for a patient’s ineligibility must be provided in the 
patient’s source data. 
 
Laboratory Values 
6. Patients must meet the following laboratory criteria at screening: 
a) absolute neutrophil count (ANC) ≥1.5 × 109/L (unless secondary to bone marrow 
involvement by DLBCL as demonstrated by recent bone marrow aspiration and 
bone marrow biopsy) 
b) platelet count ≥90 × 109/L (unless secondary to bone marrow involvement by 
DLBCL as demonstrated by recent bone marrow aspiration and bone marrow 
biopsy) 
c) total serum bilirubin ≤2.5 × upper limit of normal (ULN) unless secondary to 
Gilbert’s syndrome or documented liver involvement by lymphoma. Patients 
with Gilbert’s syndrome or with documented liver involvement by lymphoma 
may be included if their total bilirubin is ≤5 × ULN (see exclusion criterion 5 g) 
d) ALT, AST and alkaline phosphatase (AP) ≤3 × ULN or <5 × ULN in cases of 
documented liver involvement 
e) serum creatinine clearance must be ≥60 mL/minute either measured or 
calculated using a standard Cockcroft and Gault formula (Cockroft and Gault, 
1976; see Appendix A) 
General Provisions 
7. Females of childbearing potential (FCBP) must:  
a) not be pregnant as confirmed by a negative serum pregnancy test at screening 
and a medically supervised urine pregnancy test prior to starting study therapy 
b) refrain from breastfeeding and donating blood or oocytes during the course of 
the study and for 3 months after the last dose of study medication. Restrictions 
concerning blood donation apply as well to females who are not of childbearing 
potential 
c) agree to ongoing pregnancy testing during the course of the study, and after end 
of study therapy. This applies even if the patients practice complete and 
continued sexual abstinence 
d) commit to continued abstinence from heterosexual intercourse if it is in 
accordance with her lifestyle (which must be reviewed on a monthly basis) or 
agree to use and be able to comply with the use of effective contraception 
without interruption during the study and for 3 months after the last dose of study 
medication 
8. Males must use an effective barrier method of contraception without interruption, 
refrain from donating blood or sperm during the study participation and for 3 months 
after the last dose of study medication if the patient is sexually active with a FCBP 
9. In the opinion of the investigator the patients must: 
a) be able and willing to receive adequate prophylaxis and/or therapy for 
thromboembolic events  
b) be able to understand, give written informed consent and comply with all study-
related procedures, medication use, and evaluations  


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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c) not have a history of noncompliance in relation to medical regimens or be 
considered potentially unreliable and/or uncooperative 
d) be able to understand the reason for complying with the special conditions of the 
pregnancy prevention risk management plan and give written acknowledgement 
of this. 
 
 Exclusion Criteria 
Exclusionary Diagnosis 
1. Patients who have: 
a) any other histological type of lymphoma including primary mediastinal (thymic) 
large B-cell (PMBL) or Burkitt lymphoma 
b) primary refractory DLBCL (see Section 5.1.1 for definitions) 
c) a history of "double/triple hit" genetics DLBCL characterised by simultaneous 
detection of MYC with BCL-2 and/or BCL-6 translocation(s) defined by 
fluorescence in situ hybridisation. MYC, BCL-2, BCL-6 testing prior to study 
enrolment is not required 
 
Exclusionary Previous and Current Treatment 
2. Patients who have, within the 14 days prior to Day 1 dosing: 
a) not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, 
investigational anticancer therapy or other lymphomaspecific- therapy 
b) undergone major surgery or suffered from significant traumatic injury 
c) received live vaccines (see Section 6.7 for details)  
d) required parenteral antimicrobial therapy for active, intercurrent infections  
3. Patients who: 
a) have, in the opinion of the investigator, not recovered sufficiently from the 
adverse toxic effects of prior therapies  
b) were previously treated with CD19-targeted therapy or IMiDs® (e.g., 
thalidomide, LEN) 
c) have a history of hypersensitivity to compounds of similar biological or chemical 
composition to MOR00208, IMiDs® and/or the excipients contained in the study 
drug formulations 
d) have undergone ASCT within the period ≤3 months prior to the signing of the 
informed consent form. Patients who have a more distant history of ASCT must 
exhibit full haematological recovery before enrolment into the study 
e) have undergone previous allogenic stem cell transplantation 
f) have 
a 
history 
of 
deep 
venous 
thrombosis/embolism, 
threatening 
thromboembolism or known thrombophilia or are at a high risk for a 
thromboembolic event in the opinion of the investigator and who are not 
willing/able to take venous thromboembolic event prophylaxis during the entire 
treatment period  
g) concurrently use other anticancer or experimental treatments 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Exclusionary Patient’s Medical History 
4. Prior history of malignancies other than DLBCL, unless the patient has been free of 
the disease for ≥5 years prior to screening. Exceptions to the ≥5 year time limit 
include history of the following: 
a) basal cell carcinoma of the skin 
b) squamous cell carcinoma of the skin 
c) carcinoma in situ of the cervix 
d) carcinoma in situ of the breast 
e) carcinoma in situ of the bladder 
f) incidental histological finding of prostate cancer (Tumour/Node/Metastasis 
[TNM] stage of T1a or T1b) 
5. Patients with: 
a) positive hepatitis B and/or C serology (see Section 7.2.13.2 for details) 
b) known seropositivity for or history of active viral infection with human 
immunodeficiency virus (HIV) 
c) CNS lymphoma involvement – present or past medical history 
d) history or evidence of clinically significant cardiovascular, CNS and/or other 
systemic disease that would in the investigator’s opinion preclude participation 
in the study or compromise the patient’s ability to give informed consent 
e) history or evidence of rare hereditary problems of galactose intolerance, the 
Lapp lactase deficiency or glucose-galactose malabsorption 
f) gastrointestinal abnormalities including the inability to take oral medication, 
requiring intravenous alimentation, or prior surgical procedure affecting 
absorption 
g) history or evidence of severe hepatic impairment (total serum bilirubin 
> 3mg/dL), jaundice unless secondary to Gilbert’s syndrome or documented 
liver involvement by lymphoma (see inclusion criterion 6c) 
 
 
 Definition of Female of Childbearing Potential 
A sexually mature female patient or a sexually mature female partner of a male patient is 
considered to have childbearing potential unless she meets at least one of the following criteria: 
1. Age at least 50 years and naturally amenorrhoeic for at least 24 months (i.e. has not 
had menses at any time in the preceding 24 consecutive months). Amenorrhoea 
following cancer therapy or during lactation does not rule out childbearing potential 
2. Premature ovarian failure confirmed by a gynaecologist 
3. Previous bilateral salpingo-oophorectomy, or hysterectomy 
4. XY genotype, Turner syndrome, uterine agenesis. 
 
5.5 Re-screening Procedures 
Patients can be re-screened at the discretion of the investigator under certain circumstances. Re-
screening is restricted to one attempt per patient and can only be performed if one of the 
following criteria is met: 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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 the patient has already consented and met all of the inclusion and none of the exclusion 
criteria and his or her enrolment was delayed due to an unexpected change in the patient’s 
personal situation (e.g., family issues) 
 the patient previously failed to be eligible due to any event (e.g., planned surgery, 
laboratory test result) that has been resolved 
 the patient previously failed screening but has become eligible for the study based on a 
change in the inclusion and exclusion criteria as the result of a protocol amendment. 
 the patient failed screening due to non-progressed / non-relapsed disease at the time of 
screening and is later clinically diagnosed as having progressed / relapsed. 
 
A patient should only be rescreened if there is a clear indication that the patient may be eligible 
according to the currently valid study protocol. 
 
In cases where previous screening activities were discontinued and enrolment did not occur, the 
following procedures should be implemented: 
 the patient must sign and date a new informed consent form (ICF) as part of the 
re-screening procedure 
 the eligible patient will receive a new unique identification number via the interactive 
response technology 
 a new electronic case report form (eCRF) should be completed 
 the patient will be documented as rescreened in the source documents 
 all screening procedures must be completed again. 
 
A rescreened patient can be enrolled, if all of the current inclusion criteria are met and none of 
the exclusion criteria are met. 
 
6 STUDY TREATMENTS AND CONCOMITANT DRUGS 
Each investigator is responsible for ensuring that deliveries of study drugs and other study 
materials from the sponsor and other drugs from the appropriate suppliers are correctly received, 
recorded, handled and stored safely and properly in accordance with all applicable regulatory 
guidelines, and used in accordance with this protocol. The investigator can delegate these tasks 
to another person (according to the local laws and regulations). Drug accountability forms will 
be kept by each site participating in the study and will be checked during monitoring visits. 
 
Study drug must be handled and/or prepared as described in the Drug Preparation Manual, the 
IB for MOR00208, and other safety-relevant documents (e.g., Summary of Product 
Characteristics (SPC) for the European Medicines Agency [EMA] or the Prescribing Information 
[US FDA] for LEN) (see Appendix_C). 
 
6.1 MOR00208 
MOR00208 will be centrally supplied. MOR00208 drug product (DP) must be stored under 
refrigeration at 2° C to 8° C in its original package in an appropriate storage facility accessible 
only to the pharmacist(s), the investigator, or a duly designated person. 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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MOR00208 DP is a yellowish lyophilisate supplied in single-use 20 mL glass vials. Each vial 
contains 200 mg of MOR00208 for reconstitution with 5 mL water for injection (WFI). 
Reconstitution yields 40 mg/mL MOR00208 in 25 mM sodium citrate, 200 mM trehalose and 
0.02% (w/v) polysorbate 20 at pH 6.0. Each product vial is intended to deliver 200 mg of 
MOR00208 in 5 ml of reconstituted solution. The solution after reconstitution is colourless to 
slightly yellow and essentially free of foreign particles; it may contain a few white to whitish 
product-related particles. 
 
For administration, MOR00208 will be diluted into a commercially available 250 mL infusion 
container with 0.9% (w/v) sodium chloride for injection. 
 
MOR00208 will be administered IV at a dose of 12.0 mg/kg.  
 
For the first 3 cycles (Cycles 1-3) of the study, each cycle will consist of a MOR00208 infusion 
on Day 1, Day 8, Day 15 and Day 22 of the cycle. Additionally a loading dose will be 
administered on Day 4 of Cycle 1. Thereafter MOR00208 will be administered on a bi-weekly 
(every 14 days) basis with infusions on Days 1 and 15 of each 28-day cycle. 
 
 
The individual MOR00208 infusion will be prepared under aseptic conditions and administered 
at the study site, according to the directions of the sponsor, which will be provided in a Drug 
Preparation Manual. In general, a vial of MOR00208 must be used as soon as possible after 
reconstitution with WFI. After dilution for infusion, administration of MOR00208 should take 
place as soon as possible. Maximum allowed storage times and conditions will be detailed in the 
Drug Preparation Manual. 
 
The preferred procedure for destruction is for all IMPs (including used, partially used, not 
expired unused and expired unused vials, blisters, boxes or bottles) to be returned to the Drug 
Depot for destruction. 
 
In case the site is requesting formal approval for destruction of the IMP on site due to local 
requirements, the local destruction requirements for IMPs described in detail in the Drug 
Preparation Manual must be fulfilled. 
 
For the first infusion, the IV infusion rate should be 70 mL/h for the first 30 minutes and 
subsequently increased to a rate of 125 mL/h; the total infusion duration should ideally not 
exceed 2.5 hours. All subsequent MOR00208 infusions will be administered IV at a constant rate 
of 125 mL/h over a 2-hour period. MOR00208 should NOT be administered as an IV push or 
bolus. 
 
The infusion rate escalation schedules in this protocol and the Drug Preparation Manual are 
recommendations only. If required, the investigator should use clinical judgement to optimise 
patient safety by administering the infusion more slowly. 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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6.2 Lenalidomide (LEN) 
Patients will self-administer a starting dose of 25 mg oral LEN daily on Days 1–21 of each cycle. 
Treatment with LEN may be modified in a de-escalating fashion or discontinued based upon 
clinical and laboratory findings. Detailed dose modification guidelines to manage 
haematological and/or other toxicities are provided in the respective sections of the protocol. 
 
LEN will be obtained from a commercial source as capsules in various dose strengths for oral 
administration as will be outlined in the Drug Preparation Manual. If applicable, LEN will be 
labelled as per local regulations. Investigators must be registered through the Lenalidomide 
programme, as applicable in their countries (e.g., REVLIMID REMS™ programme in the US, 
T-register in Germany). Patients must be counselled on the reproductive risks associated with 
LEN, prior to enrolment and monthly, during therapy.  
 
6.3 Treatment with Study Drugs 
Treatment consisting of LEN and MOR00208 combination will be administered up to twelve 
28-day cycles at specified dose levels as scheduled until disease progression, unacceptable 
toxicity, or discontinuation for any other reason, whichever comes first. 
 
LEN can be given for up to 12 cycles in total. Treatment with LEN will have to be stopped after 
disease progression. On days when both study drugs are given together, LEN should be 
administered prior to MOR00208. 
 
MOR00208 can be administered at the dose and schedule described in Section 6.1 above, until 
disease progression, unacceptable toxicity, or discontinuation for any other reason, whichever 
comes first. 
 
It is up to the investigator to decide according to the individual risk/benefit ratio if the patient 
should further continue on MOR00208 in case of disease progression, after discussion with the 
Sponsor’s Medical Monitor or designee. For patients who will be administered MOR00208 
despite progression of disease / relapse, an Unscheduled Visit including all protocol prescribed 
procedures for the EOT Visit (except the PK sample and the anti-MOR00208 antibody sample) 
need to be performed in order to capture the event (i.e. disease progression/relapse) for the 
antibody treatment to continue further (Table 5). In such cases an EOT Visit will take place after 
these patients have finally stopped receiving the antibody. And lastly, a Safety Follow-Up will 
take place 30-Days after last administration of MOR00208.  
 
For patients receiving antibody treatment despite disease recurrence/progression, before the 
administration of MOR00208, blood parameters (haematology, serum chemistry) should be 
evaluated in the local lab according to local guidelines/standards of local medical practice for 
the administration of monoclonal antibodies. A urine pregnancy test should be performed for 
women of childbearing potential. Vital signs should be measured according to local practice for 
the administration of monoclonal antibodies. For this patient population only the antineoplastic 
therapy after the end of study drug combination treatment and AEs need to be captured in eCRF. 
Other procedures described in the column “MOR00208 Additional Treatment” in Table 5 will 
not apply for this patient population. 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 47 of 110 
 
6.4 Pre-Medication for MOR00208 Infusions 
IRRs have commonly been reported for patients with CLL or NHL treated with MOR00208. 
 
It is suggested that the pre-medication is administered between 30 minutes and 2 hours prior to 
the MOR00208 infusions. 
 
The pre-medication may include the following: 
 antipyretics (e.g., acetaminophen [paracetamol] 1000 mg per dose per mouth [p.o.] or IV 
or equivalent) 
 histamine H1 receptor blockers (e.g., diphenhydramine 25–50 mg per dose IV or 
equivalent) 
 histamine H2 receptor blockers (e.g., cimetidine 300 mg p.o., ranitidine 150 mg tablet 
p.o. or equivalent) 
 glucocorticosteroids (methylprednisolone 80–120 mg per dose IV or equivalent - please 
refer to Appendix_D) 
 meperidine (25 mg per dose p.o. or IV) may be added as required for rigors or chills. 
 
The investigator may repeat doses of individual agents as required and use other agents, doses 
and/or formulations in accordance with institutional guidelines. Equivalence for premedications 
includes variations to the stated dose due to the formulations available locally. Any 
premedication given should be reported in the eCRF. 
 
Premedication for patients who do not experience any IRRs to MOR00208 during the first 
3 infusions (doses) will be optional for subsequent infusions at the discretion of the investigator. 
Otherwise, the premedication should be continued for subsequent administrations. 
 
6.5 Patient Monitoring During MOR00208 Infusion 
Vital signs should be measured as outlined in Section 7.2.8. All supportive measures consistent 
with optimal patient care will be provided throughout the study according to institution 
standards. 
 
Precautions for anaphylaxis should be observed during MOR00208 administration. Emergency 
resuscitation equipment and medications should be readily available. Additional supportive 
measures should also be available and may include, but are not limited to, epinephrine, 
antihistamines, 
corticosteroids, 
IV 
fluids, 
vasopressors, 
oxygen, 
bronchodilators, 
diphenhydramine, and acetaminophen (paracetamol). 
 
6.6 Criteria for Dose Modifications and Drug Discontinuation 
 Management of MOR00208 Infusion-Related Reactions (IRRs) 
IRRs will be defined according to the National Cancer Institute Common Terminology Criteria 
for Adverse Events (NCI-CTCAE), Version 4.0 definition of IRR and cytokine release syndrome 
(Table 1). 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Page 48 of 110 
Table 1 
Definition of Infusion-Related Reaction 
NCI-CTCAE Version 4.0, Selection Criteria: Infusion-Related Reaction and Cytokine 
Release Syndrome 
 
Adverse 
Event 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
IRR 
Mild transient 
reaction; 
infusion 
interruption not 
indicated; 
intervention not 
indicated 
Therapy or infusion 
interruption indicated 
but responds 
promptly to 
symptomatic 
treatment (e.g., 
antihistamines, 
NSAIDS, narcotics, 
IV fluids); 
prophylactic 
medications indicated 
for ≤24 hours 
Prolonged (i.e. not rapidly 
responsive to symptomatic 
medication, brief 
interruption of infusion, or 
both); recurrence of 
symptoms following initial 
improvement; 
hospitalisation indicated 
for clinical sequelae 
Life-
threatening 
consequences; 
urgent 
intervention 
indicated 
Cytokine 
release 
syndrome 
Mild reaction; 
infusion 
interruption not 
indicated; 
intervention not 
indicated 
Therapy or infusion 
interruption indicated 
but responds 
promptly to 
symptomatic 
treatment (e.g., 
antihistamines, 
NSAIDS, narcotics, 
IV fluids); 
prophylactic 
medications indicated 
for ≤24 hours 
Prolonged (i.e. not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms 
following initial 
improvement; 
hospitalisation indicated 
for other clinical sequelae 
(e.g., renal impairment, 
pulmonary infiltrates) 
Life-
threatening; 
consequences; 
pressor or 
ventilatory 
support 
indicated 
 
Abbreviations: IRR=infusion-related reaction; IV=intravenous; NSAIDs=non-steroidal anti-inflammatories. 
Please note: An acute infusion reaction may occur with an agent that causes cytokine release (e.g., monoclonal antibodies or 
other biological agents). Signs and symptoms usually develop during or shortly after drug infusion and generally resolve 
completely within 24 hours of completion of infusion. Signs/symptoms may include: Allergic reaction/hypersensitivity 
(including drug fever); Arthralgia (joint pain); Bronchospasm; Cough; Dizziness; Dyspnoea (shortness of breath); Fatigue 
(asthenia, lethargy, malaise); Headache; Hypertension; Hypotension; Myalgia (muscle pain); Nausea; Pruritis/itching; 
Rash/desquamation; Rigors/chills; Sweating (diaphoresis); Tachycardia; Tumour pain (onset or exacerbation of tumour pain due 
to treatment); Urticaria (hives, welts, wheals); Vomiting 
 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Page 49 of 110 
6.6.1.1 Grade 2 IRRs 
If a patient presents with a grade 2 infusion reaction: 
 the infusion should be stopped immediately 
 the patient should receive appropriate further treatment with an antihistamine and/or 
acetaminophen (paracetamol) or methylprednisolone (or equivalent) if clinically 
indicated 
 once the symptoms have been resolved or reduced to “mild” according to investigator 
assessment, the infusion can be continued at an infusion rate of 50%. If, after one hour, 
the patient’s symptoms do not return and vital signs are stable, the infusion rate may be 
increased every 30 minutes, as tolerated, to the baseline rate. 
 
If a patient who developed a grade 1 or 2 IRR receives further infusions, then premedication 
should be given before all subsequent infusions of MOR00208. 
 
6.6.1.2 Grade 3 IRRs 
If a patient presents with a grade 3 IRR: 
 the infusion should be stopped immediately 
 the patient must receive appropriate treatment with an antihistamine and/or 
acetaminophen (paracetamol) or methylprednisolone (or equivalent) and, if necessary, 
further medications (i.e. epinephrine, bronchodilator) 
 a blood sample for cytokine analysis should be obtained during the event and 
approximately 24 hours later 
 only after the complete resolution of all symptoms (to ≤grade 1), and after having 
received appropriate prophylactic medication(s) as described above, the infusion may be 
resumed at an infusion rate of 25%. If, after 1 hour, the patient’s symptoms do not return 
and vital signs are stable, the infusion rate may be increased to a maximum of 50% 
 if, after the resumption of the infusion, symptoms return (irrespective of grade), the 
infusion must be stopped immediately and the infusion tubing should be disconnected 
from the patient. 
 
Based on the investigator’s decision the patient may receive further MOR00208 provided 
clinically appropriate precautions were undertaken. The patient may continue treatment with 
LEN. 
 
6.6.1.3 Grade 4 IRRs 
If a patient presents with a grade 4 IRR: 
 the infusion should be stopped immediately and the infusion tubing should be 
disconnected from the patient 
 the patient should receive appropriate treatment with an antihistamine and/or 
acetaminophen (paracetamol) or methylprednisolone (or equivalent) and, if necessary, 
further medications (i.e. epinephrine, bronchodilator) 
 a blood sample for cytokine analysis should be obtained during the event and 
approximately 24 hours later. 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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The patient must not receive further MOR00208, but may continue treatment with LEN as per 
protocol. 
 
 Management of Toxicities 
The next cycle of treatment may begin on the scheduled Day 1 if: 
 ANC is ≥1.000/mm3 (unless neutropenia is due to infiltration of bone marrow) 
 Platelets ≥50000/mm3 (unless thrombocytopenia is due to infiltration of bone marrow, 
patient may have received transfusion) and absence of active bleeding 
 No serious organ or other toxicity present. 
 
If, based on medical judgment, the treating physician considers a change in laboratory parameter 
or AE not to be a study drug-related toxicity, but to represent a natural fluctuation in or 
progression of the underlying disease, then it is at the physician’s discretion and assessment of 
the individual risk/benefit ratio to determine whether the patient should be dosed. The decision 
and rationale behind the decision should be documented in the source data. 
 
If the above conditions are not met on Day 1 of a new cycle, the subject will be evaluated once 
every seven days and a new cycle will not initiated until the toxicity has resolved as described 
above. Specific course of action for a given toxicity occurring in the course of the treatment cycle 
is described below. 
 
If treatment needs to be interrupted for ≤28 days for the same study drugs-related toxicity, the 
patient’s treatment should continue, depending on the duration of treatment interruption, at the 
next protocol scheduled visit. No missed visits or doses of either drug should be made up. 
 
If treatment with one study drug needs to be interrupted for >28 days for the same, persistent, 
drug-related toxicity, the study drug judged by the investigator to have caused the toxicity should 
be discontinued and the patient should continue to be dosed with the other study drug, as per 
protocol. 
 
If treatment with both study drugs needs to be interrupted for >28 days for the same persistent 
study drug-related toxicity, judged by the investigator to be related to both study drugs (LEN 
and MOR00208), then the End of Treatment Visit will be performed and the patient will enter 
the follow-up phase (see Section 5.3.1). 
 
6.6.2.1 Haematological and Other Toxicities 
Subjects will be evaluated for AEs at each visit with the NCI CTCAE v4.0 used as a guide for 
grading severity. The dose of study drug(s) for each patient will be interrupted and/or modified 
following toxicity as described below. Refer to Table 2 and Table 3 for instructions on dosing 
interruptions/modifications and Table 4 for LEN dose reduction instructions. 
 
Guidance on managing specific toxicities is summarised in Table 2 and Table 3. 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Table 2 
Haematological and Other Toxicities 
Grade 3/4 thrombocytopenia 
judged to be related to study 
drugs 
PLTs fall to <50000/µl 
Interrupt MOR00208* and LEN 
dosing) 
Follow CBC every 7 days 
PLTs return to ≥50000/µl 
Provided all other criteria are 
fulfilled, resume dosing of 
MOR00208 and/or LEN. LEN 
should be administered at the 
next lower dose level (Table 4) 
Grade 3/4 neutropenia judged to 
be related to study drugs 
ANC falls to <1000/µl for at 
least 7 days  
or ANC falls to <1000/µl with 
an associated body temperature 
≥38.5°C 
or ANC falls to <500/µl 
Interrupt MOR00208* and LEN 
dosing 
Follow CBC every 7 days 
Growth factors (G-CSF) and 
antimicrobial prophylaxis is to 
be used, as per local guidelines 
ANC return to ≥1000/µl 
Provided all other criteria are 
fulfilled, resume dosing of 
MOR00208 and/or LEN. LEN 
should be administered at the 
next lower dose level (Table 4) 
Other clinically significant 
toxicities judged to be related to 
study drugs 
Grade 3/4 
Interrupt the administration of 
the study drug(s)* to which the 
toxicity is judged to be related 
to. 
Toxicities resolve to grade ≤2 
Provided all other criteria are 
fulfilled, resume dosing of study 
drug(s). LEN should be 
administered at the next lower 
dose level (Table 4) 
Abbreviations: ANC=absolute neutrophil count; CBC=complete blood count; G-CSF=granulocyte colony-stimulating factor; 
LEN=lenalidomide; PLT=platelets. 
*If, based on medical judgment, the treating physician considers a laboratory parameter change or AE not to be a study drug-
related toxicity, but to represent a natural fluctuation in or progression of the underlying disease, then it is at the physician’s 
discretion and assessment of the individual risk/benefit ratio to determine whether the patient should be dosed. The decision and 
rationale behind the decision should be documented in the source data.  
 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Table 3 
Other Toxicities Judged to be Related to LEN 
Thromboembolic events  
Grade 3/4 
Interrupt LEN dosing  
Start anticoagulation as per local 
guidelines 
Continue MOR00208 treatment 
as per protocol 
Toxicities resolve to grade ≤2 
Restart LEN at investigator’s 
discretion (maintain dose level) 
Continue MOR00208 treatment 
as per protocol 
Allergic reaction or 
hypersensitivity grade 3/4 
(including but not limited to 
Stevens-Johnson syndrome, 
toxic epidermal necrolysis, 
exfoliative or bullous rash, 
angioedema) 
Grade 3/4 
Discontinue LEN permanently  
Continue MOR00208 treatment 
as per protocol 
Allergic reaction or 
hypersensitivity 
Grade >2 
Interrupt LEN dosing 
Follow at least every 7 days 
Continue MOR00208 treatment 
as per protocol 
Resolved to ≤grade 2 severity or 
at least the baseline value (for 
pre-existing conditions; at 
screening) 
Restart LEN (next lower dose 
level) 
Desquamating (blistering) rash 
≥grade 3 or nondesquamating 
rash grade 4 considered to be 
related to LEN 
 
Discontinue LEN permanently  
Continue MOR00208 treatment 
as per protocol 
Nondesquamating rash  
Grade 3/4 
Interrupt LEN dosing 
Continue treatment with 
MOR00208 as per protocol 
Resolve to grade ≤1  
Restart LEN at next lower dose 
level 
 
Tumour flare reaction 
Grade 3/4 
Interrupt LEN dosing 
Provide symptomatic treatment 
as per local guidelines 
Continue treatment with 
MOR00208 as per protocol 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Resolve to grade ≤1 
Restart LEN (maintain same 
dose level) 
Tumour flare reaction 
Grade 1/2   
Provide symptomatic treatment 
as per local guidelines 
Continue LEN without dose 
modification or interrupt LEN 
dosing at investigator’s 
discretion 
Continue treatment with 
MOR00208 as per protocol 
Abbreviation: LEN=lenalidomide. 
 
 
6.6.2.2  LEN Dose Reduction Guidelines 
General rules 
If LEN dosing was halted during the previous cycle and was restarted with a one-level dose 
reduction without requiring an interruption for the remainder of the cycle, then that reduced dose 
level will be initiated on Day 1 of the new cycle. There will be no more than one dose reduction 
from one cycle to the next. Once a patient’s LEN dose has been reduced, no dose re-escalation 
is permitted. 
 
Specific LEN dose reduction guidelines 
The daily oral dose of LEN may be reduced successively by one level from the starting dose of 
25 mg daily on Days 1–21 every 28 days (Table 4). 
 
Table 4 
LEN Dose Reduction Guidelines 
Starting dose 
25 mg daily on Days 1–21, every 28 days 
Dose Level - 1 
20 mg daily on Days 1–21, every 28 days 
Dose Level - 2 
15 mg daily on Days 1–21, every 28 days 
Dose Level - 3 
10 mg daily on Days 1–21, every 28 days 
Dose Level - 4 
5 mg daily on Days 1–21, every 28 days  
 
Patients who cannot tolerate Dose Level - 4 are to be discontinued from LEN treatment in the 
study but should continue therapy with MOR00208 alone. 
 
Additional information 
The most up-to-date information regarding constitution, dosing and most frequent AEs related 
to the administration of LEN and MOR00208 are contained in the SmPC (EMA), Prescribing 
Information (US FDA) and the current MOR00208 IB, respectively (see Appendix_C). Dose 
reductions for MOR00208 are not allowed during the course of the study. 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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6.6.2.3 Tumour Flare with LEN 
Patients in this study should be monitored for tumour flare (TFR). TFR is defined as a sudden 
and tender increase in the size of the disease bearing sites, including the lymph nodes, spleen 
and/or the liver, often accompanied by low-grade fever, non-pruritic diffuse rash and in some 
cases, an increase in the peripheral blood lymphocyte counts. TFR is an expected toxicity with 
LEN, especially in patients with a high tumour burden and may mimic disease progression. 
Therefore, careful monitoring and evaluation is important prior to discontinuing a study patient 
for progressive disease in the initial cycles of LEN therapy. There are currently no laboratory or 
radiological tests to help distinguish TFR from progressive disease. The distinction should be 
made on clinical grounds, incorporating observations such as associated physical findings, 
laboratory findings, and pace of disease before and after the initiation of treatment. TFR should 
be recorded as an AE of interest (graded using the NCI-CTCAE 4.0 criteria) and not as 
progressive disease. 
 
Treatment of TFR is at the discretion of the investigator and dependent on the severity, clinical 
situation and institutional standards. 
 
6.6.2.4 Tumour Lysis Syndrome 
TLS results from the rapid breakdown of tumour cells and the release of their intracellular 
content into the circulation resulting in metabolic derangements that can lead to acute renal 
failure and other life-threatening complications. The onset of TLS is rapid, usually within 24-48 
hours of receipt of the first dose of anticancer medication, but can also occur after the first week 
of treatment. Bulky disease, moderate renal insufficiency, a high number of circulating 
lymphoma cells and high uric acid levels (>8 mg/dL) prior to therapy, increase the likelihood of 
TLS. Early identification of patients at risk and the prevention of TLS development with the 
initiation of preventive measures as well as the careful monitoring for early signs of laboratory 
assessments consistent with TLS and the prompt initiation of supportive care are critical to the 
prevention of potentially life-threatening metabolic derangements. 
 
Medical prophylaxis and management should be initiated according to the institutional standard 
of care at the investigator’s discretion. 
 
6.6.2.5 Thromboembolism 
LEN increases the risk of thrombotic events in patients who are at high risk of thrombosis. High 
risk is defined, for example, as a history of a thromboembolic event and/or taking a concomitant 
medication associated with an increased risk of a thromboembolic event and/or a known 
hypercoagulable state, regardless of thromboembolic history. It is recommended that patients 
receive adequate anticoagulation therapy according to the institutional standards and 
investigator’s discretion. It should be tailored to the patient’s individual risk/benefit profile by 
taking into account the individual thrombotic and bleeding risk, and the quality of compliance 
with venous thromboembolic event (VTE) prophylaxis. Anticoagulants may include 
acetylsalicylic acid (e.g., aspirin) prophylaxis, low molecular weight heparin, warfarin or new 
oral anticoagulants (NOAKs, e.g., dabigatran, rivaroxaban). 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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6.7 Prior and Concomitant Therapy 
 
Administration and Recording of Prior and Concomitant Therapy – General Instructions 
Any prior, concomitant, or procedural medications or therapy given to or taken by the patient 
within 1 month prior to commencement of the study (30 days prior to signing the ICF) and up to 
the End of Treatment Visit (EOT) must be recorded in the source documents and the eCRF along 
with the indication, route and dosage. Such medications (including over-the-counter 
medications) must be listed on the concomitant medications form in the eCRF. Starting from the 
EOT Visit, only anticancer treatments and, in case of an AE, other relevant concomitant 
medications (at the discretion of the investigator) should be entered. The investigator should 
instruct the patient not to take any additional medications (including over-thecounter--products) 
during the study without prior consultation. 
 
For patients who will be administered MOR208 despite progression of disease / relapse, an 
Unscheduled Visit including all procedures described for EOT Visit need to be performed in 
order to capture the event (i.e. disease progression/relapse) for the antibody treatment to continue 
further. 
 
At the EOT visit (or at the Unscheduled Visit after disease progression / relapse) as described in 
the above paragraph), any antineoplastic therapy after end of study drug treatment must be 
recorded as well. 
 
Patients may receive concomitant medications that are medically indicated as standard care for 
the treatment of symptoms, AEs, and intercurrent illnesses. Medications to treat concomitant 
diseases like diabetes, hypertension, bronchial asthma, chronic obstructive pulmonary disease 
(COPD) etc., are allowed. Patients will also receive therapy to mitigate side effects of the study 
medication as clinically indicated, as well as best supportive care (BSC) as per institutional 
guidelines. This may include, but is not limited to, antiemetics, antidiarrhoeals, anticholinergics, 
antispasmodics, antipyretics, antihistamines, analgesics, antibiotics, and other medications 
intended to treat symptoms. 
 
Recording of Prior Lines of Anti-lymphoma Therapy 
Information should be provided on any previous DLBCLspecific- therapies since the time point 
of the first diagnosis of DLBCL. The generic or the trade name may be recorded. 
To become eligible for the MOR208C203 study the patients must have received at least one, but 
no more than three previous systemic therapy lines for the treatment of DLBCL and at least one 
therapy line must have included a CD20-targeted therapy (e.g., RTX). 
 
Planned consolidation of responding patients, i.e. by radiotherapy or second line regimens with 
or without ASCT is regarded as one therapy line. Changing to a different chemotherapy regimen 
is regarded as a separate line of therapy, unless the change was caused by toxicity of the 
employed regimen. 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Radiotherapy of the involved site (limited field radiotherapy) or radiation pre-planned to occur 
at the conclusion of systemic cytotoxic therapy will not be considered a separate prior line of 
therapy. 
 
The administration of a mAb alone with a curative/therapeutic intent (e.g., RTX monotherapy) 
counts as a separate line of therapy. On the other hand the addition of a mAb to chemotherapy 
or mAb maintenance treatment subsequent to chemotherapy/chemoimmunotherapy regimen is 
considered one treatment therapy line, provided that the mAb was part of the initial treatment 
plan. 
 
As for the ASCT, the induction, consolidation, stem cell collection, preparative regimen 
including transplantation, and maintenance will be considered a single line of therapy. 
 
Growth Factors 
Growth factors may be prescribed during the treatment and follow-up periods at the 
investigator’s discretion, according to institutional standards. Growth factors or platelet 
transfusions should not be administered during the screening period solely for the purpose of 
improving a patient’s blood values in order to meet eligibility criteria. 
 
Infection Prophylaxis and Vaccines 
Live vaccines must not be administered to patients in this study. Killed, inactivated vaccines, 
such as an injectable annual influenza vaccine, are permitted. Investigators should follow 
institutional guidelines concerning infection chemoprophylaxis for patients regarded to be at 
high risk for infection. 
 
Anticancer Therapies 
Patients should not have received a CD20-targeted therapy, chemotherapy, radiotherapy, 
investigational anticancer therapy or other lymphomaspecific- therapy within 14 days prior to 
Cycle 1 day 1 of the study. In addition, no radiotherapy (including limited field radiotherapy) is 
permitted after the baseline PET/CT scan for initial disease assessment has been performed. 
Other than the study drugs, patients should not receive any other DLBCLspecific- therapy during 
the study treatment period. The patient should not receive any investigational agent other than 
MOR00208 and LEN during the treatment period of the study. 
 
The use of concurrent antineoplastic therapies other than study drugs, including, but not limited 
to, chemotherapies, hormonal therapy, immunotherapy, biological response modifiers, mAbs 
with or without conjugation, radioisotopic therapies, stem cell transplant and targeted small 
molecules are not permitted during the entire treatment period (i.e., prior to disease progression 
during this study) of this study. After disease progression has been recorded, additional 
antineoplastic therapies are permitted at the discretion of the investigator and in accordance with 
the local guidelines and should be recorded in the eCRF. 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Systemic Glucocorticosteroids 
The use of systemic glucorticosteroids is generally discouraged because their potential 
antilymphoma activity in patients with DLBCL may confound interpretation of antitumor effects 
mediated by study drug treatment (MOR00208 and LEN). 
 
However systemic corticosteroids in doses up to 20 mg/day prednisone or equivalent (i.e. 
equipotent corticosteroid) are permitted, provided the dosing is stable (not increased within the 
last month), but only for the treatment of non-neoplastic comorbid indications (e.g, rheumatoid 
arthritis). 
 
- Screening: 
Patients may potentially receive systemic glucorticosteroids in doses above 20 mg/day 
(prednisone or equivalent) to manage severe DLBCL manifestations (e.g., compressive disease, 
rapidly progressing symptomatic adenopathy) during Screening as per institutional standards. 
For these patients the glucorticosteroids treatment needs to be tapered to a total daily dosage of 
20 mg or less of prednisone or its equivalent prior to study drug(s) administration on Cycle 1, 
Day 1. 
 
-Cycle 1 through EOT visit: 
Systemic glucocorticosteroids in doses above 20 mg/day (prednisone or equivalent) are not 
allowed during Cycle 1 through EOT visit, with the exceptions of premedication, cytokine 
release syndrome treatment at any time. Additionally, systemic doses above 20 mg/day 
(prednisone or equivalent; please refer to Appendix_D) will be allowed for antiemetic 
prophylaxis for up to 24 hours. 
 
In the event a patient experiences an exacerbation of a chronic non-neoplastic condition such as 
chronic obstructive pulmonary disease (COPD), bronchial asthma or rheumatoid arthritis, peak 
doses above 20 mg/day (prednisone or equivalent) may be allowed for a limited period of time; 
the glucocorticosteroid dosage and the allowable treatment period will be determined by the 
investigator on a case-by-case basis following agreement with the medical monitor of the study. 
The specified systemic glucocorticosteroid use at a daily dose above 20 mg, if short in duration, 
is not likely to confound the treatment effect and efficacy analysis. 
 
Similarly, patients who develop severe or life-threatening conditions that may be alleviated by 
systemic glucocorticosteroid (e.g., adrenal insufficiency) therapy are permitted to receive such 
drugs and are not required to discontinue study participation. 
 
The investigator should aim to discuss the systemic usage of glucocorticosteroids in doses above 
20 mg/day (prednisone or equivalent) with the medical monitor of the study prior to the 
implementation. 
 
Immunosuppressive therapies other than systemic glucocorticosteroids as described are not 
permitted. 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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-Other Provisions on Glucocorticosteroids: 
Single dose, topical, intranasal, inhaled eye drops or local injections (e.g., intra-articular) 
containing corticosteroids are permitted during study participation. 
 
Concomitant Therapies that May Increase the Risk of Thrombosis  
Erythropoietic agents, or other agents that may increase the risk of thrombosis, such as oestrogen 
containing therapies, should be used with caution after making a careful benefit-risk assessment 
in patients receiving lenalidomide. 
 
6.8 Treatment Compliance 
Dosing modifications due to toxicity are described in Section 6.6.2. 
 
Patients will receive MOR00208 under the direct supervision of study personnel. Each 
administration volume or dose will be checked and the vial/outer package code and volume or 
dose per administration will be recorded in each patient’s eCRF as well as in the source data. 
 
A patient will be considered compliant with the protocol if the MOR00208 dose administered is 
≥80% to ≤120% of the assigned dosage per single infusion. 
 
LEN is to be dispensed in 28-day cycles. Patients should return all unused or empty LEN 
bottles/blister packs to the site throughout the treatment period of the study, as instructed by the 
investigator. A patient will be considered compliant with the protocol if the LEN dose 
administered is ≥80% to ≤120% of the assigned dosage during a particular cycle.  
 
Drug accountability will be checked by the field monitor during site visits and at the completion 
of the study. 
 
6.9 Withdrawal from Study Treatment or Study/Site Termination 
  Withdrawal Criteria 
Patients may voluntarily withdraw from the study or be discontinued from it at the discretion of 
the investigator at any time. An excessive rate of withdrawals can render the study 
uninterpretable; therefore, unnecessary withdrawal of subjects should be avoided. 
 
The investigators are encouraged to keep a patient experiencing clinical benefit in the study 
unless significant toxicity puts the patient at risk or repeated cases of routine noncompliance puts 
the study outcomes at risk. 
 
At a minimum, all patients who discontinue study treatment, including those who refuse to return 
for a final visit, will be contacted for safety evaluations at the 30-Day Follow-up Visit. 
 
If such withdrawal occurs, or if the patient fails to return for visits, the investigator must 
determine the primary reason for a patient´s premature withdrawal from the study and record the 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 59 of 110 
information on the eCRF. If the reason for withdrawal is an AE, monitoring should continue 
until the outcome is evident. The specific event or test result(s) must be recorded in the eCRF. 
 
Following events are reasons for discontinuing a patient from the use of investigational 
product(s) and/or from the study: 
 
 Withdrawal of informed consent (subject’s decision to withdraw for any reason) 
 Significant lack of co-operation or non-compliance on the side of the patient 
 Pregnancy or lack of adequate contraception in FCBPs  
 Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, 
in the opinion of the investigator, indicates that continued participation in the study is 
not in the best interest of the subject 
 Unacceptable and unmanageable, in the view of either patient or physician, toxicity 
judged to be related to study drugs 
 Occurrence of new diseases that could influence the treatment efficacy, for which the 
study medications are contraindicated or that are treated with a medication that is not 
permitted as a concomitant medication. 
 Loss of ability to freely provide consent through imprisonment or involuntarily 
incarceration for treatment of either a psychiatric or somatic disease (e.g., infectious 
disease) 
 Death 
 Lost to follow up 
 Major protocol violation (following discussion between the sponsor’s Clinical Program 
Leader, Drug Safety Physician and the Investigators) 
 Administrative reasons 
 Termination of the study by MorphoSys or Regulatory Authorities 
 Reconsideration of the risk/benefit ratio, in consensus with Ethical Committee 
 
Patients who are withdrawn for any reason may not re-enter this clinical study at any time. 
 
 


Product Name: MOR00208 
 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 60 of 110 
 Study or Site Termination 
The investigator and the sponsor both reserve the right to terminate the study at any time at a 
given clinical study centre. The sponsor also reserves the right to terminate the entire study or 
temporarily interrupt enrolment and/or dosing of already enrolled patients for further evaluation, 
for example, if during the ongoing evaluation of the risk/benefit ratio, the sponsor decides that 
the risks outweigh the benefits of MOR00208 and/or LEN. 
 
Should a termination of a given clinical study centre or the whole study become necessary, then 
the procedures will be arranged after review by, and consultation with, all involved parties. In 
terminating a study centre, or the entire study, the sponsor and the investigators will ensure that 
adequate consideration is given to the protection of the patients’ interests. Institutional Review 
Boards (IRBs)/Independent Ethics Committees (IECs) and competent authorities will be notified 
of premature termination in accordance with applicable regulatory requirements. 
 
 
 
7 VISIT ASSESSMENTS AND PROCEDURES 
 
7.1 Visit Schedule 
Table 5 lists all of the assessments, and indicates with an “X” the visits at which these 
assessments are performed. All data obtained from these assessments must be supported in the 
patient´s source documentation.  


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Table 5 
Schedule of Assessments 
Schedule: Screening and Cycles 1–3 
Evaluation or Procedure 
Screening 
Period 
Treatment Period 
Screening 
≤28 Days 
prior to 
D1 
Cycle 1 (28 days) 
Cycle 2 (28 days) 
Cycle 3 (28 days) 
Day 
Screen 
D1 
D4 
D8 
±1 day 
D15 
±1 day 
D22 
±1 day 
D1 
±1 day 
D8 
±1 day 
D15 
±1 day 
D22 
±1 day 
D1 
±1 day 
D8 
±1 day 
D15 
±1 day 
D22 
±1 day 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X1 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease staging/Ann Arbor 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease risk assessment (IPI) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous/concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Full physical examination 
(Limited physical examination - 
L) 
X 
L 
 
 
 
 
 
 
 
 
L 
 
 
 
ECOG performance status 
X 
X1 
 
 
 
 
X 
 
 
 
X 
 
 
 
Body weight/height2  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
B-symptoms 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead resting ECG 
X 
X3 
 
 
X3 
 
X3 
 
 
 
X3 
 
 
 
Urinalysis 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
Pregnancy test (FCBP)4 
X 
X1 
 
X1 
X1 
X1 
X1 
 
 
 
X1 
 
 
 
Pregnancy and risks counselling 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
“Emergency laboratory”5 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Central laboratory blood 
sampling 1 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
Serology Hepatitis B  
X16 
 
 
 
 
 
X16 
 
 
 
X16 
 
 
 
Serology Hepatitis C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
B-, T- and NK cell flow 
cytometry (blood)1 
 
X 
 
X 
 
X 
X 
 
 
 
 
 
 
 
Anti-MOR00208 antibodies 
 
X1 
 
 
 
 
 
 
 
 
X1 
 
 
 
Optional FcγR polymorphism 
(mucosal cheek swab) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
ADCC and CD16 assessment 
(blood) 
 
X1 
 
 
 
 
 
 
 
 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Evaluation or Procedure 
Screening 
Period 
Treatment Period 
Screening 
≤28 Days 
prior to 
D1 
Cycle 1 (28 days) 
Cycle 2 (28 days) 
Cycle 3 (28 days) 
Day 
Screen 
D1 
D4 
D8 
±1 day 
D15 
±1 day 
D22 
±1 day 
D1 
±1 day 
D8 
±1 day 
D15 
±1 day 
D22 
±1 day 
D1 
±1 day 
D8 
±1 day 
D15 
±1 day 
D22 
±1 day 
Disease and disease response 
assessment (CT/PET or 
PET/MRI) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT or MRI scan for tumour 
measurement and disease 
assessment (local) 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Central pathology review and 
correlative studies involving 
tissue samples 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bone marrow aspiration & 
biopsy 
X 
 
 
 
 
 
 
 
 
 
 
 
X7 
 
MOR00208 administration 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
LEN tablets allocation 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
(S)AE assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK MOR00208 
 
X6 
X6 
 
X6 
 
X6 
 
X6 
 
X6 
 
X6 
 
Second primary malignancy 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 63 of 110 
Schedule: Cycles 4–6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Evaluation or Procedure 
Treatment Period 
Cycle 4(28 days) 
Cycle 5 (28 days) 
Cycle 6 (28 days) 
Day 
D1  
±2 days 
D15  
±2 days 
D1  
±2 days 
D15  
±2 days 
D1  
±2 days 
D15  
±2 days 
Previous/concomitant medication 
X 
X 
X 
X 
X 
X 
Full physical examination 
(Limited physical examination - L) 
 
 
L 
 
 
 
ECOG performance status 
X 
 
X 
 
X 
 
Body weight/height2  
X 
X 
X 
X 
X 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
B-symptoms 
X 
 
X 
 
X 
 
12-lead resting ECG 
 
 
 
 
X 
 
Urinalysis 
X 
 
X 
 
X 
 
Pregnancy test (FCBP)4 
X1 
 
X1 
 
X1 
 
Pregnancy and risks counselling 
X 
 
X 
 
X 
 
“Emergency laboratory”5 
X 
X 
X 
X 
X 
X 
Central laboratory blood sampling 1 
X 
 
X 
 
X 
 
Serology (Hepatitis B) 
X16 
 
X16 
 
X16 
 
B-, T- and NK cell flow cytometry 
(blood)1 
 
 
X 
 
 
 
Anti-MOR00208 antibodies 
 
 
X1 
 
 
 
Disease and disease response 
assessment (CT/PET) 
 
 
 
 
 
 
CT or MRI scan for tumour 
measurement and disease 
assessment (local) 
 
 
X 
 
 
 
Bone marrow aspiration & biopsy 
 
 
 
X7 
 
 
MOR00208 administration 
X 
X 
X 
X 
X 
X 
LEN tablets allocation 
X 
 
X 
 
X 
 
(S)AE assessment 
X 
X 
X 
X 
X 
X 
PK MOR00208 
X1 
 
X1 
 
X1 
 
Second primary malignancy 
X 
X 
X 
X 
X 
X 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 64 of 110 
Schedule: Cycles 7–12 
Evaluation or Procedure 
Treatment Period 
Cycle 7 (28 days) 
Cycle 8 (28 days) 
Cycle 9 (28 days) Cycle 10 (28 days) Cycle 11 (28 days) 
Cycle 12 (28 days) 
Day 
D1 
±2 days 
D15 
±2 days 
D1 
±2 days 
D15 
±2 days 
D1 
±2 days 
D15 
±2 days 
D1 
±2 days 
D15 
±2 days 
D1 
±2 days 
D15 
±2 days 
 
D1 
±2 days 
D15 
±2 days 
D28 
±4 days 
Previous/concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Full physical examination 
(Limited physical examination 
 - L) 
L 
 
 
 
 
 
L 
 
 
 
L 
 
 
ECOG performance status 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Body weight/height2  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
B-symptoms 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
12-lead resting ECG 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Urinalysis 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Pregnancy test (FCBP)4 
X1 
 
X1 
 
X1 
 
X1 
 
X1 
 
X1 
 
 
Pregnancy and risks 
counselling 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
“Emergency laboratory”5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Central laboratory blood 
sampling  1 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Serology (Hepatitis B) 
X16 
 
X16 
 
X16 
 
X16 
 
X16 
 
X16 
 
 
B-, T- and NK cell flow 
cytometry (blood)1 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Anti-MOR00208 antibodies 
X1 
 
 
 
X1 
 
 
 
X1 
 
 
 
 
Disease and disease response 
assessment (CT/PET) 
 
 
 
 
 
 
 
 
 
 
 
 
X 
CT or MRI scan for tumour 
measurement and disease 
assessment (local) 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Bone marrow aspiration & 
biopsy 
 
X7 
 
 
 
 
 
X7 
 
 
 
 
X7 
MOR00208 administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
LEN tablets allocation 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
(S)AE assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
PK MOR00208 
X1 
 
 
 
X1 
 
 
 
X1 
 
 
 
 
Second primary malignancy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 65 of 110 
Schedule: Additional Treatment Period and Follow-Up Period 
Evaluation or 
Procedure 
MOR00208 Additional 
Treatment Phase 
(28 Days Cycles #13–24) 
(First cycle of additional 
treatment possible up to 
2 weeks ±2 days after 
Cycle 12 Day 28) 
MOR00208 Additional Treatment Phase19, 20 
(28 Days Cycles #25 onwards) 
 
Unscheduled Visit  (in case 
MOR00208 is to be 
administered despite disease 
progression)8 
End of Treatment Visit 
(EOT) 
30 Day  
Follow-up 
Visit 
Survival 
Follow-up9 
(every 3 
months ±2 
weeks from 
last visit by 
phone) 
Day 
D1 
±2 days 
D15 
±2 days 
D1 ±2 days 
D15 ±2 days 
 
(assessments can take place 
within 7 days period of the 
actual visit) 
±2 days 
 
Previous/concom
itant 
medication10 
X17 
X17 
X17 
X17 
X 
X 
 
 
Full physical 
examination 
(Limited 
physical 
examination - L) 
L11, 17 
 
L11, 17 
 
X 
X 
L 
 
ECOG 
performance 
status 
 
 
 
 
X 
X 
 
 
Body 
weight/height2 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
 
 
B-symptoms 
X17 
 
 
 
X 
X 
X 
 
12-lead resting 
ECG 
 
 
 
 
X 
X 
 
 
Urinalysis18 
X17 
 
 
 
X18 
X18 
 
 
Pregnancy test 
(FCBP)4 
X1 
 
X1 
 
X18 
X18 
 
 
“Emergency 
laboratory”5 
X 
X 
X 
X 
 
 
 
 
Central 
laboratory blood 
sampling  1, 18 
X17 
 
 
 
X18 
X18 
 
 
Serology 
(Hepatitis B)18 
X16, 17 
 
 
 
X16, 18 
X16, 18 
 
 
Anti-MOR00208 
antibodies 
X1,12, 17 
 
 
 
 
X18 
 
 
CT or MRI scan 
for tumour 
measurement 
and disease 
X13, 17 
 
X13, 17 
 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Page 66 of 110 
Evaluation or 
Procedure 
MOR00208 Additional 
Treatment Phase 
(28 Days Cycles #13–24) 
(First cycle of additional 
treatment possible up to 
2 weeks ±2 days after 
Cycle 12 Day 28) 
MOR00208 Additional Treatment Phase19, 20 
(28 Days Cycles #25 onwards) 
 
Unscheduled Visit  (in case 
MOR00208 is to be 
administered despite disease 
progression)8 
End of Treatment Visit 
(EOT) 
30 Day  
Follow-up 
Visit 
Survival 
Follow-up9 
(every 3 
months ±2 
weeks from 
last visit by 
phone) 
Day 
D1 
±2 days 
D15 
±2 days 
D1 ±2 days 
D15 ±2 days 
 
(assessments can take place 
within 7 days period of the 
actual visit) 
±2 days 
 
assessment 
(local) 
Disease and 
disease response 
assessment 
(CT/PET) 
 
 
X17, 19 
 
X13, 14 
X13, 14, 17 
 
 
Bone marrow 
aspiration & 
biopsy 
 
X7, 15, 17 
 
 
 
 
 
 
MOR00208 
administration 
X 
X 
X 
X 
 
 
 
 
(S)AE 
assessment 
X 
X 
X 
X 
X 
X 
X 
 
PK MOR00208 
X1, 12, 17 
 
 
 
 
X18 
 
 
Second primary 
malignancy 
X 
X 
X 
X 
X 
X 
X 
X 
Antineoplastic 
therapy other 
than the study 
drug treatment21 
X21 
X21 
X21 
X21 
X21 
X21 
X21 
X 
 
Abbreviations: ADCC=antibody-dependent cell-mediated cytotoxicity; AE=adverse event; β-HCG=beta-human chorionic gonadotropin; CT=computed tomography; 
ECG=electrocardiogram; ECOG=Eastern Cooperative Oncology Group; FCBP=female of childbearing potential; IPI= International Prognostic Index; IV = intravenous; 
L= Limited physical examination; LEN=lenalidomide; MRI=magnetic resonance imaging; NK=natural killer; PET=positron emission tomography; PK=pharmacokinetics; 
SAE=serious adverse event. 
1Before study drug administration. 
2Body height will be measured at Cycle 1 Day 1 only. Body weight can be measured up to 24 hours prior to the study drug administration. 
312-lead resting ECG performed no later than 3 hours post-MOR00208 dose (see Section 7.2.10). 
4Pregnancy tests: for FCBP, two pregnancy tests must be performed before enrolment; the first, a serum pregnancy test at screening within 10 to 14 days prior to the start of study 
drug and the second, a medically supervised urine pregnancy test within 24 hours prior to the start of study drug. The results of both tests must be negative in order to receive Cycle 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 67 of 110 
1 Day 1 dosing. At all other indicated time points, a urine pregnancy test for FCBP will be performed locally and the result must be negative for dosing. A β-HCG pregnancy test 
should also be performed at the End of Study Visit. 
5Sample to be collected and evaluated in the local laboratory (up to 24 hours prior to study drug administration) and reviewed by study treating physician before study drug 
administration. 
6MOR00208 PK sample will be taken pre-dose and 1 hour ± 10 min after the end of MOR00208 infusion. 
7Repeat bone marrow biopsy to confirm a CR only in those patients who had known bone marrow involvement prior to dosing (see Section 7.2.14.2 for details). 
8For patients receiving antibody treatment despite disease progression / relapse, an Unscheduled Visit covering all assessments described under EOT visit should be completed 
(except PK sample) before the continuation of antibody therapy. These procedures, if performed within less than two weeks preceding this visit, need not be repeated. PET/CT 
need not be repeated if it was performed during previous treatment cycle.  
9After 30-Day Follow-up Visit, a call will be made to the patient (or the patient’s family) every 90 days for at least 5 years from Cycle 1 Day 1 to inquire about the patient’s status, 
second primary malignancy (SPM) and information on any antineoplastic therapies utilised since discontinuation of study treatment. 
10After disease progression has been recorded, only anticancer treatments and, in case of an AE, other relevant concomitant medications (at the discretion of the investigator) 
should be entered. Before and up to the End of Treatment Visit, the complete concomitant medication needs to be recorded. 
11A limited PE (L) will be performed on Day 1 of each Cycle, every 12 weeks +2 days from the previous PE. 
12Anti-MOR00208 antibody sample and MOR00208 PK sample (pre-dose only) will be taken in odd numbered additional treatment cycles only (i.e. treatment Cycles 13, 15, 17, 
19, 21, 23). No samples to be collected after Cycle 23. 
13Disease assessment by CT/MRI of neck, chest, abdomen & pelvis with iv contrast during additional treatment phase; Cycles 13-24: approximately every 3 months ± 2 days from 
the previous scan. First assessment during this phase can be done directly 3 months after Cycle 12 D28 PET/CT assessment. Thus, this assessment is not needed at Cycle 13 Day 1, 
and an interval longer than ~3 months is acceptable for Cycle 16 Day 1 assessment; Cycle 25 onwards: approximately once every year ± 2 weeks from the previous scan. Images 
will have to be transferred to the central imaging laboratory. 
14In case the patient is withdrawn from treatment before the end of Cycle 12 for reasons other than progression of disease. PET/CT is only required at the EOT visit if it was not 
performed in the cycle before the end of treatment visit. 
15Bone marrow assessment during additional treatment phase (Cycles 13 to 24) approximately every 3 months ± 2 weeks from the previous assessment; to be performed to confirm 
a CR only in those patients who had known bone marrow involvement prior to dosing. Refer to Section 7.2.14.2 for further details. 
16HBV-DNA to be measured and re-measured only if anti-HBc was positive at screening. If HBV-DNA is positive at screening, or during treatment, please see Section 7.2.13.2. 
17Not applicable for patients who continue receiving MOR208 despite disease progression. 
18Central laboratory tests will be performed only until Cycle 24 for each patient, as applicable. Not to be performed from Cycle 25 onwards. 
19PET/CT Cycle 25 onwards should be performed only if deemed necessary, and not more than once per year. 
20This treatment is planned for a total treatment duration (from Cycle 1 Day 1 onwards) of at least 5 years, including the safety follow-up visit and survival follow-up duration, as 
applicable. 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 68 of 110 
21Antineoplastic therapy other than study treatment can be administered, and will be recorded in eCRF only for those patients who continue to receive MOR208 despite disease 
progression / relapse, and have completed an Unscheduled Visit covering all assessments described for the EOT visit. For further clarification please refer to Section 7.2.3. 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 69 of 110 
7.2 Procedures 
All study-required procedures should occur as outlined in Table 5. Excursions from the timing 
of assessments will be considered protocol deviations and should be recorded in the source 
documents along with the reason for the excursion. 
 
For patients receiving antibody treatment despite disease progression / relapse, an 
Unscheduled Visit covering all assessments described under EOT visit should be completed 
before the continuation of antibody therapy. Blood parameters (haematology, serum 
chemistry) should be evaluated in the local lab according to local guidelines/standards of local 
medical practice for the administration of monoclonal antibodies. A urine pregnancy test should 
be performed for women of childbearing potential, prior to each infusion. Vital signs should be 
measured according to local practice for the administration of monoclonal antibodies. For this 
patient population only the antineoplastic therapy and AEs need to be captured in eCRF. Other 
procedures described in the column MOR00208 Additional Treatment will not apply for this 
patient population. 
 
 
 Screening followed by Enrolment (Start of IMP) 
The Screening Period begins on the date the Informed Consent Form (ICF) is signed and will 
last for up to 28 days. The ICF must be signed prior to beginning any assessments solely for the 
purpose of this study. Standard of care assessments done on the day of consent (but prior to 
signing the ICF) do not need to be repeated solely for the purpose of screening and may be used 
as study data, if they meet the protocol requirements. 
 
During screening, it is permitted to repeat on a single occasion the central laboratory 
assessment of serum chemistry and haematology parameters due to the variability of the 
parameters and their dependence on multitude of factors (e.g., hydration, muscle mass). This is, 
provided no safety concerns arise and that such laboratory results might have been caused by a 
transient, medically plausible event, which resolved spontaneously or as result of a medical 
intervention in the meantime (e.g., dehydration, vomiting, imaging procedure with a contrast). 
This procedure and the rationale behind it must be explicitly documented in source data. Such 
repeated assessment (once only) of the concerned parameters will not be counted as “re-
screening” for that patient. 
 
On Cycle 1 Day 1, patient eligibility must be confirmed before drug administration. Local 
laboratory parameters should be used for this purpose, as specified in Section 7.2.13 Laboratory 
Assessments. 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Page 70 of 110 
 End of Treatment (EOT) Visit 
An end of treatment visit will have to be completed for all patients, including, but not limited to 
the following circumstances: 
a. After disease progression / relapse, any time after start of the study treatment, provided 
MOR00208 will not be administered despite progression 
b. After last administration of study drugs. 
c. Withdrawal from study treatment as specified in Section 6.9. 
If the EOT visit is after 24 cycles (i.e., Cycle 25 onwards), only the applicable laboratory tests 
in the local laboratory will need to be performed. 
 
 MOR00208 Administration Despite Disease Progression 
It is up to the investigator to decide according to the individual risk/benefit ratio if the patient 
should continue on MOR00208 in case of disease progression, after discussion with the 
Sponsor’s Medical Monitor. For patients who will be administered MOR00208 despite 
progression of disease / relapse, an Unscheduled Visit including all protocol prescribed 
procedures for the EOT Visit need to be performed in order to capture the event (i.e. disease 
progression/relapse) for the antibody treatment to continue further. These procedures, if 
performed within less than two weeks preceding this visit, need not be repeated. PET/CT need 
not be repeated if it was performed during previous treatment cycle. Note: Central laboratory 
tests will need to be performed only until Cycle 24 for each patient, as applicable. 
 
Following procedures will be performed (and documented in source) for these patients during 
the period of MOR00208 administration despite disease progression (prior to each infusion): 
a. Emergency Laboratory (Local Lab) evaluations consisting of haematology, serum 
chemistry according to local guidelines/standards of local medical practice for the 
administration of monoclonal antibodies. 
b. A urine pregnancy test for women of childbearing potential 
c. Vital signs 
 
These patients will follow a visit schedule as mentioned under “MOR00208 Additional 
Treatment Phase”, whereas their treatment cycle and visit numbers will be captured in a 
continuum with their previous applicable treatment visit, prior to disease progression. For this 
patient population only the antineoplastic therapy and AEs are going to be captured in eCRF. 
Other procedures described in the column MOR00208 Additional Treatment will not apply for 
this patient population. 
 
In such cases an EOT Visit will take place after these patients have finally stopped receiving the 
antibody. At this EOT visit only anticancer therapy and AEs will be recorded. And lastly, a 
Safety Follow-Up will take place 30-Days after last administration of MOR00208. 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 71 of 110 
 Safety Follow-up Visit 
A Safety Follow-Up will take place 30-Days after last administration of IMP. Following 
assessments will be performed and recorded in eCRF: 
a. Limited physical examination 
b. Adverse events including second primary malignancies 
c. Antineoplastic therapy 
 
 Survival Follow-up 
After Safety Follow-up Visit, a phone call will be made to the patient (or the patient’s family) 
every 90 days (+ 2 weeks) for to cover a duration of up to 5 years from Cycle 1 Day 1 to inquire 
about the patient’s status, second primary malignancy (SPM) and information on any 
antineoplastic therapies utilised since discontinuation of study treatment. For patients who are lost 
to follow-up, at least three attempts of contact by the site should be made and documented in the 
source data. 
 
 Diagnostic Biopsy 
Patients must be eligible and willing to undergo a biopsy of a lymph node or other pathological 
tissue, providing enough tumour tissue for correlative studies, as a part of participation in this 
study. Histological confirmation of the diagnosis of DLBCL will be performed by a central 
pathologist, retrospectively after enrolment. Surgically acquired tissue samples are preferred, but 
core biopsies are permitted. Bone marrow biopsies are not adequate for this purpose and should 
be performed only for disease staging. 
 
Should it not be possible to obtain a fresh tumour tissue sample from the patient, archival paraffin 
embedded tumour tissue acquired < 3 years prior to screening for this protocol must be available 
for this purpose. 
 
The local pathology report indicating DLBCL diagnosis is acceptable for determining a patient’s 
eligibility. Central pathology review is mandatory, but retrospective in nature. Tissue samples 
(or archival paraffin blocks, as stated above) should be submitted within 30 days of patient 
enrolment in the study. Patients can be enrolled prior to submission of tissue sample(s). 
 
In case of discrepancies between the assessments of the local and the central pathologists, the 
one of the central pathologist prevails. If the DLBCL diagnosis of the local pathologist cannot 
be confirmed by the central pathologist, and a patient’s treatment has already commenced, they 
may remain in the study. 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 72 of 110 
 Demographic Data/Relevant Medical History and Current Medical 
Conditions/Baseline Stage and Prognostic Classification 
Demographic variables to be recorded will include age, gender, race, body height, and body 
weight. Weight and height should be measured while the patient is without shoes, but dressed. 
 
At the time of signing of the ICF, relevant medical history and current medical conditions should 
be recorded. The medical history of DLBCL should be documented in detail, including baseline 
symptoms as well as a detailed history of prior cancer therapies for DLBCL, with start and stop 
dates, number of therapy line(s), disease progression during or after therapy, as well as 
discontinuations due to intolerability or any other clinically significant illness. Any previous 
therapy (e.g., chemotherapy, immunotherapy, or radiation therapy) for DLBCL should be 
recorded in the eCRF. Also, examinations leading to the diagnosis of the latest progression of 
DLBCL should be documented in the patient’s source documents. This may include, for 
example, results of laboratory examinations, imaging results, or clinical symptoms related to 
DLBCL. The assessment of the lymphoma should include staging. In order to reflect the patient’s 
status at the time of enrolment, the standard staging system used for DLBCL reflecting the 
number of sites of involvement and their relation to the diaphragm, the existence of B-symptoms, 
and the presence of extranodal disease, will be documented (see Appendix_E for Ann Arbor 
Staging). 
 
Additionally the disease risk assessment as per IPI (see Appendix_B) and patient status as per 
Eastern Cooperative Oncology Group (ECOG) performance status criteria (see Appendix_F), 
will be recorded. 
 
Examples of clinical significant systemic diseases, which may exclude patient participation 
include, but are not limited to: 
a) A diagnosis of a myocardial infarction within the 6 months prior to enrolment, 
New York Heart Association (NYHA) class II or higher congestive heart failure, 
uncontrolled angina pectoris, severe uncontrolled ventricular arrhythmias, 
clinically significant pericardial disease, or electrocardiographic evidence of 
acute ischaemia or significant conduction system abnormalities, in the opinion of 
the investigator. Patients with stable, asymptomatic atrial fibrillation are allowed 
in the study provided they do not meet the other cardiac exclusion criteria 
b) Systemic diseases (e.g., cardiovascular, renal, hepatic) that would in the 
investigator’s opinion preclude participation in the study or compromise the 
patient’s ability to give informed consent 
c) History or evidence of clinically significant peripheral nervous system, 
cerebrovascular, or CNS diseases, meningeal (e.g., meningeosis leukaemica), or 
epidural malignancy including brain metastasis or cerebrovascular event(s) with 
clinically significant sequelae. Screening for cerebrospinal fluid (CSF)/CNS 
involvement is not required but may be performed at the discretion of the 
investigator. 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 73 of 110 
 Vital Signs 
Vital signs will be measured at the time points described in the Schedule of Assessments  
(Table 5). 
 
These assessments include body temperature, systolic and diastolic blood pressure readings 
(mmHg), heart rate (beats per minute [bpm]), and respiratory rate (respirations per minute 
[rpm]). Vital signs will be measured immediately prior to infusion, 15 ± 5, 30 ± 10, and then 
every 60 ±15 minutes during infusion and at end of infusion (± 20 min). The actual time of vital 
sign measurements should be accurately documented. If the infusion is interrupted and/or 
subsequently restarted, vital signs should be assessed every 60 ± 15 minutes after the first hour. 
 
The frequency or the length of the monitoring period may be adapted if clinically indicated, for 
example if in the opinion of the investigator the vital sign results, at the time of event onset, are 
clinically significant. In such a case the patient’s vital sign measurements should continue to be 
recorded until they have returned to normal or pre-infusion levels and an AE recorded. If 
possible, before vital signs are measured, the patient should be resting for at least 5 minutes. The 
same position should be used each time vital signs are measured for a given patient, and blood 
pressure should be measured from the arm contralateral to the site of study drug administration. 
Body temperature should be measured according to normal hospital practice. 
 
  Physical Examination (PE) 
7.2.9.1 Full PE 
A full PE will be performed by the Investigator or a qualified designee during the screening and 
at the EOT Visit. 
 
Full PE must be performed according to the best standards of local medical practice but should 
include at least vital signs and palpable tumour assessments, general appearance, skin, head, 
eyes, ears, nose, throat including Waldeyer lymphatic structures, lungs, breasts and axillae (if 
applicable including bi-dimensional measurement of cervical, supraclavicular, axillary and 
inguinal lymph nodes), cardiovascular system, back and spine, abdomen (if applicable including 
spleen size below the costal margin), extremities, infusion site, lymph nodes, and neurological 
examination. 
 
7.2.9.2 Limited PE 
Limited PEs may be focused on tumour response assessment (e.g., lymph nodes, liver, spleen) 
and AEs per investigator discretion will be performed on Day 1 of Cycles 1, 3, 5, 7, 10 and 12. 
Additionally, a limited PE will be performed on the 30-Day Follow-up Visit. 
 
During the course of the Additional Treatment Phase of the study a limited PE will be performed 
on Day 1 every 12 weeks ± 2 weeks. 
 
Symptom-driven full PEs may be performed as clinically indicated at any study visit. 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 74 of 110 
7.2.9.3 Body Weight and Height Measurements 
Body height will be measured at Cycle 1 Day 1 only. 
 
Body weight can be measured up to 24 hours prior to MOR00208 administration on Day 1 of 
each cycle. This baseline weight will be used to calculate the MOR00208 dose during the given 
cycle provided the weight does not deviate >±10% from baseline during the course of this cycle. 
In cases where the patient’s body weight changes more than ± 10% from baseline, the current 
weight will be used to calculate the next and subsequent doses of MOR00208. Using actual body 
weight prior to each MOR00208 infusion is also allowed, if this is preferred by investigators. 
 
Weight measurements should be performed at each visit and the values will need to be entered 
into the eCRF on the actual day of measurement. 
 
7.2.9.4 B-Symptoms 
B-symptoms are defined as any one or more of the disease-related symptoms or signs mentioned 
in Appendix_E. 
 
Assessment of the presence or absence of B-symptoms will be performed at screening and on 
Day 1 for all cycles, as well as the End of Treatment Visit and at the 30-Day Follow-up Visit. 
 
 Electrocardiogram 
Standard 12-lead resting ECGs will be obtained at the various time points described in the 
Schedule of Assessments (Table 5). ECGs will be recorded after the patient has rested in a supine 
position for at least 5 minutes. Heart rate, PR, QRS, RR and QT intervals will be determined. 
All ECGs will be performed and interpreted locally. The investigator will evaluate the clinical 
significance of each value outside the reference ranges according to the nature and degree of the 
observed abnormality. Any new abnormal values considered to be clinically significant should 
be reported as AEs. 
 
If clinically significant abnormalities are observed or artefacts are present that result in an 
inability to adequately interpret the results, the ECG will be repeated. An average of all intervals 
measured in all ECG tracings recorded at a given time point may be taken if necessary. 
 
 Adverse Event Monitoring 
AEs will be assessed at each visit and reported as specified in Section 8.2 of the protocol. 
 
For screening failure patients only SAEs will be recorded in the eCRF. 
 
 Monitoring of Second Primary Malignancies 
SPMs will be monitored as events of interest and should be included as part of the assessment of 
AEs throughout the course of the study. Investigators are to report any SPMs as serious AEs, 
regardless of causal relationship to the study drugs, occurring at any time, for the duration of the 
study, from Cycle 1, Day 1 up to and including the follow-up period of up to 3 years. Events of 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 75 of 110 
SPM are to be reported using the SAE report form and must be considered an important medical 
event even if no other serious criteria apply; these events must also be documented in the 
appropriate page(s) of the eCRF and the patient’s source documents. 
 
Documentation on the diagnosis of the SPMs must be provided at the time of reporting as an 
SAE (e.g., any confirmatory histology or cytology results, X-rays, computed tomography [CT] 
scans). 
 
 Laboratory Assessments 
Detailed instructions and amounts of biological samples needed for the respective laboratory 
measurements will be summarised in the laboratory manual. All samples will be collected as 
non-fasting samples. 
 
7.2.13.1 Safety and Haematology Laboratory Testing 
Clinical laboratory tests will be performed according to Table 6. During the course of the study, 
local (“emergency”) and central laboratories will be used. 
 
Central laboratory results are required for determining patient eligibility for study enrolment and 
will be used in the primary statistical analysis of the study results. Note: for eligibility 
confirmation prior to study drug administration at Cycle 1 Day 1, local laboratory results should 
be used. During the course of the study, all scheduled central laboratory results should be 
reviewed as soon as possible after Day 1 of each cycle. 
 
During screening, it is permitted to repeat on a single occasion the central laboratory assessment 
of serum chemistry and haematology parameters due to the variability of the parameters and their 
dependence on multitude of factors (e.g., hydration, muscle mass). This is, provided no safety 
concerns arise and that such laboratory results might have been caused by a transient, medically 
plausible event, which resolved spontaneously or as result of a medical intervention in the 
meantime (e.g., dehydration, vomiting, imaging procedure with a contrast). This procedure and 
the rationale behind it must be explicitly documented in source data. Such repeated assessment 
(once only) of the concerned parameters will not be counted as “re-screening” for that patient. 
 
Local (“emergency”) laboratory results will be used for treatment or clinically related decisions, 
or for the immediate safety needs of a study patient. “Emergency laboratory” (local) results 
should be reviewed as soon as possible after their receipt and before dosing so that the 
administration of the investigational medicinal product (IMP) may be adjusted or interrupted if 
necessary. 
 
The signed and interpreted laboratory results (both local and central) will be kept in the patient’s 
source documentation. The laboratory results should be reviewed, dated and signed in a timely 
manner by the investigator. Any clinically significant discrepancies will be evaluated on a case-
by-case basis. All blood samples will be processed and handled according to standard laboratory 
procedures. The time of blood collection should be documented in the source data. 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 76 of 110 
If an abnormal laboratory value of grade 4 or an abnormal laboratory value judged to be clinically 
significant that was not present at baseline, is not reported as an AE, then the investigator should 
clearly document the rationale for not doing so in the source documentation. 
 
Any abnormal laboratory findings (identified either through local or central laboratory analysis) 
that constitute an AE should be reported as such and should be followed up until the outcome is 
known. Also, additional diagnostic tests may be indicated to determine a more precise diagnosis 
of the patient’s condition (e.g., ordering a white blood cell (WBC) differential count to help 
characterise a high or low WBC count, or ordering a determination of red blood cell (RBC) 
indices to help characterise a low haematocrit). 
 
Central laboratory tests will be performed only until Cycle 24 for each patient, as applicable. 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Table 6 
Laboratory Evaluations 
Evaluation 
Analysis 
“Emergency laboratory”1 
(EDTA blood and serum 
sample) 
Serum creatinine, haemoglobin, WBCs, WBC differential, 
platelets, sodium, potassium, AST, ALT, total bilirubin 
Haematology 
(EDTA blood) 
WBC with differential count, haematocrit, haemoglobin, mean 
corpuscular volume, mean corpuscular haemoglobin 
concentration, platelet count, RBC count, lymphocytes, 
monocytes, neutrophils, band neutrophils, eosinophils, basophils 
At screening: will include a peripheral blood smear 
Erythrocyte sedimentation rate kit from central lab will be used, 
however, the test as such has to be performed locally at the site.  
Serum chemistry 
(serum sample) 
ALT, total albumin, alkaline phosphatase, amylase, AST, 
bicarbonate, bilirubin (total), urea, total calcium, chloride, 
creatinine, creatinine kinase, GGT, glucose, LDH, lipase, 
phosphate, potassium, protein (total), sodium, uric acid, 
magnesium, β2-microglobulin, C-reactive protein 
Coagulation parameters 
(sodium citrate blood) 
Activated partial thromboplastin time, prothrombin time, 
international normalisation ratio, immunoglobulin concentrations 
(IgG, IgM, IgA) 
Serology parameters 
(serum sample) 
Hepatitis B: HbsAg, anti-Hbc and anti-HBs. HBV-DNA if 
anti-Hbc positive (until Cycle 24),   
Hepatitis C: HCV antibody (HCV RNA quantification if 
anti-HCV-positive) 
Pregnancy test  
(serum sample) 
β-HCG serum, females of childbearing potential only 
Pregnancy test  
(urine) 
β-HCG urine, females of childbearing potential only. The 
pregnancy test assay should have a minimum sensitivity of 
25 IU/mL (urine sticks will be provided centrally, until Cycle 24).  
Urinalysis 
Appearance, colour, urine bilirubin, glucose, haemoglobin, 
ketones, pH, protein, specific gravity, urobilinogen.  
Microscopy will only be performed if clinically indicated 
Genotyping 
FcγRIIa and FcγRIIIa polymorphism 
CD16 expression on 
peripheral NK cells 
(heparinised blood) 
(exploratory assay) 
CD16 expression on NK cells (Flow cytometry) 
Immunogenicity 
(serum sample) 
Anti-MOR00208 antibodies 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Abbreviations: 
ADCC=antibody-dependent 
cell-mediated 
cytotoxicity; 
ALT=alanine 
transaminase; 
AST=aspartate 
aminotransferase; β-HCG=beta-human chorionic gonadotropin; EDTA=thylenediaminetetraacetic acid; GGT=gamma-
glutamyltransferase; anti-HBc=hepatitis B core antibody; anti-HBs=hepatitis B surface antibody; HbsAg=hepatitis B surface 
antigen; LDH=lactate dehydrogenase; NK=natural killer; RBC=red blood cell; WBC=white blood cells. 
1WBC differential can be automated or manual as per institutional standards. Reticulocytes may be determined only when 
clinically indicated. 
 
7.2.13.2 Hepatitis Virus Serology 
Patients will be examined according to the schedule in Table 5 for viral hepatitis B and C 
serology. Hepatitis B biomarkers include hepatitis B surface antigen (HbsAg), total anti-hepatitis 
B core antibody (anti-Hbc) and hepatitis B surface antibody (anti-HBs). Patients with a positive 
test for anti-Hbc can only be included if hepatitis B viral DNA (HBV DNA) is not detected. In 
these patients only, HBV DNA should be assessed at various subsequent visits as outlined in 
Table 5. Note: Central laboratory tests will need to be performed only until Cycle 24 for each 
patient, as applicable. 
 
In the context of exclusion criteria, seropositive for or active viral infection with hepatitis B virus 
(HBV) means: 
a) HBV surface antigen positive 
b) HBV surface antigen negative, HBV surface antibody positive and/or HBV core antibody 
positive and detectable viral DNA. Note: Subjects who are HBV surface antigen negative 
and viral DNA negative are eligible. 
c) Patients who exhibit the classical vaccination profile of HBV surface antibody positive, 
HBV core antibody negative, and HBV surface antigen negative are eligible. 
 
If HBV-DNA becomes detectable during treatment, patients should be prophylactically treated 
and followed-up for potential hepatitis B reactivation as per local medical practice or institutional 
guidelines for CD20 antibodies such as RTX. If the HBV-DNA assay is positive, then patients 
can only stay in the study if they are assessed by a physician experienced in the treatment of 
 
continued 
 
Evaluation 
Analysis 
Pharmacokinetics 
(serum sample) 
MOR00208 
 
ADCC assessment 
(heparinised blood) 
(exploratory assay) 
ADCC with peripheral blood mononuclear cells (Flow cytometry) 
B-/T-/NK cell counting 
(heparinised blood) 
(exploratory assay) 
Cell counts (Flow Cytometry) 
Analysis of exploratory 
biomarkers 
(pathology samples) 
For example: CD19, CD20, BCL-2, BCL-6  


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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hepatitis B and pre-emptive treatment is initiated, if deemed appropriate, and/or according to 
local practice/guidelines. 
 
Hepatitis C serology is to be done at screening only. Hepatitis C biomarkers include 
anti-hepatitis C virus antibody (anti-HCV). For patients who are positive for anti-HCV antibody, 
HCV-RNA should be measured 
 
A positive Hepatitis C test is defined as a positive test for Hepatitis C Virus (HCV) antibodies 
and a positive test for HCV RNA. 
 
7.2.13.3 Pregnancy Testing 
A pregnancy test will be performed for females of childbearing potential (FCBP) at various pre- 
and post-treatment time points either by urine pregnancy test or beta-human chorionic 
gonadotropin (β-HCG) test of a serum sample (see Table 5). The pregnancy test assay should 
have a minimum sensitivity of 25 IU/mL. At screening and the End of Treatment Visit, a serum 
β-HCG pregnancy test should be performed for FCBP.  
 
FCBP must have two negative pregnancy tests prior to starting the study drug. The first 
pregnancy test must be performed within the 10–14 days prior to the start of study drug and the 
second pregnancy test must be performed within the 24 hours prior to the start of study drug. 
The patient must not receive study drug until the study doctor has verified that the results of 
these pregnancy tests are negative. 
 
Subsequent pregnancy tests will be conducted: 
 every week for the first 28 days of the study 
 every 28 days thereafter (or every 14 days if the patient has irregular periods) 
 if the FCBP patient misses a period 
 if the FCBP patient has unusual menstrual bleeding 
 at the EOT Visit 
 fourteen (14) days and 28 days (if irregular periods) and 28 days only (with regular 
periods) after stopping LEN. 
 
Note: Central laboratory tests will need to be performed only until Cycle 24 for each patient, as 
applicable. 
 
In addition, pregnancy and risk counselling will be conducted at the time points specified in the 
LEN Pregnancy Risk Minimisation Plan for Clinical Trials. 
 
7.2.13.4 PK Assessments 
Concentration-time profiles and PK parameters will be assessed for MOR00208 according to the 
Schedule of Assessments (Table 5). Neither samples nor concentration-time profiles or PK 
parameters will be assessed for LEN. 
 
Serum samples for PK analysis of MOR00208 will be handled and stored as specified in the 
laboratory manual at the study site until shipment on dry ice to an external analytical laboratory. 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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At each sampling time point, the obtained serum sample should be split into 2 aliquots (a primary 
and a back-up sample). 
 
7.2.13.5 Immunogenicity 
Serum samples for anti-MOR00208 antibody analysis will be collected according to the 
Schedule of Assessments (Table 5). 
Serum samples for anti-MOR00208 antibody analysis will be handled and stored as specified in 
the laboratory manual at the study site until shipment on dry ice to an external analytical 
laboratory. At each sampling time point, the obtained serum sample should be split into 
2 aliquots (a primary and a back-up sample). 
 
7.2.13.6 Other Laboratory Evaluations 
A mucosal cheek swab will be used for DNA analysis of FcγRIIa and FcγRIIIa polymorphisms. 
The evaluation will be performed at a specified laboratory. 
 
Genotyping is optional; it will only be performed if the patient specifically consents to this 
analysis. A patient can participate in the study regardless of whether they consent to undergo 
genotyping. 
 
Biomarker analysis on collected tissue samples, for example CD19 and CD 20 expression 
assessments will be performed at a central specified laboratory. 
 
For evaluation of the status of the patient’s immune system, B-, T- and NK cells in peripheral 
blood will be measured frequently throughout the study (exploratory assay). The absolute and 
percentage changes from baseline will be evaluated. 
 
Baseline CD16 expression on NK cells in peripheral blood will be evaluated at baseline 
(exploratory assay). In addition, the ADCC capacity of the patient will be assessed. 
 
 Efficacy Assessments 
Efficacy will be evaluated in terms of ORR, DCR, DoR, PFS, OS, TTP and TTNT: For 
definitions see Section 10.6. 
 
Disease response assessments will be made according to the revised response criteria based on 
the guidelines of the IWG reported by Cheson et al. (2007) (see Appendix_G). Response 
assessment made by the central radiology + clinical review at Cycle 12 Day 28 (+4 days) (and / 
or at the EOT visit, as applicable) will be considered for the main efficacy analysis (primary 
endpoint).  
 
Local assessment of efficacy / disease response will be recorded in addition to central review at 
the end of Cycle 12 (for decisions concerning the additional Cycle 13 through Cycle 24 
MOR00208 treatment) and at the EOT Visit (to determine whether the disease has progressed), 
and at additional time points specified in Table 5. Disease assessment by CT/MRI during 
additional treatment phase will be done as follows: 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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 
Cycle 13 until Cycle 24: First assessment during this phase can be done after 
approximately 3 months + 2 days after Cycle 12 D28 PET/CT assessment. Thus, this 
assessment is not needed at Cycle 13 Day 1, and an interval longer than 3 months is 
acceptable for Cycle 16 Day 1 assessment. Thereafter, it will be repeated approximately 
every 3 months ± 2 days from the previous scan. 
 
Cycle 25 onwards: approximately once every year from the previous scan. 
 
7.2.14.1 Tumour Imaging Assessment 
In the course of the study, disease and response assessments as well as tumour measurements 
will be performed. 
 
Initial disease and disease response assessments for the primary endpoint will be made by 
positron emission tomography (PET)/ CT (CT should be done with IV contrast) at screening and 
Day 28 (±4 days) of Cycle 12 and at the EOT Visit, in the cases where a patient is withdrawn 
from treatment before the end of Cycle 12 for reasons other than progressive disease. PET/CT 
scanning during additional treatment phase (Cycle 13 onwards) with MOR00208 will be 
performed at the decision of the investigator, and should not be performed more than 
approximately once per year. 
 
Tumour measurements and disease assessment (local) will be performed as indicated in Table 5 
by CT. The CT portion of PET/CT will be acceptable in place of CT for tumour measurement 
and disease assessment, only when the CT portion is of adequate diagnostic-quality, and using 
adequate intravenous contrast. 
 
Magnetic resonance imaging (MRI) may be used in lieu of CT, and PET/MRI in lieu of PET/CT 
for patients with contraindications to the administration of contrast agents, or due to other 
medical reasons, at the same time points as CT, or in addition to CT, at the discretion of the 
investigator (in this case, MRI may be performed as/when appropriate). The method used at 
baseline should be used throughout the study unless otherwise medically indicated. 
 
If available and of acceptable quality, previously performed PET/CT examinations, in 
accordance with the standard of care, that were done up to four weeks prior to the date of 
informed consent may be used for a patient’s baseline central radiology assessment. Additional 
PET/CT or CT or MRI examinations may be performed by the investigator in the course of the 
study, if deemed necessary (e.g., to confirm the occurrence of a CR or to make important 
treatmentrelated- decisions). Whenever feasible, in such cases the investigator should seek prior 
approval of the sponsor for the additional imaging. 
 
If the patient discontinues from treatment, a PET/CT scan is only required at the EOT Visit if it 
was not performed in the cycle prior to the end of treatment. CT may be performed in lieu of 
PET/CT if the patient discontinues from treatment within Cycle 1. 
 
The same scan modality should be used for all assessments, and all patients are required to have 
scans of the neck/chest/abdomen/pelvis. All scans conducted during the study will be provided 
to a central imaging laboratory for independent radiological and clinical evaluation. 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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If it is impossible for the patient to have their PET examination in fasted state, adequate 
procedures should be in place to measure and control blood glucose level. 
 
7.2.14.2 Bone Marrow 
At the screening visit, a uni- or bilateral bone marrow aspirate and a biopsy should be obtained 
to assess bone marrow involvement. Results from a bone marrow examination done within the 
4 weeks prior to the date of informed consent will be acceptable if the patient’s disease has been 
stable since then. 
 
The achievement of CR in the course of MOR208C203 study must be confirmed locally, by 
clinical and radiologic evaluation along with bone marrow confirmation. The latter applies only 
in case the bone marrow was involved by lymphoma before study entry. If bone marrow was not 
involved by lymphoma before commencing the study treatment, then bone marrow confirmation 
biopsy is not required. The repeated bone marrow examination is also not required for patients 
in whom bone marrow has already been cleared of the infiltrate at previous evaluation, i.e. their 
previous response was CR. 
 
Histological examination of the bone marrow should be performed locally at the protocol 
specified time-points (see Table 5). 
 
 
8 SAFETY MONITORING 
The patients will be closely observed and questioned for any kind of AE during the study 
procedures and at follow-up appointments throughout the study period with non-leading 
questioning (e.g., “How do you feel?”). AEs also may be detected when they are volunteered by 
the patient during or between study visits or through physical examination, laboratory tests, or 
other assessments. 
 
Study personnel must remain vigilant for the occurrence of AEs, particularly those that may be 
lifethreatening-. Personnel who are trained in the acute management of IRRs, cytokine release 
syndrome, anaphylaxis, and other emergencies, and who have access to appropriate clinical 
supplies, should be readily available. 
 
All AEs should be treated appropriately. Such treatment may include changes in study drug 
treatment including possible interruption or discontinuation, starting or stopping concomitant 
treatments, changes in the frequency or nature of assessments, hospitalisation, or any other 
medically required intervention. Once an AE is detected, it should be followed up, and an 
assessment should be made at each visit (or more frequently, if necessary) of any changes in its 
severity, its suspected relationship to the study drug(s), any of the interventions required to treat 
it, and its outcome. 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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8.1 Definition of Adverse Events, Serious Adverse Events, 
Adverse Events of Special Interest 
An AE is defined as any untoward medical occurrence in a patient or clinical patient administered 
a medicinal product, which does not necessarily have a causal relationship to this treatment. 
 
An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a study drug, whether or not 
it is considered related to that study drug. 
 
AEs include any clinically significant deterioration of a patient’s medical status after the signing 
of the ICF. Also, an increase in the frequency or intensity of a pre-existing episodic event or 
conditions and events resulting from protocol mandated procedures (e.g., invasive procedures) 
fall under the definition of AEs. In addition, overdoses (defined as exceeding the planned dose 
by more than 20%) should be recorded as AEs. 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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As far as possible, each AE should be evaluated to determine the following: 
 relationship to the study drug (suspected/not suspected) 
 duration (start and end date or if continuing at end of study) 
 intensity: the intensity of all AEs will be graded as mild, moderate, or severe using the 
following definitions: 
o mild: 
tolerable 
o moderate:       interferes with normal activity 
o severe:  
incapacitating (causes inability to perform usual activities or 
     work) 
 toxicity grade: determined according to the NCI-CTCAE version 4.0 of May 28, 2009, 
using the following definitions: 
o grade 1:  
mild; asymptomatic or mild symptoms; clinical or diagnostic 
 
 
observations only; intervention not indicated 
o grade 2: 
moderate; minimal, local or noninvasive intervention indicated; 
 
 
limiting age-appropriate instrumental activities of daily living 
 
 
(refers to preparing meals, shopping for groceries or clothes, 
 
 
using the telephone, managing money, etc.) 
grade 3: 
severe 
or 
medically 
significant 
but 
not 
immediately 
life-threatening; hospitalisation or prolongation of hospitalisation 
indicated; disabling; limiting self-care activities of daily living  
o grade 4: 
life-threatening consequences; urgent intervention indicated 
o grade 5: 
death related to AE 
 outcome 
 action taken (no action taken; study drug temporarily interrupted; study drug permanently 
discontinued due to this AE; concomitant medication taken; non-drug therapy given; 
hospitalisation/prolonged hospitalisation) 
 seriousness: whether it is serious, where a SAE is defined as one that: 
o results in death 
o is life-threatening 
o requires inpatient hospitalisation or prolongation of existing hospitalisation 
(hospitalisation signifies that the patient was an inpatient for at least one overnight 
stay) unless hospitalisation is for: 
 routine treatment or monitoring of the studied indication, not associated with 
deterioration of symptoms related to NHL 
 elective or preplanned treatment for a pre-existing condition that is unrelated 
to NHL and has not worsened since signing of the informed consent 
 social reason and respite care in the absence of any deterioration in the 
patient’s general condition 
 hospitalisation signifies that the patient was an inpatient for at least one 
overnight stay 
o results in persistent or significant disability or incapacity 
o is a congenital anomaly or birth defect 
o is medically significant, i.e. defined as an event that jeopardises the patient or 
may require medical intervention to prevent one of the outcomes listed 
previously. 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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The term “life-threatening” refers to an event in which the patient was, in the view of the 
reporting investigator, at immediate risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe. Medical judgment 
should be exercised in deciding whether an AE is serious in other situations: important AEs that 
are not immediately lifethreatening- or do not result in death or hospitalisation but may 
jeopardise the patient or may require intervention to prevent one of the other outcomes listed in 
the previous definitions should also be considered as serious. 
 
AEs of special interest are TFR, TLS, SPM, IRRs and allergic reactions to study drug ≥grade 3, 
cytokine release syndrome and overdoses. 
 
Unlike routine safety assessments, SAEs and AEs of special interest are monitored continuously 
and have special reporting requirements (see Section 8.2). 
 
The investigator should determine the causality (relationship to the study drugs) based on his/her 
clinical experience and on the information given in the IB for MOR00208 and the SmPC / 
Prescribing Information for lenalidomide. The causal relationship of all AEs to the study drug 
will be judged as either suspected or not suspected. A suspected causal relationship means at 
least a reasonable possibility that the event is caused by the study drug. If no relationship has 
been provided by the investigator, the event will be considered as related to the study drug. 
 
Information about adverse drug reactions already known about the investigational study drugs 
can be found in the IB for MOR00208 and the SmPC from lenalidomide, or will be 
communicated in the form of Investigator Notifications. This information will be included in the 
patient ICF and should be discussed with the patient during the study, as needed. 
 
8.2 Adverse Event and Serious Adverse Event Recording and 
Reporting 
All AEs (except non-serious AEs for screening failures) that occur after the provision of 
informed consent and up to 30 days after last study drug administration will be recorded in the 
eCRF and in the patient’s medical records, whether or not they are considered by the investigator 
to be related to the study drug. Thereafter, only AEs assessed as related should be recorded. All 
AEs should be recorded using acceptable diagnoses, if possible. For screening failure patients, 
non-serious AEs will not be recorded in the eCRF but only in the patient’s medical records. 
 
In addition, all SAEs and AEs of special interest will be recorded on the SAE report form. Study 
centres and investigators are instructed to report all SAEs and AEs of special interest to the 
contract research organisation (CRO) mentioned below within 24 hours using the 
studyspecific- SAE report form. Preferably, the diagnosis instead of the individual symptoms 
should be reported. For overdoses, the diagnosis and if applicable the accompanying symptoms 
caused by the overdose should be reported. 
 
If an AE has already been reported, it is not necessary to report each individual sign and symptom 
of that AE as a separate AE. For example, if a myocardial infarction is reported as an AE, there 
is no need to report elevated creatine phosphokinase and abnormal ECG, or other related signs, 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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symptoms, or laboratory values as separate AEs. However, if such events occur in isolation, and 
myocardial infarction is not diagnosed, then each event should be reported as an AE. 
 
All non-serious AEs must be followed up for a final outcome. An outcome of “unknown” is not 
considered to be an acceptable final outcome. An outcome of “not yet resolved” is an acceptable 
final outcome for non-serious AEs at the end of a patient’s participation in a study. All SAEs 
must be followed up for a final outcome until resolution or, if resolution becomes unlikely, until 
stabilisation or death. The follow-up for SAEs that are a progression of DLBCL only until the 
end of a patient’s participation in a study is acceptable. This includes obtaining information on 
recovery and any sequelae and, in the case of a fatal outcome, the cause of death. 
 
Events that are clearly caused by progression of the underlying disease (for example 
transformation to more aggressive histology) should not be recorded as AEs or SAEs. These data 
will be captured as efficacy assessment data only. If there is any uncertainty as to whether an 
event is due to disease progression, it should be recorded as an adverse event. 
 
Deaths that occur during the protocol-specified adverse event reporting period that are being 
attributed to progression of the underlying disease should not be recorded as AEs or SAEs. All 
other on-study deaths, regardless of relationship to study drug, must be recorded on the Adverse 
Event eCRF and immediately reported to the Sponsor. Death should be considered an outcome 
and not a distinct event. The event or condition that caused the fatal outcome should be recorded 
as the single medical concept on the Adverse Event eCRF. Generally, only one such event should 
be reported. 
 
During survival follow-up, deaths attributed to progression of the underlying disease should be 
recorded in the eCRF. 
 
Notification of initial or followup- SAE information (by using the standard SAE form provided 
by the sponsor) must be sent by fax to the CRO at the following numbers as appropriate: 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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For any safetyrelated- or protocol related questions, please use the contact numbers below (24/7 
coverage): 
 
24/7 Medical Emergency 
Coverage (out of office 
hours) 
Medical Emergency 
Coverage (during Medical 
Monitor office hours) 
 
 
8.3 Pregnancies 
As detailed in the Schedule of Assessments (Table 5) and Section 7.1, serum pregnancy testing 
will be carried out at the Screening, and End of Treatment Visits (performed centrally). During 
the treatment period of the study, urine pregnancy testing will be performed locally and can be 
repeated if required. Any pregnancy that occurs during study participation should be reported 
using a Clinical Trial Pregnancy Form. To ensure patient safety, each pregnancy of a study 
patient or a female partner of a study patient must also be reported within 24 hours of learning 
of its occurrence to 
by fax at the following number: 
 
Female study patients who become pregnant must be withdrawn from the study treatment period 
(IMP is to be discontinued immediately). 
 
A newly diagnosed pregnancy in a patient or female partner of a study patient who has received 
study medication is not considered an SAE unless it meets any criteria of seriousness or it is 
suspected that the study medication interacted with a contraceptive method and led to pregnancy. 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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If the pregnancy results in clinical consequences/complications in mother or child, e.g., if the 
child is born with a birth defect, this should be reported as an SAE of mother or child as 
applicable. 
 
The pregnancy should be followed up to determine outcome, including spontaneous or voluntary 
termination, details of birth, and the presence or absence of any birth defects or congenital 
abnormalities or maternal and newborn complications. Every infant has to be followed up for 
2 months after delivery. 
 
 
9 DATA HANDLING AND ARCHIVING 
 
9.1 Completing and Signing Case Report Forms 
Electronic CRFs will be used in this study. Data will be entered by trained site personnel, with 
reasons given for any missing data. Any errors should be corrected within the electronic system. 
The audit trail will record all changes made, the date and time of the correction, and the person 
correcting the error. The appropriate electronic signature will be provided. The investigator will 
receive a copy of their eCRF in a readable format after database lock for archiving. 
 
9.2 Clinical Data Management 
The CRO will be responsible for the processing and quality control of the data according to the 
CRO’s standard operating procedures (SOPs). Data management will be carried out by the CRO. 
The handling of data, including data quality control, will comply with all applicable regulatory 
guidelines. 
 
Details for data validation and edit checks will be described in appropriate data management 
documents. Queries will be handled via the eCRF system. Data cleaning will continue until all 
queries are resolved. 
 
Medical coding will use Medical Dictionary for Regulatory Activities (MedDRA, Version 18.0 
or higher) for AEs and medical history and the WHO-drug dictionary enhanced for medication. 
 
9.3 Archiving and Filing 
All study documentation at the investigator site and sponsor site will be archived in accordance 
with International Conference on Harmonisation (ICH) E6 Good Clinical Practice (GCP) 
guidance and the clinical trial agreement. 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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10 STATISTICAL METHODS AND PLANNED ANALYSIS 
 
10.1  Populations for Analysis 
The following analysis populations will be used: 
 
Full analysis set (FAS): 
The FAS includes all patients who received at least one dose of MOR00208 and one 
dose of LEN. This means that both study drugs must have been applied at least once. 
 Per protocol set (PPS): 
The PPS is the subset of all subjects in the FAS without any major protocol 
non-compliances. All patients in the FAS, had at least one dose of MOR00208 and one 
dose of LEN drug. Patients without any post-baseline assessment of DLBCL response 
or having major protocol deviations will be excluded from the PPS. 
 Safety analysis set (SAF): 
All patients who received at least one dose of MOR00208 or LEN study drug. 
 
Primary, secondary and supportive efficacy parameters will be evaluated using the FAS and PPS, 
while safety parameter evaluations will use the safety set (SAF), as well as for evaluations on 
immunogenicity and biomarkers. 
 
The primary analysis of the primary efficacy endpoint will be based on the FAS, whereas the 
analysis using the PPS has a supportive function. Decisions about whether a protocol deviation 
is relevant for the exclusion of a patient from the PPS will be made before database closure. 
 
10.2 Primary Endpoint 
1. The primary efficacy endpoint will be ORR (ORR = CR + PR) 
 
10.3 Secondary Endpoints 
2. DCR, DoR, PFS, OS, TTP and TTNT 
3. Incidence and severity of AEs 
4. Determination and characterisation of a potential anti-MOR00208 antibody formation 
5. PK analysis of MOR00208 
6. Absolute and percentage change from baseline in measurements of B-, T- and NK cell 
populations 
7. Analysis of exploratory and diagnostic biomarkers (e.g., CD19, CD20, BCL2, and BCL6 
expression, CD16 expression on NK cells, ADCC capacity, and gene expression profiling 
for cell of origin subtyping and evaluation of AEs and ORR stratified by FcγRIIIa and 
FcγRIIa polymorphism) are planned to be investigated during the course of the study. 
 
10.4 General Statistical Methods 
Tabulation of summary statistics, graphical presentations, and statistical analyses will be 
performed using appropriate statistical software. Continuous, quantitative variable summaries 


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Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
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will include the number of patients (N) (with non-missing values/valid cases), mean, standard 
deviation, minimum, 25th quartile, median, 75th quartile and maximum, except for 
pharmacokinetic metrics, where additional statistics may be used. 
 
Categorical, qualitative variable summaries will include the frequency and percentage of 
patients/entries, who/which are in the particular category. 
 
The assumed overall type I error rate/significance level for the primary and secondary efficacy 
parameters is 5%, two-sided. Two-sided confidence limits will be evaluated at 95%, p-values 
from inferential tests comparing specific patient cohorts/patient subgroups will be compared 
to 5%. 
 
Missing values will not be substituted by estimated values. All statistical evaluations will be 
based on valid cases except for procedures described for calculating response rates or in case of 
censoring within the Kaplan-Meier methodology. In the case of incomplete start or stop dates of 
AEs or concomitant medication appropriate conservative imputation methods will be specified 
in the Statistical Analysis Plan (SAP). 
 
Baseline values will be defined as the last pre-administration observation used for calculating 
post-administration changes from baseline. 
 
All data obtained and entered into the database will be provided in separate data listings showing 
individual patient values. A SAP detailing the statistical analyses and possible deviations from 
the protocol will be prepared before hard lock of database. 
 
10.5 Patient Disposition 
An overview table will be provided for all patients and will include the number of patients 
enrolled, the number of patients in each analysis population set, the number of completers and 
the number of withdrawals and the reasons for withdrawal. Compliance parameters for drug 
administration will be tabulated. 
 
Demographic information will be summarised using descriptive statistics or counts and 
percentages. 
 
General medical histories and DLBCLspecific- medical histories will be summarised by counts 
and percentages using appropriate classification codes. Concomitant medications will be 
recorded and tabulated with counts/percentages showing the number of medications/percentage 
used in each medication class. 
 
10.6 Analysis of Efficacy Data 
 Primary Efficacy Endpoint ORR 
Local and independent response evaluations (progressive disease, SD, PR and CR) will be 
tabulated with counts/percentages for each visit available. Missing response evaluations will be 
taken into account, with patients with missing responses included in the denominator for 
calculating the rates). 


Product Name: MOR00208 
Protocol Number: MOR208C203 
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Objective response is defined as being when a patient is classified as having a CR or PR after 
DLBCL evaluation using the IWG treatment response criteria for malignant lymphoma (Cheson 
et al., 2007; see Appendix_G). 
 
The ORR, for the primary efficacy endpoint, is defined as the proportion of patients with a CR 
or PR (ORR = CR + PR) up until disease progression, based on central radiological + clinical 
evaluations. 
 
The denominator for calculating the rate will be based upon the total number of patients in the 
FAS population. As a sensitivity analysis, patients without any post-baseline assessment of 
response will be included in the denominator for ORR calculation. The number of responding 
patients and respective rates as well as the 95% confidence limits will be presented. 
 
The SAP will specify further sensitivity and supportive analyses, as well as possible evaluation 
of further response parameters (e.g., best response). 
 
 Secondary Endpoints 
10.6.2.1 Disease Control Rate (DCR) 
The DCR is defined as CR + PR + SD (i.e. ORR + SD) and will be evaluated as for ORR. 
 
10.6.2.2 Duration of Response (DoR) and Time to Next Treatment (TTNT) 
DoR is defined as the time interval between the initial time point of tumour response (CR or PR 
whichever status is recorded first) and the first date that recurrence of progressive disease is 
documented. Response duration by the local and central assessment will be tabulated with 
descriptive statistics. 
 
Disease progression is defined as the first occurrence of progressive disease according to the 
revised response criteria (Cheson et al., 2007) as assessed by central radiology / clinical readers. 
 
TTNT is defined as the time from study entry (= first dosing) to the institution of next therapy 
for any reason including disease progression, treatment toxicity and patient preference. TTNT 
will be descriptively analysed. 
 
10.6.2.3 Time to Event Variables: Progression-Free Survival (PFS), Overall Survival 
(OS), and Time to Progression (TTP) 
PFS is defined as the time elapsed between study entry (= first dosing) and lymphoma 
progression or death from any cause, whichever occurs first. Patients not experiencing a 
lymphoma progression or death from any cause will be censored at the last available tumour 
assessment. The same holds true for patients who are lost-to-follow-up. 
 
OS is defined as time from study entry (= first dosing) until the date of death from any cause. 
Patients who are alive but have dropped out early will be censored at the time of the last available 
study visit assessment. 


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TTP is defined as the time from study entry (= first dosing) until documented lymphoma 
progression or death as a result of lymphoma. The events of interest are only disease progression 
and death from lymphoma. Death from other causes will not be taken into account (will be 
censored) in the TTP evaluation. Patients not experiencing progressive disease will be censored 
at the last NHL assessment. Deaths from other causes will be censored at the time of death. Early 
drop-outs without any documented date of progression will be censored at the time of the last 
NHL assessment. 
 
Kaplan-Meier methodology will be used to evaluate median survival, presenting corresponding 
statistical parameters and Kaplan-Meier survival curves. Further analyses concerning influence 
of IPI and GC/non-GC B-cells will be specified in the SAP. 
 
TTP will be compared to the TTP of the patients’ most recent therapy by tabulating descriptive 
statistics (including 95% confidence limits). 
 
For the purposes of the protocol the day of enrolment is defined as the date of the first treatment 
(study entry). 
 
The SAP will provide further details on how to evaluate the influence of IPI and GC/non-GC B-
cells on ORR, DCR, PFS, OS, DoR, TTP and TTNT. Analyses will apply Kaplan-Meier methods 
using these parameters as factors, as well as stratifying analyses results by these factors or 
including these factors in appropriate multivariate models (e.g., analysis of variance [ANOVA]). 
 
The analysis of incidence and severity of AEs has been described below. 
 
10.6.2.4 Immunogenicity Analysis 
The absolute number and percentage of patients, who develop anti-MOR00208 antibodies, and 
the results of semi-quantitative anti-MOR00208 antibody titre determinations of confirmed 
positive sample assessments will be tabulated. Further details will be specified in the SAP. 
 
10.6.2.5 Pharmacokinetic Analysis 
Appropriate PK parameters for MOR00208, with a focus on, but not limited to, accumulation 
ratios, will be computed based on non-compartmental data analysis and summarised using 
descriptive statistics. Mean concentrations (on original and on log-linear scale) will be visualised 
in figures. Further details of the PK analysis will be specified in the SAP. 
 
10.6.2.6 Biomarkers 
Blood and protein biomarkers which are important in the mechanism of action of, or could 
predict response to, the study drugs will be descriptively tabulated, presenting absolute and 
change to baseline values, if applicable. 
 
For example: 
a. FcγRIIa and FcγRIIIa genotyping results will be descriptively tabulated, whereas ORR 
and selective AEs tabulations will be split by these factors  


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Protocol Number: MOR208C203 
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b. Flow cytometry results of CD16 expression on NK cells will be descriptively tabulated, 
as well as ADCC results. 
 
10.7 Analysis of Safety Data 
 Adverse Events 
MedDRA (version 18.0 or higher) coded AEs will be used to show the incidence of all AEs by 
SOC, PT, relationship to treatment, severity and seriousness. 
An AE summary table will present the number of events, number of patients and the percentage 
of patients having TEAEs, SAEs, and TEAEs that led to study discontinuation. 
 
AE frequency tables will display event and patient counts by MedDRA, SOC and PT for each 
treatment arm. Such summaries will be displayed for all TEAEs, TEAEs by maximum 
severity/toxicity, TEAEs by relationship to study drug, SAEs, drug-related TEAEs and TEAEs 
that led to study discontinuation. 
 
 Clinical Laboratory Evaluations 
The analysis of laboratory parameters for each treatment arm will be presented separated into 
blood parameters (e.g., haematology, serum chemistry, coagulation, serology for hepatitis B and 
C) urine parameters (e.g., urinalysis) and serum pregnancy test. 
 
Descriptive summaries of actual (absolute) values and selected change-from-baseline values for 
continuous laboratory parameters of interest will be presented. Investigator assessments of the 
clinical relevance of each laboratory parameter will be analysed by frequency tabulations. 
 
The assessment of categorical urinalysis variables will be tabulated by time point, results for 
example of hepatitis B and C serology and pregnancy test results will be summarised using 
counts/percentages. Further details (e.g., tabulation of shifts, special analyses with respect to NCI 
CTC grading) will be detailed in the SAP. 
 
 Physical Examination, Vital Signs and Electrocardiogram (12-lead 
ECG) 
Complete and limited PE results will be summarised by body system and tabulated as 
counts/percentages. New and worsening abnormal physical examination findings during the 
study will be entered as AEs and analysed within the AE tables in detail. Descriptive summaries 
of vital sign parameters will be calculated. Summary ECG assessments will be tabulated by time 
point using frequency tabulations. Results of the 12-lead ECG (PR, QRS, QT, RR interval 
values) will be flagged to show whether a value is below or above the normal limit and summary 
statistics will be provided for ECG parameters. 
 
10.8 Sample Size Determination 
Approximately 80 patients with R-R DLBCL who meet the inclusion criteria and have none of 
the exclusion criteria will be randomly enrolled into the study. The study will be performed with 
an interim stop for the evaluation of the safety of the LEN dosage. No adjustment of sample size 


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Protocol Number: MOR208C203 
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or adaptation of efficacy evaluations will be made at this point. As the primary purpose of this 
study is to evaluate the clinical efficacy of 25 mg daily oral LEN combined with 12 mg/kg 
MOR00208 administered by IV infusion in patients with R-R DLBCL, no formal statistical 
hypothesis testing will be performed. 
 
For the determination of a suitable sample size, it is assumed that the combination treatment 
could improve the ORR from a value of 20% (under monotherapy) to 35% (under combination 
therapy). Applying an exact binomial test with a two-sided significance level of 5% and a power 
of 85% the estimated sample size is 73 patients (calculation performed by nQuery Advisor® 
7.0). According to this scenario an observed ORR of 32% would lead to a statistically significant 
study outcome. Assuming a drop-out rate of 10%, a total sample size of about 80 patients is 
estimated. 
 
The sample size determination has been conducted using various possible monotherapy and 
combination effect ORR rates and various power assumptions. Literature evaluation of study 
results concerning the ORR rates of LEN or comparable products (as mono- or 
combination-therapy) as well as former study results for MOR00208 were used to justify 
assumptions on response rates (Witzig et al., 2011; Wang et al., 2013). 
 
10.9 Safety Run-In 
The study will consist of two parts, which will be performed sequentially. The first part of the 
study (safety run-in) will conclude with an interim safety review after the first 6 patients have 
been accrued (see Section 5.1). This interim safety assessment will evaluate the number and type 
of AEs occurring during the first cycle, as well as the laboratory values (e.g., biochemistry and 
haematology) and other relevant safety data as necessary, with a view to providing a 
recommendation on the LEN dose to be used in the study, going forward. 
 
The second part of the study will only be authorised to open for enrolment following the outcome 
of this evaluation. If, during the second part of the study, the safety profile of the combination is 
satisfactory, study patient accrual will continue until the full goal of approximately 80 patients 
is achieved. 
11 SPECIAL REQUIREMENTS AND PROCEDURES 
 
11.1 Charters 
A charter outlining the central independent assessment (radiological and clinical) and review 
processes will be made available. 
 
11.2 Protocol Amendments and Other Changes in Study Conduct  
Any changes to the protocol will be made in the form of an amendment. 
 
Changes to the conduct of the study are not permitted. Any unforeseen changes in the study 
conduct will be recorded in the clinical study report. 
 


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11.3 Regulatory and Ethical Considerations, Including the 
Informed Consent Process 
Prior to initiation of a study site, MorphoSys will obtain favourable opinion/approval from the 
appropriate regulatory bodies/local health authorities (in accordance with local regulations) and 
the IRB/IEC to conduct the study in accordance with ICH GCP and applicable country-specific 
regulatory requirements. 
 
No substantial changes to the final approved protocol will be initiated without the IRB’s/IEC’s 
prior written approval or favourable opinion and approval by the regulatory bodies/local health 
authorities of a written amendment, except when necessary to eliminate immediate hazards to 
the patients or when the change involves only logistics or administration. 
 
This clinical study was designed and shall be conducted and reported in accordance with the 
protocol, with ICH E6 GCP guidelines, with applicable local regulations, and with the ethical 
principles laid down in the Declaration of Helsinki, including, but not limited to: 
 IRB/IEC review and favourable opinion/approval of the study protocol and any 
subsequent amendments 
 patient informed consent 
 investigator reporting requirements 
 MorphoSys will provide full details of the above procedures, either verbally, in writing, 
or both. 
 
The investigator will obtain freely given written consent from each patient after an appropriate 
explanation of the aims, methods, anticipated benefits, potential hazards and any other aspect of 
the study that is relevant to the patient's decision to participate.  
 
The ICF must be signed, with name and date noted by the patient, before the patient is exposed 
to any study-related procedure, including screening tests for eligibility. 
 
11.4 Quality Control (Study Monitoring) 
Study monitoring will be performed in accordance with ICH E6 GCP guidelines, the sponsor’s 
and CRO’s SOPs, the sponsor’s and CRO’s written instructions, the protocol, and all applicable 
laws and regulations. 
 
The sponsor’s monitors will contact the site prior to the start of the study to review with the site 
staff the protocol, study requirements, and their responsibilities to satisfy regulatory, ethical, and 
the sponsor’s requirements. 
 
MorphoSys will monitor the study to ensure that the: 
 data are authentic, accurate, and complete 
 safety and rights of patients are being protected 
 study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements. 


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The investigator and the head of the medical institution (where applicable) agree to allow the 
monitor direct access to all source data documents. 
 
11.5 Quality Assurance 
According to ICH E6 GCP guidelines, the sponsor or regulatory authorities may audit the 
investigational sites. The sponsor’s Quality Assurance Unit and/or their authorised 
representative(s), independent of the Clinical Operations and Clinical Development Department, 
are responsible for auditing the study. The investigator must accept such audits by the sponsor’s 
Quality Assurance Unit and/or their authorised representative(s) and ensure access to all source 
data/documents. 
 
The investigator must accept that regulatory authorities may conduct an inspection to verify 
compliance of the study with GCP guidelines. If informed that a regulatory inspection will take 
place, the investigator must inform the sponsor without delay. 
 
11.6 Insurance 
This study is covered under the sponsor’s Liability Insurance Policy covering damage to patients 
according to applicable legal requirements. A copy of the Certificate of Insurance and/or an 
information leaflet containing essential information about the insurance coverage will be 
provided to the investigator as required by Regulatory Authorities, IRBs or IECs. 
 
The investigator must inform the patients accordingly and must also point out that the patients 
are allowed to undergo other medical treatment (except in an emergency) only with the 
investigator’s prior approval or to receive additional medication only with the investigator’s prior 
approval. 
 
11.7 Publication Policy 
Any presentation or publication of data from this study will be intended as a joint publication by 
the investigator(s)/appropriate study site personnel and appropriate sponsor personnel. 
Authorship will follow the International Committee of Medical Journal Editors (ICMJE) 
Uniform Requirements for Manuscripts Submitted to Biomedical Journals and will be defined 
prior to the first publication. 
 
For multicentre studies, it is mandatory that the first publication be based on data from all centres, 
and that the data are analysed and submitted as stipulated in the protocol by a statistician assigned 
by the sponsor. 
 
Thus, no investigator or institution may publish any results of the study conducted at their site, 
before such a first multicentre publication is made which covers the data from all sites. The 
authors have the final responsibility for the decision to submit their manuscript and shall be given 
full access to the data resulting from the study. 
 


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The coordinating investigator and/or authors shall coordinate any intended publication of study 
results with the sponsor, to enable the sponsor to ensure that results are presented in a responsible 
and coherent manner. 
 
The sponsor reserves the right to review all manuscripts and abstracts at least 60 days before 
their submission for publication or presentation. This is not intended to restrict or hinder 
publication or presentation, but is to allow the sponsor to protect the confidentiality of 
information and to provide comments that may not yet be available to the investigator. 
 
At the sponsor’s request, any confidential information (other than study results) will be deleted 
and all reasonable comments made by the sponsor will be incorporated prior to the submission 
for publication or presentation. In the rare event that such publication would affect the 
patentability of any invention to which the sponsor has rights, the sponsor has the right to request 
an additional delay to the proposed publication of no more than 90 days so as to allow the sponsor 
to protect its intellectual property rights. 
 
The results of the study may be used by MorphoSys AG for the purposes of national and 
international registration, publication, and information for medical professionals. If necessary, 
the authorities will be notified of the investigators’ names, addresses, qualifications, and extent 
of involvement. 
 


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Vose JM, Habermann TM, Czuczman MS, et al. Single-agent lenalidomide is active in patients 
with relapsed or refractory aggressive non-Hodgkin lymphoma who received prior stem cell 
transplantation. Br J Haematol. 2013;162:639-47. 
 
Wang M, Fowler N, Wagner-Bartak N, et al. Oral lenalidomide with rituximab in relapsed or 
refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. 
Leukemia. 2013;27:1902-9. 
 
Wiernik PH. Lenalidomide in lymphomas and chronic lymphocytic leukemia. Expert Opin 
Pharmacother. 2013;14:475-88. 
 
Wiernik PH, Lossos IS, Tuscano JM, et al. Lenalidomide monotherapy in relapsed or refractory 
aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008;26:4952-7. 
 
Witzig TE, Vose JM, Zinzani PL, et al. An international phase II trial of single-agent 
lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 
2011;22:1622-7. 
 
Woyach JA, Awan F, Flinn IW, et al. A Phase I Trial of the Fc Engineered CD19 Antibody 
XmAb®5574 (MOR00208) Demonstrates Safety and Preliminary Efficacy in Relapsed Chronic 
Lymphocytic Leukemia. Blood. 2014;124(24):3553-60. 
 
Younes A, Kim S, Romaguera J, et al. Phase I multidose-escalation study of the anti-CD19 
maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks 
to patients with relapsed/refractory B-cell lymphoma. J Clin Oncol. 2012; 30: 2776-82. 
 
Zhang H, Vakil V, Braunstein M, et al. Circulating endothelial progenitor cells in multiple 
myeloma: implications and significance. Blood. 2005;105:3286-9. 
 
Zinzani PL, Pellegrini C, Gandolfi L, et al. Combination of lenalidomide and rituximab in elderly 
patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin 
Lymphoma Myeloma Leuk. 2011;11:462-6. 
 
Zinzani PL, Rigacci L, Cox MC, et al. Lenalidomide monotherapy in heavily pretreated patients 
with non-Hodgkin lymphoma: an Italian observational multicenter retrospective study in daily 
clinical practice. Leuk Lymphoma. 2014 (doi: 10.3109/10428194.2014.964702).  
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 102 of 110 
13 APPENDICES 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 103 of 110 
Appendix A: 
Cockcroft-Gault Formula: 
 
 
 
This formula presumes weight to be measured in kilograms and creatinine to be measured in 
mg/dL. 
 
When serum creatinine is measured in µmol/L: 
 
Where Constant is 1.23 for men and 1.04 for women. 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 104 of 110 
Appendix B: 
International Prognostic Index (IPI): 
 age older than 60 
 lactate dehydrogenase level higher than normal 
 ECOG performance status score of 2 or greater (see Appendix_F) 
 stage III or IV disease 
 more than one involved extranodal disease site 
 
The International Prognostic Index (IPI) gives one point for each of the above characteristics, 
for a total score ranging from zero to five correlating with the following risk groups: 
 
 low risk: 0–1 points 
 low-intermediate risk: 2 points 
 high-intermediate risk: 3 points 
 high risk: 4–5 points 
 
 
 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 105 of 110 
Appendix C: 
Information on Investigational and Registered Products 
The Investigator’s Brochure for MOR00208, Summary of Product Characteristics (EMA) or 
Prescribing Information (US FDA) for LEN will be supplied to the study sites. 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 106 of 110 
Appendix D: 
Equivalent Doses for Corticosteroids: 
 
Name (INN) 
Example 
Equivalent doses for 
80 – 100 – 120 mg 
methylprednisolone 
Potency 
Hydrocortisone 
Hydrocortone® 
400 – 500 – 600 mg 
1 
Prednisone 
Decortin® 
100 – 125 – 150 mg 
4 
Prednisolone 
Decortin® H 
100 – 125 – 150 mg 
4 
Methylprednisolone 
Urbason® 
80 – 100 – 120 mg 
5 
Dexamethasone 
Fortecortin® 
14 – 16 – 20 mg 
30 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 107 of 110 
Appendix E: 
Ann Arbor Staging* - Cotswolds Recommendations** 
(Sources: *Carbone PP, Kaplan HS, Musshoff K, et al. Report of the committee on Hodgkin's 
disease staging classification. Cancer Res. 1971; 31:1860-61. **Lister TA, Crowther D, Sutcliffe 
SB, et al. Staging for Hodgkin's disease. Report of a committee convened to discuss the 
evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol. 
1989; 7:1630-36, [Erratum; J Clin Oncol. 1990; 8:1602]) 
 
Stage I: involvement of a single lymphatic region (I), or localised involvement of a single 
extralymphatic organ or site (IE). 
 
Stage II: involvement of two or more lymphatic regions on the same side of diaphragm (II) or 
localised involvement of an extralymphatic organ or site and one or more lymph node regions 
the same side of diaphragm (IIE). 
 
Stage III: involvement of two or more lymphatic regions on both sides of diaphragm (III) which 
may also be accompanied either by localised involvement of an extralymphatic organ or site 
(IIIE), or by involvement of the spleen (IIIS). 
 
Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs or tissue, 
with or without associated lymph node involvement.  
Bone marrow or liver involvement will always be considered as stage IV. 
 
Criteria for B-symptoms 
The presence of: (a) unintentional weight loss of more than 10% within the previous 6 months 
and/or  (b) fevers of greater than 100.5° F or 38.0° C for at least 3 consecutive days without 
other evidence of infection and/or (c) drenching night sweats without evidence of infection, is 
denoted by the suffix letter ‘B’. ‘A’ indicates the absence of these symptoms. 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
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Page 108 of 110 
Appendix F: 
ECOG Performance Status 
 
Grade Performance status 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up 
and about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 
5 
Dead 
Publication: Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and 
Response Criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-55. 
  
Credit: the Eastern Cooperative Oncology Group, Robert Comis M.D., Group Chair. 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
Confidential 
Page 109 of 110 
Appendix G: 
Response Criteria 
The response criteria in this study are those defined in the table below. All are based on the 
International Working Group Response Criteria (Cheson et al., 2007). 
 
Response  
Definition 
Nodal masses 
Spleen, liver 
Bone marrow 
CR 
Disappearance of 
all evidence of 
disease 
a) FDG-avid or PET 
positive prior to 
therapy; mass of any 
size permitted if PET 
negative 
b) Variable FDG-avid 
or PET negative; 
regression to normal 
size on CT 
Not palpable, 
nodules 
disappeared 
Infiltrate cleared 
on repeat biopsy; 
if indeterminate 
by morphology, 
immunohisto-
chemistry should 
be negative 
PR 
Regression of 
measurable disease 
and no new sites 
≥50% decrease in SPD 
of up to 6 largest 
dominant masses; no 
increase in size on CT 
a) FDG-avid or PET 
positive prior to 
therapy; one or more 
PET positive at 
previously involved 
site 
b) 
Variable FDG-
avid or PET negative; 
regression on CT 
≥50% decrease in 
SPD of nodules 
(for single nodule 
in greatest 
transverse 
diameter); no 
increase in size of 
liver or spleen 
Irrelevant if 
positive prior to 
therapy; cell 
type should be 
specified 
SD 
Failure to attain 
CR/PR but criteria 
for  progressive 
disease not met 
a) FDG-avid or PET 
positive prior to 
therapy; PET positive 
at prior sites of 
disease and no new 
sites on CT or PET 
b) 
Variable FDG-
avid or PET negative; 
no change in size of 
previous lesions on 
CT 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C203 
Date: 24 February 2021 
IND Number: 114,856 
Protocol Amendment 5, Final Version 8.0 
EudraCT Number: 2014-004688-19 
 
MorphoSys AG 
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Relapsed 
disease or 
progressive 
disease 
Any new lesion or 
increase by ≥50% 
of previously 
involved sites from 
nadir 
Appearance of a new 
lesion(s) >1.5 cm in 
any axis, ≥50% 
increase in SPD of 
more than one node, 
or ≥50% increase in 
longest diameter of a 
previously identified 
node >1 cm in short 
axis 
Lesions PET positive if 
FDG-avid lymphoma 
or PET positive prior 
to therapy 
>50% increase 
from nadir in the 
SPD of any 
previous lesions 
New or recurrent 
involvement 
Abbreviations: CR=complete response; CT=computed tomography; FDG=[18F]fluorodeoxyglucose; PET=positron emission 
tomography; PR=partial response; SD=stable disease; SPD=sum of the product of the diameters.