Clinical trial NCT02639910
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma
Keywords: CD19 MOR208 MOR00208 CLL SLL COSMOS tafasitamab
Sponsor: MorphoSys AG
Start date: 2016-11-01; Completion date: 2021-12-01
Enrollment: 24 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a two-cohort, multicenter, open-label study of tafasitamab (MOR208) combined with idelalisib or venetoclax in adult patients with R/R CLL or R/R SLL pretreated with a BTK inhibitor (e.g., ibrutinib) as single agent or as part of combination therapy. Patients completing the study treatment are invited to participate in an optional biomarker sub-study.

Detailed description:
The purpose of this study is to evaluate the clinical safety and preliminary efficacy of tafasitamab (MOR208) combined with idelalisib or venetoclax. The study will include safety run-in phase for each cohort with an evaluation of the safety data by an Independent Data Monitoring Committee.

An optional sub-study has been introduced to collect biological samples for investigations on biomarkers (e.g., CD19 expression) after tafasitamab treatment.

Arms: arm 1: tafasitamab (MOR208) in combination with idelalisib arm 2: tafasitamab (MOR208) in combination with venetoclax
Interventions: intervention 1: Tafasitamab intervention 2: Idelalisib intervention 3: Venetoclax
Intervention descriptions: intervention 1: tafasitamab (MOR208) dose: 12 mg/kg intravenous infusion intervention 2: idelalisib dose: 150 mg twice daily orally intervention 3: venetoclax dose: 400 mg once daily orally

Protocol documents:
Prot_001.pdf: 
Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
Confidential 
Page 1 of 160 
REDACTED PROTOCOL 
The information contained in the attached report is the property of MorphoSys AG and should not be shared or used 
for any purpose other than that for which it was provided. Laws require that MorphoSys AG protects patient privacy. 
MorphoSys AG may have legal and contractual obligations not to disclose technical information related to vendors. 
 
CLINICAL STUDY PROTOCOL 
Protocol Number:  MOR208C205 
 
Protocol Title:  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 
 
 
 
 
 
IND Number: 
114,856 
EudraCT Number: 
2015-002915-14 
Phase of Development: 
II 
Sponsor: 
MorphoSys AG 
Sponsor's Address: 
Semmelweisstr. 7 
D-82152 Planegg 
GERMANY 
Date of Protocol: 
ClinicalTrials.gov Identifier: 
10 January 2019 
NCT02639910 
 
-CONFIDENTIAL- 
This document and its contents are the property of and confidential to 
MorphoSys AG.  Any unauthorized copying or use of this document is 
prohibited. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
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SIGNATURES 
 
CTP Amendment No. 7, Version 11.0, dated 10 January 2019 
 
Approved/Authorized By: 
 
Signature: 
 
Date: 
 
 
XXXXXXXXXX 
 
(DD-MMM-YYYY) 
 
XXXXXXXXXXXXX 
 
 
 
MorphoSys AG 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature: 
 
Date: 
 
 
XXXXXXXXXX 
 
(DD-MMM-YYYY) 
 
XXXXXXXXXX 
 
 
 
MorphoSys AG 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
Confidential 
Page 3 of 160 
Country Coordinating Investigator’s Signature (in countries 
where required) 
 
I have read the entire clinical study protocol. I agree that this protocol version contains all the 
information required to conduct this study. 
Investigator: 
Signature: 
 
Date: 
 
 
 
 
(DD-MMM-YYYY) 
Printed Name: 
 
 
 
 
 
 
 
Address: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
Confidential 
Page 4 of 160 
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 coinvestigator(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. 
Signature: 
 
Date: 
 
 
 
 
(DD-MMM-YYYY) 
Printed Name: 
 
 
 
 
 
 
 
Address: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
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Page 5 of 160 
Contact Details of Key Study Personnel 
 
Sponsor's Medical Expert 
XXXXXXXXXX  
Clinical Program Leader 
Telephone: 
+ XXXXXXXXXX 
Fax: 
 
+ XXXXXXXXXX 
E-mail: 
XXXXXXXXXX 
Address: 
Semmelweisstr. 7  
 
D-82152 Planegg GERMANY 
Sponsor’s Clinical Project 
Manager 
XXXXXXXXXX  
Clinical Trial Leader 
Telephone: 
+ XXXXXXXXXX 
Fax: 
 
+ XXXXXXXXXX 
E-mail: 
XXXXXXXXXX 
Contact for Serious Adverse 
Events (SAEs) 
XXXXXXXXXX 
Europe: 
Fax: 
+ XXXXXXXXXX 
E-mail: 
XXXXXXXXXX 
United States: 
Fax: 
+ XXXXXXXXXX 
E-mail: 
XXXXXXXXXX 
Medical Monitor 
(24/7 Medical Coverage) 
Globally*: 
Telephone: 
+ XXXXXXXXXX 
 
* This is a chargeable telephone number allowing a global reach 
from both landlines and mobile phones) 
XXXXXXXXXX  
On this internet page a list of country-specific toll-free telephone 
numbers is provided. Note that not all countries globally have 
access to toll-free numbers as indicated on the “24/7 Medical Help 
desk” index. Countries without toll-free numbers need to dial the 
chargeable number as indicated above. Furthermore, toll-free 
numbers are not available from mobile phones. 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
Confidential 
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1 TABLE OF CONTENTS 
1.1 Overall of Contents 
1 
TABLE OF CONTENTS ......................................................................................... 6 
1.1 
Overall of Contents.............................................................................................................. 6 
1.2 
List of Tables ...................................................................................................................... 11 
1.3 
List of Figures .................................................................................................................... 12 
2 
PROTOCOL SYNOPSIS ....................................................................................... 13 
3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..................... 23 
4 
BACKGROUND ..................................................................................................... 28 
4.1 
Overview of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma .. 28 
4.2 
Treatment of Chronic Lymphocytic Leukemia .............................................................. 28 
4.3 
Idelalisib in Hematological Malignancies ........................................................................ 31 
4.4 
Venetoclax in Hematological Malignancies ..................................................................... 32 
4.5 
Overview of MOR00208 .................................................................................................... 33 
4.5.1 
Nonclinical Studies ................................................................................. 33 
4.5.2 
Clinical Experience with MOR00208 in CLL ........................................ 35 
4.5.3 
Safety of MOR00208 ............................................................................. 36 
5 
STUDY PURPOSE/RATIONALE ........................................................................ 38 
5.1 
Disease Background and Rationale ................................................................................. 38 
5.2 
Rationale for the Use of Idelalisib in CLL/SLL .............................................................. 39 
5.3 
Rationale for the Use of MOR00208 in CLL/SLL .......................................................... 39 
5.4 
Rationale for the Use of Venetoclax in CLL/SLL ........................................................... 40 
5.5 
Rationale for the Combination of MOR00208 and Idelalisib in CLL/SLL ................. 40 
5.6 
Rationale for the Combination of MOR00208 and Venetoclax in CLL/SLL .............. 41 
5.7 
Rationale for Dose and Schedule of MOR00208 Administration ................................. 43 
5.8 
Rationale for Washout Period of Previous Treatment ................................................... 44 
5.8.1 
Therapeutic Antibodies from Previous Combination Treatment with 
Ibrutinib .................................................................................................. 44 
5.8.2 
Previous Treatment with Ibrutinib and Other BTK Inhibitors ............... 44 
5.9 
Rationale for Biomarker Assessment .............................................................................. 45 
6 
STUDY OBJECTIVES AND ENDPOINTS ........................................................ 46 
6.1 
Study Objectives ................................................................................................................ 46 
6.1.1 
Primary Objective ................................................................................... 46 
6.1.2 
Secondary Objectives ............................................................................. 46 
6.1.3 
Exploratory Objectives ........................................................................... 46 
6.2 
Study Endpoints ................................................................................................................ 46 
6.2.1 
Primary Endpoint.................................................................................... 46 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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6.2.2 
Secondary Endpoints .............................................................................. 46 
6.2.3 
Exploratory Endpoints ............................................................................ 46 
7 
INVESTIGATIONAL PLAN ................................................................................ 47 
7.1 
Description of Study Design ............................................................................................. 47 
7.2 
Patient Selection Criteria .................................................................................................. 50 
7.2.1 
Inclusion Criteria .................................................................................... 50 
7.2.2 
Exclusion Criteria ................................................................................... 52 
7.2.3 
Withdrawal Criteria ................................................................................ 54 
7.2.4 
Study Treatment Discontinuation ........................................................... 54 
7.3 
Investigator Study or Site Termination ........................................................................... 55 
7.4 
End of Study and Subsequent Treatment ....................................................................... 56 
8 
TREATMENTS ...................................................................................................... 56 
8.1 
Study Treatments .............................................................................................................. 56 
8.1.1 
MOR00208 ............................................................................................. 56 
8.1.2 
Idelalisib ................................................................................................. 57 
8.1.3 
Venetoclax .............................................................................................. 58 
8.2 
Pre-Medication for MOR00208 Infusions ....................................................................... 59 
8.3 
Patient Monitoring During MOR00208 Infusion ........................................................... 59 
8.4 
Management of MOR00208 Infusion-Related Reactions .............................................. 59 
8.5 
Definition for Tumor Lysis Syndrome and Prophylaxis in Cohort B ........................... 62 
8.5.1 
Definition of Tumor Lysis Syndrome .................................................... 62 
8.5.2 
Prophylaxis for Tumor Lysis Syndrome in Cohort B ............................. 63 
8.6 
Dose Modifications of MOR00208 ................................................................................... 65 
8.7 
Dose Modifications of Idelalisib ....................................................................................... 65 
8.8 
Dose Modifications of Venetoclax .................................................................................... 65 
8.8.1 
General Rules ......................................................................................... 65 
8.8.2 
Dose Modifications During the Ramp-up Phase .................................... 66 
8.8.3 
Dose Modifications After the Ramp-up Phase ....................................... 66 
8.8.4 
Dose Modifications of Venetoclax for Use with CYP3A, P-gp, BCRP 
and OATP Inhibitors .............................................................................. 66 
8.9 
Guidance for Managing Specific Adverse Events for the Combination of MOR00208 
and Idelalisib ...................................................................................................................... 69 
8.9.1 
Management of Hepatic Events .............................................................. 72 
8.9.2 
Management of Gastrointestinal Events ................................................. 73 
8.9.3 
Management of Pulmonary Events......................................................... 74 
8.9.4 
Management of Serious Infections (PJP, CMV, PML) .......................... 74 
8.9.5 
Management of Dermatological Events ................................................. 75 
8.9.6 
Management of Hematological and Immunological Events .................. 76 
8.9.7 
Management of Tumor Lysis Syndrome ................................................ 77 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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8.9.8 
Teratogenicity ......................................................................................... 77 
8.10 Guidance for Managing Specific Adverse Events for the combination of MOR00208 
and Venetoclax ................................................................................................................... 78 
8.10.1 
Management of Tumor Lysis Syndrome ................................................ 81 
8.10.2 
Management of Hematologic Toxicities ................................................ 82 
8.10.3 
Management of Teratogenicity ............................................................... 83 
8.11 Rules for Permanent Stop of Study Medication Intake ................................................. 84 
8.12 Treatment Accountability and Compliance .................................................................... 84 
8.13 Prior and Concomitant Therapy ...................................................................................... 85 
9 
STUDY PROCEDURES ........................................................................................ 88 
9.1 
Schedule of Procedures and Assessments ........................................................................ 88 
9.2 
Study Periods and Procedures ......................................................................................... 95 
9.2.1 
Patient Information and Informed Consent ............................................ 95 
9.2.2 
Screening Period ..................................................................................... 95 
9.2.3 
Documentation of Screening Failures .................................................... 96 
9.2.4 
Pregnancy and Risks Counselling .......................................................... 96 
9.2.5 
Subject Numbering ................................................................................. 96 
9.2.6 
Re-screening ........................................................................................... 97 
9.2.7 
Treatment Period .................................................................................... 97 
9.2.8 
Unscheduled Visit .................................................................................. 98 
9.2.9 
End of Treatment Visit ........................................................................... 98 
9.2.10 
Follow-up Period .................................................................................... 99 
9.2.10.1 
30-Day Safety Follow-up Visit .............................................................. 99 
9.2.10.2 
Follow-up for Drug Discontinuation/Patient Withdrawal from Study ... 99 
9.3 
Study Assessments ........................................................................................................... 100 
9.3.1 
Demographic Characteristics and Other Baseline Assessments ........... 100 
9.3.1.1 
Weight/Height ...................................................................................... 100 
9.3.1.2 
Demography ......................................................................................... 100 
9.3.1.3 
Medical History/Current Medical Conditions ...................................... 100 
9.3.1.4 
Disease Staging .................................................................................... 100 
9.3.1.5 
FcγRII/III Gene Mucosal Cheek Swab ................................................. 100 
9.3.2 
Assessment of Safety ............................................................................ 101 
9.3.2.1 
Pregnancy Testing ................................................................................ 101 
9.3.2.2 
Vital Signs ............................................................................................ 101 
9.3.2.3 
Physical Examination ........................................................................... 101 
9.3.2.4 
Electrocardiogram ................................................................................ 102 
9.3.2.5 
Laboratory Assessments ....................................................................... 102 
9.3.2.6 
Risk Assessment for Tumor Lysis Syndrome for Patients Treated with 
Venetoclax ............................................................................................ 105 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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9.3.2.7 
Adverse Events ..................................................................................... 106 
9.3.3 
Assessment of Efficacy ........................................................................ 106 
9.3.3.1 
Tumor Response Assessment ............................................................... 106 
9.3.3.2 
Tumor Response Assessment for CLL ................................................. 107 
9.3.3.3 
Tumor Response Assessment for SLL ................................................. 111 
9.3.3.4 
Bone Marrow Aspiration and Biopsy ................................................... 114 
9.3.3.5 
B-Symptoms ......................................................................................... 114 
9.3.3.6 
Assessment of MRD Response ............................................................ 114 
9.3.4 
Assessment of Pharmacokinetics ......................................................... 114 
9.3.5 
Assessment of Immunogenicity ........................................................... 114 
9.3.6 
Biomarker Assessment ......................................................................... 115 
9.3.7 
Disease Risk Assessment ..................................................................... 115 
9.3.8 
ECOG Performance Status ................................................................... 116 
10 
SAFETY MONITORING .................................................................................... 116 
10.1 Definition of Adverse Events, Serious Adverse Events and Adverse Events of Special 
Interest .............................................................................................................................. 116 
10.2 Methods and Timing for Capturing and Assessing Safety Parameters ...................... 119 
10.3 Diagnosis Versus Signs and Symptoms ......................................................................... 119 
10.4 Safety Review by the Independent Data Monitoring Committee ............................... 119 
10.5 Adverse Event and Serious Adverse Event Recording and Reporting ....................... 120 
10.6 Pregnancies ...................................................................................................................... 123 
10.7 Deaths ............................................................................................................................... 123 
11 
DATA HANDLING AND ARCHIVING ........................................................... 124 
11.1 Completing and Signing Case Report Forms ................................................................ 124 
11.2 Clinical Data Management ............................................................................................. 124 
11.3 Archiving and Filing........................................................................................................ 124 
12 
STATISTICAL METHODS AND PLANNED ANALYSES ............................ 125 
12.1 Determination of Sample Size ........................................................................................ 125 
12.2 Analysis Sets ..................................................................................................................... 125 
12.3 Patient Disposition ........................................................................................................... 126 
12.4 Demographic and Baseline Characteristics .................................................................. 126 
12.5 Safety Analysis ................................................................................................................. 126 
12.5.1 
Clinical Laboratory Evaluations ........................................................... 127 
12.5.2 
Physical Examination, Vital Signs and Electrocardiogram .................. 127 
12.6 Efficacy Analysis .............................................................................................................. 127 
12.6.1 
Analysis of Secondary Efficacy Endpoint – ORR ................................ 127 
12.7 Immunogenicity Analysis ................................................................................................ 127 
12.8 Pharmacokinetic Analysis ............................................................................................... 127 
12.9 Biomarkers ....................................................................................................................... 128 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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12.10 Primary Analysis ............................................................................................................. 128 
12.11 Final Analysis ................................................................................................................... 128 
12.12 Independent Data Monitoring Committee .................................................................... 128 
13 
STUDY MANAGEMENT ................................................................................... 128 
13.1 Regulatory Requirements and Ethical Considerations ................................................ 128 
13.1.1 
Institutional Review Board/Independent Ethics Committee ................ 129 
13.1.2 
Informed Consent ................................................................................. 129 
13.2 Data Handling .................................................................................................................. 129 
13.3 Source Documents ........................................................................................................... 129 
13.4 Use of Computerized Systems ........................................................................................ 130 
13.5 Monitoring ....................................................................................................................... 130 
13.6 Quality Control and Quality Assurance ........................................................................ 130 
13.7 Protocol Amendment and Protocol Deviation .............................................................. 131 
13.7.1 
Protocol Amendment ............................................................................ 131 
13.7.2 
Protocol Deviations .............................................................................. 131 
13.8 Investigator Contract and Insurance ............................................................................. 131 
13.9 Publication Policy and Disclosure of Data .................................................................... 131 
14 
REFERENCES ..................................................................................................... 133 
15 
APPENDICES ...................................................................................................... 140 
15.1 Appendix A: Binet and Rai Staging System .................................................................. 140 
15.2 Appendix B: Information on Investigational and Registered Products ..................... 141 
15.3 Appendix C: Diagnostic Criteria for CLL and SLL According to the IWCLL 
Guidelines 2008 ................................................................................................................ 142 
15.4 Appendix D: Indication of Treatment According to the IWCLL Guidelines 2008 ... 143 
15.5 Appendix E: Cockcroft-Gault Formula ........................................................................ 144 
15.6 Appendix F: Definitions of Childbearing Potential and Highly Effective Birth Control 
Methods ............................................................................................................................ 145 
15.7 Appendix G: New York Heart Association Functional Classification ........................ 146 
15.8 Appendix H: Equivalent Doses for Corticosteroids ..................................................... 147 
15.9 Appendix I: Effect of Idelalisib on Other Medicinal Products that are CYP3A 
Substrates ......................................................................................................................... 148 
15.10 Appendix J: Response Definition for CLL by the IWCLL Guidelines 2008 ............. 152 
15.11 Appendix K: Criteria for B-Symptoms ......................................................................... 153 
15.12 Appendix L: ECOG Performance Status ...................................................................... 154 
15.13 Appendix M: Optional Biological Marker Sub-Study ................................................. 155 
15.13.1 
Sub-Study Purpose/Rationale ............................................................... 155 
15.13.2 
Sub-Study Objectives and Endpoints ................................................... 156 
15.13.2.1 Study Objectives ................................................................................... 156 
15.13.2.2 Exploratory Study Endpoints ............................................................... 156 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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15.13.3 
Sub-Study Design ................................................................................. 156 
15.13.3.1 Description of Sub-Study design .......................................................... 156 
15.13.3.2 Study Periods ........................................................................................ 156 
15.13.4 
Patient Selection Criteria ...................................................................... 156 
15.13.4.1 Inclusion Criteria .................................................................................. 156 
15.13.4.2 Exclusion Criteria ................................................................................. 156 
15.13.5 
End of Sub-Study ................................................................................. 156 
15.13.6 
Sub-Study Procedures .......................................................................... 157 
15.13.6.1 Schedule of Procedures and Assessments ............................................ 157 
15.13.6.2 Study Assessments ............................................................................... 159 
15.13.6.3 CD19 assessment (CD19 ABC) ........................................................... 159 
15.13.6.3.1 Analysis of genetic and/or transcriptional CD19 alterations ................ 159 
15.13.6.3.2 Assessment of MOR00208 serum concentrations (PK samples) ......... 159 
15.13.7 
Safety Monitoring ................................................................................. 159 
15.13.8 
Study Management and Data Handling ................................................ 159 
15.13.9 
Sub-Study Statistical Methods and Planned Analyses ......................... 160 
 
1.2 List of Tables 
(Excluding those in the appendix) 
Table 1: 
Efficacy of Idealisib in Relapsed CLL in Phase III Trial of Idelalisib plus 
Rituximab Versus Placebo plus Rituximab (Furman et al., 2014) ................... 32 
Table 2: 
Adverse Events at Least Possibly Attributable to MOR00208 in Phase I Study 
of MOR00208 in R/R CLL (Woyach et al., 2014a) ......................................... 37 
Table 3: 
Definition of Infusion-Related Reactions and Cytokine Release Syndrome .... 60 
Table 4: 
Definitions of Laboratory and Clinical Tumor Lysis Syndrome ...................... 62 
Table 5: 
Recommended TLS Prophylaxis Based on Tumor Burden From Clinical Trial 
Data of Venetoclax ........................................................................................... 64 
Table 6: 
Dose Modification for Toxicity During Venetoclax Treatment ....................... 66 
Table 7: 
Management of Potential Venetoclax Interactions with CYP3A Inhibitors or 
Inducers, BCRP and P-gp Inhibitors and Substrates ........................................ 68 
Table 8: 
Guidance for Study Drug (Idelalisib/MOR00208) Dose Modifications Based 
on Type and Severity of Treatment-Emergent Adverse Events or Laboratory 
Abnormalities ................................................................................................... 69 
Table 9: 
Recommended Dose Modifications for Toxicities ........................................... 78 
Table 10: 
Schedule of Procedures and Assessments ........................................................ 89 
Table 11: 
Safety Laboratory Evaluations........................................................................ 103 
Table 12: 
Lugano Classification Criteria for SLL (adapted from Cheson et al., 2014) .. 112 
Table 13: 
Biomarker Assessment ................................................................................... 115 
Table 14: 
Disease Risk Assessment ................................................................................ 116 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
Confidential 
Page 12 of 160 
 
1.3 List of Figures 
Figure 1: 
Study Design ..................................................................................................... 49 
Figure 2: 
Ramp-up Dosing Schedule for Venetoclax ...................................................... 58 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
Confidential 
Page 13 of 160 
2 PROTOCOL SYNOPSIS 
Title of Study
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 
Investigational Drugs 
MOR00208 is an Fc-enhanced, humanized, monoclonal antibody 
targeting the B cell surface antigen (CD19) 
Idelalisib 
(Zydelig®) 
is 
a 
small 
molecule 
inhibitor 
of 
phosphoinositide-3-kinase (PI3K) delta, which is hyperactive in 
B cell malignancies 
Venetoclax (Venclexta® in the US and Venclyxto® in the EU) is a 
small molecule inhibitor of the B-cell lymphoma 2 (BCL-2) protein, 
which is over-expressed in B cell malignancies 
Protocol Number 
MOR208C205 
IND Number 
114,856 
EudraCT Number 
2015-002915-14 
Sponsor and CRO 
Sponsor: 
MorphoSys AG 
Semmelweisstr. 7 
82152 Planegg 
Germany 
 
Clinical Research Organization (CRO): 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
Study Phase  
Phase II 
Investigators/Study Sites 
Approx. 22 sites 
Planned Sample Size 
Approx. 12 patients per cohort 
Background/Study Purpose 
and Rationale 
Chronic lymphocytic leukemia (CLL) is the most common 
hematological malignancy. The median age at diagnosis is 72 years 
(Eichhorst et al., 2011). Treatment is tailored to the disease and 
patient characteristics, taking comorbidities, age and prognostic 
factors into considerations which results in substantial variability of 
progression-free survival (PFS) and overall survival ranging from 
several months to >10 years. 
Several combination regimens such as FCR (fludarabine, 
cyclophosphamide, rituximab) are currently available for the first-
line treatment of CLL/small lymphocytic lymphoma (SLL) patients. 
Following their approval in recent years, novel agents (ibrutinib, 
idelalisib, obinutuzumab and venetoclax) provide further effective 
therapeutic options for CLL/SLL patients. Owing to its efficacy and 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
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Page 14 of 160 
safety profile, the BTK inhibitor ibrutinib has developed into an 
important 
treatment 
option 
for 
treatment 
naïve 
and 
relapsed/refractory patients. Despite the prolonged median PFS 
under treatment with ibrutinib it is expected that the majority of 
CLL patients will relapse. Patients with relapsed and refractory CLL 
(R/R CLL) who received ibrutinib and had to discontinue treatment 
due to progression or intolerance have a particularly dismal 
prognosis. According to Jain et al. (2015), the median survival for 
all the patients was 3.1 months after discontinuing ibrutinib and did 
not differ signiﬁcantly between transformed and untransformed 
patients with CLL. In a recent publication, Maddocks et al. (2015) 
report a median survival following CLL progression of 17.6 months 
and show that the disease tends to progress quickly in patients, 
especially when the drug therapy is stopped. Most recently 
published very limited retrospective data showed that alternate 
kinase inhibitor (KI) choice, including idelalisib treatment after 
ibrutinib discontinuation, achieved an overall response rate (ORR) 
of 50% without any complete responses (CR) (Mato et al., 2015). 
More accurate data on ORR are available with venetoclax 
monotherapy from prospective study in CLL patients relapsed or 
refractory to ibrutinib therapy showing an ORR of 60.5% (Jones et 
al., 2015).  
Importantly, patients in whom ibrutinib (or other BTK inhibitor) 
failed had frequently been pretreated with anti-CD20 antibodies in 
previous lines of therapy and are considered largely refractory to 
available anti-CD20 treatment approach. Overall, the lack of 
effective treatment for this patient population constitutes an urgent 
unmet medical need. 
MOR00208 is an Fc-optimized, humanized monoclonal antibody 
targeting the B cell antigen CD19 and has been shown to 
significantly enhance in vitro antibody dependent cell mediated 
cytotoxicity 
(ADCC), 
antibody 
dependent 
cell 
mediated 
phagocytosis (ADCP) and direct cytotoxic effects (apoptosis) on the 
tumor cells (Horton et al., 2008). MOR00208 has significant single-
agent activity in preclinical model and displays synergy with 
idelalisib (a small molecule inhibitor of PI3K delta) and with 
venetoclax (a small molecule inhibitor of BCL-2) which are 
approved for CLL treatment (MorphoSys data on file). 
A phase I trial demonstrated safety and preliminary efficacy of 
MOR00208 in patients with relapsed or refractory CLL/SLL 
(Woyach et al., 2014a). In all 27 patients enrolled into this trial, the 
drug was generally well tolerated, infusion reactions of grade 1 and 
2 being the most common toxicities; the maximum tolerated dose 
(MTD) was not reached. Efficacy in that phase I trial was 
encouraging, with approximately 67% of patients achieving a partial 
response (PR) by clinical criteria and 30% according to 
International Workshop on Chronic Lymphocytic Leukemia 
(IWCLL) 2008 criteria. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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MOR00208 has demonstrated clinically significant single-agent 
efficacy in clinical studies in a variety of B cell non-Hodgkin’s 
lymphomas (NHLs) with durable overall response rates (ORR) of 
up to 27% (Jurczak et al., 2015). Idelalisib and MOR00208 have a 
safety profile which allows for the treatment of frail and elderly 
patients who constitute the main population of R/R CLL patients. 
Based on the current clinical and preclinical data the combination 
of MOR00208 with idelalisib or venetoclax are therefore 
investigated in R/R CLL or R/R SLL patients pretreated with a BTK 
inhibitor (e.g., ibrutinib). 
Study Objectives (Key 
Primary and Secondary) 
PRIMARY OBJECTIVE: 
To determine the safety of MOR00208 combined with idelalisib or 
venetoclax 
 
SECONDARY OBJECTIVES: 
1. To determine the quality of the response 
2. To assess the potential immunogenicity of MOR00208 
3. To assess the pharmacokinetic (PK) profile of MOR00208 
 
EXPLORATORY OBJECTIVES: 
 
To assess minimal residual disease (MRD) in patients 
achieving a complete or partial response 
 
To explore putative predictive biomarkers 
 
To determine and correlate prognostic factors with 
efficacy parameters 
Study Endpoints (Key 
Primary and Secondary) 
PRIMARY ENDPOINT:  
Incidence and severity of adverse events (AEs) 
 
SECONDARY ENDPOINTS: 
1. Overall response rate (ORR): defined for Cohort A as 
percentage of patients achieving a complete response 
(CR), a partial response (PR) or a partial response with 
lymphocytosis (PRL), and for Cohort B as percentage of 
patients achieving a CR or a PR 
2. Anti-MOR00208 antibody formation 
3. Pharmacokinetic analysis for MOR00208 
EXPLORATORY ENDPOINTS: 
 
Proportion of patients with MRD-negativity 
 
Absolute and percentage change from baseline in 
measurements for B-, T- and NK cell populations 
 
Analysis of exploratory and diagnostic biomarkers from 
blood (e.g., CD19 expression, BTK and phospholipase C 
(PLC)γ2 mutational status, CD16 expression on NK cells, 
antibody dependent cell mediated cytotoxicity (ADCC) 
capacity, cytogenetics and mutational analysis). 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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Design and 
Methodology/Patient 
Population 
This is a two-cohort, multicenter, open-label study of MOR00208 
combined with idelalisib or venetoclax in adult patients with R/R 
CLL or R/R SLL pretreated with a BTK inhibitor (e.g., ibrutinib) as 
single agent or as part of combination therapy. 
Patients will be treated in this trial in either Cohort A (MOR00208 
and idelalisib) or Cohort B (MOR00208 and venetoclax) for up to 
24 cycles at maximum or until progression of disease, withdrawal 
of consent, unacceptable toxicity, death or patient being lost to 
follow-up, whichever occurs first. The study will include a safety 
run-in phase for each cohort enrolling 10- approximately 12 patients 
per combination treatment. The safety run-in phase will be 
concluded with an evaluation of the safety data of all treated patients 
once 10 patients completed at least one cycle of treatment in Cohort 
A or at least 5 weeks of combination treatment in Cohort B. This 
evaluation will be done by an Independent Data Monitoring 
Committee (IDMC). In Cohort A there will be an additional safety 
evaluation of the safety data from the first 3 patients, who completed 
at least one cycle of treatment. The first 3 patients in Cohort A will 
be dosed sequentially, at least 48 hours apart. The next 7-9 patients 
may be dosed in parallel after the safety evaluation and a positive 
recommendation from the IDMC. In Cohort B all 10-12 patients will 
be dosed sequentially, at least one week apart. 
Patients completing the main study will be invited to participate in 
an optional biological marker sub-study as described in detail in 
Section 15.13 Appendix M. 
Key Inclusion/Exclusion 
Criteria 
INCLUSION CRITERIA: 
 
Diagnosis/Trial Population 
1. Age ≥18 years 
2. Chronic lymphocytic leukemia (CLL) or small lymphocytic 
lymphoma (SLL): 
a) 
history of diagnosis of CLL or SLL that meets IWCLL 
diagnostic criteria (Hallek et al., 2008) 
b) 
histologically confirmed diagnosis of SLL by lymph 
node biopsy and documented within medical records 
c) 
indication for treatment as defined by the IWCLL 
guidelines (Hallek et al., 2008) 
3. Patients must have both of the following: 
a) 
relapsed or refractory disease as defined in the protocol 
while receiving a BTK inhibitor (e.g., ibrutinib) therapy 
or intolerance of such therapy 
b) 
single-agent or combination therapy with a BTK 
inhibitor for at least one month must be the patient’s 
most recent prior anticancer therapy 
4. Eastern Cooperative Oncology Group (ECOG) performance 
status of 0 to 2 
5. Patients with a past medical history of autologous or 
allogeneic stem cell transplantation must exhibit full 
hematological recovery without any evidence or ongoing 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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treatment of active graft versus host disease before enrolment 
into the study. 
 
Laboratory Values 
6. Patients must meet the following laboratory criteria at 
screening: 
 
Adequate bone marrow function as follows: 
a) absolute neutrophil count (ANC) ≥1.0 × 109/L  
b) platelet count ≥30 × 109/L in the absence of clinically 
significant evidence of bleeding 
c) Cohort B only: hemoglobin ≥ 8.0 g/dL  
 
Adequate hepatic and renal function as follows: 
d) total serum bilirubin ≤1.5 × upper limit of normal (ULN) 
or ≤3 × ULN in cases of documented liver involvement 
by CLL. (For patients with Gilbert's disease, serum 
bilirubin up to ≤3 x ULN is allowed provided normal 
direct bilirubin.) 
e) alanine transaminase (ALT) and aspartate 
aminotransferase (AST) ≤2.5 × ULN or <3 × ULN in 
cases of documented liver involvement by CLL 
f) serum creatinine clearance calculated using a standard 
Cockcroft-Gault formula (Cockroft & Gault, 1976) must 
be: 
 Cohort A only: ≥30 mL/min 
 Cohort B only: ≥50 mL/min  
 
Other Inclusion Criteria 
7. Females of childbearing potential (FCBP, as defined in the 
protocol) must: 
a) not be pregnant as confirmed by a negative serum 
pregnancy test at screening and a 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 (Note: All females are 
prohibited to donate blood within the before mentioned 
time frame) 
c) agree to ongoing pregnancy testing during the course of 
the study, and until 3 months 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 or 
agree to use and be able to comply with the use of highly 
effective contraception without interruption during the 
study and for 3 months after the last dose of study 
medication 
e) FCBP using hormonal contraceptives should add a barrier 
method as a second form of contraception since it is 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
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Page 18 of 160 
currently unknown whether idelalisib or venetoclax may 
affect the effectiveness of hormonal contraceptives 
8. Males must use a highly effective method of contraception 
without interruption, if the patient is sexually active with a 
FCBP, and refrain from donating blood or sperm during the 
study participation and for 3 months after the last dose of 
study medication 
9. In the opinion of the Investigator the patients must: 
a) be able to understand, give written informed consent to, 
and comply with all study-related procedures, medication 
use, and evaluations 
b) not have a history of noncompliance in relation to 
medical regimens or be considered potentially unreliable 
and/or uncooperative 
 
EXCLUSION CRITERIA: 
 
Diagnosis 
1. 
Patients who have: 
a) 
non-Hodgkin’s lymphomas other than CLL/SLL 
b) 
transformed CLL/SLL or Richter’s syndrome as defined 
by the IWCLL guidelines (Hallek et al., 2008) 
c) 
active and uncontrolled autoimmune cytopenia 
 
Previous and Current Treatment 
2. 
Patients who have received treatment with a BTK inhibitor 
(e.g., ibrutinib) within 5 days prior to Day 1 dosing. 
3. 
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 
b) 
systemic corticosteroids in doses greater than prednisone 
equivalent to 20 mg/day (Exception: Patients with signs 
of rapidly progressing disease per discussion between 
the Investigator and sponsor’s medical monitor)  
c) 
received live vaccines. (Note: Vaccinations against 
influenza with inactivated virus or vaccination for 
pneumococcal diseases are allowed.) 
4. 
Patients who: 
a) 
have, in the opinion of the Investigator, not recovered 
sufficiently from the adverse toxic effects of prior 
therapies 
b) 
have a history of previous severe allergic reactions to 
prior monoclonal antibody therapy, and/or 
hypersensitivity to the active substances or to any of the 
inactive ingredients / excipients contained in the study 
drug formulations (for details see FDA Prescribing 
Information or EMA SmPC of Zydelig®(Cohort A only) 
or Venclexta® & Venclyxto® (Cohort B only)) 
c) 
concurrently use other anticancer or experimental 
treatments 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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EudraCT Number: 2015-002915-14 
 
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d) 
were previously treated with 
 
CD19-targeted therapy (applicable for Cohort A 
and B) 
 
Cohort A only: a PI3K inhibitor treatment (e.g., 
idelalisib, duvelisib) 
 
Cohort B only: a BCL-2 inhibitor treatment (e.g., 
venetoclax) 
e) 
Cohort B only: has a known allergy to both xanthine 
oxidase inhibitors and rasburicase 
f) 
Cohort B only: has received strong or moderate CYP3A 
inhibitors or inducers within 7 days, or has consumed 
grapefruit, grapefruit products, Seville oranges or star 
fruit within 3 days prior to the first dose of venetoclax 
(see for details in the protocol) 
 
Patient’s Medical History 
5. 
Prior history of malignancies other than CLL, 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 
(Tumor/Nodes/Metastasis [TNM] stage of T1a or T1b) 
6. 
Patients with myelodysplastic syndrome 
7. 
Patients with 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 
8. 
Patients with diagnosis of myocardial infarction within 
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 ischemia or significant 
conduction system abnormalities, in the opinion of the 
Investigator. (Note: Patients with stable, asymptomatic atrial 
fibrillation are allowed in the study provided they do not meet 
the other cardiac exclusion criteria) 
9. 
Patients who: 
a) 
suffered significant traumatic injury or underwent major 
surgery within 14 days prior to treatment start 
b) 
have not recovered from sequelae of traumatic injury or 
surgical operations until Day 1 dosing 
10. Patients with central nervous system (CNS) involvement or 
impairment: 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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a) 
CNS primary or secondary malignancy in present or past 
medical history (unless patient has been free of the 
disease for ≥ 5 years prior to screening)1 
b) 
CNS, meningeal or epidural malignancies (e.g., brain 
metastases, known leukemic meningeosis)1 
1 Note: Screening for cerebrospinal fluid (CSF)/CNS 
involvement is not required but may be performed at the 
discretion of the Investigator. 
c) 
CNS lesions/cerebrovascular event(s) with clinically 
significant sequelae 
d) 
history or evidence of clinically significant 
cerebrovascular CNS that would in the Investigator’s 
opinion preclude participation in the study or 
compromise the patient’s ability to give informed 
consent. 
11. Patients with: 
a) 
chronic diarrhoea and malabsorption syndrome 
b) 
any evidence of ongoing systemic viral, bacterial, or 
fungal infection (including Pneumocystis jirovecii 
pneumonia and Cytomegalovirus infection) 
c) 
history of serious allergic reactions including 
anaphylaxis and toxic epidermal necrolysis 
d) 
Cohort A only: ongoing inflammatory bowel disease as 
ulcerative colitis or Crohn’s disease  
e) 
Cohort A only: severe chronic obstructive pulmonary 
disease (COPD), pulmonary emphysema or drug-
induced pneumonitis diagnosed in previous medical 
history 
12. Patients with known seropositivity for or history of active 
viral infection with human immunodeficiency virus (HIV) 
(Additional information: no safety data on the use of CD19 
antibodies in HIV positive patients are currently available) 
13. Patients with known positive hepatitis B and/or C serology 
(as defined in the protocol). 
 
Dose, Route of 
Administration, Treatment 
Regimen 
Patients will be treated with MOR00208 and idelalisib or 
venetoclax for up to 24 cycles at maximum or until progression of 
disease, withdrawal of consent, unacceptable toxicity, death or 
patient is lost to follow-up, whichever occurs first. 
MOR00208 dose: 12 mg/kg 
For the first 3 months of the study, each 28-day cycle will consist of 
a MOR00208 intravenous infusion of the dose of 12 mg/kg 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 biweekly basis (every 
14 days) with infusions on Days 1 and 15 of each cycle from Cycle 
4 to 6, and on a monthly basis on Day 1 of each cycle from Cycle 7. 
Idelalisib dose:  


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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EudraCT Number: 2015-002915-14 
 
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Patients will self-administer the dose of 150 mg twice daily orally 
continuously during the study duration. 
Venetoclax dose:  
To mitigate the risk for tumor lysis syndrome (TLS), treatment of 
patients with venetoclax will be initiated at 20 mg up daily dose 
from Cycle 1 Day 8 (C1D8) for 7 days, followed by a weekly ramp-
up dosing schedule (50 mg, 100 mg, 200 mg daily dose) to the 
recommended daily dose of 400 mg, starting from C2D8. Patients 
will self-administer venetoclax throughout the study duration 
except during hospitalization. 
Study Participation 
Duration 
Treatment with MOR00208 and idelalisib or venetoclax will 
continue until disease progression. If a compound specific adverse 
reaction occurs that requires the discontinuation of MOR00208, 
idelalisib or venetoclax the other therapy will be continued until 
progression of disease, withdrawal of consent, unacceptable 
toxicity, death or patient being lost to follow-up, whichever occurs 
first. 
The duration of the main study is limited to a maximum of 5 years 
in total. Patients who have not progressed at the end of the treatment 
period (after 24 treatment cycles) or at the end of the total study 
duration may continue with MOR00208 treatment upon 
Investigator’s discretion. 
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. 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. 
Idelalisib 100 and 150 mg film-coated tablets in bottles of 
60 tablets, as commercially available. 
Venetoclax 10 mg, 50 mg and 100 mg film-coated tablets as 
commercially available for oral administration. 
Safety Assessments 
The safety and tolerability of study drug treatments will be 
evaluated based on AEs (incidence 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 4.03 or higher. 
The safety run-in phase will be evaluated by an IDMC. 
Efficacy Assessments 
Criteria of the International Workshop on Chronic Lymphocytic 
Leukemia (IWCLL) for CLL subjects (Hallek et al., 2008) will be 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
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Page 22 of 160 
used to determine rates of response and progression for patients with 
CLL, with the modification that treatment-related lymphocytosis 
(Note: PRL is applicable in Cohort A only) in the absence of other 
signs or symptoms of disease progression will not be considered as 
progressive disease (Cheson et al., 2012; Hallek et al., 2012; NCCN 
NHL 2015 Guidelines). For patients with SLL, assessments will be 
performed using the Lugano Classification criteria for SLL subjects 
(Cheson et al., 2014). 
Patients who develop a partial response will be assessed using MRD 
testing from peripherial blood (PB) and from bone marrow if PB 
MRD negativity is reached. Furthermore, patients who develop a 
complete response as per standard criteria will be assessed using 
MRD testing and bone marrow aspiration/biopsy as described in 
IWCLL (Hallek et al., 2008). 
Pharmacokinetics 
The PK profile of MOR00208 will be investigated during the course 
of the study. 
Immunogenicity 
Immunogenicity 
of 
MOR00208 
(anti-MOR00208 
antibody 
analysis) will be investigated during the course of the study. 
Biomarker Assessments 
Blood for the analysis of exploratory biomarkers will be collected 
throughout the study and will be analyzed for markers which are 
important in the mechanism of action of, or could predict response 
to, the study drugs. Exploratory biomarkers (e.g., absolute and 
percentage change from baseline in measurements for B-, T-, NK 
cell populations; CD19 expression on B cells, CD16 expression on 
NK cells; ADCC capacity and optional FcγR genotyping) are 
planned to be investigated in the course of the study. 
Disease Risk Assessment 
Critical prognostic information, in particular the cytogenetic risk 
factors, serum marker of β2-microglobulin, expression of CD38 and 
ZAP-70, optional mutational analysis (e.g., IGHV, TP53, 
NOTCH1, BTK and PLCγ2) are determined at baseline and will be 
used to evaluate patient subpopulation in regards to the parameters 
investigated. 
Statistical Methods and 
Planned Analyses 
The primary objective of the main study is to evaluate the safety of 
MOR00208 combined with idelalisib or venetoclax. The trial is 
designed as a two-cohort study (Cohort A: MOR00208 and 
idelalisib; Cohort B: MOR00208 and venetoclax). 
The primary and secondary endpoints will be analyzed descriptively 
for each cohort using appropriate statistics (counts/ percentages for 
discrete variables, mean, median, standard deviation, minimum, 
maximum, number of valid observations for continuous variables). 
For specific variables, P values and 95% confidence limits will be 
presented. Kaplan-Meier estimates will be used where applicable. 
No formal statistical hypothesis testing is planned. 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
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Page 23 of 160 
3 LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ABC 
Antibodies bound per cell 
ADCC 
Antibody dependent cell mediated cytotoxicity 
ADCP 
Antibody dependent cell mediated phagocytosis 
AE 
Adverse event 
AESI 
Adverse event of special interest 
AIHA 
Autoimmune hemolytic anemia 
Akt 
Protein kinase B (PKB) 
ALC 
Absolute lymphocyte count 
ALL 
Acute lymphoblastic leukemia 
ALP 
Alkaline phosphatase 
ALT (SGPT) 
Alanine transaminase (serum glutamic pyruvic transaminase) 
ANC 
Absolute neutrophil count 
Anti-HBc 
Hepatitis B core antibody 
ASCO 
American Society of Clinical Oncology 
AST (SGOT) 
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) 
ASCT 
Autologous stem cell transplantation 
ATP 
Adenosine triphosphate 
AUC 
Area under the plasma concentration time curve 
BCL-2 
B-Cell Lymphoma 2 
BCRP 
Breast cancer resistance protein 
BEN 
Bendamustine 
BID 
bis in diem, twice daily 
bpm 
Beats per minute 
BR 
Bendamustine/rituximab combination therapy 
brpm 
Breaths per minute 
BTK 
Bruton's tyrosine kinase 
C1D1 
Cycle 1 Day 1 
CD 
Cluster of differentiation 
CDC 
Complement-dependent cytotoxicity 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CIRS 
Cumulative Illness Rating Scale 
CrCl 
Creatinine clearance 
CLL 
Chronic lymphocytic leukemia 
CML 
Chronic myeloid leukemia 
CMV 
Cytomegalovirus 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
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CNS 
Central nervous system 
COPD 
Chronic obstructive pulmonary disease 
CO2 
Carbon dioxide 
CR 
Complete response/remission 
CRi 
Complete response with incomplete marrow recovery 
CRO 
Contract research organization 
CSF 
Cerebrospinal fluid 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTFG 
Clinical Trial Facilitation Group 
CxD1 
Day 1 of any cycle 
CxD15 
Day 15 of any cycle 
DLBCL 
Diffuse large B cell lymphoma 
DLT 
Dose-limiting toxicity 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of response 
DP 
Drug product 
eCRF 
Electronic Case Report Form 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
Electronic data capture 
EDTA 
Ethylenediaminetetraacetic acid 
EMA 
European Medicines Agency 
EORTC 
European Organisation for Research and Treatment of Cancer 
EOT 
End of treatment 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
FAS 
Full analysis set 
FCBP 
Females of childbearing potential 
FCR 
Fludarabine/cyclophosphamide/rituximab combination therapy 
FcγR 
Fc (fragment crystallizable) gamma receptors 
FDA 
Food and Drug Administration 
FDG 
[18F]fluorodeoxyglucose 
FISH 
Flourescence in-situ hybridization 
FL 
Follicular lymphoma; follicular B cell non-Hodgkin’s lymphoma 
FSH 
Follicle stimulating hormone 
FU 
Follow-up 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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GCB 
Germinal center B-cell like 
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte colony-stimulating factor 
GGT 
Gamma-glutamyl transpeptidase 
Gi/L 
Giga per liter = 1 x 109/L 
GLP 
Good Laboratory Practice 
HCG 
Human chorionic gonadotropin 
HCL 
Hairy cell leukemia 
Hb 
Hemoglobin 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
Hct 
Hematocrit 
HIV 
Human immunodeficiency virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
Ig 
Immunoglobulin 
IGHV 
Immunoglobulin heavy-chain variable 
IHC 
Immunohistochemistry 
IND 
Investigational New Drug application 
INN 
International Nonproprietary Name 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
ITK 
Interleukin-2 inducible tyrosine kinase 
IV 
Intravenous(ly) 
IWCLL 
International Workshop on Chronic Lymphocytic Leukemia 
KI 
Kinase inhibitor 
LD 
Longest diameter 
LDi 
Longest traverse diameter of a lesion 
LDH 
Lactate dehydrogenase 
LDT 
Lymphocyte doubling time 
LEN 
Lenalidomide 
LPD 
Longest perpendicular diameter 
LVD 
Longest vertical dimension 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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mAb 
Monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRD 
Minimal residual disease 
MTD 
Maximum tolerated dose 
mTOR 
Mechanistic target of rapamycin (formerly: mammalian target of rapamycin) 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NHL 
Non-Hodgkin’s lymphoma 
NK 
Natural killer (cells) 
NSAID 
Non-steroidal anti-inflammatory drug 
NYHA 
New York Heart Association 
OATP 
Organic anion-transporting polypeptide 
ORR 
Overall response rate 
OS 
Overall survival 
PB 
Peripheral blood 
PCR 
Polymerase chain reaction 
PD 
1. Pharmacodynamic(s),  2. Progressive disease 
PE 
Physical examination 
PFS 
Progression-free survival 
P-gp 
P-glycoprotein 
PI 
Principal Investigator 
PIS 
Patient Information Sheet 
PI3K 
Phosphoinositide-3-kinase 
PJP 
Pneumocystis jirovecii pneumonia 
PK 
Pharmacokinetic(s) 
PKAS 
PK analysis set 
PLC 
Phospholipase C 
PO 
per os, oral(ly) 
PPD 
Cross product of the LDi and perpendicular diameter 
PPS 
Per-protocol set 
PR 
Partial response/remission 
PRL 
Partial response with lymphocytosis 
PT 
Preferred Term 
RBC 
Red blood cell 
RNA 
Ribonucleic acid 
R/R CLL 
Relapsed or refractory chronic lymphocytic leukemia 
R/R SLL 
Relapsed or refractory small lymphocytic lymphoma 


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RTX 
Rituximab 
SAE 
Serious adverse event 
SAF 
Safety analysis set 
SAP 
Statistical Analysis Plan 
SCID 
Severe combined immunodeficiency 
SD 
Stable disease 
SDi 
Shortest axis perpendicular to the LDi 
SLL 
Small lymphocytic lymphoma 
smIG 
Surface immunoglobulins 
SmPC 
Summary of Product Characteristics 
SOC 
System Organ Class 
SPD 
Sum of the products of the perpendicular diameters for multiple lesions 
TEAE 
Treatment emergent adverse event 
TEN 
Toxic epidermal necrolysis 
TLS 
Tumor lysis syndrome 
TNM 
Tumor/Nodes/Metastasis staging 
TP53 
Tumor protein p53 
UGT 
UDP-glucuronosyltransferase (uridine 5'-diphospho-glucuronosyltransferase) 
ULN 
Upper limit of normal 
US 
United States of America 
WBC 
White blood cell 
WFI 
Water for injection 
WHO 
World Health Organization 
WHO DDE 
World Health Organization Drug Dictionary Enhanced 
ZAP-70 
Zeta-chain-associated protein kinase 70 
 
 
 


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4 BACKGROUND 
4.1 Overview of Chronic Lymphocytic Leukemia and Small Lymphocytic 
Lymphoma 
Chronic lymphocytic leukemia (CLL) is the most common leukemia and one of the most 
common B cell chronic lymphoproliferative disorders in the Western world with an incidence 
rate (provided as number of newly diagnosed patients per year per 100,000 population) in the 
US of 6.75 (men) and 3.65 (women), with a similar incidence rate in Europe, notably 5.87 
(men) and 4.01 (women) (Sant et al., 2010; Yamamoto and Goodman, 2008). The median age 
at diagnosis is 72 years (Eichhorst et al., 2011). 
CLL is characterized by the progressive accumulation of functionally incompetent 
lymphocytes, which are usually of monoclonal origin. The diagnosis of CLL is based on the 
International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines requiring an 
absolute B lymphocyte count in the peripheral blood >5000/microliter (µl) with a majority of 
morphologically mature-appearing small lymphocytes and demonstration of clonality of 
circulating B lymphocytes by flow-cytometry of the peripheral blood (Hallek et al., 2008). A 
majority of the lymphocyte population should express the following markers: expression of 
either kappa or lambda light chains, expression of B cell associated markers (CD19, CD20 
(usually weak), CD23, expression of the T-cell marker CD5, low levels of surface 
immunoglobulins (smIG). 
Patients with CLL are frequently clinically asymptomatic at initial diagnosis. Upon further 
development of the disease, a spectrum of CLL specific clinical features might develop such 
as B-symptoms, lymphadenopathy, hepatosplenomegaly, and organ infiltration. Laboratory 
features frequently observed in CLL patients that often become clinically significant are: 
immunoglobulin abnormalities and a status of immunodeficiency that contributes to increased 
likelihood of infections, autoimmune hemolytic anemia, thrombocytopenia, and pancytopenia. 
Small lymphocytic lymphoma (SLL) is considered a CLL variant that lacks the clonal 
lymphocytosis required for the CLL diagnosis, but otherwise shares pathological and 
immunophenotypic features (Campo et al., 2011). The definition of SLL requires the presence 
of lymphadenopathy and/or splenomegaly. Moreover, the number of B lymphocytes in the 
peripheral blood should not exceed 5 x 109/L. In SLL, the diagnosis should be confirmed by 
histopathologic evaluation of a lymph node biopsy whenever possible (Hallek et al., 2008). 
The incidence of SLL is approximately 25% of CLL in the US (Dores et al., 2007). 
The natural history of CLL is very variable with survival times ranging from several months 
to >10 years after diagnosis. Several prognostic scores have been developed over time. The 
clinical staging systems according to Binet and Rai have found a wide range of application; 
see Appendix A for Binet classification (Binet et al., 1981). Since then a multitude of 
prognostic parameters have been identified. Prognostic markers in widespread clinical use are 
lymphocyte doubling time, β2-mircroglobulin and cytogenetic markers (Shanafelt et al., 2006). 
4.2 Treatment of Chronic Lymphocytic Leukemia 
In general practice, newly diagnosed patients with asymptomatic early-stage disease (Rai 0, 
Binet A) should be monitored without therapy unless they have evidence of disease 


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progression. Whereas patients at intermediate (stages I and II) and high risk (stages III and IV) 
according to the modified Rai classification or at Binet stage B or C usually benefit from the 
initiation of treatment (Hallek et al., 2008). Prognostic markers such as patient age and 
comorbidities are the key aspects for treatment selection in symptomatic CLL requiring 
systemic treatment. There are several options in first-line treatment, which include 
combination therapy with purine analogs (e.g., fludarabine/cyclophosphamide/rituximab 
[FCR] regimen), alkylating agents (e.g., chlorambucil) and/or monoclonal antibodies (mAb) 
to the CD20-antigen (e.g., rituximab, ofatumumab, obinutuzumab). Special considerations 
apply to elderly and comorbid patients and patients with the adverse prognostic cytogenetic 
marker del(17p). For the group of patients with del(17p), one of the following treatment 
strategies is generally considered: ibrutinib, FCR, alemtuzumab in combination with 
corticosteroids or possibly allogeneic stem cell transplantation. 
Patients with R/R CLL frequently become refractory to chemotherapy and anti-CD20 
therapies. Several treatment options can be considered, including re-treatment with the 
patients’ previous regimen. 
Ibrutinib and the combination of idelalisib/rituximab have been approved by EMA and FDA. 
In addition, venetoclax has been recently approved. For patients with R/R CLL, ibrutinib is a 
commonly used therapeutic option which is also often feasible in elderly and comorbid 
patients. Ibrutinib has demonstrated significant efficacy in relapsed CLL with durable 
remissions, including in patients with del(17p)13.1, with moderate toxicity. Recent data 
demonstrate even more impressive efficacy in previously untreated patients with CLL. 
Therefore, ibrutinib has been approved by FDA and EMA in 2016 as a first-line treatment for 
patients with CLL. The approval is based on data from the randomized, multi-center, open-
label Phase 3 RESONATE-2 trial, which evaluated the use of ibrutinib versus chlorambucil in 
269 treatment-naive patients with CLL or SLL aged 65 years or older. Ibrutinib significantly 
prolonged progression-free survival (median PFS was not reached for ibrutinib vs. 18.9 months 
for chlorambucil) reducing the risk of progression or death by 84% versus chlorambucil. 
Ibrutinib was also associated with a significantly higher overall response rate versus 
chlorambucil (ORR of 86% vs. 35%, respectively) (Burger et al., 2015). In several combination 
trials, ibrutinib has been administered with therapeutic monoclonal antibodies (e.g., rituximab 
and ofatumumab), chemotherapy (e.g., FCR and BR), and select targeted immune therapies 
(e.g., lenalidomide). Combination approaches have generally yielded improved overall 
response rates (ORRs) in part through earlier resolution of persistent lymphocytosis (Byrd et 
al., 2014b). Most recent results from a large randomized phase III study showed that the 
combination of ibrutinib and bendamustine/rituximab (BR) decreases the risk of progression 
and death remarkably (Chanan-Khan et al., 2015).  
The emerging resistance to and off-target side effects of ibrutinib have led to active 
development of second-generation and more specific BTK inhibitors, such as acalabrutinib 
(ACP-196), ONO/GS-4059, and BGB-3111. Acalabrutinib, which is more potent and selective 
than ibrutinib with reduced off-target side effects, has recently demonstrated clinical efficacy 
in relapsed CLL patients and showed encouriging preliminary results offering a favorable 
safety profile and high response rates that appear durable also in treatment-naive patients in 
Phase 1/2 studies. (Byrd et al., 2016a; Byrd et al., 2016b; Wierda et al., 2016). Currently, a 


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Phase 3 study (NCT02477696) directly comparing ACP-196 with ibrutinib in high-risk 
patients with relapsed CLL has commenced. 
Response rates for ibrutinib are high compared with other treatments for CLL; however, some 
patients develop progressive CLL or transform when receiving ibrutinib. CLL patients who 
progress early on ibrutinib are difﬁcult to treat and have poor outcomes. The clinical experience 
is that R/R CLL patients pretreated with ibrutinib experience a very aggressive course of 
disease with a median overall survival of only 3.1 months (Jain et al., 2015). Many of the 
patients enrolled on clinical trials with ibrutinib had relapsed CLL with poor prognostic 
features. In a recent publication, Maddocks et al. (2015) report a median survival following 
CLL progression of 17.6 months and show that the disease tends to progress quickly in patients, 
especially when the drug therapy is stopped. 
It was demonstrated in a recent retrospective analysis of CLL patients at 10 large US cancer 
centres that the majority of patients who discontinue a kinase inhibitor (KI) therapy (e.g. 
idelalisib after ibrutinib discontinuation) due to toxicity or progression respond to subsequent 
alternate KI therapy with the following  outcome: median PFS=11. 9 months for all patients 
(n=40); median PFS=7 months for CLL progressors. These very limited data showed that 
alternate KI choice, including idelalisib treatment after ibrutinib discontinuation, achieved an 
overall response rate (ORR) of 50% (95% CI, 33.4%-66.6%; n=38) without any complete 
responses (CR) (Mato et al., 2015). Moreover, further limited data were recently published on 
salvageability after ibrutinib discontinuation from the UK without specifying ORR but 
describing that 50% of patients with ≥3 prior treatment lines (total n=12) remained alive where 
4 patients out of those 12 patients received idelalisib therapy following ibrutinib 
discontinuation (Hillmen et al., 2016). 
More accurate data on ORR are available with venetoclax monotherapy from prospective study 
in CLL patients relapsed or refractory to ibrutinib therapy (ClinicalTrials.gov Identifier: 
NCT02141282) showing an overall response rate of 60.5% with a 95% confidence interval of 
43.4-76.0% (Jones et al., 2015).   
Importantly, according to a recent multivariable analysis an anti-CD20 antibody of rituximab 
in combination with venetoclax therapy significantly increases CR rates (51%, n=49 vs. 20%, 
n=116, respectively) and the durability of remissions over venetoclax monotherapy for patients 
with R/R CLL without prior BTK inhibitor therapy (Roberts et al., 2016). These encouriging 
data suggest that adding an antibody to a small molecule can further deepen the response and 
increase clinical benefits for the patients which might translate into improved survival. 
The presence of del(17p)/tumor protein p53 (TP53) mutation and complex karyotype may also 
contribute to the genomic instability in CLL cells, and prior therapies can promote subclonal 
mutations and refractory disease in patients with CLL. BTK mutations and clonal evolution 
may occur and produce ibrutinib resistance. There are recent data reported on acquired 
ibrutinib resistance and BTK mutation (C481S and phospholipase Cγ2-mutation) in patients 
with CLL who progressed on ibrutinib therapy (Woyach et al., 2014b). However, it is still 
unclear whether BTK mutations contribute to clonal evolution and promote transformations of 
CLL on ibrutinib therapy. 


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Patients with increased genomic instability may be at risk for relapse; combination therapies 
designed to avoid the development of resistance appear to be the most rational choice for such 
patient population. 
Patients with progressive CLL need additional therapy quickly after ibrutinib discontinuation 
for effective salvage (Woyach et al., 2014c), even though the therapeutic options after ibrutinib 
treatment are very limited. In this respect, the population of ibrutinib-pretreated R/R CLL 
patients and those with intolerance to ibrutinib are in urgent need of novel therapeutic options. 
4.3 Idelalisib in Hematological Malignancies 
Idelalisib inhibits the phosphotidylinositol 3-kinase-delta (p110) (PI3K), which is 
hyperactive in B cell malignancies including CLL. PI3Kis central to multiple signaling 
pathways that drive proliferation, survival, homing and retention of malignant cells in 
lymphoid tissue and bone marrow. Idelalisib is an oral phenylquinazolin derivative that 
selectively inhibits the adenosine triphosphate (ATP)-binding at the PI3K p110-d catalytic 
domain. This prevents phosphorylation and subsequent activation of protein kinase B (Akt) 
and mechanistic target of rapamycin (mTOR), which results in lymphoma cell death. 
Idelalisib is approved by the FDA for the treatment of patients with relapsed chronic 
lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab 
alone would be considered appropriate therapy due to other comorbidities. Furthermore, as 
monotherapy for the treatment of patients with relapsed follicular B-cell non-Hodgkin 
lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL) who have received at least 
two prior systemic therapies. EMA has approved idelalisib in combination with rituximab for 
the treatment of adult patients with chronic lymphocytic leukemia (CLL) who have received 
at least one prior therapy, or as first-line treatment in the presence of 17p deletion or TP53 
mutation in patients unsuitable for chemo-immunotherapy. Furthermore, as monotherapy for 
the treatment of adult patients with follicular lymphoma (FL) that is refractory to two prior 
lines of treatment. 
In clinical studies, idelalisib has proven to show clinically meaningful anti-lymphoma effects 
in a range of hematological malignancies in addition to the approved indications FL and CLL 
including mantle cell lymphoma and a mix of indolent lymphoma indications (Hewett et al., 
2015). 
Idelalisib was investigated as single agent in 125 patients with indolent lymphomas (follicular 
lymphoma, SLL, marginal-zone lymphoma, lymphoplasmocytic lymphoma) after failure of 
prior pretreatment (Gopal et al., 2014). The ORR across all lymphoma entities in this study 
was 57%. The response rate in the SLL population of this study was 61%. 
A pivotal phase III study investigated idelalisib at a dose of 150 mg twice daily in combination 
with RTX versus RTX single agent treatment in R/R CLL patients deemed ineligible for further 
cytotoxic chemotherapy because of significant myelosuppression related to previous 
chemotherapy, creatinine clearance (CrCl) < 60 mL/min, or a Cumulative Illness Rating Scale 
(CIRS) value > 6 (Furman et al., 2014). 
Compared with single agent RTX, combination therapy resulted in a significantly higher rate 
of PFS at 24 weeks (93% vs. 46%) and a significantly higher 12-month overall survival rate 


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(92% vs. 80%). The ORR among patients receiving combination therapy was impressive (81% 
vs. 13% for RTX only); see Table 1. 
 
Table 1: 
Efficacy of Idealisib in Relapsed CLL in Phase III Trial of Idelalisib plus 
Rituximab Versus Placebo plus Rituximab (Furman et al., 2014) 
 
Idelalisib plus 
Rituximab 
(N=110) 
Placebo plus 
Rituximab 
(N=110) 
 
Median PFS 
(primary endpoint) 
Not reached1 
5.5 months 
 
Rate of PFS at 24 weeks 
93% 
46% 
HR = 0.15,  P < 0.001 
Rate of OS at 12 months 
92% 
80% 
HR = 0.28,  P = 0.02 
Overall response rate 
81% 
13% 
OR = 29.92,  P < 0.001 
1 Disease progression occurred in only 12 patients. 
Abbreviations: PFS=progression-free survival; OS=overall survival; HR=hazard ratio; OR=odds ratio. 
 
The most common adverse events (AEs) in the idelalisib/RTX group (≥15%) were: pyrexia, 
fatigue, nausea, chills, diarrhea, infusion-related reaction (IRR), and cough. The majority of 
the AEs were Grade 1 or 2. Most common (≥5%) serious adverse events (SAEs) were 
pneumonia, pyrexia, and febrile neutropenia. The AE profile observed for the combination 
therapy was not significantly different from that observed for the single agent idelalisib studies 
in particular the study described above on 125 patients with indolent B-NHL entities (Gopal et 
al., 2014). 
The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee has most 
recently carried out a safety review started after a higher rate of serious adverse events related 
to infections, such as pneumonia, occurred. These were seen in three clinical trials among 
patients, who received idelalisib in addition to other cancer medicines. In its conclusion, 
Committee for Medicinal Products for Human Use had confirmed, that the medicine’s benefits 
outweigh its risks in the treatment of CLL. 
 
4.4 Venetoclax in Hematological Malignancies 
Venetoclax is a selective and orally bioavailable small-molecule inhibitor of B-cell lymphoma 
2 (BCL-2), an antiapoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL 
cells where it mediates tumor cell survival and has been associated with resistance to 
chemotherapeutics. Venetoclax helps restore the process of apoptosis by binding directly to 
the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer 
membrane permeabilization and the activation of caspases. In nonclinical studies, venetoclax 
has demonstrated cytotoxic activity in tumor cells that overexpress BCL-2. 


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Venetoclax is the first FDA-approved treatment that targets the BCL-2 protein, which supports 
cancer cell growth and is overexpressed in many patients with CLL. The FDA approved 
venetoclax (Venclexta) under accelerated approval based on overall response rate for the 
treatment of patients with CLL with 17p deletion, as detected by an FDA approved test, who 
have received at least one prior therapy. The EMA recently approved venetoclax (Venclyxto®) 
as monotherapy for the treatment of CLL in the presence of 17p deletion or TP53 mutation in 
adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or for 
the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who 
have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor. 
The efficacy of venetoclax was established in an open-label, single-arm, multicenter clinical 
trial with relapsed or refractory CLL with 17p deletion who had received at least one prior 
therapy (Stilgenbauer et al., 2016). Results of this trial show that venetoclax monotherapy is 
active and well tolerated in patients, providing a new therapeutic option for this very poor 
prognosis population. 107 patients were enrolled into the study. An overall response by 
independent review was achieved in 85 of 107 patients including 7.5% CR+CRi. The median 
time to first response was 0.8 months (range: 0.1 to 8.1 months). Responses with venetoclax 
seem durable, with median duration of overall response and progression-free survival not yet 
reached after a median follow-up of 12 months. Minimal residual disease (MRD) was 
evaluated in peripheral blood and bone marrow for patients who achieved CR or CRi, 
following treatment with venetoclax. Three percent (3/106) were MRD negative in the 
peripheral blood and bone marrow (less than one CLL cell per 104 leukocytes). The most 
common grade 3/4 adverse events were neutropenia (40%), infection (20%], anaemia (18%), 
and thrombocytopenia (15%). 11 patients died in the study within 30 days of the last dose of 
venetoclax; seven due to disease progression and four from an adverse event (none assessed as 
treatment related). 
Further studies of venetoclax are ongoing in CLL in sequence or in combination with other 
agents (e.g. obinutuzumab, rituximab, ibrutinib, bendamustine). Moreover, there is a recently 
initiatied Phase 3 study in patients with multiple myeloma (NCT02755597). 
4.5 Overview of MOR00208 
MOR00208 (also referred to as XmAb®5574) is an Fc-enhanced mAb that binds to the human 
B cell surface antigen CD19. MOR00208 possesses significantly increased tumor cytotoxicity 
when compared with the parental, non-enhanceed, murine 4G7 CD19 antibody. The increased 
binding of MOR00208 to Fc gamma receptors (FcγR), due to the engineered mutations, 
significantly enhances in vitro antibody dependent cell mediated cytotoxicity (ADCC), 
antibody dependent cell mediated phagocytosis (ADCP), and its direct cytotoxic effects 
(apoptosis) on the tumor cells when compared with the non-enhanced parental murine antibody 
(Horton et al., 2008). MOR00208 has not been shown to mediate complement-dependent 
cytotoxicity (CDC). 
 
4.5.1 Nonclinical Studies 
More specifically, in preclinical studies, MOR00208 has been shown to significantly enhance 
in vitro ADCC, ADCP, and direct cytotoxic effects (apoptosis) on CD19+ tumor cell lines 


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spanning a broad range of human lymphomas and leukemias (Burkitt’s lymphoma, CLL, hairy 
cell leukemia (HCL), CD19+ chronic myeloid leukemia (CML), diffuse large B cell lymphoma 
(DLBCL) and acute lymphoblastic leukemia (ALL), expressing levels of CD19 antigen 
ranging from 15,000 to 105,000 molecules/cell. Similar effects have also been observed in 
relation to freshly isolated patient CLL or ALL cells and are also expected to translate to 
primary non-Hodgkin’s lymphoma (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-enhanced parental 
antibody regarding its ability to induce a marked reduction in tumor growth, inhibit tumor 
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, lenalidomide 
(LEN) used in the treatment of patients with CLL and NHL, were investigated in a human IV 
lymphoma model in SCID mice (IB). In this orthotopic model for disseminated B cell 
malignancies, the median survival was superior for all groups receiving MOR00208 
combination therapy (with fludarabine, BEN or LEN) 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, pharmacology studies were restricted to human and cynomolgus monkey cell-based 
in vitro systems, CD19+ human B cell tumor 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 5 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; an 8-week toxicity study in which MOR00208 was 
administered IV every 2 weeks at a dose of 2, 10 or 50 mg/kg for 8 consecutive weeks with a 
90-day recovery period; and a 13-week toxicity study in which MOR00208 was administered 
IV weekly to sexually mature cynomolgus monkeys at doses of 10, 30 or 100 mg/kg for 13 
consecutive weeks with a 132-day recovery period. The aim of the latter Good Laboratory 
Practice (GLP)-compliant, multiple-dose toxicology studies was to support the use of 
MOR00208 in human clinical studies. As expected pharmacological effect, a reversible lack 


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of germinal centers in lymphoid organs and markedly reduced peripheral CD20+ B cell counts 
were observed, which were consistent with lowered IgG levels in serum as well as a reversible 
reduction in the T-cell dependent antibody response. There were no MOR00208-related effects 
on body weight, clinical signs, food consumption, blood pressure, electrocardiography, 
respiratory rate, ophthalmology, neurobehavioural observations, hematology, coagulation, 
urine or cytokine analysis. MOR00208 had no effects on menstrual cycle length in females and 
no histopathology/microscopic changes to male and female reproductive organs. Overall, 
MOR00208 administration to the cynomolgus monkey was very well tolerated at doses up to 
100 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 leukocytes, lymphocytes and hematopoietic 
precursor cells was observed. 
 
4.5.2 Clinical Experience with MOR00208 in CLL 
Protocol XmAb5574-01: 
A Phase 1 Study of XmAb®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 trial exploring the use of MOR00208 (also known as 
XmAb®5574 or MOR208) in adult patients diagnosed according to International Workshop on 
CLL guidelines (Hallek et al., 2008) with active, treatment-requiring R/R CLL/SLL. Results 
of the study were reported by Woyach et al. (2014a). 
Twenty-seven patients were enrolled to 6 escalating dose levels, with expansion at the highest 
dose level of 12 mg/kg. Nine doses of MOR00208 were infused over 8 weeks. The maximum 
tolerated dose (MTD) was not reached; the drug was generally well tolerated, IRRs of grade 1 
or 2 being the most common toxicities. Treatment-related grade 3 or 4 AEs occurred in 5 
patients and included neutropenia, thrombocytopenia, increased aspartate aminotransferase 
(AST), febrile neutropenia, and tumor lysis syndrome (TLS). MOR00208 showed preliminary 
efficacy, with 18 patients (66.7%) responding by physical examination criteria and laboratory 
studies, and 8 patients (29.6%) responding by computed tomography (CT) criteria. MOR00208 
showed a terminal elimination half-life of approximately 14 days. A dose of 12 mg/kg was 
recommended for use in subsequent studies. 
 
 


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4.5.3 Safety of MOR00208 
MOR00208 has a novel mechanism of action that may have the potential to add to the care of 
patients with NHL, particularly CLL and SLL. Based on the available data from the completed 
clinical study of MOR00208 (Protocol XmAb®5574-01), the preliminary data from the 
ongoing MOR208C201 and MOR208C202 clinical studies, 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 trial (e.g., by the inclusion and exclusion criteria) 
and by frequent monitoring of potential adverse drug reactions throughout the entire study. 
The anticipated possible risks associated with administration of MOR00208 to patients include 
the following AEs with a suspected relationship to MOR00208 treatment: 
 IRRs (mostly Grade 1/2) 
 Febrile neutropenia 
 Neutropenia 
 Thrombocytopenia 
 Tumour lysis syndrome 
 Upper respiratory tract infections 
 Fatigue 
 Chills  
 Pyrexia 
 Nausea 
 Diarrhoea 
 Headache 
 Rash 
 Aspartate- (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, absolute lymphocyte count (ALC) reduction, IRRs, TLS, neutropenia/ 
thrombocytopenia, hepatitis B reactivation, progressive multifocal leukoencephalopathy, 
mucocutaneous reactions, and infections. 
The incidence of toxicities observed in the first in human phase I trial of MOR00208 in CLL 
is shown in Table 2. The MTD was not reached in this trial, and the drug was generally well 
tolerated. 
The possible risks associated with the administration of MOR00208 are described in detail in 
the MOR00208 IB. 
 


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Table 2: 
Adverse Events at Least Possibly Attributable to MOR00208 in Phase I Study of 
MOR00208 in R/R CLL (Woyach et al., 2014a) 
Toxicity 
0.3 
mg/kg
(N=1) 
1 
mg/kg
(N=1) 
3 
mg/kg 
(N=3) 
6 
mg/kg
(N=3) 
9 
mg/kg
(N=3) 
12 
mg/kg
(N=16) 
Total 
(%) 
Any Event 
1 
1 
3 
3 
2 
14 
24 (88.9)
Dose Limiting Toxicities 
 
 
 
 
 
 
 
Grade 4 neutropenia 
lasting ≥ 7 days with febrile 
neutropenia 
 
 
 
 
 
1 
1 (3.7) 
Other Grade3/4 
Toxicities 
 
 
 
 
 
 
 
Neutropenia 
 
1 
 
 
 
1 
2 (7.4) 
Thrombocytopenia 
 
 
 
 
 
2 
2 (7.4) 
Tumor lysis syndrome 
 
 
 
 
 
1 
1 (3.7) 
Increased AST 
 
 
 
 
 
1 
1 (3.7) 
Grade 1/2 Toxicities 
Occurring in >1 Patient 
 
 
 
 
 
 
 
Infusion reaction 
1 
1 
1 
2 
2 
11 
18 (66.7) 
Increased AST 
1 
 
2 
1 
 
 
4 (14.8) 
Increased ALT 
 
 
2 
1 
 
2 
5 (18.5) 
Neutropenia 
1 
 
 
 
 
1 
2 (7.4) 
Thrombocytopenia 
 
 
 
 
1 
2 
3 (11.1) 
Fever 
1 
 
1 
 
1 
1 
4 (14.8) 
Chills 
1 
 
1 
1 
 
 
3 (11.1) 
Peripheral sensory 
neuropathy 
 
 
 
1 
 
2 
3 (11.1) 
Diarrhea 
 
 
 
1 
 
1 
2 (7.4) 
Flushing 
1 
 
 
 
 
1 
2 (7.4) 
Hyperuricemia 
 
 
1 
 
 
1 
2 (7.4) 
Hypocalcemia 
 
 
1 
 
 
1 
2 (7.4) 
Increased lipase 
 
 
1 
 
 
1 
2 (7.4) 
 


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5 STUDY PURPOSE/RATIONALE 
 
5.1 Disease Background and Rationale 
CLL is a lymphoproliferative disorder characterized by progressive accumulation of 
morphologically mature but functionally incompetent lymphocytes in the blood, bone marrow, 
and lymphoid tissues. The disease affects mainly the elderly. Its clinical course of ranges from 
indolent disease (Rai 0, Binet A) with long-term survival over 12 years to aggressive disease 
(Rai III/IV, Binet C) (Binet, 1981; Rai, 1987) with median survival of 2 years (Montserrat, 
1995). 
SLL and CLL are generally considered a different manifestation of the same disease. Whereas 
CLL is found in the blood and bone marrow, SLL primarily presents in the lymph nodes. The 
median age at diagnosis of CLL is 72 years (Eichhorst et al., 2011). The natural history of SLL 
is generally indolent or slowly progressive; SLL, however, is considered incurable. 
Traditional therapy of R/R CLL consisted in the administration of chemotherapeutic agents 
which could be combined with anti-CD20 targeted treatments. Over time patients with R/R 
CLL became increasingly refractory to chemotherapy and anti-CD20 treatment, or were not 
eligible for intensive chemotherapy regimen due to advanced age or comorbidities. 
Therefore, the approval of novel small molecules like ibrutinib, venetoclax and idelalisib 
combined with RTX for CLL has been an important milestone. In particular, the treatment with 
single agent ibrutinib has become a cornerstone of the treatment of R/R CLL. Despite the 
prolonged median PFS under treatment with ibrutinib, it is expected that most CLL patients 
will relapse. R/R CLL patients who relapse after or during ibrutinib treatment have a dismal 
prognosis insofar as most therapeutic options have been exploited to this point and CLL takes 
an increasingly aggressive course. So far, limited survival data are available on patients 
discontinuing ibrutinib. According to Jain et al. (2015), the median survival for all the patients 
was 3.1 months after discontinuing ibrutinib and did not differ signiﬁcantly between 
transformed and untransformed (those who progressed and those who discontinued for other 
reasons) patients with CLL. In a recent publication, Maddocks et al. (2015) report a median 
survival following CLL progression of 17.6 months and show that disease tends to progress 
quickly in patients, especially when the drug therapy is stopped. Available limited ORR data 
in this particular patient population with ibrutinib discontinuation are summarized in Section 
4.2.   
Despite recently approved therapeutic agents and combination therapies, CLL remains an 
incurable disease and most patients eventually relapse and/or die. There still remains an unmet 
medical need for improved and novel combination treatments for subjects with CLL requiring 
treatment, especially for ibrutinib-pretreated patients with R/R CLL. 
 
 


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5.2 Rationale for the Use of Idelalisib in CLL/SLL 
Phosphoinositide-3-kinases (PI3Ks) play an essential role in cellular growth, differentiation, 
migration, and metabolism. Impaired PI3K signaling leads to deficiencies within the immune 
system, whereas uncontrolled PI3K signaling can lead to autoproliferation and the 
development of leukemias. The hematopoietic-selective isoform PI3K-δ specifically helps to 
regulate the activation, proliferation, migration and survival of B lymphocytes. 
Idelalisib is a first-in-class, orally administered, potent reversible small-molecule inhibitor of 
PI3K-γ and δ, approved in combination with rituximab for the treatment of R/R CLL and as 
monotherapy for relapsed FL and SLL. 
In a pivotal phase III trial in patients with relapsed CLL who were not able to receive cytotoxic 
agents, recipients of idelalisib plus RTX had significantly improved PFS, overall survival, 
overall response and lymph node response, compared with recipients of placebo plus RTX. In 
a pivotal phase II trial, idelalisib monotherapy was effective in patients with relapsed indolent 
NHL who were refractory to RTX and an alkylating agent, including in the subgroups of 
patients with follicular lymphoma or SLL. Idelalisib had a generally manageable AE profile. 
Furthermore, recently published in vitro results suggest that idelalisib may serve as an 
alternative therapy in the setting of ibrutinib resistance at clinically achievable doses since 
BTK-mutated CLL cells may still be sensitive to other agents that target the B-cell receptor 
signaling pathway including idelalisib (Cheng et al., 2015). 
5.3 Rationale for the Use of MOR00208 in CLL/SLL 
The effects of MOR00208 appear to involve ADCC, ADCP, and direct cytotoxic activity 
(apoptosis). MOR00208 demonstrated single-agent activity in R/R CLL/SLL, R/R DLBCL, 
follicular lymphoma and other indolent NHLs (Jurczak et al., 2015; Woyach et al., 2014a). 
MOR00208 elicits only mild hematological AEs and has a manageable toxicity profile. The 
predominant AEs are IRRs, a class effect of many therapeutic antibodies, which typically occur 
during the first to third application. 
As RTX-based regimens have become standard first-line treatment in CLL, 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. The CD19 antigen is an attractive target in CLL as CD19 is typically expressed and 
has a signalling function that contributes to the malignant phenotype and is not down-regulated 
in patients pretreated with CD20-targeted agents. Thus, it might be possible to overcome the 
absolute or relative RTX resistance in R/R CLL by using MOR00208 instead of RTX and 
thereby to improve the clinical outcome in the R/R CLL patient population. In addition, there 
are accumulated data that CLL cells become CD20 negative after ibrutinib therapy but remain 
CD19 positive (unpublished data by Woyach). 
In summary, further clinical investigation of MOR00208 is warranted in subjects with 
CLL/SLL. 


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5.4 Rationale for the Use of Venetoclax in CLL/SLL 
The balance between pro-apoptotic and anti-apoptotic proteins is often dysregulated in 
hematologic malignancies, and particularly lymphoid cancers, and thus contributes to the 
survival of malignant B-cells (Anderson et al., 2016). Permeabilization of the mitochondrial 
outer membrane and thus triggering of apoptosis is determined by the balance of activity 
between 3 subfamilies of the BCL2 family of proteins: the mediators (BAX and BAK), which 
disrupt the mitochondrial membrane; the antiapoptotic proteins (BCL2, BCLxL, BCLw,MCL-
1, and A1), which act to constrain BAX and BAK; and the BH3-only proteins (BIM, BID, 
PUMA, NOXA, HRK, and BAD), which are activated under conditions of cellular stress and 
function to inhibit the antiapoptotic proteins or to activate BAX and BAK (Anderson et al., 
2016; Czabotar et al., 2014; Llambi et al., 2011). 
The BCL-2 protein inhibits apoptosis and was found to be over-expressed in CLL (Anderson 
et al., 2016). Venetoclax is a selective and potent inhibitor of BCL-2 (Souers et al. 2013). 
Preclinical studies confirmed that venetoclax selectively inhibits BCL-2 and thus induces 
apoptosis of lymphoid cells while avoiding the BCLxL mediated platelet toxicity (Souers et 
al. 2013; Vogler et al., 2013). 
Venetoclax is the first FDA-approved treatment that targets the BCL-2 protein, which supports 
cancer cell growth and is overexpressed in many patients with CLL. The FDA approved 
venetoclax (Venclexta) under accelerated approval based on overall response rate for the 
treatment of patients with CLL with 17p deletion, as detected by an FDA approved test, who 
have received at least one prior therapy. The EMA recently approved venetoclax (Venclyxto®) 
as monotherapy for the treatment of CLL in the presence of 17p deletion or TP53 mutation in 
adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or for 
the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who 
have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor. 
 
5.5 Rationale for the Combination of MOR00208 and Idelalisib in 
CLL/SLL 
The rationale for idelalisib and MOR00208 is described in detail in Sections 5.2 and 5.4. 
The AE profiles of MOR00208 and idelalisib are largely non-overlapping. The administration 
of MOR00208 is mainly associated with mild to moderate IRRs, which occur especially at the 
beginning of treatment. Apart from that, mild hematological AEs have been observed, whereas 
idelalisib was associated mainly with pyrexia, fatigue, nausea, cough, pneumonia, chills, rash, 
abdominal pain, and diarrhea. In addition, hematological AEs such as neutropenia and 
laboratory abnormalities such as hypertriglyceridemia, hyperglycemia, ALT and AST 
elevations or even fatal and/or serious hepatotoxicity, severe diarrhea or colitis, pneumonitis, 
and intestinal perforation have been found associated with the use of idelalisib. According to 
clinical experience with CLL patients treated with idelalisib combined with RTX or 
ofatumumab, current clinical trials have not shown a clinically significant increase in the 
number of observed AEs, particularly not in hematological AEs. Therefore, MOR00208 is 
considered to be a reasonable candidate for combination therapy with idelalisib from safety 
perspective. 


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Anti-CD20 RTX is commonly used in all treatment lines in CLL/SLL and it is assumed that 
the majority of patients who are eligible for the trial will have had prior RTX exposure with 
ultimate experience of progression or relapse after such treatment. Thus, it is assumed that 
MOR00208 in combination with idelalisib conveys benefit to this patient population that 
would otherwise not be achieved by continuing RTX-based regimen. Beyond that both 
compounds have a confirmed clinical activity in R/R CLL, MOR00208 demonstrated a 
synergistic activity with idelalisib in a series of in vitro experiments (MorphoSys data on file) 
and idelalisib showed promising in vitro results in the setting of ibrutinib resistance (Cheng et 
al., 2015). Therefore, one can expect that the combination of anti-CD19 MOR00208 and 
idelalisib in a clinical setting may be more beneficial compared with single agent treatment 
and might be possible to overcome the ibrutinib resistance in this particular patient population. 
Furthermore, idelalisib monotherapy is an accepted treatment for R/R CLL patients since 
idelalisib with or without RTX is included as preferred option for patients with R/R CLL 
disease regardless of their age and comorbidities according to Version 2.2015 of the NCCN 
Guidelines for Non-Hodgkin’s Lymphomas (updates in Version 1.2015 of the NCCN 
Guidelines for Non-Hodgkin’s Lymphomas from Version 5.2014 include that from 
idelalisib+RTX was changed to idelalisib±RTX in various R/R CLL patient populations). 
Therefore, it is the opinion of the sponsor that MOR00208 in combination with idelalisib but 
without RTX is a reasonable investigational treatment opportunity in this clinical trial. 
Consequently, MorphoSys has developed the present protocol of an open-label study to 
evaluate the safety and preliminary efficacy of a combined treatment of MOR00208 with 
idelalisib in adult patients with R/R CLL previously treated with a BTK inhibitor (e.g., 
ibrutinib) in Cohort A. The main objective of this study is to offer a novel treatment option to 
patients whose disease relapsed or became refractory during or after therapy with a BTK 
inhibitor such as ibrutinib or who did not tolerate such therapy, taking into consideration that 
these patients have particularly dismal prognosis. 
As the combination therapy of MOR00208 and idealisib will be evaluated for the first time in 
a clinical setting, a safety run-in phase was introduced in the study design. The study will 
include a safety run-in phase, which will be started with an evaluation of the safety data of 
3 patients who completed at least one cycle of treatment. This evaluation will be done by an 
Independent Data Monitoring Committee (IDMC). After the evaluation of the safety data from 
the first 3 patients for Cycle 1 of treatment and a positive recommendation from the IDMC the 
next 7-9 patients may be dosed in parallel. An additional IDMC review will take place after 10 
patients have completed at least 1 cycle of treatment. The IDMC will evaluate the number and 
type of AEs occurring during the first cycle, as well as the laboratory parameters (e.g., clinical 
biochemistry and hematology) and other relevant safety data as necessary, with the prospect 
of providing a recommendation on the study, going forward. 
5.6 Rationale for the Combination of MOR00208 and Venetoclax in 
CLL/SLL 
The rationale for venetoclax and MOR00208 is described in detail in Sections 5.3 and 5.4. 
The toxicity profile of venetoclax and MOR208 is potentially overlapping, however with 
significantly lower incidences of reported toxicities for MOR208. Non-hematologic ADRs 


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including diarrhea, nausea, vomiting, headache, fatigue, upper respiratory tract infections, and 
pyrexia frequently occur with administration of venetoclax in patients with CLL (incidence > 
15%). These ADRs were also observed with treatment of MOR208, however with a lower 
incidence (≤ 8%). TLS is the major risk of treatment with venetoclax. TLS and relevant 
laboratory abnormalities were reported in 6% of CLL patients with recommended risk 
stratification, dosing regimen and prophylaxis. Also under treatment with MOR208 four 
patients (3%) developed TLS so far. Two in the ALL indication (9%), one in NHL (1%) and 
one in CLL (4%). To prevent an increase of this risk by concomitant use of both drugs in trial 
MOR208C205, treatment with MOR208 will start one week before the start of the ramp-up 
treatment with venetoclax at the lowest dose of 20 mg. Neutropenia is a frequent adverse drug 
reaction of venetoclax: Grade 3 or 4 events were experienced in 41% of patients, 6% of the 
patients had serious AE of neutropenia. Under MOR208 treatment > Grade 3 neutropenia was 
reported for 9 % of patients overall (7% in NHL, 18% in ALL, and 11% in CLL). None of 
them were serious. To reduce the risk for neutropenia preventive treatment with G-CSF may 
be considered if clinically indicated. Therefore, MOR00208 is considered to be a reasonable 
candidate for combination therapy with venetoclax from safety perspective. 
Importantely, MOR00208 demonstrated a synergistic activity with venetoclax in vitro 
experiments (MorphoSys data on file). A preclinical in vitro combination study was performed 
in order to investigate the potential of venetoclax to enhance the cytotoxic potential of 
MOR00208 against CD19-positive target cells. The general concept of this study was based 
on the fact that cytotoxic agents such as venetoclax are very potent in reducing initial tumor 
load. This is thought to increase the benefit of immune therapies which are known to be 
positively affected by low tumor mass, e.g. via more favorable effector-to-target (E:T) ratios. 
In a FACS-based ADCC assay the combination resulted in a synergistic enhancement of the 
cytotoxic activity compared to either drug alone. Combination of MOR00208 with venetoclax 
showed enhanced maximal cytotoxicity compared to MOR00208 alone and provide a 
promising rationale for the combination of MOR00208 and venetoclax in clinical trials. 
Moreover, both compounds have a confirmed clinical activity as single agent in R/R CLL as 
previously detailed in the protocol and further data described in Section 4.2 suggest that adding 
an antibody to a small molecule like venetoclax can further deepen the response and increase 
clinical benefits for the patients which might translate into improved survival. Therefore, one 
can expect that the combination of anti-CD19 MOR00208 and venetoclax in a clinical setting 
may be more beneficial compared with single agent treatment. 
Consequently, MorphoSys has developed the present protocol of an open-label study to 
evaluate the safety and preliminary efficacy of a combined treatment of MOR00208 with 
venetoclax in adult patients with R/R CLL previously treated with a BTK inhibitor (e.g., 
ibrutinib) in Cohort B. The main objective of this study is to offer a novel treatment option to 
patients whose disease relapsed or became refractory during or after therapy with a BTK 
inhibitor such as ibrutinib or who did not tolerate such therapy, taking into consideration that 
these patients have particularly dismal prognosis. As the combination therapy of MOR00208 
and venetoclax will be evaluated for the first time in a clinical setting, a safety run-in phase 
was introduced in the study design as described in Section 7.1 and 10.4.  
 


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5.7 Rationale for Dose and Schedule of MOR00208 Administration 
Based on the data from the following 3 clinical studies: 
 XmAb5574-01, phase I trial in R/R CLL/SLL patients – completed 
 MOR208C201, phase IIa trial in R/R NHL – ongoing 
 MOR208C202, phase IIa trial in R/R ALL – terminated 
where MOR00208 was administered as monotherapy, an integrated analysis was performed on 
safety, efficacy and PK data. As a result, no relationship between MOR00208 dose or 
MOR00208 exposure and toxicity-related events could be observed. This analysis also 
included R/R NHL patients from study MOR208C201, which were dosed at 12 mg/kg on a 
weekly basis for 3 months. Sixteen of these patients entered further maintenance treatment 
(biweekly or monthly MOR00208 administrations), and several of these 16 patients have been 
treated with MOR00208 for more than 1 year; treatment is still ongoing with no increase in 
incidences of toxicity-related events for MOR00208. For this reason, MOR00208 given at a 
dose of 12 mg/kg is considered to be safe and well tolerated, if applied on a weekly schedule 
for more than 2 months. 
Furthermore, it could be shown in R/R CLL and R/R DLBCL patients that clinical efficacy 
clearly correlated with drug exposure over the first 2 cycles and that 12 mg/kg administered 
weekly for 2 cycles was the regimen which led most reliably to such beneficial drug levels. It 
could also be shown that several patients who continued treatment after more than 2 months 
and therefore kept high drug levels over time further improved in their clinical response. 
Taken together, MOR00208 administered at 12 mg/kg was found to be safe and well tolerated 
in R/R CLL/SLL, NHL and ALL patients. Thus, 3 cycles of weekly dosing at 12 mg/kg (plus 
a loading dose on Day 4 of Cycle 1) followed by further treatment of biweekly dosing at the 
same dose level, followed by monthly treatment from Cycle 7 Day 1, is the regimen of choice 
for study MOR208C205. 
 
 


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5.8 Rationale for Washout Period of Previous Treatment 
The disease may progress quickly, especially when ibrutinib therapy is stopped, which points 
to a need for clinical trials to allow shorter washout periods for these patients (Maddocks et 
al., 2015). Therefore, it is the opinion of the sponsor that a rather short washout period serves 
the best interest of the patients. Patients should resume anticancer treatment after the 
discontinuation of previous ibrutinib (or other BTK inhibitor) therapy as soon as possible due 
to the high unmet medical need for this patient population. 
5.8.1 Therapeutic Antibodies from Previous Combination Treatment with Ibrutinib 
Patients may have received combination treatment of ibrutinib with a therapeutic antibody 
prior to be enrolled into study MOR208C205. Although therapeutic antibodies typically show 
half-lives in the range of 2 to 3 weeks (e.g., RTX: median half-life 22 days in NHL patients, 
32 days in CLL patients according to the FDA Prescribing Information), the washout phase for 
such patients is set to only 14 days. Therefore, a certain amount of the therapeutic antibody 
from previous treatment is still expected to be present after 14 days. 
5.8.2 Previous Treatment with Ibrutinib and Other BTK Inhibitors 
The terminal elimination half-life of ibrutinib is 4 to 6 hours according to FDA Prescribing 
Information (Appendix B) and 4 to 13 hours according to the European Summary of Product 
Characteristics (SmPC; Appendix B). Other BTK inhibitors are currently in phase I-III clinical 
development e.g., acalabrutinib (ACP-196; Acerta Pharma/AstraZeneca), CC-292 (AVL-292; 
Celgene), ONO-4059 (Ono/Gilead Sciences) and BGB-3111 (BeiGene). Acalabrutinib has a 
short mean half-life of 1 hour (Byrd et al., 2016b). The PK-PD relationship of CC-292 was 
assessed in healthy donors. After single oral dose of 2 mg/kg plasma concentration peaked 
within 30-120 minutes and declined to near or below the lower limit of detection within 24 
hours post dose (Westlin et al., 2012; Evans et al., 2013). Based on results from a phase I study 
in patients with non-germinal center B-cell like diffuse large B cell lymphoma (non-GCB 
DLBCL) (ONO-4059POE001), ONO-4059 has a half-life of approximately 5-7 hours (Dyer 
et al., 2014). It can thus be assumed that the proposed 5-day washout period will suffice to 
largely clear ibrutinib and other BTK inhibitors from systemic circulation and also from 
peripheral compartments. 
The half-life of BTK, i.e., the target protein of ibrutinib and other BTK inhibitors, is estimated 
up to 20 hours (Saffran et al., 1994; Yu et al., 2006; Evans et al., 2013). It can thus be assumed 
that the pharmacological effect of ibrutinib and other BTK inhibitors, i.e., the inhibition of 
BTK, will have already ceased after the proposed 5-day washout phase. This is also supported 
by the finding that free BTK protein levels recovered toward 75% of predose values within 
approximately 4 days after treatment with CC-292 (Evans et al., 2013). 
Given the homology between BTK and interleukin-2 inducible tyrosine kinase (ITK), it was 
confirmed using molecular and phenotypic analysis that ibrutinib irreversibly inhibits ITK 
(Dubovsky et al., 2013). This also may be the case for the other above mentioned BTK 
inhibitors. ITK expression in FcγR-stimulated NK cells leads to increased calcium 
mobilization, granule release, and cytotoxicity (Khurana et al., 2007). As FcγR stimulation is 
requisite for antibody-dependent NK-cell mediated cytotoxicity (ADCC), it could be shown 
that ibrutinib abrogates RTX anti-tumor efficacy as a result of inhibition of FcγR-stimulated 
NK cell function in vitro and in vivo (Kohrt et al., 2014). 


Product Name: MOR00208 
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IND Number: 114,856 
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However, human NK cells have a turnover time in blood of about 2 weeks (Zhang et al., 2007), 
and thus it can be assumed that after a 5-day washout period of ibrutinib, before MOR00208 
administration, NK cell activity will start to recover and will have fully recovered after the 
second dose of MOR00208 (C1D4). 
Taken together, the proposed 5 day washout period is (i) sufficient to largely clear BTK 
inhibitors from the circulation based on available PK parameters, (ii) sufficient to largely revert 
the pharmacodynamic effect of BTK inhibitors based on the available data on the stability of 
the BTK protein and (iii) sufficiently allows clinical activity of MOR00208 as NK cell activity 
can be assumed. 
 
5.9 Rationale for Biomarker Assessment 
Several prognostic markers have been described that can be used as stratification factors for 
CLL/SLL therapies. These include del(17p), del(11q), del(13q14), trisomy 12, 
immunoglobulin heavy-chain variable (IGHV), NOTCH1 and TP53 mutations as well as 
serum parameters (thymidine kinase, β2 microglobulin) or CLL cell markers (CD38, ZAP-70). 
There is increasing evidence from prospective clinical trials that detection of certain 
chromosomal deletions has prognostic significance in CLL. For example, patients with 
leukemia cells that have del(17p) and/or TP53 mutations have an inferior prognosis and appear 
to be resistant to standard chemotherapy regimens (Hallek et al., 2008, Stilgenbauer et al., 
2014). The presence of del(17p)/TP53 mutation and complex karyotype may also contribute 
to the genomic instability in CLL cells, and prior therapies can promote subclonal mutations 
and refractory disease in patients with CLL.  
BTK mutations and clonal evolution may occur and produce ibrutinib resistance. There are 
recent data reported on acquired ibrutinib resistance and BTK mutation (C481S) and 
phospholipase Cγ2 mutation in patients with CLL who progressed on ibrutinib therapy 
(Woyach et al., 2014b). Further, expression levels of BCL2/BH3 protein family members have 
been analyzed and certain ratios might correlate with response to BCL2 inhibitors (Roberts et 
al., 2012). 
Therefore, detection of these and other cytogenetic abnormalities could have prognostic value 
and may guide therapeutic decisions. 
 


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Protocol Number: MOR208C205 
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6 STUDY OBJECTIVES AND ENDPOINTS 
 
6.1 Study Objectives 
6.1.1 Primary Objective 
To determine the safety of MOR00208 combined with idelalisib or venetoclax 
6.1.2 Secondary Objectives 
1. To determine the quality of the response 
2. To assess the potential immunogenicity of MOR00208 
3. To assess the pharmacokinetic (PK) profile of MOR00208 
6.1.3 Exploratory Objectives 
 To assess minimal residual disease (MRD) in patients achieving a complete or partial 
response 
 To explore putative predictive biomarkers 
 To determine and correlate prognostic factors with efficacy parameters 
 
6.2 Study Endpoints 
6.2.1 Primary Endpoint 
Incidence and severity of adverse events (AEs) 
6.2.2 Secondary Endpoints 
1. Overall response rate (ORR): defined for Cohort A as percentage of patients achieving 
a complete response (CR), a partial response (PR) or a partial response with 
lymphocytosis (PRL), and for Cohort B as percentage of patients achieving a CR or a 
PR 
2. Anti-MOR00208 antibody formation 
3. Pharmacokinetic analysis for MOR00208 
6.2.3 Exploratory Endpoints 
 Proportion of patients with MRD-negativity 
 Absolute and percentage change from baseline in measurements for B-, T- and NK cell 
populations 
 Analysis of exploratory and diagnostic biomarkers from blood (e.g., CD19 expression, 
BTK and PLCγ2 mutational status, CD16 expression on NK cells, antibody dependent 
cell mediated cytotoxicity (ADCC) capacity, cytogenetics and mutational analysis). 
 


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Protocol Number: MOR208C205 
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IND Number: 114,856 
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7 INVESTIGATIONAL PLAN 
 
7.1 Description of Study Design 
This is a multicenter, two-cohort, open-label phase II study of MOR00208 combined with 
idelalisib (Cohort A) or venetoclax (Cohort B) for the treatment of adult patients with R/R CLL 
or R/R SLL pretreated with a BTK inhibitor as a single agent or as part of a combination 
therapy. Recruitment of a patient into Cohort A or B is at the discretion of the Investigator. A 
total of approximately 12 patients are planned to be enrolled in each cohort in Europe and the 
US. Figure 1 illustrates the design of the main study. 
The main study will include a safety run-in phase for each cohort enrolling 10- approximately 
12 patients per combination treatment. MOR00208 will be administered at a dose of 
12.0 mg/kg as intravenous (IV) infusion, idelalisib in Cohort A as 150 mg oral tablets twice 
daily and venetoclax in Cohort B as 400 mg oral tablets daily dose. To mitigate the risk for 
TLS treatment of patients with venetoclax will be initiated after an initial treatment with 
MOR00208 at 20 mg up from C1D8 for 7 days, followed by a weekly ramp-up dosing schedule 
to the recommended daily dose of 400 mg. The safety run-in phase will be concluded with an 
evaluation of the safety data of all treated patients once 10 patients completed at least one 
treatment cycle in Cohort A or at least 5 weeks of combination treatment in Cohort B. The first 
3 patients in Cohort A will be dosed sequentially at least 48 hours apart. In Cohort B all 10- 
approximately 12 patients will be dosed sequentially, at least one week apart. 
In Cohort A there will be two safety evaluations. After completion of the first cycle the safety 
data of the first three patients will be evaluated. This evaluation will be done by an IDMC 
composed of experts in the field of oncology and clinical biostatistics who have no other role 
in the study and do not have an affiliation with the Investigators or the sponsor. After the 
evaluation of the safety data from the first 3 patients for Cycle 1 of treatment and a positive 
recommendation from the IDMC the next 7- approximately 9 patients may be dosed in parallel. 
An additional IDMC review will take place after 10 patients completed at least 1 cycle of 
treatment.  
In Cohort B the safety evaluation will be performed by an IDMC after the first 10 patients 
completed at least 5 weeks of combination treatment. The evaluation will be done by the IDMC 
as already described. Importantly, all patients in Cohort B, who participate in the safety run-in 
phase, will be hospitalized on the day of the first two dose escalations of venetoclax (C1D8 
and C1D15).  
The criteria for the evaluation of safety of the combination therapy will be defined by the 
IDMC and laid down in the IDMC Charter of the trial. 
If safety evaluation results in a recommended dose reduction of idelalisib or venetoclax, the 
sponsor will reconsider dosing and amend the protocol accordingly.  
During the study, MOR00208 will be administered as infusions 12.0 mg/kg in 28-day cycles. 
From Cycle 1 to 3, each cycle will consist of weekly infusions (on Day 1, Day 8, Day 15 and 
Day 22). In Cycle 1, an additional loading dose will be administered on Day 4. From Cycle 4 
to 6, MOR00208 will be administered on a biweekly basis with infusions on Day 1 and Day 15 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
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of each cycle. Thereafter, MOR00208 will be administered on Day 1 of each cycle starting 
with Cycle 7 Day 1. 
Idealisib will be self-administered twice daily starting on Day 1 of each cycle. Venetoclax will 
be self-administered (except during hospitalization) starting from Cycle1 Day8 and on Day1 
of each cycle onwards. Treatment with idelalisib or venetoclax may be modified in a de-
escalating fashion or discontinued based upon clinical and laboratory findings. In case idealisib 
or venetoclax treatment was stopped due to side effects suspected to be related to idealisib or 
venetoclax, the patient may continue MOR00208 treatment. 
Progressive disease will require discontinuation of study medication.  
Patients who benefit from treatment are allowed to continue MOR00208 treatment beyond 
Cycle 24 at Investigator’s discretion. The total duration of the main study will be limited to a 
maximum of 5 years from first patient first visit or up to the timepoint of approximately 30 days 
after last patient received his last treatment, whichever comes first. 
 
Patients completing the main study will be invited to participate in an optional biological 
marker sub-study as described in detail in Section 15.13 Appendix M. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
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IND Number: 114,856 
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Figure 1: 
Study Design 
Cycle 1 to 3
Cohort A: 
Idelalisib Days 1-28
MOR00208 Days 1,8,15,22*1
(28-day cycles)
Cohort A: 
Idelalisib Days 1-28 
MOR00208 Days 1&15 
(28-day cycles)
EOT
R/R CLL or
R/R SLL
pretreated 
with BTK
inhibitor
(e.g. 
ibrutinib)
Screen-
ing
Cycle 4 to 6
*1 Additional loading dose of 
MOR00208 on Cycle 1 Day 4
30 day 
Follow-
Up Visit
Abbreviations: EOT=end of treatment; BTK=Bruton’s tyrosine kinase; R/R CLL=relapsed or refractory chronic lymphocytic leukemia; 
R/R SLL=relapsed or refractory small lymphocytic lymphoma.
Cohort B: 
Venetoclax Days 1-28*2
MOR00208 Days 1,8,15,22*1
(28-day cycles)
Cohort B:
Venetoclax Days 1-28 
MOR00208 Days 1&15 
(28-day cycles)
*2 Weekly ramp up of Venetoclax starting on Cycle 1 Day 8
(C1D8: 20mg, C1D15: 50mg, C1D22:100mg, C2D1: 200mg). 
Venetoclax dosis 400mg up from Cycle 2 Day 8
Cohort A: 
Idelalisib Days 1-28 
MOR00208 Day 1 
(28-day cycles)
Cycle 7 to 24
Cohort B:
Venetoclax Days 1-28 
MOR00208 Day 1 
(28-day cycles)
 


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7.2 Patient Selection Criteria 
All patients must sign informed consent and meet the following selection criteria at screening 
and baseline to participate in the study. 
 
7.2.1 Inclusion Criteria 
Diagnosis/Trial Population 
1. Age ≥18 years 
2. Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL): 
a) history of diagnosis of CLL or SLL that meets IWCLL diagnostic criteria 
(Appendix C) 
b) histologically confirmed diagnosis of SLL by lymph node biopsy and documented 
within medical records 
c) indication for treatment as defined by the IWCLL guidelines (Appendix D) 
3. Patients must have both of the following: 
a) relapsed1 or refractory2 disease while receiving a BTK inhibitor (e.g., ibrutinib) or 
intolerance of such therapy 
b) single-agent or combination therapy with a BTK inhibitor for at least one month 
must be the patient’s most recent prior anticancer therapy 
1 relapsed disease is defined as progressive disease in subjects who have previously 
achieved a PR or CR to most recent BTK inhibitor therapy 
2 refractory disease is defined as progressive disease in subjects who have previously 
not achieved a PR or CR to most recent BTK inhibitor therapy, or stable disease as 
best response after 12 months of receiving the most recent BTK inhibitor therapy  
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 
5. Patients with a past medical history of autologous or allogeneic stem cell 
transplantation must exhibit full hematological recovery without any evidence or 
ongoing treatment of active graft versus host disease before enrolment into the study. 
Laboratory Values 
6. Patients must meet the following laboratory criteria at screening: 
 Adequate bone marrow function as follows: 
a) absolute neutrophil count (ANC) ≥ 1.0 × 109/L 
b) platelet count ≥ 30 × 109/L in the absence of clinically significant evidence of 
bleeding 
c) Cohort B only: hemoglobin ≥ 8.0 g/dL 
 Adequate hepatic and renal function as follows: 
d) total serum bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in cases of documented liver 
involvement by CLL (For patients with Gilbert’s disease, serum bilirubin up to 3 × 
ULN is allowed provided normal direct bilirubin.) 
e) ALT and AST ≤ 2.5 × ULN or <3 ×ULN in cases of documented liver involvement 
by CLL 


Product Name: MOR00208 
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f) serum creatinine clearance calculated using a standard Cockcroft-Gault formula 
(Cockroft & Gault, 1976; see Appendix E) must be: 
 Cohort A only: ≥ 30 mL/min 
 Cohort B only: ≥ 50 mL/min 
 
Other Inclusion Criteria 
7. Females of childbearing potential (FCBP; see Appendix F) must: 
a) not be pregnant as confirmed by a negative serum pregnancy test at screening and a 
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 (Note: All female 
patients are prohibited to donate blood within the before mentioned time frame) 
c) agree to ongoing pregnancy testing during the course of the study, and until 
3 months 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 or agree to use and be able to comply with the use of highly 
effective contraception (see Appendix F) without interruption during the study and 
for 3 months after the last dose of study medication 
e) FCBP using hormonal contraceptives should add a barrier method as a second form 
of contraception since it is currently unknown whether idelalisib or venetoclax may 
affect the effectiveness of hormonal contraceptives 
8. Males must use a highly effective method of contraception (see Appendix F) without 
interruption, if the patient is sexually active with a FCBP, refrain from donating blood 
or sperm during the study participation and for 3 months after the last dose of study 
medication 
9. In the opinion of the Investigator the patients must: 
a) be able to understand, give written informed consent to, and comply with all study-
related procedures, medication use, and evaluations 
b) not have a history of noncompliance in relation to medical regimens or be 
considered potentially unreliable and/or uncooperative 
 
 


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7.2.2 Exclusion Criteria 
Diagnosis 
1. Patients who have: 
a) non-Hodgkin’s lymphomas other than CLL/SLL 
b) transformed CLL/SLL or Richter’s syndrome as defined by the IWCLL (Hallek et 
al., 2008) 
c) active and uncontrolled autoimmune cytopenia 
Previous and Current Treatment 
2. Patients who have received treatment with a BTK inhibitor within 5 days prior to Day 1 
dosing. 
3. 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 
b) systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day 
(Exception: Patients with signs of rapidly progressing disease per discussion 
between the Investigator and sponsor’s medical monitor) 
c) received live vaccines. (Note: Vaccinations against influenza with inactivated virus 
or vaccination for pneumococcal diseases are allowed.) 
4. Patients who: 
a) have, in the opinion of the Investigator, not recovered sufficiently from the adverse 
toxic effects of prior therapies 
b) have a history of previous severe allergic reactions to prior monoclonal antibody 
therapy, and/or hypersensitivity to the active substances or to any of the inactive 
ingredients / excipients contained in the study drug formulations (for details see 
FDA Prescribing Information or EMA SmPC of Zydelig® (Cohort A only) or 
Venclexta® & Venclyxto® (Cohort B only)) 
c) concurrently use other anticancer or experimental treatments 
d) were previously treated with: 
 CD19-targeted therapy (applicable for Cohort A and B) 
 Cohort A only: a PI3K inhibitor treatment (e.g., idelalisib, duvelisib)  
 Cohort B only: a BCL-2 inhibitor treatment (e.g., venetoclax)  
e) Cohort B only: has a known allergy to both xanthine oxidase inhibitors and 
rasburicase 
f) Cohort B only: has received strong or moderate CYP3A inhibitors or inducers 
within 7 days, or has consumed grapefruit, grapefruit products, Seville oranges or 
star fruit within 3 days prior to the first dose of venetoclax (see for details in the 
protocol) 
Patient’s Medical History 
5. Prior history of malignancies other than CLL, 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 


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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 (Tumor/Nodes/Metastasis [TNM] 
stage of T1a or T1b) 
6. Patients with myelodysplastic syndrome 
7. Patients with 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 
8. Patients with diagnosis of myocardial infarction within 6 months prior to enrolment, 
New York Heart Association (NYHA; see Appendix G) class II or higher congestive 
heart failure, uncontrolled angina pectoris, severe uncontrolled ventricular arrhythmias, 
clinically significant pericardial disease, or electrocardiographic evidence of acute 
ischemia or significant conduction system abnormalities, in the opinion of the 
Investigator. (Note: Patients with stable, asymptomatic atrial fibrillation are allowed in 
the study provided they do not meet the other cardiac exclusion criteria) 
9.  Patients who: 
a) suffered significant traumatic injury or underwent major surgery within 14 days 
prior to treatment start 
b) have not recovered from sequelae of traumatic injury or surgical operations until 
Day 1 dosing 
10. Patients with central nervous system (CNS) involvement or impairment: 
a) CNS primary or secondary malignancy in present or past medical history (unless 
patient has been free of the disease for ≥ 5 years prior to screening)1 
b) CNS, meningeal or epidural malignancies (e.g., brain metastases, known leukemic 
meningeosis)1 
1 Note: Screening for cerebrospinal fluid (CSF)/CNS involvement is not 
required but may be performed at the discretion of the Investigator 
c) CNS lesions/cerebrovascular event(s) with clinically significant sequelae 
d) history or evidence of clinically significant cerebrovascular CNS that would in the 
Investigator’s opinion preclude participation in the study or compromise the 
patient’s ability to give informed consent. 
11. Patients with: 
a) chronic diarrhoea and malabsorption syndrome 
b) any evidence of ongoing systemic viral, bacterial, or fungal infection (including 
Pneumocystis jirovecii pneumonia and Cytomegalovirus infection) 
c) history of serious allergic reactions including anaphylaxis and toxic epidermal 
necrolysis 
d) Cohort A only: ongoing inflammatory bowel disease as ulcerative colitis or 
Crohn’s disease 
e) Cohort A only: severe chronic obstructive pulmonary disease (COPD), or 
pulmonary emphysema or drug-induced pneumonitis diagnosed in previous 
medical history 


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IND Number: 114,856 
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12. Patients with known seropositivity for or history of active viral infection with human 
immunodeficiency virus (HIV). (Additional information: no safety data on the use of 
CD19 antibodies in HIV positive patients are currently available) 
13. Patients with known positive hepatitis B and/or C serology 
a) hepatitis B virus (HBV): patients with positive serology for HBV, defined as 
positivity for hepatitis B surface antigen (HBsAg) or total hepatitis B core antibody 
(anti-HBc). (Note: Patients positive for anti-HBc may be included if HBV DNA is 
not detectable, but have to be monitored in 2-month intervals via HBV DNA 
testing) 
b) hepatitis C virus (HCV): patients with positive HCV serology (defined as positive 
for HCV antibody [anti-HCV]) unless confirmed negative for HCV-ribonucleic 
acid (RNA) 
7.2.3 Withdrawal Criteria 
Patients may withdraw voluntarily from participation in the study or from study treatment at any 
time and for any reason. A patient’s participation in the study may terminate at his/her request 
or on the basis of the Investigator’s clinical judgment. The reason for patient withdrawal will be 
documented in the source data and noted on the electronic case report form (eCRF). 
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 Safety 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 
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. 
At the discretion of the sponsor, patients may also be removed from the study. 
It should be clearly documented in the source data whether patients withdrew their consent and 
will not enter the follow-up phase, or if patients withdrew their consent for study drug treatment 
but will continue further participation in the study. 
Among the reasons for premature withdrawal are: 
 Intercurrent illness (a condition, injury, or disease unrelated to the primary diagnosis that 
became apparent during treatment and necessitated the patient's termination from the 
study) 
 General or specific changes in the patient’s condition that renders him/her ineligible for 
further treatment according to the inclusion/exclusion criteria 
 Important protocol deviation (the patient’s findings or conduct failed to meet the protocol 
entry criteria or failed to adhere to the protocol requirements, e.g., drug noncompliance, 
failure to return for defined number of visits) 
7.2.4 Study Treatment Discontinuation 
Besides withdrawal of consent, there are further reasons for premature study treatment 
discontinuation of a patient, which may include but are not limited to: 
 Death 


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 Adverse events 
 Abnormal laboratory value(s) 
 Abnormal test procedure result(s) 
 Pregnancy 
 Progression of disease 
 Loss to follow-up 
 Withdrawal of a patient at the specific request of the sponsor. 
Please note: 
 Patients who are withdrawn for any reason may not re-enter this clinical study at any 
time. 
 For patients who are lost to follow-up, at least three attempts of contact should be made 
by the site and documented in the source data. 
 
7.3 Investigator 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 center. The sponsor also reserves the right to terminate the entire study, a 
specific cohort or temporarily interrupt enrolment in a specific cohort 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 
the combination partner idelalisib or venetoclax. 
Should a termination of a given clinical study center, a specific cohort or the whole study be 
necessary, then the procedures will be arranged after review by, and consultation with, all 
involved parties. In terminating a study center, a specific cohort 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. 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
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IND Number: 114,856 
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EudraCT Number: 2015-002915-14 
 
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7.4 End of Study and Subsequent Treatment 
The end of the main study is reached for an individual patient, if any of the following applies: 
 Patient has withdrawn consent (see Section 7.2.3) 
 Patient has completed 30-Day Safety Follow-up visit  
 Study treatment was permanently discontinued (see Section 7.2.4) 
The individual end of the main study is defined by the above criteria, whichever occurs first. 
The end of the main study is defined as 5 years after the first patient was enrolled (C1D1) or 
approximately 30 days after last patient received his last treatment, whichever comes first. The 
whole study will end after the completion of both the main and sub-study (see for details in 
Section 12.11 and 15.13.5). At the end of the study, access to MOR00208 treatment can be made 
available to those patients who continue to derive benefit from MOR00208 treatment. 
 
8 TREATMENTS 
 
8.1 Study Treatments 
In this open-label study the treatment consisting of MOR00208 and idelalisib or venetoclax will 
be as scheduled, until disease progression, unacceptable toxicity, or discontinuation for any other 
reason, whichever comes first. 
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. All 
dosages prescribed to the patient and all dose changes during the study must be recorded in the 
eCRF. 
Study drug must be handled and/or prepared as described in the Study Drug Preparation Manual, 
the Investigator Brochure (IB) for MOR00208, and other safety-relevant documents (e.g., the 
Prescribing Information by US FDA and the European SmPC for idelalisib or the Prescribing 
Information by US FDA for venetoclax). 
MOR00208 and idelalisib or venetoclax will be centrally supplied. Other medications will be 
provided by the investigative site and not by the sponsor. 
8.1.1 MOR00208 
MOR00208 drug product (DP) must be stored under refrigeration at 2 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. 
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). 


Product Name: MOR00208 
Protocol Number: MOR208C205 
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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 colorless 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 months (3 cycles) of 
the study, each cycle will consist of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 
of the cycle. In addition, a loading dose will be administered on Day 4 of Cycle 1. Thereafter, 
MOR00208 will be administered on a biweekly basis (every 14 days) with infusions on Day 1 
and Day 15 of each cycle from Cycle 4 to 6, and on a monthly basis on Day 1 of each cycle from 
Cycle 7 Day 1. 
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 Study 
Drug Preparation Manual. In general, a vial of MOR00208 must be used as soon as possible after 
reconstitution with WFI. Any solution remaining in the vial has to be discarded. 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 Study Drug Preparation Manual. 
For the first infusion, the intravenous (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 an approximately 2-hour period. MOR00208 should not be 
administered as an IV push or bolus. 
8.1.2 Idelalisib 
Idelalisib is supplied as film coated tablets of 150 mg or 100 mg. They are to be stored at 20 to 
30°C (US only). Tablets should be dispensed from the original bottle.  
The recommended starting dose is 150 mg orally, twice daily (BID). It may be taken with or 
without food approximately at the same time of the day. Ideally, doses should be taken at 
~12-hour intervals (e.g., at ~8 AM and at ~8 PM) on a BID schedule beginning ~30 minutes 
prior to the initial MOR00208 infusion. 
Treatment may be continued as scheduled until progression of disease, withdrawal of consent, 
unacceptable toxicity, death or patient is lost to follow-up, whichever occurs first. 
If the patient misses a dose of idelalisib within 6 hours of the time it is usually taken, the patient 
should take the missed dose as soon as possible and resume the normal dosing schedule. If a 
patient misses a dose by more than 6 hours, the patient should not take the missed dose and 
simply resume the usual dosing schedule. 
Idelalisib (Zydelig®) contains the azo coloring agent sunset yellow FCF (E110), which may 
cause allergic reactions. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
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8.1.3 Venetoclax 
Venetoclax 10 mg, 50 mg and 100 mg tablets as commercially available for oral administration. 
They are to be stored at or below 30°C (86°F; US only). 
Venetoclax dose should be administered according to a weekly ramp-up schedule over 5 weeks 
to the recommended daily dose of 400 mg. Figure 2 illustrates this initial ramp-up. Dosing 
schedule for ramp-up phase as follows, daily dose of venetoclax: 20 mg 1st week of combination 
treatment, 50 mg 2nd week, 100 mg 3rd week, 200 mg 4th week and 400 mg 5th week and 
thereafter. The 5-week ramp-up dosing schedule, starting on C1D8, is designed to gradually 
reduce tumor burden (debulk) and decrease the risk of tumor lysis syndrome (TLS). Assessment 
of patient-specific factors for level of risk of TLS and prophylaxis for TLS should be performed 
prior to first dose of venetoclax (see Section 8.10.1).  
The first 4 weeks of venetoclax treatment will be supplied with respective venetoclax tablets, 
according to the ramp-up schedule. Once the ramp-up phase is completed, the 400 mg dose is 
achieved using 100 mg tablets supplied as monthly package of 120 tablets. 
Venetoclax should be taken as scheduled orally once daily until disease progression or 
unacceptable toxicity is observed. Venetoclax tablets should be taken with a meal and water at 
approximately the same time each day. Tablets should be swallowed whole and not chewed, 
crushed, or broken prior to swallowing. If the patient misses a dose within 8 hours of the time it 
is usually taken, the patient should take the missed dose as soon as possible and resume the 
normal daily dosing schedule. If a patient misses a dose by more than 8 hours, the patient should 
not take the missed dose and should resume the usual dosing schedule the next day. If the patient 
vomits following dosing, no additional dose should be taken that day. The next prescribed dose 
should be taken at the usual time. 
 
Figure 2: 
Ramp-up Dosing Schedule for Venetoclax 
 
 


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8.2 Pre-Medication for MOR00208 Infusions 
IRRs have commonly been reported for patients with CLL or NHL treated with MOR00208. 
Therefore, pre-medication including: 
 
Antipyretics (e.g., acetaminophen [paracetamol] 500-1000 mg per dose orally [PO] or 
IV or equivalent), 
 
Histamine H1 receptor blockers (e.g., diphenhydramine 25–50 mg per dose IV or 
equivalent) and 
 
Glucocorticosteroids (methylprednisolone 80–120 mg per dose IV or equivalent (see 
Appendix H) 
should be given for the first 3 infusions. In medically justified cases, the Investigator may repeat 
doses of individual agents as required and use other agents, doses and/or formulations in 
accordance with institutional guidelines. Any pre-medication given should be reported in the 
eCRF. 
Pre-medication 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 pre-medication should be continued for subsequent administrations of 
MOR00208. 
8.3 Patient Monitoring During MOR00208 Infusion 
Vital signs should be measured as outlined in Section 9.3.2.2. 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). 
8.4 Management of MOR00208 Infusion-Related Reactions 
Infusion-related reactions (IRRs) will be defined according to the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 (see Table 3) 
or higher. 
 
 
 


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Table 3: 
Definition of Infusion-Related Reactions 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; 
hospitalization 
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; 
hospitalization 
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-inflammatory 
drugs. 
 
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; 
tumor pain (onset or exacerbation of tumor pain due to treatment); urticaria (hives, welts, 
wheals); vomiting. 


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Management of 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 ≤Grade 1 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 pre-medication 
should be given before all subsequent infusions of MOR00208. 
Management of 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). 
 
Once the symptoms have been resolved or reduced 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 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 study 
drug(s), provided clinically appropriate precautions are undertaken. Infusion of 
MOR00208 should be discontinued permanently upon the third Grade 3 infusion 
reaction. 
Management of 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). 
The patient must not receive further infusions of MOR00208 that is judged by the Investigator 
to be the cause of the IRR, but should continue treatment with the other study drug as per 
protocol. 
 


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8.5 Definition for Tumor Lysis Syndrome and Prophylaxis in Cohort B 
8.5.1 Definition of Tumor Lysis Syndrome 
The tumor lysis syndrome occurs when tumor cells release their contents into the bloodstream, 
either spontaneously or in response to therapy, leading to the characteristic findings of 
hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. These electrolyte and 
metabolic disturbances can progress to clinical toxic effects, including renal insufficiency, 
cardiac arrhythmias, seizures, and death due to multiorgan failure (Howard et al., 2011). Clinical 
manifestations may include nausea, vomiting, lethargy, oedema, fluid overload, congestive heart 
failure, cardiac dysrhythmias, seizures, muscle cramps, tetany, syncope and possibly sudden 
death. The clinical manifestations may have their onset prior to initiation of cytotoxic therapy 
but more commonly present within 12–72 h after administration of cytotoxic therapy (Cairo et 
Bishop, 2004). 
In the current classification system the tumor lysis syndrome can be classified as laboratory or 
clinical as described in Table 4. In laboratory tumor lysis syndrome, two or more metabolic 
abnormalities must be present during the same 24-hour period within 3 days before the start of 
therapy or up to 7 days afterward. Clinical tumor lysis syndrome requires the presence of 
laboratory tumor lysis syndrome plus an increased creatinine level, seizures, cardiac 
dysrhythmia, or death (Howard et al., 2011). 
Table 4: 
Definitions of Laboratory and Clinical Tumor Lysis Syndrome 
Metabolic 
Abnormality 
Criteria for Classification of 
Laboratory Tumor Lysis 
Syndrome 
Criteria for Classification of 
Clinical Tumor Lysis Syndrome 
Hyperuricemia 
Uric acid >8.0 mg/dL 
(475.8 μmol/L) in adults or above 
the upper limit of the normal range 
for age in children 
 
Hyperphosphatemia 
Phosphorus >4.5 mg/dL 
(1.5 mmol/L) in adults or 
>6.5 mg/dL (2.1 mmol/L) in 
children 
 
Hyperkalemia 
Potassium >6.0 mmol/L 
Cardiac dysrhythmia or sudden death 
probably or definitely caused by 
hyperkalemia 
Hypocalcemia 
Corrected calcium <7.0 mg/dL 
(1.75 mmol/L) or ionized calcium 
<1.12 (0.3 mmol/L) * 
Cardiac dysrhythmia, sudden death, 
seizure, neuromuscular irritability 
(tetany, paresthesias, muscle twitching, 
carpopedal spasm, Trousseau’s sign, 
Chvostek’s sign, laryngospasm, or 
bronchospasm), hypotension, or heart 
failure probably or definitely caused by 
hypocalcemia 


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Acute kidney injury ** Not applicable 
Increase in the serum creatinine level of 
0.3 mg/dL (26.5 μmol/L) (or a single 
value >1.5 times the upper limit of the 
age-appropriate normal range if no 
baseline creatinine measurement is 
available) or the presence of oliguria, 
defined as an average urine output of 
<0.5 mL/kg/hr for 6 hr 
* The corrected calcium level in milligrams per deciliter = measured calcium level in milligrams per 
deciliter + 0.8 × (4 − albumin in grams per deciliter). 
** Acute kidney injury is defined as an increase in the creatinine level of at least 0.3 mg per deciliter 
(26.5 μmol per liter) or a period of oliguria lasting 6 hours or more. By definition, if acute kidney injury 
is present, the patient has clinical tumor lysis syndrome (Levin et al., 2007) 
 
8.5.2 Prophylaxis for Tumor Lysis Syndrome in Cohort B 
Patients enrolling in Cohort B will be assessed for TLS risk and categorized in a risk category at 
screening Prior to the initiation of the first doses of MOR00208 medical prophylaxis for TLS 
should be initiated according to the institutional standard of care. 
Administration of venetoclax can cause rapid reduction in tumor and thus poses a risk for TLS 
in the initial 5-week ramp-up phase with venetoclax. Changes in blood chemistries consistent 
with TLS that require prompt management can occur as early as 6 to 8 hours following the first 
dose and at each dose increase. The risk of TLS is a continuum based on multiple factors, 
including tumor burden and comorbidities. Therefore, tumor burden assessments, including 
radiographic evaluation (e.g., CT scan), blood chemistry (potassium, uric acid, phosphorus, 
calcium, and creatinine) should be performed in all patients and the pre-existing abnormalities 
should be corrected prior to initiation of treatment with venetoclax. Reduced renal function 
(creatinine clearance [CrCl] <80 mL/min) further increases the risk. The risk may decrease as 
tumor burden decreases. Table 5 describes the recommended TLS prophylaxis and monitoring 
during treatment with venetoclax based on tumor burden determination from clinical trial data. 
Importantly, all patients in Cohort B, who participate in the safety run-in phase, will be 
hospitalized on the day of the first two dose escalations of venetoclax (C1D8 and C1D15). 
 
 


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Table 5: 
Recommended TLS Prophylaxis Based on Tumor Burden From Clinical Trial 
Data of Venetoclax 
 
Prophylaxis 
Blood Chemistry  
Monitoringc,d 
Tumor Burden 
Hydrationa  
Antihyperuricemics Setting and Frequency of
Assessments 
Low 
All LN <5 cm AND 
Oral 
Allopurinolb  
Outpatient 
  
ALC <25 x109/L 
(1.5-2 L) 
  
 Pre-dose, 6 to 8 
hours, 24 hours at 
first dose of 20 mg 
and 50 mg 
  
  
  
  
 Pre-dose at subsequent 
ramp-up doses 
Medium 
Any LN 5 cm to <10 cm Oral (1.5-2 L) 
Allopurinol 
Outpatient 
  
OR 
and 
  
 Pre-dose, 6 to 8 
  
ALC ≥25 x109/L 
consider additional 
intravenous 
  
hours, 24 hours at 
first dose of 20 mg 
and 50 mg 
  
  
  
  
 Pre-dose at subsequent 
ramp-up doses 
  
  
  
  
 Consider 
hospitalization for  
patients with CrCl 
  
  
  
  
<80mL/min at first  
dose of 20 mg and 
  
  
  
  
50 mg; see below for 
monitoring in hospital 
High 
Any LN ≥10 cm 
Oral (1.5-2 L) 
Allopurinol; 
In hospital at first 
  
OR 
and 
consider 
dose of 20 mg and 
  
ALC ≥25 x109/L 
intravenous 
rasburicase if 
50 mg 
  
AND any LN ≥5 cm 
(150-200 
baseline uric 
 Pre-dose, 4, 8,12 
  
  
mL/hr as tolerated) 
acid is elevated 
and 24 hours 
Outpatient at subsequent 
ramp-up doses 
  
  
  
  
 Pre-dose, 6 to 8 hours, 
24 hours 
Note: Consider all patient comorbidities before final determination of prophylaxis and monitoring schedule. 
aAdminister intravenous hydration for any patient who cannot tolerate oral hydration. 
bStart allopurinol or xanthine oxidase inhibitor 2 to 3 days prior to initiation of venetoclax. 
cEvaluate blood chemistries (potassium, uric acid, phosphorus, calcium, and creatinine); review in real time. 
dFor patients at risk of TLS, monitor blood chemistries at 6 to 8 hours and at 24 hours at each subsequent ramp-up 
   dose 


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8.6 Dose Modifications of MOR00208 
In a phase I study of MOR00208 in CLL, the MTD was not reached and the drug was generally 
well tolerated, IRRs of grade 1 or 2 being the most common toxicities. Treatment-related grade 
3 or 4 AEs occurred in 5 out of 27 patients and included neutropenia, thrombocytopenia, 
increased AST, febrile neutropenia, and TLS. There was one CLL patient with dose-limiting 
toxicity (DLT) of grade 4 neutropenia lasting ≥ 7 days with febrile neutropenia 
Dose reductions of MOR00208 are not allowed during the course of the study due to the 
relatively mild AE profiles of MOR00208. 
In the case of clinically significant grade ≥3 toxicities that are not described in Table 8 & 
Table 9 and Sections 8.9 & 8.10: 
 MOR00208 doses should be omitted until the toxicity grading diminishes in severity to 
grade ≤1 or returns to a baseline grade, provided the condition was pre-existing at 
baseline 
 Missed doses of MOR00208 should not be made up for. If the patient misses a subsequent 
MOR00208 dose, the second missed dose should be administered immediately after the 
toxicity resolves. 
 During monthly treatment with MOR00208, every missed dose should be administered 
immediately after the toxicity resolves. 
If the Investigator considers a clinical finding and/or laboratory parameter change to represent 
natural fluctuation or progression of the underlying disease, then it will be at the Investigator’s 
discretion (and depend on the 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. 
For MOR00208 dose modification instructions for specific toxicities, see Table 8 & Table 9 and 
Sections 8.9 & 8.10. 
 
8.7 Dose Modifications of Idelalisib 
In the event of severe or life-threatening toxicities related to idelalisib, the drug must be withheld 
until the toxicity is resolved. If resuming idelalisib after interruption, reduce the dose to 100 mg 
twice daily. Re-escalation to 150 mg twice daily is allowed at the Investigator’s discretion.  
Recurrence of severe or life-threatening idelalisib-related toxicity upon rechallenge should result 
in permanent discontinuation of idelalisib.  
For dose modification instructions for specific toxicities related to idelalisib, see Section 8.9 and 
Table 8. 
8.8 Dose Modifications of Venetoclax 
8.8.1 General Rules 
Dose should be interrupted or reduced for toxicities. For patients who have had a dosing 
interruption greater than 1 week during the first 5 weeks of ramp-up phase or greater than 


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2 weeks when at the daily dose of 400 mg, reassess for risk of TLS to determine if reinitiation 
with a reduced dose is necessary (e.g., all or some levels of the dose ramp-up schedule).  
For dose modification instructions for specific (hematologic and other) toxicities related to 
venetoclax see Table 6 below and Table 9 in Section 8.10. 
 
Table 6: 
Dose Modification for Toxicity During Venetoclax Treatment 
Dose at Interruption, mg 
Restart Dose, mga  
400 
300 
300 
200 
200 
100 
100b 
50 
50b 
20 
20b 
10 
aDuring the ramp-up phase, continue the reduced dose for 1 week before increasing the 
dose. 
bDose reductions below 100 mg are not allowed after the ramp-up phase. 
 
8.8.2 Dose Modifications During the Ramp-up Phase 
Dose should be interrupted or reduced for toxicities according to Table 6 and Table 9. 
Ramp-up phase of venetoclax will be performed at regular scheduled visits. In cases when dose 
modification of venetoclax needs to be performed at an unscheduled visit (e.g., due to dosing 
interruption or reduction of venetoclax which leads to changed treatment schedule of 
venetoclax), relevant evaluations and safety measures should be performed (see Section 9.2.8). 
In exceptional cases duly justified due to other reasons, during the safety run-in phase patients 
might discontinue venetoclax treatment permanently per discussion between the Investigator 
and sponsor’s medical monitor to ensure patient safety.  
8.8.3 Dose Modifications After the Ramp-up Phase 
Dose should be interrupted or reduced for toxicities according to Table 6 and Table 9. 
Note: Dose modifications below 100 mg daily dose are not allowed, once the individual highest 
dose of venetoclax is reached. Patients who need dose reductions below 100 mg daily dose 
should discontinue venetoclax treatment permanently and may proceed with MOR00208 
treatment only, per discussion between the Investigator and sponsor’s medical monitor. 
8.8.4 Dose Modifications of Venetoclax for Use with CYP3A, P-gp, BCRP and OATP 
Inhibitors 
Concomitant use of venetoclax with strong or moderate CYP3A inhibitors (e.g., strong: 
ketoconazole, conivaptan, clarithromycin, indinavir, itraconazole, lopinavir, ritonavir, telaprevir, 
posaconazole and voriconazole; moderate: erythromycin, ciprofloxacin, diltiazem, fluconazole, 
verapamil) or inducers (e.g., strong: carbamazepine, phenytoin, rifampin, St. John’s wort; 
moderate: bosentan, efavirenz, etravirine, modafinil, nafcillin) during ramp-up phase is 


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contraindicated. Co-administration of CYP3A4 inducers may lead to decreased venetoclax 
exposure and consequently a risk for lack of efficacy. Concomitant use of venetoclax with strong 
CYP3A inhibitors increases venetoclax exposure (i.e., Cmax and AUC) and may increase the risk 
for TLS during ramp-up phase. For patients who have completed the ramp-up phase and are on 
a steady daily dose of venetoclax, reduce the venetoclax dose by at least 50% when moderate 
CYP3A inhibitors and 75% when strong CYP3A inhibitors must be used concomitantly, but not 
below 100 mg. Patients should be monitored more closely for signs of toxicities and the dose 
may need to be further adjusted. The venetoclax dose that was used prior to initiating the CYP3A 
inhibitor should be resumed 2 to 3 days after discontinuation of the inhibitor. 
Venetoclax is a P-gp, breast cancer resistance protein (BCRP) and organic anion-transporting 
polypeptide (OATP) inhibitor in vitro. Therefore, avoid concomitant use of venetoclax with 
P-gp and BCRP inhibitors and substrates (BCRP substrates: e.g., digoxin, dabigatran, 
everolimus, sirolimus; P-gp substrates: e.g., digoxin, everolimus, and sirolimus) and consider 
alternative treatments. If a statin (OATP substrate) is used concomitantly with venetoclax, close 
monitoring of statin-related toxicity is recommended. In vitro data suggest venetoclax has 
inhibition potential on P-gp substrates at therapeutic dose levels in the gut. Co-administration 
of a single dose of rifampin, a P-gp inhibitor, increased venetoclax Cmax by 106% and AUC∞by 
78%. Therefore, if a narrow therapeutic index P-gp inhibitor must be used, then it should be 
taken at least 6 hours before venetoclax and reduce the venetoclax dose by at least 50%, but not 
below 100 mg after the ramp-up phase. Monitor these patients more closely for signs of 
toxicities. Resume the venetoclax dose that was used prior to initiating the P-gp inhibitor 2 to 
3 days after discontinuation of the inhibitor.  
The recommendations for managing drug-drug interactions are summarized in Table 7. 
 
 
 


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Table 7: 
Management of Potential Venetoclax Interactions with CYP3A Inhibitors or 
Inducers, BCRP and P-gp Inhibitors and Substrates 
Inhibitors 
Ramp-Up Phase 
Steady Daily Dose 
(After Ramp-Up Phase) 
Strong and moderate 
CYP3A inhibitors and 
inducers 
Contraindicated 
Avoid inhibitor use or reduce venetoclax 
dose by at least 75% when strong and 
50% when moderate CYP3A inhibitors, 
but not below 100 mg  
P-gp and BCRP inhibitors 
and substrates  
P-gp and BCRP inhibitors, or narrow therapeutic index P-gp substrates; 
furthermore, grapefruit products, Seville oranges, and starfruit 
(carambola) should be avoided during treatment with venetoclax.  
If a P-gp inhibitor must be used, reduce venetoclax dose by at least 50%, 
but not below 100 mg after the ramp-up phase. 
If a narrow therapeutic index P-gp substrate must be used, it should be 
taken at least 6 hours before venetoclax. 
 
 
 


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8.9 Guidance for Managing Specific Adverse Events for the Combination 
of MOR00208 and Idelalisib 
Recommendations for managing specific adverse events (based on the FDA Prescribing 
Information and the European SmPC) are summarized in Table 8. 
 
Table 8: 
Guidance for Study Drug (Idelalisib/MOR00208) Dose Modifications Based on 
Type and Severity of Treatment-Emergent Adverse Events or Laboratory 
Abnormalities  
 
NCI CTCAE Grade 
Recommendation 
Idelalisib 
MOR00208 
HEMATOLOGICAL ADVERSE EVENTS 
Neutropenia 
Grade 2  
(<1.5-1.0 x 109/L)  
Maintain current dose level and 
schedule. 
Maintain dosing as per protocol.  
Grade 3  
(<1.0-0.5 x 109/L) 
Maintain current idelalisib dose 
level and schedule. Monitor ANC at 
least weekly. Consider growth factor 
support. 
Maintain dosing as per protocol. 
Monitor ANC at least weekly. 
Consider growth factor support. 
Grade 4  
(<0.5 x 109/L) or occurrence of 
neutropenic fever or infection 
Withhold idelalisib and monitor 
ANC at least weekly until ANC 
≥0.5x109/L and/or neutropenic fever 
or infection is resolved. Thereafter 
may resume idelalisib at lower 
(100 mg BID) dose at Investigator’s 
discretion. Consider growth factor 
support.  
Withhold MOR00208 and monitor 
ANC at least weekly until ANC 
≥0.5x109/L and/or neutropenic 
fever or infection is resolved. 
Thereafter, may resume as per 
protocol. Consider growth factor 
support.  
Thrombocytopenia 
Grade 2  
(<75-50 x 109/L) 
Maintain current dose level and 
schedule. 
Maintain dosing as per protocol.  
Grade 3  
(<50-25 x 109/L) 
Maintain current dose level and 
schedule. Monitor platelets at least 
weekly. 
Maintain dosing as per protocol. 
Monitor platelets at least weekly. 
Grade 4  
(<25 x 109/L) 
Withhold idelalisib until platelet 
count reach ≥25x109/L. Consider 
transfusion support. Monitor 
platelets at least weekly. May 
resume idelalisib at lower (100 mg 
BID) dose level when platelet counts 
have returned to ≥25x109/L. 
Withhold MOR00208 until platelet 
count reach ≥25x109/L. Consider 
transfusion support. Monitor 
platelets at least weekly. Thereafter, 
may resume dosing as per protocol. 
Anemia 
Grade ≤3  
(Grade 3 defined as: Hemoglobin 
<8.0 g/dL; <4.9 mmol/L; <80 g/L; 
transfusion indicated) 
Maintain dosing as per protocol. 
Consider transfusion and growth 
factor support in accordance with 
institutional guidelines. 
Maintain dosing as per protocol. 
Consider transfusion and growth 
factor support in accordance with 
institutional guidelines. 
Grade 4  
(Life-threatening consequences; 
urgent intervention indicated) 
Withhold idelalisib until Grade 3 
and monitor at least weekly. 
Thereafter, maintain dosing as per 
protocol.  
Withhold MOR00208 until Grade 3 
and monitor at least weekly.  
Thereafter, maintain dosing as per 
protocol.  


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NCI CTCAE Grade 
Recommendation 
Idelalisib 
MOR00208 
NON-HEMATOLOGICAL ADVERSE EVENTS 
Dermatological Events 
Grade 2 
Maintain current dose and schedule. 
Monitor patients for the 
development of severe cutaneous 
reactions. 
Maintain dosing as per protocol. 
Monitor patients for the 
development of severe cutaneous 
reactions. 
 
Grade 3 or 4 
 
Withhold idelalisib until Grade 1 is 
reached. May resume at lower dose 
(100 mg BID) at Investigator’s 
discretion. Discontinue idelalisib 
permanently if rechallenge results in 
recurrence of Grade 3-4 toxicity. 
Withhold MOR00208 until Grade 
≤2 is reached and thereafter may 
resume dosing as per protocol. 
CAVE: Stevens-Johnson 
syndrome/ Toxic epidermal 
necrolysis 
If Stevens-Johnson syndrome or 
toxic epidermal necrolysis is 
suspected, treatment with idelalisib 
should be immediately and 
permanently discontinued and the 
patient treated accordingly. 
If Stevens-Johnson syndrome or 
toxic epidermal necrolysis is 
suspected, treatment with 
MOR00208 should be immediately 
and permanently discontinued and 
the patient treated accordingly. 
Gastrointestinal Events (Diarrhea/Colitis) 
All Grades 
Obtain patient history, perform physical examination and diagnostic work-
up to rule out infectious etiology. Provide adequate symptomatic support 
including oral hydration/i.v. fluid supplementation, dietary modification 
and antimotility agents as warranted. Supportive care should provided until 
diarrhea Grade≤1. If the infection can be ruled-out follow below mentioned 
diarrhea-management recommendations.  
For patients who develop severe abdominal pain, particularly if early during 
therapy, the possibility of a bowel obstruction or perforation should be 
considered. Appropriate clinical and radiographic examination should be 
performed, and supportive care and surgical intervention should be 
considered. Idelalisib treatment should be discontinued permanently in 
patients who experience intestinal perforation (see details in Section 8.9.2). 
Grade 2  
(increase of 4-6 stools per day over 
baseline – moderate diarrhea) 
Maintain dosing as per protocol. 
Monitor at least weekly until 
resolved.  
Maintain dosing as per protocol. 
Monitor at least weekly until 
resolved.  
Grade 3  
(increase of ≥ 7 stools per day over 
baseline, fecal incontinence – 
severe diarrhea) 
Withhold idelalisib until Grade ≤1. 
Monitor at least weekly until 
resolved, then may resume at lower 
dose (100 mg BID). 
Maintain dosing as per protocol.  
In case diarrhea/colitis does not 
respond to antimotilty agents or 
patient’s general  condition 
deteriorates, withhold MOR00208 
until Grade ≤2 is reached and 
thereafter may resume dosing as per 
protocol.  
Grade 4  
(life-threatening) 
Discontinue idelalisib permanently.  Withhold MOR00208 until Grade 
≤2 is reached and thereafter may 
resume dosing as per protocol. 
 
 
 
 


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NCI CTCAE Grade 
Recommendation 
Idelalisib 
MOR00208 
Hepatic Events (Elevations in ALT, AST, or bilirubin) 
Grade 2 
(ALT/AST>3-5xULN) 
(Bilirubin>1.5-3xULN) 
Maintain current dose level and 
schedule. Monitor ALT, AST and 
bilirubin at least weekly. 
Maintain dosing as per protocol. 
Monitor ALT, AST and bilirubin at 
least weekly.  
Grade 3 
(ALT/AST>5-20xULN) 
(Bilirubin>3-10xULN) 
Withhold idelalisib. Monitor for 
liver toxicity at least weekly until all 
abnormalities are Grade 1 or to 
baseline values.Then may resume at 
lower dose (100 mg BID). 
Withhold MOR00208. Monitor for 
liver toxicity at least weekly until 
all abnormalities are Grade ≤1 or to 
baseline values. Thereafter, may 
resume dosing as per protocol. 
Grade 4  
(ALT/AST>20xULN) 
(Bilirubin>10xULN) 
Discontinue idelalisib permanently. 
Withhold MOR00208. Monitor for 
liver toxicity at least weekly until 
all abnormalities are Grade ≤1 or to 
baseline values. Thereafter, may 
resume dosing as per protocol. 
 
Pulmonary Events (Pneumonitis or Organizing pneumonia) 
Grade 1 
 
Maintain current dose and schedule 
if patient is asymptomatic. 
CAVE: If pneumonitis or organizing 
pneumonia is suspected with any 
severity of symptoms, interrupt 
idelalisib treatment until the etiology 
of the pulmonary symptoms has 
been determined. Patients with 
pneumonitis or organizing 
pneumonia thought to be caused by 
idelalisib should be treated with 
discontinuation of idelalisib and 
administration of corticosteroids. 
Monitor patient until resolved. 
Maintain dosing as per protocol. 
Monitor patient until resolved or 
symptoms subside. 
Grade 2 
Discontinue idelalisib permanently.  Maintain dosing as per protocol. 
Monitor patient until resolved. 
Grade ≥3 
Discontinue idelalisib permanently.  Withhold MOR00208 until toxicity 
diminishes in severity to Grade ≤2. 
Thereafter, may resume dosing as 
per protocol. 
Serious infections 
Pneumocystis jirovecii pneumonia (PJP) 
Prophylaxis for PJP during and 
after idelalisib treatment 
 
Prophylaxis for PJP should be administered to all patients throughout 
idelalisib treatment, and for a period of 2 to 6 months after 
discontinuation. The duration of post-treatment prophylaxis should be 
based on clinical judgment and may take into account a patient’s risk factors 
such as concomitant corticosteroid treatment and prolonged neutropenia. 
Any Grade 
Idelalisib 
treatment 
should 
be 
interrupted 
in 
patients 
with 
suspected PJP infection of any grade 
and permanently discontinued if PJP 
infection is confirmed. Appropriate 
MOR00208 administration should be 
withheld for patients with suspected 
PJP infection of any grade and 
permanently discontinued if PJP 
infection is confirmed. Appropriate 


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NCI CTCAE Grade 
Recommendation 
Idelalisib 
MOR00208 
medical 
therapy 
or 
other 
interventions should be instituted. 
medical 
therapy 
or 
other 
interventions should be instituted. 
Cytomegalovirus (CMV) 
CMV monitoring 
A central CMV laboratory test (serology and polymerase chain reaction 
[PCR]) will be performed for all patients at screening. Patient with negative 
serology should be monitored locally in accordance with institutional 
guidelines. Patient with positive serology or with other evidence of a history 
of CMV infection should be carefully monitored with a PCR based 
methodology: 
 
monthly, if the initial PCR result 
was negative 
without 
associated clinical signs of CMV infection 
 
weekly, if significant CMV viremia is detected. 
Any Grade 
For patients with evidence of CMV 
viremia and clinical signs of CMV 
infection, 
idelalisib 
should 
be 
immediately interrupted until the 
infection has resolved per discussion 
between 
the 
Investigator 
and 
sponsor’s medical monitor. If the 
benefits of resuming idelalisib are 
judged to outweigh the risks, 
consideration should be given to 
administering pre-emptive CMV 
therapy 
in 
accordance 
with 
institution 
al guidelines. 
For patients with evidence of CMV 
viremia and clinical signs of CMV 
infection, MOR00208 should be 
immediately interrupted until the 
infection has resolved per discussion 
between 
the 
Investigator 
and 
sponsor’s medical monitor. If the 
benefits of resuming MOR00208 are 
judged 
to 
outweigh 
the 
risks, 
consideration should be given to 
administering 
pre-emptive 
CMV 
therapy 
in 
accordance 
with 
institutional guidelines. 
 
8.9.1 Management of Hepatic Events 
Hepatotoxicity (Elevations in ALT, AST or bilirubin) 
Background: Fatal and/or serious hepatotoxicity occurred in 14% of idelalisib treated patients. 
Elevations in ALT and AST of Grade 3 and 4 (>5xULN) have been observed in clinical studies 
of idelalisib. In general, these laboratory findings occurred within the first 12 weeks of treatment; 
they were generally asymptomatic and were reversible with dose interruption. Most patients 
resumed treatment at a lower dose without recurrence. After resumption of treatment at a lower 
dose, 26% of patients had recurrence of ALT and AST elevations. The anticipated possible risks 
associated with the administration of MOR00208 to patients include ALT and AST increases; 
however, there was only one non-serious Grade 3 AE reported related to MOR00208 in a phase I 
trial of R/R CLL. 
Management: In the event of Grade 3 hepatic adverse events of elevations in ALT, AST or 
bilirubin, idelalisib treatment should be withheld. Liver enzymes and bilirubin should be 
monitored at least weekly until all abnormalities reached Grade ≤1 or returned to baseline values, 
then idelalisib treatment may be resumed at lower dose (100 mg BID). Idelalisib treatment must 
be discontinued permanently in the event of Grade 4 hepatic adverse events of elevations in 
ALT, AST or bilirubin. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
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In the event of Grade 3 or 4 hepatic adverse events of elevations in ALT, AST or bilirubin, 
MOR00208 administration should be withheld and liver enzymes and bilirubin should be 
monitored at least weekly until all abnormalities reached Grade ≤1. Thereafter, dosing of 
MOR00208 may be resumed as per protocol. 
8.9.2 Management of Gastrointestinal Events 
Diarrhea/colitis 
Background: Fatal and/or serious and severe diarrhea or colitis occurred in 14% of idelalisib 
treated patients across clinical trials. Diarrhea due to idelalisib can occur at any time and responds 
poorly to antimotility agents. Median time to resolution across trials ranged between 1 week and 
1 month following interruption of idelalisib therapy and, in some instances, use of 
corticosteroids. Cases of severe drug-related colitis occurred relatively late (months) after start 
of idelalisib therapy, sometimes with rapid aggravation, but resolved within a few weeks with 
dose interruption and additional symptomatic treatment (e.g., anti-inflammatory agents such as 
enteric budesonide). There is very limited experience from the idelalisib treatment of patients 
with a history of inflammatory bowel disease. 
Only mild and moderate (Grade ≤2) non-serious gastrointestinal AEs including diarrhea, 
constipation and abdominal pain occurred among CLL patients treated with MOR00208. 
Management: Providing an antidiarrheal (e.g., loperamide) may lessen symptoms. Consideration 
should be given to intervene with enteric steroidal (e.g., budesonide) or non-steroidal (e.g., 
sulfasalazine) anti-inflammatory agents. 
In the event of Grade 3 diarrhea/colitis, treatment with idelalisib must be withheld until Grade 
≤1. Patient should be monitored at least weekly until diarrhea/colitis has resolved, thereafter, 
treatment with idelalisib may be resumed at lower dose (100 mg BID). 
In the event of Grade 3 diarrhea/colitis, MOR00208 treatment should be maintained as per 
protocol. In case diarrhea/colitis does not respond to antimotilty agents or patient’s general  
condition deteriorates, MOR00208 must be withheld until Grade ≤2 is reached and thereafter 
dosing of MOR00208 may be resumed as per protocol. 
In the event of Grade 4 diarrhea/colitis treatment with idelalisib must be discontinued 
permanently and MOR00208 administration should be withheld until Grade ≤2 is reached and 
thereafter dosing of MOR00208 may be resumed as per protocol . 
Intestinal perforation 
Background: Fatal and serious intestinal perforation occurred in idelalisib treated patients. At 
the time of perforation, some patients had moderate to severe diarrhea. Advise patients to 
promptly report any new or worsening abdominal pain, chills, fever, nausea, or vomiting. 
Management: In patients who develop severe abdominal pain, particularly if early during 
therapy, the possibility of a bowel obstruction or perforation should be considered. Appropriate 
clinical and radiographic examination should be performed and supportive care and surgical 
intervention should be considered. Idelalisib treatment should be discontinued permanently in 
patients who experience intestinal perforation. MOR00208 administration should be withheld 
until the event resolved and thereafter, dosing of MOR00208 may be resumed as per protocol at 
the Investigator’s discretion. 


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8.9.3 Management of Pulmonary Events 
Pneumonitis 
Background: Fatal and serious pneumonitis occurred in patients treated with idelalisib. Clinical 
manifestations included interstitial infiltrates and organizing pneumonia. Patients taking 
idelalisib who present with pulmonary symptoms such as cough, dyspnea, hypoxia, interstitial 
infiltrates on a radiologic exam, or a decline by more than 5% in oxygen saturation, and patients 
presenting with serious lung events that do not respond to conventional antimicrobial therapy 
should be evaluated for pneumonitis. Pneumonitis did not occur in patients treated with 
MOR00208.  
Management: Idelalisib and MOR00208 treatment should be maintained if patient is 
asymptomatic. If pneumonitis or organizing pneumonia is suspected with any severity of 
symptoms, idelalisib treatment should be interrupted until the etiology of the pulmonary 
symptoms has been determined. Patients with pneumonitis or organizing pneumonia thought to 
be caused by idelalisib should be treated with discontinuation of idelalisib and administration of 
corticosteroids. Patient should be monitored until pneumonitis or organizing pneumonia is 
resolved.  
In the event of Grade ≥2 pneumonitis idelalisib treatment must be discontinued permanently.  
In the event of Grade ≥3 pneumonitis MOR00208 treatment must be withheld until toxicity 
diminishes in severity to Grade ≤2. Thereafter, dosing of MOR00208 may be resumed as per 
protocol at Investigator’s discretion. 
8.9.4 Management of Serious Infections (PJP, CMV, PML) 
Background: Adverse drug reactions of any grade reported in clinical studies such as infections 
including opportunistic infections as well as bacterial and viral infections such as pneumonia, 
bronchitis, and sepsis (including PJP and CMV) were very common in patients with hematologic 
malignancies receiving idelalisib. Moreover, serious and fatal infections have occurred in 
patients treated with idelalisib, including opportunistic infections such as PJP and CMV. 
In clinical studies with idelalisib higher frequencies of infections including Grade 3 and 4 
infections were observed in idelalisib arms compared to control arms without idelalisib 
treatment. Most frequently observed were infections in the respiratory system and septic events. 
In many instances, the pathogen was not identified; however, both conventional and 
opportunistic pathogens including PJP and CMV were identified. Nearly all PJP infections, 
including fatal cases, occurred in the absence of PJP prophylaxis. There have been cases of PJP 
after stopping idelalisib treatment. 
Cases of progressive multifocal leukoencephalopathy (PML) have been reported following the 
use of idelalisib within the context of prior- or concomitant immunosuppressive therapies that 
have been associated with PML. Physicians should consider PML in the differential diagnosis in 
patients with new or worsening neurological, cognitive or behavioural signs or symptoms. 
Management of PJP: Please note: Prophylaxis for PJP should be administered to all patients 
throughout idelalisib treatment and for a period of 2 to 6 months after discontinuation. The 
duration of post-treatment prophylaxis should be based on clinical judgment and may take into 
account a patient’s risk factors such as concomitant corticosteroid treatment and prolonged 


Product Name: MOR00208 
Protocol Number: MOR208C205 
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neutropenia. Prophylaxis shall be administered in accordance with institutional guidelines (e.g., 
with trimethoprim+sulfamethoxazole, dapsone, aerosolized pentamidine, or atovaquone). 
Idelalisib and MOR00208 treatment should be interrupted in patients with suspected PJP 
infection of any grade and permanently discontinued if PJP infection is confirmed. Appropriate 
medical therapy or other interventions should be instituted. 
Management of CMV: A central CMV laboratory test (serology and polymerase chain reaction 
[PCR]) will be performed for all patients at screening. Patients with negative serology should be 
monitored locally in accordance with institutional guidelines. Patients with positive serology or 
with other evidence of a history of CMV infection should be carefully monitored with a PCR 
based methodology: 
 monthly, if the initial PCR result was negative without associated clinical signs of CMV 
infection  
 weekly, if significant CMV viremia is detected. 
For patients with evidence of CMV viremia and clinical signs of CMV infection, idelalisib and 
MOR00208 should be immediately interrupted until the infection has resolved per discussion 
between the Investigator and sponsor’s medical monitor. If the benefits of resuming idelalisib 
and/or MOR00208 are judged to outweigh the risks, consideration should be given to 
administering pre-emptive CMV therapy in accordance with institutional guidelines. 
Note: All patients should be monitored for respiratory signs and symptoms throughout the trial 
and should be advised to report new respiratory symptoms promptly to their Investigator. 
Management of PML: If PML is suspected then appropriate diagnostic evaluations should be 
undertaken and treatment suspended until PML is excluded. If any doubt exists, referral to a 
neurologist and appropriate diagnostic measures for PML including MRI scan preferably with 
contrast, cerebrospinal fluid (CSF) testing for John Cunningham viral DNA and repeat 
neurological assessments should be considered. 
8.9.5 Management of Dermatological Events 
Severe cutaneous reactions / rash 
Background: Rare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have 
occurred when idelalisib was administered concomitantly with other medicinal products 
associated with these syndromes (BEN, RTX, allopurinol, and amoxicillin). Stevens-Johnson 
syndrome and toxic epidermal necrolysis occurred within one month of combination treatment, 
resulting in several deaths. Other severe or life-threatening (Grade ≥3) cutaneous reactions, 
including dermatitis exfoliative, rash, rash erythematous, rash generalized, rash macular, rash 
maculo-papular, rash papular, rash pruritic, exfoliative rash, and skin disorder, have been 
reported in idelalisib-treated patients. 
Management: Patients should be monitored for the development of severe cutaneous reactions. 
In the event of Grade 3 or 4 severe cutaneous reactions treatment with idelalisib must be 
withheld until Grade ≤1 is reached. Thereafter, idelalisib treatment may be resumed at lower 
dose (100 mg BID) at the Investigator’s discretion. Idelalisib treatment must be discontinued 
permanently if rechallenge with idelalisib results in recurrence of Grade 3-4 toxicity. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
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In the event of Grade 3 or 4 severe cutaneous reactions MOR00208 administration should be 
withheld until Grade ≤2 is reached and thereafter MOR00208 treatment may be resumed as per 
protocol. 
CAVE: If Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected, treatment with 
idelalisib and MOR00208 should be immediately and permanently discontinued and the patient 
treated accordingly. 
 
8.9.6 Management of Hematological and Immunological Events 
Neutropenia 
Background: Treatment-emergent Grade 3 or 4 neutropenia occurred in 31% of idelalisib-treated 
patients across clinical trials and in 7% of MOR00208-treated patients in a phase I clinical trial 
in R/R CLL. There was one CLL patient treated with MOR00208 who experienced DLT of 
Grade 4 neutropenia lasting ≥7 days with febrile neutropenia in a phase I clinical trial of R/R 
CLL. 
Management: Blood counts including absolute neutrophil count (ANC) should be monitored at 
least every 2 weeks during the first 6 months of therapy with idelalisib, and at least weekly in 
patients while neutrophil counts are less than 1.0x109/L.  
In the event of a Grade 4 neutropenia (<0.5x109/L) idelalisib treatment and MOR00208 
administration must be withheld. ANC should be monitored at least weekly until ANC 
≥0.5x109/L and/or neutropenic fever or infection is resolved. Thereafter, idelalisib treatment may 
be resumed at lower dose (100 mg BID) at the Investigator’s discretion and MOR00208 
treatment may be resumed as per protocol. Growth factors support can be considered. 
Thrombocytopenia 
Background: Treatment-emergent Grade ≥3 thrombocytopenia occurred in idelalisib-treated 
patients across clinical trials and in 7% of MOR00208-treated patients in a phase I clinical trial 
in R/R CLL. 
Management: Platelet count should be monitored at least weekly if platelet counts are <50x 
109/L. In the event of a Grade 3 thrombocytopenia (<50-25x109/L) idelalisib dose and 
MOR00208 administration should be maintained. In the event of a Grade 4 thrombocytopenia 
(<25x109/L) idelalisib treatment and MOR00208 administration must be withheld until platelet 
counts reach ≥25x109/L. Transfusion support can be considered. When platelet counts have 
returned to ≥25x109/L, idelalisib treatment may be resumed at lower dose (100 mg BID) and 
MOR00208 treatment may be resumed as per protocol.  
Anemia 
Background: There was no serious AE related to MOR00208 treatment reported in CLL patients. 
Management: In patients with Grade ≤3 anemia dosing of idelalisib and MOR00208 should be 
maintained as per protocol. Transfusion and growth factor support can be considered in 
accordance with institutional guidelines. In patients with Grade 4 idelalisib and MOR00208 
should be withheld until Grade 3 and hemoglobin should be monitored at least weekly. 
Thereafter, dosing may be maintained as per protocol.  


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Protocol Number: MOR208C205 
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Anaphylaxis 
Background: Serious allergic reactions, including anaphylaxis, have been reported in patients on 
idelalisib.  
Management: In patients who develop serious allergic reactions, idelalisib and MOR00208 
administration must be discontinued permanently and appropriate supportive measures should 
be instituted. 
8.9.7 Management of Tumor Lysis Syndrome 
Background: Based on the results of the phase I clinical study of MOR00208 in patients with 
CLL/SLL and the preliminary results of the MOR208C201 and MOR208C202 studies, the 
anticipated possible risks associated with administration of MOR00208 to patients include TLS 
with a suspected relationship to MOR00208 treatment. In the phase I trial of MOR00208 in 
patients with CLL/SLL one patient did develop TLS which required rasburicase and intravenous 
fluids, however, subsequent infusions were tolerated without incident. It is notable that this 
patient had received no prior chemotherapy and had been treated only with single agent CD20 
antibody therapy prior to receipt of MOR00208. Patients with TLS may experience 
hyperkalemia, hypocalcemia, hyperuricemia, hyperphosphatemia, cardiac dysrhythmias, and 
acute renal failure. Definition of TLS is described in Section 8.5.1. 
Management: Subjects with TLS should receive rapid reversal of hyperkalemia, intravenous 
hydration, antihyperuricemic agents, and appropriate cardiac and renal support, including 
dialysis as indicated. Medical prophylaxis and management should be initiated according to the 
institutional standard of care. Withholding of treatment with MOR00208 and idelalisib can be 
considered at the Investigator’s discretion. Upon recovery to baseline functioning, such patients 
should continue study treatment to maintain tumor control. 
8.9.8 Teratogenicity 
Embryo-fetal toxicity, pregnancy and lactation 
Based on findings in animals, idelalisib may cause fetal harm when administered to a pregnant 
woman. Therefore, fertile males and females of childbearing potential should abstain from sexual 
intercourse or use highly effective contraception (see Appendix F) while taking idelalisib and 
for 3 months after stopping treatment. If a female patient becomes pregnant or decides to 
breastfeed during the course of the study, all study therapy must be discontinued. 
 
 


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Protocol Number: MOR208C205 
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8.10 Guidance for Managing Specific Adverse Events for the combination of 
MOR00208 and Venetoclax 
Recommendations for managing specific adverse events (based on the FDA Prescribing 
Information) are summarized in Table 9. 
 
Table 9: 
Recommended Dose Modifications for Toxicities 
NCI 
CTCAE 
Gradea 
Occurrence 
Action 
Venetoclax 
MOR00208 
Tumor Lysis Syndrome 
All Grades 
(Blood chemistry 
changes or 
symptoms 
suggestive of TLS) 
 
 
Any 
Withhold the next day’s dose of 
venetoclax. If resolved within 24 
to 48 hours of last dose, resume 
venetoclax at the same dose. 
Maintain MOR00208 dosing 
as per protocol. 
For any blood chemistry changes 
requiring more than 48 hours to 
resolve, resume venetoclax at a 
reduced dose. 
For any events of clinical TLS, b 
resume venetoclax at a reduced 
dose following resolution. 
Withhold MOR000208 for any 
events of clinical TLSb. After 
resolution MOR00208 therapy 
may be resumed at the 
discretion of the physician. 
 
Non-Hematologic Toxicities 
Grade 3 or 4 
non- hematologic 
toxicities 
1st occurrence 
Interrupt venetoclax. 
Once the toxicity has resolved 
to Grade 1 or baseline level, 
venetoclax therapy may be 
resumed at the same dose. No 
dose modification is required. 
Interrupt MOR00208. 
Once the toxicity has resolved 
to Grade 1 or baseline level, 
MOR00208 therapy may be 
resumed. 


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NCI 
CTCAE 
Gradea 
Occurrence 
Action 
Venetoclax 
MOR00208 
2nd and subsequent 
occurrences 
Interrupt venetoclax. 
Follow dose reduction 
guidelines in Table 6 when 
resuming treatment with 
venetoclax after resolution. A 
larger dose reduction may 
occur at the discretion of the 
physician, but not below 
100 mg daily dose after the 
ramp-up phase. 
Interrupt MOR00208. 
After resolution MOR00208 
therapy may be resumed at the 
discretion of the physician. 
Hematologic Toxicities 
Grade 3 or 4 
neutropenia 
with infection 
or fever  
or  
Grade 4 
hematologic 
toxicities 
(except 
lymphopenia)  
1st occurrence 
Interrupt venetoclax. 
To reduce the infection risks 
associated with neutropenia, 
granulocyte-colony stimulating 
factor (G-CSF) may be 
administered with venetoclax if 
clinically indicated. Once the 
toxicity has resolved to Grade 1 
or baseline level, venetoclax 
therapy may be resumed at the 
same dose. 
Interrupt MOR00208.  
To reduce the infection risks 
associated with neutropenia, 
granulocyte-colony 
stimulating factor (G-CSF) 
may be administered with 
MOR00208 if clinically 
indicated. Once the toxicity 
has resolved to Grade 1 or 
baseline level, MOR00208 
therapy may be resumed. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
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NCI 
CTCAE 
Gradea 
Occurrence 
Action 
Venetoclax 
MOR00208 
2nd and subsequent 
occurrences 
Interrupt venetoclax. 
Consider transfusion and 
growth factor support as 
clinically indicated in 
accordance with institutional 
guidelines. Follow dose 
reduction guidelines in Table 6 
when resuming treatment with 
venetoclax after resolution. A 
larger dose reduction may 
occur at the discretion of the 
physician, but not below 
100 mg daily dose after the 
ramp-up phase. 
Interrupt MOR00208. 
Consider transfusion and 
growth factor support as 
clinically indicated in 
accordance with institutional 
guidelines. MOR00208 
therapy may be resumed after 
resolution. as follows: 
Neutropenia:  
Withhold MOR00208 and 
monitor ANC at least weekly 
until ANC ≥0.5x109/L and/or 
neutropenic fever or infection 
is resolved. Thereafter, may 
resume as per protocol. 
Thrombocytopenia: withhold 
MOR00208 until platelet 
count reach ≥25x109/L and 
monitor at least weekly. 
Thereafter, may resume as per 
protocol. 
Anemia:  
Withhold MOR00208 until 
Grade 3 and monitor at least 
weekly. Thereafter, may 
resume as per protocol. 
Consider discontinuing venetoclax for patients who require dose reductions to less than 100 mg for more 
than 2 weeks during the ramp-up phase. Dose modifications below 100 mg are not allowed after the ramp-
up phase and patient should discontinue venetoclax treatment. 
aAdverse reactions were graded using NCI CTCAE version 4.03. 
bClinical TLS was defined as laboratory TLS with clinical consequences such as acute renal failure, 
cardiac arrhythmias, or sudden death and/or seizures. 
 


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8.10.1 Management of Tumor Lysis Syndrome 
Background: Tumor lysis syndrome is an important identified risk when initiating venetoclax. 
In the initial Phase 1 dose-finding trials, which had shorter (2-3 week) ramp-up phase and higher 
starting dose, the incidence of TLS was 12% (9/77; 4 laboratory TLS, 5 clinical TLS), including 
2 fatal events and 3 events of acute renal failure, 1 requiring dialysis. The risk of TLS was 
reduced after revision of the dosing regimen and modification to prophylaxis and monitoring 
measures. In venetoclax clinical trials, patients with any measurable lymph node ≥10 cm or those 
with both an ALC ≥25 x 109/L and any measurable lymph node ≥5 cm were hospitalized to 
enable more intensive hydration and monitoring for the first day of dosing at 20 mg and 50 mg 
during the ramp-up phase. In 66 patients with CLL starting with a daily dose of 20 mg and 
increasing over 5 weeks to a daily dose of 400 mg, the rate of TLS was 6%. All events either 
met laboratory TLS criteria (laboratory abnormalities that met ≥2 of the following within 24 
hours of each other: potassium >6 mmol/L, uric acid >476 µmol/L, calcium <1.75 mmol/L, or 
phosphorus >1.5 mmol/L); or were reported as TLS events. The events occurred in patients who 
had a lymph node(s) ≥5 cm or ALC ≥25 x 109/L. No TLS with clinical consequences such as 
acute renal failure, cardiac arrhythmias or sudden death and/or seizures was observed in these 
patients. All patients had CrCl ≥50 mL/min. 
Based on the results of the phase I clinical study of MOR00208 in patients with CLL/SLL and 
the preliminary results of the MOR208C201 and MOR208C202 studies, the anticipated possible 
risks associated with administration of MOR00208 to patients include TLS with a suspected 
relationship to MOR00208 treatment. In the phase I trial of MOR00208 in patients with 
CLL/SLL one patient did develop TLS which required rasburicase and intravenous fluids, 
however, subsequent infusions were tolerated without incident. It is notable that this patient had 
received no prior chemotherapy and had been treated only with single agent CD20 antibody 
therapy prior to receipt of MOR00208. 
Management: Patients enrolling in Cohort B will be assessed for TLS risk and should receive 
appropriate prophylaxis for TLS as described in detail in Section 8.5 and 9.3.3.6. Importantly, 
all patients in Cohort B, who participate in the safety run-in phase, will be hospitalized on the 
day of the first two dose escalations of venetoclax (C1D8 and C1D15). Nephrology or acute 
dialysis service should be consulted or contacted on admission per institutional standards to 
ensure emergency dialysis is available and the appropriate staff is aware and prepared to handle 
any necessary intervention for TLS. 
MOR000208 should be withheld for any events of clinical TLS (clinical TLS is defined as 
laboratory TLS with clinical consequences such as acute renal failure, cardiac arrhythmias, or 
sudden death and/or seizures). After resolution MOR00208 therapy may be resumed at the 
discretion of the physician. 
During the ramp-up phase with venetoclax blood chemistries should be monitored and 
abnormalities should be managed promptly. Dosing should be interrupted if needed. More 
intensive measures should be employed (intravenous hydration, frequent monitoring, 
hospitalization) as overall risk increases. For any events of clinical TLS, resume venetoclax at a 
reduced dose following resolution. Concomitant use of venetoclax with strong or moderate 
CYP3A inhibitors or inducers within 7 days prior to the first dose of venetoclax and during ramp-
up phase of venetoclax is contraindicated. P-gp and BCRP inhibitors increases venetoclax 
exposure may increase the risk of TLS; therefore, concomitant use of venetoclax with P-gp and 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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BCRP inhibitors at initiation and during ramp-up phase should be avoided and requires 
venetoclax dose adjustment. 
Patients should be advised of the potential risk of TLS to immediately report any signs and 
symptoms associated with this event (fever, chills, nausea, vomiting, confusion, shortness of 
breath, seizure, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle pain, and/or 
joint discomfort) to their doctor for evaluation, and to be adequately hydrated every day when 
taking venetoclax to reduce the risk of TLS. 
8.10.2 Management of Hematologic Toxicities 
Background: Grade 3 or 4 neutropenia and febrile neutropenia occurred in 41% (98/240) and 
5% of patients treated with venetoclax, respectively. Dosage adjustments of venetoclax due to 
adverse reactions occurred in 9.6% of patients. The most frequent adverse reactions leading to 
dose adjustments of venetoclax were neutropenia, febrile neutropenia, and thrombocytopenia. 
Most hematological toxicities AEs were first reported in the initial months of treatment of 
venetoclax, with highest incidence and prevalence of AEs in the first month and decreasing with 
time on study (Davids et al., 2016). Moreover, autoimmune hemolytic anemia (AIHA) and 
anemia were reported among the most frequent serious adverse reactions (≥2%). The most 
frequent adverse reactions leading to drug discontinuation were thrombocytopenia and AIHA. 
Serious infections including events of sepsis with fatal outcome have been reported in patients 
treated with venetoclax. 
Treatment-emergent Grade 3 or 4 neutropenia occurred in 7% of MOR00208-treated patients in 
a phase I clinical trial in R/R CLL. There was one CLL patient treated with MOR00208 who 
experienced DLT of Grade 4 neutropenia lasting ≥7 days with febrile neutropenia in a phase I 
clinical trial of R/R CLL.  
Management: Interrupt venetoclax and MOR00208 at 1st occurrence of Grade 3/4 neutropenia 
with infection or fever, or Grade 4 hematologic toxicities (except lymphopenia). Once the 
toxicity has resolved to Grade 1 or baseline level, venetoclax and MOR00208 therapy may be 
resumed at the same dose of venetoclax.  
At 2nd and subsequent occurrences interrupt venetoclax and MOR00208. Consider transfusion 
and growth factor support as clinically indicated in accordance with institutional guidelines. 
Follow dose reduction guidelines in Table 6 when resuming treatment with venetoclax after 
resolution. A larger dose reduction may occur at the discretion of the physician, but not below 
100 mg daily dose after the ramp-up phase. 
At 2nd and subsequent occurrences withhold MOR00208 and may resume as follows: 
 Neutropenia: monitor ANC at least weekly until ANC ≥0.5x109/L and/or neutropenic 
fever or infection is resolved 
 Thrombocytopenia: monitor platelet count at least weekly until platelet count reach 
≥25x109/L 
 Anemia: monitor at least weekly until Grade 3 
Thereafter, may resume as per protocol.  


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0  
EudraCT Number: 2015-002915-14 
 
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Patients should be advised to contact their doctor immediately if they develop a fever or any 
signs of infection. 
Testing for AIHA (e.g. direct Coombs test, reticulocyte count) should be performed in patients 
receiving venetoclax treatment in accordance with institutional guidelines if AIHA is suspected 
of any grade.  
Measures including antimicrobial therapy for any signs of infection including sepsis should be 
considered.  
8.10.3 Management of Teratogenicity 
Embryo-fetal Toxicity, Pregnancy and Lactation 
Based on its mechanism of action and findings in animals, venetoclax may cause embryofetal 
harm when administered to a pregnant woman. In an embryo-fetal study conducted in mice, 
administration of venetoclax to pregnant animals at exposures equivalent to that observed in 
patients at the recommended dose of 400 mg daily resulted in post-implantation loss and 
decreased fetal weight. There are no adequate and well-controlled studies in pregnant woman 
using venetoclax. Advise females of reproductive potential to avoid pregnancy during treatment. 
If venetoclax is used during pregnancy or if the patient becomes pregnant while taking 
venetoclax, the patient should be apprised of the potential hazard to the fetus. 
Pregnancy - Risk Summary 
There are no available human data on the use of venetoclax in pregnant women. Based on toxicity 
observed in mice, venetoclax may cause fetal harm when administered to pregnant women. In 
mice, venetoclax was fetotoxic at exposures 1.2 times the human clinical exposure based on 
AUC at the recommended human dose of 400 mg daily. If venetoclax is used during pregnancy 
or if the patient becomes pregnant while taking venetoclax, the patient should be apprised of the 
potential risk to a fetus. The background risk in the general population of major birth defects is 
2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. 
Animal data. In embryo-fetal development studies, venetoclax was administered to pregnant 
mice and rabbits during the period of organogenesis. In mice, venetoclax was associated with 
increased postimplantation loss and decreased fetal body weight at 150 mg/kg/day (maternal 
exposures approximately 1.2 times the human AUC exposure at the recommended dose of 
400 mg daily). No teratogenicity was observed in either the mouse or the rabbit. 
Lactation - Risk Summary 
There are no data on the presence of venetoclax in human milk, the effects of venetoclax on the 
breastfed child, or the effects of venetoclax on milk production. Because many drugs are excreted 
in human milk and because the potential for serious adverse reactions in breastfed infants from 
venetoclax is unknown, advise nursing women to discontinue breastfeeding during treatment 
with venetoclax. 
Females and Males of Reproductive Potential 
Venetoclax may cause fetal harm. Females of reproductive potential should undergo pregnancy 
testing before initiation of venetoclax. Advise females of reproductive potential to use effective 
contraception during treatment with venetoclax and for at least 30 days after the last dose. Based 
on findings in animals, male fertility may be compromised by treatment with venetoclax. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0  
EudraCT Number: 2015-002915-14 
 
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8.11 Rules for Permanent Stop of Study Medication Intake 
If treatment needs to be interrupted for ≤ 28 days for drug-related toxicity of the same study drug 
(idelalisib or venetoclax or MOR00208), treatment should continue at the next protocol 
scheduled visit whenever possible. Missing visits or doses of either drug should not be made up 
for, with exception for the make up of a missed MOR00208 dose during the monthly MOR00208 
treatment, as described in Section 8.12. 
If treatment with one study drug needs to be interrupted for >28 days for the same, persistent, 
drug-related toxicity, 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 
(idelalisib/venetoclax and MOR00208), then the End of Treatment (EOT) visit will be performed 
and the patient will enter the follow-up period. 
 
8.12 Treatment Accountability and Compliance 
The pharmacist or other designated individual will maintain records of study treatment delivered 
to the study site; the inventory at the site; the distribution to and use by each patient; and the 
return of materials to the sponsor or disposal. These records should include dates, quantities, 
batch/serial numbers, expiration dates, in-clinic temperature log, and unique code numbers 
assigned to the product and study patients. 
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. 
At each visit after initiation of treatment, site staff will record compliance of patients with their 
assigned regimen. Patients will be instructed to bring unused/partially used/empty medication 
containers of idelalisib or venetoclax back for inspection on Day 1 of each cycle, starting with 
Cycle 2, or on the EOT visit as compliance will be assessed by tablet counts. 
Patients are to be reminded of the importance of compliance with their assigned regimen, with 
an emphasis on taking their study drug on schedule, and maintaining the prescribed interval 
between doses. 
Investigators will maintain records that document adequately that the patients were provided 
with the correct study treatment kits and will reconcile the products received from the drug 
dispensing center. Drug accountability will be checked by the field monitor during site visits and 
at the completion of the trial. 
Noncompliance in general is defined as taking ≤80% or >120% of one MOR00208 dose and/or 
≤80% or >120% of the idelalisib or venetoclax intake per cycle during any outpatient evaluation 
period.  
Moreover, one MOR00208 dose can be missed between Cycles 1 and 3, between Cycles 4 and 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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EudraCT Number: 2015-002915-14 
 
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12 and one dose between Cycles 13 and 24 without the patient being non-compliant. Note that 
MOR00208 dose omissions due to toxicity are covered in Sections 8.6 and 8.9. 
Discontinuation for noncompliance is at the Investigator’s discretion and is to be noted on the 
eCRF. 
8.13 Prior and Concomitant Therapy 
Patients are allowed to continue the medications that they are taking at baseline. Patients may 
also receive concomitant medications that are medically indicated as standard care for the 
treatment of symptoms and intercurrent illnesses. Medications to treat concomitant diseases, e.g., 
diabetes, hypertension, bronchial asthma and COPD are allowed. Patients may also receive 
therapy to mitigate side effects of the study medication as clinically indicated, as well as best 
supportive care as per institutional guidelines. This may include, e.g., antiemetics, antidiarrheals, 
anticholinergics, antispasmodics, antipyretics, antihistamines, analgesics, antibiotics, and other 
medications intended to treat symptoms. The Investigator should instruct the patient not to take 
any additional medications (including over-the-counter products) during the study without prior 
consultation. 
Investigators should document all medications (e.g., prescription drugs, over-the-counter drugs, 
herbal or homeopathic remedies, nutritional supplements) taken within 30 days prior to signature 
of ICF. 
The following prior and concomitant therapy will be recorded in the eCRF: 
 Medication and other therapy (including non-drug procedure) taken by/administered to 
the patient within 30 days prior to signature of ICF 
 Medication and other therapy (including non-drug procedure) taken by/administered to 
the patient during the course of the study 
 All prior medications/non-drug procedures, if deemed relevant by the Investigator, shall 
be entered into the eCRF.  
The entry must include the dose, regimen, route of administration, indication, and dates of use 
(start, end). 
After the baseline visit, medication to treat minor treatment-emergent illness(es) is generally 
permitted; however, the therapies listed below are expressly prohibited throughout the study. 
 
The following medications are prohibited: 
 Treatment with a BTK inhibitor within 5 days prior to Day 1 dosing 
 CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy 
or other lymphoma specific therapy within 14 days prior to Day 1. 
 Systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day within 
14 days prior to Day 1 dosing (Exception: Patients with signs of rapidly progressing 
disease per discussion between the Investigator and sponsor’s medical monitor) 
 Live vaccines within 14 days prior to Cycle 1 Day 1 and during the treatment period. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0  
EudraCT Number: 2015-002915-14 
 
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Note:  
 Vaccinations against influenza with inactivated virus or vaccination for 
pneumococcal diseases are allowed.  
 Cohort B only: Do not administer live attenuated vaccines after treatment with 
venetoclax until B-cell recovery occurs. 
 Other than study drugs anti-cancer therapies 
 Cohort B only: 
 Within 7 days prior to the first dose of venetoclax: Strong or moderate CYP3A 
inhibitors (e.g., strong: ketoconazole, conivaptan, clarithromycin, indinavir, 
itraconazole, lopinavir, ritonavir, telaprevir, posaconazole and voriconazole; 
moderate: erythromycin, ciprofloxacin, diltiazem, fluconazole, verapamil), 
strong or moderate CYP3A inducers (e.g., strong: carbamazepine, phenytoin, 
rifampin, St. John’s wort; moderate: bosentan, efavirenz, etravirine, modafinil, 
nafcillin) 
 Within 3 days prior to the first dose of venetoclax: Consumption of grapefruit, 
grapefruit products, Seville oranges (including marmalade containing Seville 
oranges), or star fruit 
 During ramp-up phase of venetoclax: Strong or moderate CYP3A inhibitors or 
inducers 
Growth Factors 
Growth factors may be prescribed at the Investigator’s discretion, according to the principles of 
medical practice and the 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 the eligibility criteria. 
Anticoagulants 
Warfarin therapy is allowed with caution during the study treatment with idelalisib or venetoclax. 
The international normalized ratio (INR) should be monitored closely in patients receiving 
warfarin upon co-administration and following ceasing treatment with idelalisib in Cohort A and 
with venetoclax in Cohort B. Discussion with the sponsor’s medical monitor is highly 
recommended about the use of other anticoagulation therapies, such as systemic or low-
molecular weight heparin. 
Infection Prophylaxis 
Investigators should follow institutional guidelines on infection chemoprophylaxis for patients 
regarded to be at high risk for infection. 
Corticosteroids 
After first dosing with study drug, patients are allowed to receive topical, enteric, inhaled, or 
systemic corticosteroids for therapy of CLL manifestations, comorbid conditions, autoimmune 
anemia and/or thrombocytopenia or for pretreatment of MOR00208 infusions. Patients who 
develop conditions that may be alleviated by systemic corticosteroid therapy are permitted to 
receive such drugs and are not required to discontinue study participation. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0  
EudraCT Number: 2015-002915-14 
 
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Anticancer Therapies 
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, radio-isotopic therapies, and targeted small molecules are not 
permitted during the entire treatment period of this study. Allogeneic stem-cell transplantation 
is considered to be a protocol prohibited anticancer therapy. 
 
Cohort A only: The following medications should be avoided (as per SmPC of idealisib): 
Effects of other medicinal products on idelalisib: 
 Co-administration of idelalisib with moderate or strong CYP3A inducers such as 
rifampicin, phenytoin, St. John’s wort (Hypericum perforatum), or carbamazepine should 
be avoided. Idelalisib exposure and thus efficacy may be reduced when coadministered 
with CYP3A inducers. 
 No initial dose adjustment of idelalisib is considered necessary when administered with 
CYP3A/ P-glycoprotein (P-gp) inhibitors (e.g., ketoconazole), but an intensified 
monitoring of adverse reactions is recommended. 
Effects of idelalisib on other medicinal products: 
 The primary metabolite of idelalisib, GS-563117, is a strong CYP3A4 inhibitor. Thus, 
idelalisib has the potential to interact with medicinal products that are metabolized by 
CYP3A, which may lead to increased serum concentrations of the other product (see 
Appendix I). When idelalisib is co-administered with other medicinal products, the label 
information for the other product must be consulted for the recommendations regarding 
co-administration with CYP3A4 inhibitors. Concomitant treatment of idelalisib with 
CYP3A substrates with serious and/or life-threatening adverse reactions (e.g., alfuzosin, 
amiodarone, cisapride, pimozide, quinidine, ergotamine, dihydroergotamine, quetiapine, 
lovastatin, simvastatin, sildenafil, midazolam, triazolam) should be avoided and 
alternative medicinal products that are less sensitive to CYP3A4 inhibition should be 
used if possible. 
 CYP2C8 substrates: In vitro, idelalisib both inhibited and induced CYP2C8, but it is not 
known whether this translates to an in vivo effect on CYP2C8 substrates. Caution is 
advised if idelalisib is used together with narrow therapeutic index drugs that are 
substrates of CYP2C8 (e.g., paclitaxel). 
 Substrates of inducible enzymes (e.g., CYP2C9, CYP2C19, CYP2B6 and UGT): In vitro, 
idelalisib was an inducer of several enzymes, and a risk for decreased exposure and 
thereby decreased efficacy of substrates of inducible enzymes such as CYP2C9, 
CYP2C19, CYP2B6 and UGT cannot be excluded. Caution is advised if idelalisib is used 
together with narrow therapeutic index drugs that are substrates of these enzymes (e.g., 
warfarin, phenytoin, S-mephenytoin). 
 Breast cancer resistance protein (BCRP), organic anion-transporting polypeptide 
(OATP)1B1, OATP1B3 and P-gp substrates: Co-administration of multiple doses of 
idelalisib 150 mg twice daily to healthy subjects resulted in comparable exposures for 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0  
EudraCT Number: 2015-002915-14 
 
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rosuvastatin (AUC 90% CI: 87, 121) and digoxin (AUC 90%; CI: 98, 111 [sic, SmPC]), 
suggesting no clinically relevant inhibition of BCRP, OATP1B1/1B3 or systemic P-gp 
by idelalisib. A risk for P-gp inhibition in the gastrointestinal tract, that could result in 
increased exposure of sensitive substrates for intestinal P-gp such as dabigatran etexilate, 
cannot be excluded. 
 
Cohort B only: The following medications should be avoided: 
Avoid concomitant use of venetoclax with strong or moderate CYP3A inhibitors or inducers 
after the ramp-up phase of venetoclax. P-gp and BCRP inhibitors, or narrow therapeutic index 
P-gp substrates; furthermore, grapefruit products, Seville oranges, and starfruit (carambola) 
should be avoided during treatment with venetoclax. Consider alternative treatments.  
The recommendations for managing drug-drug interactions and dose modifications of venetoclax 
are summarized in Table 7 and detailed in Section 8.8.4. 
 
 
9 STUDY PROCEDURES 
 
9.1 Schedule of Procedures and Assessments 
The Schedule of Procedures and Assessments is presented on the following pages (Table 10). 
All examinations/assessments that need to be performed at a specific visit are indicated with an 
“X” and the respective date, obtained from these assessments need to be documented in the 
source data. Each cycle consists of 28 days. 
Note: Missed visits should not be made up. 
 In case a visit (C4D1, C7D1, C13D1, etc.), where a radiological examination needs to be 
performed, is missed, the radiological examination needs to be performed as soon as 
possible after the missed visit, preferably within the scheduled timeframe of the 
respective visit (of ±7 days for the assessments on Cycle 4 and Cycle 7 and ± 14 days 
window for the following examinations). 
 In case a CxD1 visit is missed and therefore no idelalisib or venetoclax is given out to 
the patient, idelalisib or venetoclax should be provided to the patient at the next possible 
timepoint, either during an unscheduled visit or at CxD15. If missed visit was due to 
toxicity please follow the guidance for toxicity management. 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0  
EudraCT Number: 2015-002915-14 
 
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Table 10: 
Schedule of Procedures and Assessments 
Evaluation or Procedure 
Screening
Period 
Treatment Period 
Screening
≤28 Days 
prior to D1 
Cycle 1 
Cycle 2 
Cycle 3 
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 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease risk assessment: 
Cytogenetic testing; 
β2-microglobulin (serum); 
Expression of CD38 and ZAP-
70 
 
X1 
 
 
 
 
 
 
 
 
 
 
 
 
Optional mutational analysis 
(e.g., IGHV, TP53, NOTCH1, 
BTK, PLCγ2, CD19) 
 
X1 
 
 
 
 
 
 
 
 
 
 
 
 
Previous/concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete physical 
examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Limited physical examination 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
ECOG performance status 
X 
X1 
 
 
 
 
X 
 
 
 
X 
 
 
 
Weight/height 2 
X 
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 
 X1 
 
 
X3 
 
 X3 
 
 
 
 X3 
 
 
 
Urinalysis 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
HIV testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test 
(FCBP)4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 1,4 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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Evaluation or Procedure 
Screening
Period 
Treatment Period 
Screening
≤28 Days 
prior to D1 
Cycle 1 
Cycle 2 
Cycle 3 
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 
Pregnancy and risks 
counselling 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
“Emergency laboratory” 1, 5 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Central laboratory (blood) 
Hematology  
X 
X1 
 
 
X1 
 
X1 
 
X1 
 
X1 
 
X1 
 
Central laboratory (blood) 
Serum chemistry  
X 
X1 
 
 
X1 
 
X1 
 
X1 
 
X1 
 
X1 
 
Central laboratory (blood) 
Coagulation  
X 
X1 
 
 
 
 
X1 
 
 
 
X1 
 
 
 
Serology (hepatitis B and C) 
  X12 
 
 
 
 
 
 
 
 
 
X12 
 
 
 
CMV testing  
X14 
 
 
 
 
 
X14 
 
 
 
X14 
 
 
 
B-, T- and NK cell (blood) 1 
 
X 
 
X 
 
 
X17 
 
X16 
 
 
 
 
 
CD19 assessment (CD19ABC 
and % CD19 + cells) (blood) 1
 
X 
 
X16 
X16 
 
X17 
 
 
 
 
 
 
 
Anti-MOR00208 antibodies 1 
 
X 
 
 
 
 
X
 
 
 
X 
 
 
 
Optional FcγR polymorphism 
(mucosal cheek swab) 1 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CD16 assessment 
(CD16ABC) (blood) 1 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
MRD (blood) 1 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Disease response assessment:
CT/MRI of neck, chest, 
abdomen, pelvis 7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
MOR00208 administration 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispensation of 
idelalisib/venetoclax tablets 
 
X17 
 
X16 
X16 
X16 
X 
X16 
 
 
X 
 
 
 
Venetoclax ramp-up 18 
 
 
 
20mg 
50mg 
100mg 
200mg 
400mg 
 
 
 
 
 
 
TLS risk assessment 1,16,18 
X 
 
 
X 
X 
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 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0  
EudraCT Number: 2015-002915-14 
 
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Schedule of Procedures and Assessments (continued) 
 
Additional Treatment Periods 
 
Follow-up Period 
Evaluation or Procedure 
 
Cycle 4 - Cycle 6 
 
Cycle 7 - Cycle 24 
End of Treatment 
Visit (EOT) 
30-Day Safety 
Follow-up Visit 
Day 
D1 ±2 days 
D15 ±2 days 
 
D1 ±2 days 
Preferably within ≤30 
days of last dose of 
study treatment 
±2 days 
Concomitant medication 
X 
X 
X 
X 
X 
Complete physical 
examination 
 
 
 
X 
 
Limited physical 
examination 
X 
X 
X 
 
X 
ECOG performance status 
X 
 
X 
X 
 
Weight 2 
X 
X 
X 
X 
 
Vital signs 
X 
X 
X 
X 
 
B-symptoms 
X 
 
X 
X 
X 
12-lead resting ECG 
X 
 
X 
X 
 
Urinalysis 
X 
 
X 
X 
 
Serum pregnancy test 
(FCBP) 4 
 
 
 
X 
 
Urine pregnancy test 1 
X 
 
X 
 
 
Emergency Laboratory 1, 5
X 
X 
X 
 
 
Central laboratory (blood) 
Hematology) 
X1 
 
X1 
X 
 
Central laboratory (blood) 
Serum chemistry  
X1 
 
X1 
X 
 
Central laboratory (blood) 
Coagulation 
X1 
 
X1 
X 
 
Anti-MOR00208 antibodies 
X1, 9 
 
X1, 9 
X 
 
B, T, and NK cell (blood) 1 
X10 
 
X 
 
Disease response 
assessment: CT/MRI of 
neck, chest, abdomen, pelvis 
7 
X7 
 
X7 
X7, 8 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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Additional Treatment Periods 
 
Follow-up Period 
Evaluation or Procedure 
 
Cycle 4 - Cycle 6 
 
Cycle 7 - Cycle 24 
End of Treatment 
Visit (EOT) 
30-Day Safety 
Follow-up Visit 
Day 
D1 ±2 days 
D15 ±2 days 
 
D1 ±2 days 
Preferably within ≤30 
days of last dose of 
study treatment 
±2 days 
For CR / PR patients only: 
bone marrow aspiration & 
biopsy, MRD assessment 
X11 
 
X11 
X11 
 
MOR00208 administration 
X 
X 
X 
 
 
Dispensation of 
idelalisib/venetoclax tablets 
X 
 
X 
 
 
(S)AE assessment 
X 
X 
X 
X 
X 
CD19 assessment 
(CD19ABC and % CD19+ 
cells) (blood) 
 
 
 
X 
 
PK MOR00208 
X1, 9 
 
X1, 9 
X
 
Antineoplastic therapy 
after end of study treatment  
 
 
 
 
X 
Serology (hepatitis B and C)
X12 
 
X12 
 
 
MRD (blood) 1
X13 
 
X13 
 
 
CMV testing 
X14 
 
X14 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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EudraCT Number: 2015-002915-14 
 
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Abbreviations: ABC=antibodies bound per cell; AE=adverse event; β-HCG=beta-human chorionic gonadotropin; BTK=Bruton's tyrosine kinase; 
CMV=Cytomegalovirus; CD19=cluster of differentiation 19; CT=computed tomography; ECG=electrocardiogram; ECOG=Eastern Cooperative 
Oncology Group; FCBP=female of childbearing potential; HIV=human immunodeficiency virus; IGHV=immunoglobulin heavy-chain variable 
gene; MRD=minimal residual disease; MRI=magnetic resonance imaging; NK=natural killer; PK=pharmacokinetics; PRO=patient-reported 
outcomes; SAE=serious adverse event; TLS=tumor lysis syndrome. 
 
Disease risk assessment as per IWCLL guideline: cytogenetic tests: FISH: Minimum required tests are del (17p), del (11q), del (13q), trisomy 12,
karyotyping. IGHV information can be obtained from previous CLL history; should otherwise be obtained from baseline investigation, 
Β2 microglobulin (serum), CD38 (cytometry), ZAP-70 (cytometry). 
 
1Before study drug administration. 
2Body height will be measured at Cycle 1 Day 1 (C1D1) only. Weight and height should be measured while the patient is without shoes but 
dressed. 
312-lead resting ECG performed 1 hour ±10 minutes post-MOR00208 dosing 
4Pregnancy tests for FCBP: a serum pregnancy test must be performed at screening within 7 days prior to the start of study drug and a local 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 C1D1 dosing. 
A β-HCG pregnancy test should also be performed at the EOT visit. At all other indicated timepoints, a urine pregnancy test for FCBP will be 
performed locally. Pregnancy test must be negative for dosing. 
5Emergency laboratory sample to be collected and evaluated in the local laboratory as indicated 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. 
7Baseline CT/MRI scan has to be performed within 14 days before C1D1. CT scans performed prior to screening as part of the regular clinical 
work-up of the patient will be allowed up to 6 weeks before C1D1. However, a CT scan must be performed within the 14 day period prior to C1D1 
for those patients with signs of rapidly progressing disease at screening. CLL response assessment according to IWCLL guideline (Hallek et al., 
2008). SLL response assessment according to the Lugano Classification criteria (Cheson et al., 2014). For CLL and SLL: CTs or MRIs will be 
performed at C4D1, C7D1, C13D1, C19D1, etc. Time window is ±7 days for visits C4D1 and C7D1 and ±14 days for the following examinations. 
A CT/MRI scan has to be performed at least 8 weeks after CR was identified by clinical criteria (and before a BM biopsy is obtained for CR 
confirmation). If a regular CT/MRI scan is scheduled within these 8 weeks according to the schedule of assessment (C4, C7, C13, etc.) this 
examination should be postponed to meet the confirmation timeline. The following regular CT/MRI scan can be postponed/ 
skipped, if this examination is within 8 weeks of the CR confirmatory scan. 
8In case the patient is withdrawn from treatment for reasons other than progression of disease, a CT is only required at the EOT visit if this was 
not performed within 28 days before EOT. 


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9During Cycles 4 through 24, anti-MOR00208 antibody samples and MOR00208 PK samples (all to be collected pre-dose only) will be collected 
in odd numbered cycles only (i.e., Cycles 5, 7, 9, 11, etc.) 
10B/T/NK cell count only in Cycle 4 of additional treatment period. 
11For patients with CR: a MRD assessment from bone marrow aspirate and a local analysis of bone marrow aspiration/biopsy has to be performed
for confirmation of CR at least 8 weeks after the CR criteria for tumor response are first met. The result of the CT scan need to be obtained first; 
if this does not confirm a CR, then a biopsy should not be performed.  
For patients with PR and PB MRD negativity: an MRD assessment from bone marrow aspirate/peripheral blood has to be performed at least 
8 weeks after the PB MRD negativity was detected. 
12If positive for hepatitis B serology needs to be followed up locally every 2 months. 
13Periphal blood sample for MRD assessment has to be taken at C4D1, C7D1, C13D1, C19D1, etc. until BM MRD negativity was confirmed. 
For CR patients only: An additional PB sample needs to be obtained at the time when CR is confirmed by CT. 
14Patients with positive serology or with other evidence of a history of CMV infection at screening should be carefully monitored with PCR  
(a) monthly, if initial PCR result has been negative without associated clinical signs of CMV infection or  
(b) weekly, if significant CMV viremia has been detected. 
15During ramp-up of venetoclax patients will receive 20 mg (C1D8), 50 mg (C1D15), 100 mg (C1D22), 200 mg (C2D1) and 400 mg (C2D8), if 
no contraindications 
16Cohort B –Venetoclax+MOR00208 patients only. 
17Cohort A – Idelalisib+MOR00208 patients only. 
18In cases when an unscheduled visit needs to be performed during ramp-up phase of venetoclax (e.g., due to dosing interruption or reduction of 
venetoclax which leads to changed treatment schedule of venetoclax), no risk reassessment for TLS needs to be performed at respective regular 
visit(s) when MOR00208 is administered. 
 


Product Name: MOR00208 
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9.2 Study Periods and Procedures 
9.2.1 Patient Information and Informed Consent 
The participation of the patients and the investigation of their eligibility are subject to informed 
consent. Only patients who are able and willing to consent freely to participate after receiving 
detailed information both verbally and in writing are eligible for enrolment. 
Prior to start of any study-related examination, the Investigator or designated staff will inform 
the patients about the nature, importance, implications, and risks of the trial. The patients will be 
informed about the study medication, method of administration, blood sampling, imaging 
techniques, rules of conduct, and any restrictions that might apply. Possible effects (both 
beneficial and adverse) of the study medication will be discussed. The extent of the examinations 
to be performed and the invasive and non-invasive investigation methods will be explained. 
Optional mutational analyses are planned within this trial. (For details please refer to Sections 
9.3.6 and 9.3.7.) The examination should be explained to the patients, who are asked to consent 
voluntarily to this examination on a seperate Pharmacogenomics ICF. The participation in the 
pharmacogenomics examination is entirely optional and has no influence on the overall study 
participation. 
The patients will be given ample opportunity to ask questions concerning any and all aspects of 
the study. All patients will be informed that participation is entirely voluntary and that they can 
cease participation at any time without necessarily giving a reason and without any penalty or 
loss of benefits to which they were entitled. All patients will have to sign the Informed Consent 
Form (ICF) as proof of consent and will receive a copy of the Patient Information Sheet (PIS) 
and ICF. 
9.2.2 Screening Period 
The Screening Period begins on the date when the ICF is signed; it will last for up to 28 days 
and is followed by Cycle 1 Day 1 (C1D1). In exceptional cases, the screening period may be 
extended at the discretion of the investigator for a total of up to 42 days due to any 
technical/logistic reasons (e.g., extended imaging equipment breakdown and/or servicing, delays 
in the delivery of central laboratory results). The reason for such extension along with an 
evaluation by the investigator ensuring that such extension does not pose any health risk for the 
patient should be documented in the patient’s source data.  
The assessments to be performed at screening may be grouped as follows: 
 
Assessment of in/exclusion criteria (see Section 7.2.1 and 7.2.2) 
 
Pregnancy and risks counselling; pregnancy test for FCBP. Two pregnancy tests must 
be performed: the first, a serum pregnancy test at screening within 7 days prior to the 
start of study drug and the second, a local 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 
C1D1 dosing (see Section 9.3.2.1). 
 
Documentation of demography, medical history, previous/concomitant medications, 
weight/height (see Section 9.3.1) 
 
Disease assessment of CLL and SLL (CT or MRI scan of neck, chest, abdomen, pelvis) 
within 14 days before C1D1 (see Sections 9.3.3.1 and 9.3.3.3) 
 
ECOG performance status (see Section 9.3.8) 


Product Name: MOR00208 
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IND Number: 114,856 
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 
Disease staging (see Appendix A) 
 
B-symptoms (see Section 9.3.3.5) 
 
Complete physical examination (see Section 9.3.2.3) 
 
Vital signs (see Section 9.3.2.2) 
 
12-lead resting ECG (see Section 9.3.2.4) 
 
Blood sampling for hematology, serum chemistry and coagulation (central laboratory) 
(see Section 9.3.2.5) 
 
Viral testing: hepatitis B and C, CMV, HIV (see Virus_Serology) 
 
Urinalysis (see Table 11) 
 
Recording of (S)AEs (see Section 10.5) 
The assessments performed during screening will be used for generating the baseline data. 
During screening, it is permitted to repeat on a single occasion the central laboratory assessment 
of serum chemistry and hematology 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. 
An important procedure to be done at screening is: 
 
Pregnancy and risks counselling 
9.2.3 Documentation of Screening Failures 
During screening, patients may prove to be ineligible for participation in the study. The following 
documents and data should be collected in the eCRF for screening failures: 
 
Signed ICF 
 
Demography 
 
In/exclusion criteria which were not fulfilled by the patient 
 
Information on AEs (recording or confirmation that none occurred) 
No other data will be entered in the eCRF for Screen Failure patients. 
9.2.4 Pregnancy and Risks Counselling 
In addition, pregnancy and risk counselling will be conducted during the screening period. 
9.2.5 Subject Numbering 
Each patient is identified in the study by a 7 digit Subject Number, which is assigned when the 
patient is enrolled for screening and is retained as the primary identifier for the patient throughout 
study participation. The Subject Number (Subject No.) consists of the country number (two 
digits), the Center Number (three digits) as assigned by Morphosys to the investigative site with 
a sequential patient number (two digits) suffixed to it, so that each patient is identified. Upon 
signing the informed consent form, the patient is assigned to the next sequential Subject Number 
available to the Investigator. 


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Once assigned, the Subject No. must not be reused for any other patient.  
9.2.6 Re-screening 
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 any of the 
following criteria is met: 
1. 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). 
2. The patient previously failed to be eligible due to any event (e.g., planned surgery, 
laboratory test result) or any technical/logistic reason (e.g. screening period elapsed due 
to unexpected leave or absence of patient) that has been resolved. 
3. 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. 
A patient should only be re-screened 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: 
1. The patient must sign and date a new informed consent form (ICF) as part of the 
re-screening procedure. 
2. A new Subject ID will be assigned to the patient. 
3. The patient will be documented as re-screened in the source documents. 
4. A recording of medical histories, physical examinations, prior treatments for CLL/SLL, 
AEs, and concurrent medications will be transcribed from the previously used to the new 
eCRF if the conditions and medications still apply to the current status of the re-screened 
patient as documented in the source documents. All screening procedures must be 
completed again. 
A re-screened patient can be enrolled, if all of the current inclusion criteria and none of the 
exclusion criteria are met. 
9.2.7 Treatment Period 
The treatment period consists of a total of 24 cycles, each cycle lasting 28 days. For the first 
3 months (3 cycles) of the study each 28-day cycle will consist of a MOR00208 infusion on 
Day 1, Day 8, Day 15 and Day 22 of the cycle. In addition, a loading dose will be administered 
on Day 4 of Cycle 1. Thereafter, MOR00208 will be administered on a biweekly basis (every 14 
days) with infusions on Day 1 and Day 15 from Cycle 4 to Cycle 6. MOR00208 will be given 
on a monthly basis on Day 1 from Cycle 7 to Cycle 24. 
One to four visits are foreseen for each treatment cycle. Day 1 is the main visit of each cycle, 
where the largest number of examinations and assessments will be performed (for detail, see 
Table 10). Idelalisib or venetoclax tablets will be handed to the patients on Day 1 of each cycle. 
 
 


Product Name: MOR00208 
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Patients who continue to derive benefit from therapy with MOR00208 can stay on MOR00208-
treatment even beyond Cycle 24. In this case, the patient should be followed up at further visits 
(C25D1, C26D1, etc.) as specified for Cycle 7 to Cycle 24 (see the Schedule of Assessments, 
Table 10). Examinations which are not performed on every cycle, e.g., radiological and PK 
examinations, should also be followed up according to the specifications made in Table 10. 
Patients who achieved a confirmed CR or PR with bone marrow MRD negativity are allowed to 
stop idelalisib or venetoclax treatment and proceed with monthly MOR00208 treatment per 
discussion between the Investigator and sponsor’s medical monitor. 
9.2.8 Unscheduled Visit 
The Investigator may at his/her discretion arrange for a patient to have an unscheduled 
assessment, especially in the case of AEs that require follow-up or an AE considered by the 
Investigator to be possibly related to the use of study drug. The unscheduled visit page in the 
CRF must be completed. 
Ramp-up phase of venetoclax will be performed at regular scheduled visits. In cases when dose 
modification of venetoclax needs to be performed at an unscheduled visit (e.g., due to dosing 
interruption or reduction of venetoclax which leads to changed treatment schedule of 
venetoclax), the following evaluations and safety measures should be performed at respective 
unscheduled visit to reinitiate the weekly dosing of venetoclax:  
 Risk reassessment and prophylaxis for TLS (see Sections 8.5, 8.10.1 and 9.3.2.6) 
o Evaluation and monitoring of blood chemistry locally (e.g., potassium, uric acid, 
phosphorus, calcium, and creatinine) 
o Assessment of tumor burden (ALC, physical examination), and comorbidities or 
symptoms suggestive of TLS 
 Hospitalization as prescribed 
 Central laboratory of hematology and serum chemistry. Other laboratory parameters 
(e.g., coagulation parameters, urinalysis) may be determined only if clinically indicated 
 Vital signs 
 12-lead resting ECG only if clinically indicated 
 Recording of (S)AEs 
9.2.9 End of Treatment Visit 
Patients will continue on study treatment until documented disease progression, intolerable 
toxicity, withdrawal of consent to continue study treatment, death, physician decision or early 
termination of the study. At that time, an End of Treatment (EOT) visit will be performed.  
Assessments are to be completed preferably within ≤30 days of last study medication intake. The 
EOT visit will involve: 
 
Documentation of concomitant medications 
 
Blood sampling B-/T-/NK-cell count, CD19 expression assessment (see Section 9.3.6), 
for anti-MOR00208 antibodies (Section 9.3.5), MOR00208 PK sample (see 
Section 9.3.4) and a MRD assessment (only in case of CR or PR; see Section 9.3.3.6) 


Product Name: MOR00208 
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 
Disease response assessment of CLL and SLL (CT or MRI scans of neck, chest, 
abdomen, pelvis) 
 
Bone marrow aspiration and biopsy (required for confirmation of CR) 
 
B-symptoms (see Section 9.3.3.5) 
 
Serum pregnancy test for FCBP (see Section 9.3.2.1) 
 
ECOG performance status (see Section 0) 
 
Blood sampling for hematology, serum chemistry and coagulation (central laboratory) 
(see Section 9.3.2.5) 
 
Urinalysis (see Table 11) 
 
Complete physical examination (see Section 9.3.2.3) 
 
Vital signs and weight (see Section 9.3.2.2) 
 
12-lead resting ECG (see Section 9.3.2.4) 
 
Recording of (S)AEs (see Sections 10.2and 10.5) 
Assessments can take place within 7 days of the actual EOT visit. 
9.2.10 Follow-up Period 
9.2.10.1 30-Day Safety Follow-up Visit 
Regardless of the reason for study drug discontinuation, patients will have a safety follow-up 
visit scheduled 30 days after the last dose of the study treatment to follow up for AEs and SAEs 
that may have occurred after discontinuation from the study treatment. 
9.2.10.2 Follow-up for Drug Discontinuation/Patient Withdrawal from Study 
If a patient discontinues study treatment and is withdrawn from the study for any reason, the 
study site should immediately notify the medical monitor. The date and the reason for study 
discontinuation must be recorded on the eCRF. Patients who discontinue prematurely are to 
attend an EOT visit, if possible, and complete all assessments.  
In the event that a patient discontinues prematurely from the study due to a TEAE or serious 
TEAE, the TEAE or serious TEAE will be followed until it resolves (returns to normal or 
baseline values) or stabilizes, or until it is judged by the Investigator to be no longer clinically 
significant. 
Once a patient is withdrawn from the study, the patient may not re-enter the study. 
 
 


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9.3 Study Assessments 
9.3.1 Demographic Characteristics and Other Baseline Assessments 
9.3.1.1 Weight/Height 
Body weight (reported in kilogram, kg) and body height should be measured with clothes on but 
without shoes. Height will be measured at C1D1 only, and weight should be measured at each 
visit. The values should be entered into the eCRF indicating the actual day of measurement.  
For inpatients, body weight can be measured up to 24 hours before study drug administration on 
Day 1 of each cycle. This baseline weight will be used to calculate the study drug dose during 
the given cycle provided the weight does not deviate more than ±10% from baseline during the 
course of this cycle. In case body weight changes more than ±10% from baseline, the current 
weight will be used to calculate the next and subsequent doses of study drug. 
For outpatients, the patient weight must be measured on Day 1 of each cycle. This baseline 
weight will be used to calculate the study drug dose during the given cycle, provided the patient 
confirms that their body weight has not changed more than ±10% from baseline. In case body 
weight changes more than ±10% from baseline, the current weight will be used to calculate the 
next and subsequent doses of study drug. 
For both in- and outpatients, weight measurement will need to be performed at each visit and the 
values will need to be entered into the eCRF indicating the actual day of measurement. For 
outpatients, weight measurement may take place pre- or post dose. 
9.3.1.2 Demography 
Demographic baseline characteristics include age (including date of birth), sex and race. 
9.3.1.3 Medical History/Current Medical Conditions 
Medical history deserves particular attention because it is paramount for elibigility. Relevant 
medical history and current medical conditions will be recorded at the time of signing of the ICF. 
The medical history of CLL/SLL should be documented in detail, including baseline symptoms 
as well as a detailed history of prior cancer therapies for CLL/SLL, with start and stop dates, 
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 CLL/SLL should be recorded in the eCRF. 
Findings supporting the diagnosis of the latest progression of CLL/SLL should be recorded in 
the patient’s source documents. Such findings may consist of laboratory examinations, imaging 
results or clinical symptoms related to CLL/SLL. 
9.3.1.4 Disease Staging 
Assessments at baseline should also include Binet and modified Rai staging. For details please 
refer to Appendix A. 
9.3.1.5 FcγRII/III Gene Mucosal Cheek Swab 
Before study drug administration, mucosal cheek swabs should be done for FcγR genotyping. 
The assessment is optional (also see Table 13). 


Product Name: MOR00208 
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9.3.2 Assessment of Safety 
9.3.2.1 Pregnancy Testing 
For FCBP, two pregnancy tests must be performed; the first, a serum pregnancy test (β-HCG) at 
screening within 7 days prior to the start of study drug, and the second, a local 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 C1D1 dosing. A β-HCG serum pregnancy test should also be performed at the 
EOT visit. At all other timepoints indicated in the Schedule of Assessments (Table 10), a urine 
pregnancy test for FCBP will be performed locally and the result must be negative for dosing. 
9.3.2.2 Vital Signs 
Vital signs will be measured at the timepoints described in the Schedule of Assessments (Table 
10). These assessments include body temperature, systolic and diastolic blood pressure readings 
(mmHg), heart rate (beats per minute [bpm]), and respiratory rate (breaths per minute [brpm]). 
Vital signs will be measured immediately prior to infusion, 15 ± 5 minutes, 30 ± 10 minutes, 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. 
During the safety run-in phase the following measures need to be performed on Cycle 1 Day 1 
and Cycle 1 Day 4: 
 Patients No. 1-3 (safety run-in phase): vital signs should be measured 1 hour after end of 
infusion (± 20 min) and 2 hours after end of infusion (± 20 min). 
 Patients No. 4- approximately 12 (safety run-in phase): vital signs should be measured 1 
hour after end of infusion (± 20 min).  
The frequency or the length of the monitoring period may be adapted if clinically indicated, e.g., 
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 institutional practice. 
9.3.2.3 Physical Examination 
A complete physical examination (PE) will be performed by the Investigator or a qualified 
designee during the screening and at the EOT visit. 
Complete PE must be performed according to the best standards of local medical practice, but 
should include at least palpable tumor assessment, general appearance, skin, head, eyes, ears, 
nose, throat including Waldeyer lymphatic structures, lungs, breasts and axillae, cardiovascular 
system, back and spine, abdomen, extremities, infusion site, lymph nodes, and neurological 
examination. 
Limited PEs may be focused on tumor response assessment (lymph nodes, liver, spleen, etc.) 
and AEs (e.g., attention on respiratory signs and symptoms) at the Investigator’s discretion. Such 
limited PEs will be performed as indicated in the Schedule of Assessments (Table 10). Limited 


Product Name: MOR00208 
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PE will be performed on Day 1 and 15 of Cycle 1 to 6, on Day 1 of all further visits, and at EOT. 
Symptom-driven full PEs may be performed as clinically indicated at any study visit. 
9.3.2.4 Electrocardiogram 
Standard 12-lead resting ECGs should be obtained at the various timepoints described in the 
Schedule of Assessments (Table 10). ECGs should be recorded after the patient has rested in a 
supine position for at least 5 minutes. Heart rate, PR, QRS, RR and QT intervals should be 
determined. All ECGs should be performed and interpreted locally. The Investigator should 
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 should be repeated. An average of all 
intervals measured in all ECG tracings recorded at a given timepoint may be taken if necessary. 
9.3.2.5 Laboratory Assessments 
Clinical laboratory tests should be performed according to Table 10 and Table 11. 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 statistical analysis of the study results. During the course of the study, all 
scheduled central laboratory results should be reviewed as soon as possible after Day 1 of each 
cycle. 
It is permitted to repeat on a single occasion the central laboratory assessment of serum chemistry 
and hematology parameters during screening due to the variability of the parameters and their 
dependence on a multitude of factors (see Section 9.2.2). 
 
 


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Table 11: 
Safety Laboratory Evaluations 
Evaluation 
Analysis 
“Emergency laboratory” 
(EDTA blood and serum 
sample) 
 
AST, ALT, bilirubin (total, direct and indirect),  direct Coombs test, 
hemoglobin, platelets, potassium, serum creatinine, sodium, WBCs, 
including WBC differential (including ANC) 1 
Cohort B only: Additional values to be analyzed: calcium, creatinine,  
inorganic phosphorus (phosphate), potassium and uric acid 
Hematology 
(EDTA blood) 
Direct Coombs test, erythrocyte count (RBC count), hematocrit, 
hemoglobin, mean corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration, mean corpuscular volume, platelet count, 
reticulocytes, WBC with differential count (absolute counts and % of 
leukocytes: basophils, eosinophils, lymphocytes, monocytes, 
neutrophils) 
At screening: should include a peripheral blood smear. 
 
Serum chemistry 
(serum sample) 
ALT, total albumin, ALP, amylase, AST, β2-microglobulin, 
bicarbonate, bilirubin (total, direct and indirect), blood urea nitrogen, 
calcium (total), chloride, cholesterol, creatinine, creatinine kinase, 
GGT, glucose, LDH, lipase, magnesium, phosphate, potassium, 
protein (total), serum CrCl calculated using a standard Cockcroft-
Gault formula, sodium, triglycerides, uric acid 
 
Coagulation parameters 
(sodium citrate blood) 
Activated partial thromboplastin time, prothrombin time, international 
normalized ratio 
Viral parameters 
(serum or plasma sample) 
Hepatitis B: HBsAg, anti-HBc and HBsAb. HBV DNA if anti-HBc 
positive, optional  
Hepatitis C: HCV antibody (HCV RNA quantification if anti-HCV 
positive) 
CMV: CMV antibody and CMV copy number per mL (PCR based) 
HIV-1/-2 Ag and Ab Screening (HIV-1/-2 Ab differentiation if HIV 
positive) 
Pregnancy test  
(serum sample) 
β-HCG serum, females of childbearing potential only 
Pregnancy test  
(urine) 
β-HCG urine, females of childbearing potential only 
Urinalysis 
Clarity (clear, slightly cloudy, cloudy, turbid), bilirubin, color, 
glucose, hemoglobin, ketones, leukocyte esterase, nitrite, pH, protein, 
specific gravity, urobilinogen. 
Microscopy will only be performed if clinically indicated. 
 
Abbreviations: ALP= alkaline phosphatase; ALT=alanine transaminase; anti-HBc=hepatitis B core antibody; 
ANC=absolute neutrophil count; AST=aspartate amino-transferase; β-HCG=beta-human chorionic gonadotropin; 
CMV=Cytomegalovirus; CrCl=creatinine clearance; DNA=deoxyribonucleic acid; EDTA=ethylenediaminetetra-
acetic acid; GGT=gamma-glutamyltransferase; HBsAb=hepatitis B surface antibody; HBsAg=hepatitis B surface 
antigen; HBV=hepatitis B virus; HIV=human immunodeficiency virus; LDH=lactate dehydrogenase; 
PCR=polymerase chain reaction; RNA= ribonucleic acid; RBC=red blood cell; WBC=white blood cells. 
1WBC differential can be automated or manual as per institutional standards. Reticulocytes may be determined 
only if clinically indicated. 


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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 may be adjusted or interrupted if 
necessary. Emergency laboratory assessments may be performed up to 24 hours before 
administration of study drugs. 
Detailed instructions and amounts of biological samples needed for the respective laboratory 
measurements will be summarized in the Laboratory Manual. All samples will be collected as 
non-fasting samples. 
Table 11 summarizes laboratory assessments for a safe study conduct and for the evaluation of 
safety.  
Safety and Hematology Laboratory Testing 
The laboratory results of the centrally assessed clinical and safety relevant parameters will 
automatically be entered into the eCRF. The signed and interpreted laboratory results (both local 
and central) are to be kept in the patient’s source documentation. The laboratory results should 
be reviewed, dated and signed in a timely manner by the Investigators. Any clinically significant 
discrepancies between local and central laboratory results will be evaluated by the Investigator 
and medical monitor on a case-by-case basis. All blood samples should be processed and handled 
according to standard laboratory procedures. The time of blood collection should be documented 
in the eCRF. 
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 hematocrit). 
Virus Serology 
Patients will be examined according to the Schedule of Assessments (Table 10) for viral hepatitis 
B / C, HIV and Cytomegalovirus (CMV) serology.  
Hepatitis B and C 
Hepatitis B biomarkers include hepatitis B surface antigen (HBsAg), total hepatitis B core 
antibody (anti-HBc) and hepatitis B surface antibody (HBsAb). For patients who are positive for 
anti-HBc, hepatitis B viral DNA (HBV DNA) should be measured. 
Seropositive for or active viral infection with HBV: 
a) HBsAg positive 
b) HBsAg negative, HBsAb positive and/or anti-HBc positive and detectable viral DNA. 
Note: patients who are HBsAg negative and viral DNA negative are eligible 
c) Patients who had HBV but have received an antiviral treatment and show no detectable 
viral DNA for 6 months prior to the time of signing of the ICF are eligible 


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d) Patients who exhibit the classical vaccination profile of HBsAb positive, anti-HBc 
negative, and HBsAg 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 
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 hepatitis C 
virus antibody (anti-HCV). For patients who are positive for anti-HCV, HCV RNA should be 
measured.  
A positive hepatitis C test is defined as a positive test for anti-HCV and a positive test for HCV 
RNA. 
HIV 
Currently, there are no safety data on the use of CD19 antibodies in HIV positive patients 
available. Patients with known HIV infections will therefore be excluded from the clinical trial. 
In order to ensure that this patient population (which may also include patients with positive but 
unknown HIV status) will be adequately identified all patients must undergo HIV testing during 
screening. HIV testing during screening will be done using standard antibody tests. 
Cytomegalovirus 
A central CMV laboratory test (serology and PCR) will be performed for all patients at screening. 
Patient with negative serology should be monitored locally in accordance with institutional 
guidelines. Patients with positive serology or with other evidence of a history of CMV infection 
should be carefully monitored with a PCR based methodology: 
 monthly, if the initial PCR result was negative without associated clinical signs of CMV 
infection  
 weekly, if significant CMV viremia is detected. 
9.3.2.6 Risk Assessment for Tumor Lysis Syndrome for Patients Treated with 
Venetoclax 
Patients enrolling in Cohort B will be assessed for TLS risk and categorized in a risk category at 
screening as described below: 
1. Low-risk category: the presence of all measurable lymph nodes with the largest diameter 
<5 cm by radiologic assessment* baseline AND absolute lymphocyte counts <25 ×109/L 
2. Medium-risk category: the presence of all measurable lymph nodes with the largest 
diameter ≥5 cm and <10 cm by radiologic assessment* OR absolute lymphocyte count 
≥25 ×109/L 
3. High-risk category: the presence of any lymph node with the largest diameter ≥10 cm 
by radiologic assessment* OR the presence of BOTH an absolute lymphocyte count  
≥25 ×109/L AND a measurable lymph node with the largest diameter ≥5 cm by radiologic 
assessment*.  


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* Baseline CT/MRI scan at screening as defined in Footnote_7 to Table 10. 
Reassessment of the patient's risk category should be performed before first and each subsequent 
dose escalation of venetoclax on C1D8, C1D15, C1D22, C2D1 and C2D8 based upon blood 
chemistry, tumor burden (ALC, physical examination), comorbidities or symptoms suggestive 
of TLS. In cases when an unscheduled visit needs to be performed during ramp-up phase of 
venetoclax (e.g., due to dosing interruption or reduction of venetoclax which leads to changed 
treatment schedule of venetoclax), no risk reassessment for TLS needs to be performed at 
respective regular visit(s) when MOR00208 is administered. Furthermore, during the safety run-
in phase of Cohort B discussion will occur between the Investigator and sponsors’s medical 
monitor regarding the plan for TLS prophylaxis, including hydration, as necessary. 
9.3.2.7 Adverse Events 
Please refer to Section 10 (Safety Monitoring). 
 
9.3.3 Assessment of Efficacy 
9.3.3.1 Tumor Response Assessment 
Criteria of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) for CLL 
subjects (Hallek et al., 2008) will be used to determine rates of response and progression for 
patients with CLL, with the modification that treatment-related lymphocytosis (Note: PRL is 
applicable in Cohort A only) in the absence of other signs or symptoms of disease progression 
will not be considered as progressive disease (Cheson et al., 2012; Hallek et al., 2012; NCCN 
NHL 2015 Guidelines). For patients with SLL, assessments will be performed using the Lugano 
Classification criteria for SLL subjects (Cheson et al., 2014). 
The secondary endpoint overall response rate (ORR) will be derived from the local review of 
radiology and clinical data. 
Patients who develop a PR will be assessed using MRD testing from peripherial blood as well 
as from bone marrow, in case PB MRD negativity status was reached. Furthermore, patients who 
develop a complete response as per standard criteria will be investigated using MRD testing and 
bone marrow aspiration/biopsy as described in IWCLL (Hallek et al., 2008). 
Overall response assessments include physical exams, recording of symptoms, radiographic and 
hematological evaluations to evaluate for both AEs and for disease progression per the schedule 
of assessments. If a patient shows signs of progression, the patient may continue on treatment 
until progression is confirmed by CT scan. The CT scan should be performed and collected with 
resolution sufficient to allow accurate and consistent comparison of target lesion measurements 
with subsequent CT scans. The same scan modality should be used for all assessments, and all 
patients are required to have scans of the neck/chest/abdomen/pelvis. 
Baseline tumor assessments must be performed a maximum of 14 days before C1D1. As 
response is a secondary endpoint of the trial and that PD will be followed by physical 
examination, CT scans performed prior to screening as part of the regular clinical work-up of the 
patient will be allowed up to 6 weeks before C1D1. This is to prevent the re-irradiation of patients 
who have recently undergone a CT scan. However, a CT scan must be performed within the 14 
day period prior to C1D1 for those patients with signs of rapidly progressing disease at screening. 


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MRI may be used in lieu of CT for patients with contraindications to the administration of 
contrast agents, or due to other medical reasons, at the same timepoints 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. 
Any suspected case of disease progression should be confirmed with a CT scan. Radiological 
assessment of efficacy response will be required to be reviewed at C4D1, C7D1, C13D1, C19D1, 
etc., and at the EOT visit (in case the last tumor evaluation was not performed within 28 days). 
There is a time window of ±7 days for the assessments on Cycle 4 and Cycle 7 and ± 14 days 
window for the following examinations. Patients should continue to be followed and adhere to 
study-related procedures until progression has been confirmed. 
A CT/MRI scan has to be performed at least 8 weeks after CR was identified by clinical criteria 
(and before a BM biopsy is obtained for CR confirmation). Clinical criteria should be based on 
physical examination and/or laboratory values.  
In case of this confirmatory CT/MRI scan the following shall apply: 
 If a regular CT/MRI scan is scheduled within less than 8 weeks after identification of the 
CR by clinical criteria, then this examination should be postponed to meet the 
confirmation timeline of at least 8 weeks.  
 
and/or 
 
 The following regular CT/MRI scan can be postponed/skipped, if this examination is 
within 8 weeks of the CR confirmatory scan. 
 
9.3.3.2 Tumor Response Assessment for CLL 
Definitions of Tumor Response and Progression 
Responses will be categorized locally as CR, PR, PRL, SD, or PD.  
(Note: PRL is applicable in Cohort A only.) 
The best overall response in the course of the study will be determined. The best overall response 
is the best response recorded from the start of treatment until disease progression, withdrawal 
from study or death (taking as a reference for disease progression the smallest measurements 
recorded since treatment started). 
At baseline, up to 6 lymph nodes should be selected as index lesions that will be used to 
quantitate the status of the disease during study treatment. Ideally, the index lesions should be 
located in disparate regions of the body. However, it is optimal if mediastinal and retroperitoneal 
areas of disease are assessed whenever these sites are involved. Any other measurable and 
abnormal nodal lesions not selected for quantitation as index lesions may be considered non-
index lesions. In addition, non-measurable evidence of CLL such as nodal lesions with both 
diameters <1.0 cm, extranodal lesions, bone lesions, leptomeningeal disease, ascites, pleural or 
pericardial effusions, lymphangitis of the skin or lung, abdominal masses that are not confirmed 
and followed by imaging techniques, cystic lesions, previously irradiated lesions, and lesions 
with artifacts may be considered as non-index disease. The presence or absence of non-index 
disease should be recorded at baseline and at the stipulated intervals during treatment. The non-


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index disease at baseline will be used as a general reference to further characterize regression or 
progression of CLL during assessments of the overall tumor response during treatment. 
Measurements are not required and these lesions should be followed as “present” or “absent”. 
A table of response definition by the IWCLL 2008 is provided in Appendix J. 
 
 
Complete Response 
To satisfy criteria for a CR, all of the following criteria must be met: 
 No evidence of new disease 
 ALC in peripheral blood of < 4 x 109/L 
 Regression of all index nodal masses to normal size ≤ 1.5 cm in the longest diameter 
(LDi) 
 Normal spleen and liver size 
 Regression to normal of all nodal non-index disease and disappearance of all detectable 
non-nodal, non-index disease 
 Morphologically negative bone marrow defined as < 30% of nucleated cells being 
lymphoid cells and no lymphoid nodules in a bone marrow sample that is normocellular 
for age 
 Peripheral blood counts meeting all of the following criteria: 
o 
ANC > 1.5 x 109/L without need for exogenous growth factors (e.g., G-CSF) 
o 
Platelet count ≥ 100 x 109/L without need for exogenous growth factors 
o 
Hemoglobin ≥ 110 g/L (11.0 g/dL) without red blood cell transfusions or need for 
exogeneous growth factors (e.g., erythropoietin) 
Subjects who fulfill all the criteria for a CR (including bone marrow criteria) but who have a 
persistent anemia, thrombocytopenia, or neutropenia or a hypocellular bone marrow that is 
related to prior or ongoing drug toxicity (and not to CLL) will be considered as a CR with 
incomplete marrow recovery (CRi). 
 
 


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Partial Response 
To satisfy criteria for a PR, all of the following criteria must be met: 
 A decrease in the number of blood lymphocytes by 50% or more from the value before 
therapy 
 Reduction in lymphadenopathy by CT scans as defined by the following: 
o A decrease in lymph node size by 50% or more either in the sum products of up to 
6 lymph nodes, or in the largest diameter of the enlarged lymph node(s) 
o No increase in any lymph node, and no new enlarged lymph node. In small lymph 
nodes (< 2 cm), an increase of less than 25% is not considered to be significant 
 A reduction in the noted pretreatment enlargement of the spleen or liver by 50% or more, 
as detected by CT scan 
 The blood count should show one of the following results: 
o Neutrophils more than 1.5 x 109/L (1500/µL) without need for exogenous growth 
factors 
o Platelet counts greater than 100 x 109/L (100,000/µL) or 50% improvement over 
baseline without need for exogenous growth factors 
o Hemoglobin greater than 110 g/L (11.0 g/dL) or 50% improvement over baseline 
without requiring red blood cell transfusions or exogenous erythropoietin 
Stable Disease 
To satisfy criteria for SD, the following criteria must be met: 
 No evidence of new disease 
 There is neither sufficient evidence of tumor shrinkage to qualify for PR nor sufficient 
evidence of tumor growth to qualify for definitive PD 
Definitive Progressive Disease 
The occurrence of any of the following events indicates definitive PD: 
 Evidence of any new disease: 
o 
A new node that measures > 1.5 cm in the longest diameter (LD) and > 1.0 cm in the 
longest perpendicular diameter (LPD) 
o 
New or recurrent splenomegaly, with a minimum longest vertical dimension (LVD) 
of 14 cm 
o 
New or recurrent hepatomegaly, with a minimum LVD of 20 cm 
o 
Unequivocal reappearance of an extranodal lesion that had resolved 
o 
A new unequivocal extranodal lesion of any size 
o 
New non-index disease (e.g., effusions, ascites, or other organ abnormalities related 
to CLL) 


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Isolated new effusions, ascites, or other organ abnormalities are not sufficient evidence alone of 
a PD unless histologically confirmed. Thus, a declaration of PD should not be made if this is the 
only manifestation of apparently new disease. 
 Evidence of worsening of index lesions, spleen or liver, or non-index disease: 
o 
Increase by ≥ 50% from the nadir in the sum of the products of the perpendicular 
diameters (SPD) of index lesions 
o 
Increase from the nadir by ≥ 50% in the LD of an individual node or extranodal mass 
that now has an LD of > 1.5 cm and an LPD of > 1.0 cm 
o 
Splenic progression, defined as an increase in splenic enlargement by ≥ 50% from 
nadir (with a minimum 2 cm increase and a minimum LVD of 14 cm) 
o 
Hepatic progression, defined as an increase in hepatic enlargement by ≥ 50% from 
nadir (with a minimum 2 cm increase and a minimum LVD of 20 cm) 
o 
Unequivocal increase in the size of non-index disease (e.g., effusions, ascites, or 
other organ abnormalities related to CLL) 
o 
Transformation to a more aggressive histology (e.g., Richter’s syndrome) as 
established by biopsy (with the date of the biopsy being considered the date of CLL 
progression if the subject has no earlier objective documentation of CLL 
progression). 
 Decrease in platelet count or hemoglobin that is attributable to CLL, is not attributable to 
an autoimmune phenomenon, and is confirmed by bone marrow biopsy showing an 
infiltrate of clonal CLL cells 
o 
The current platelet count is < 100 x 109/L and there has been a decrease by > 50% 
from the highest on-study platelet count 
o 
The current hemoglobin is < 110 g/L (11.0 g/dL) and there has been a decrease by > 
20 g/L (2 g/dL) from the highest on-study hemoglobin 
If there is uncertainty regarding whether there is true progression, the subject should continue 
study treatment and remain under close observation. In particular, worsening of constitutional 
symptoms in the absence of objective evidence of worsening CLL will not be considered 
definitive disease progression; in such subjects, both CLL-related and non-CLL-related causes 
for the constitutional symptoms should be considered. Worsening of disease during temporary 
interruption of study treatment (e.g., for intercurrent illness) is not necessarily indicative of 
resistance to study treatment. In these instances, CT or MRI or other relevant evaluations should 
be considered in order to document whether definitive disease progression has occurred. If 
subsequent evaluations suggest that the subject has experienced persistent definitive CLL 
progression, then the date of progression should be the timepoint at which progression was first 
objectively documented. 
 
 


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Lymphocytosis During Therapy 
Upon initiation of idelalisib treatment, transient increase of absolute lymphocyte count is 
expected in most patients because idelalisib can mobilize CLL cells from tissues into the 
peripheral blood. This characteristic pharmacological action can be prominent early in therapy 
but can persist over time and should not be confused with disease progression in subjects who 
have persistent control of other CLL-related signs and symptoms. In the absence of other 
objective evidence of disease progression, lymphocytosis alone will not preclude subjects 
from meeting the criteria for PR if other criteria for PR are met and will not be considered 
evidence of disease progression if occurring in isolation. Thus, subjects with worsening 
lymphadenopathy, organomegaly, bone marrow involvement, progressive cytopenias, 
appearance of new disease, or transformation to a more aggressive lymphoid malignancy 
histology (e.g., Richter’s syndrome) will be considered to have progressed according to IWCLL 
criteria for progressive disease. Subjects with lymphocytosis without any of these other events 
will not be considered to have progressed and should be continued on study drug until the 
occurrence of definitive disease progression (Note: PRL is applicable in Cohort A only). 
 
9.3.3.3 Tumor Response Assessment for SLL 
Tumor measurements will be performed by CT as indicated in Table 12. MRI may be used in 
lieu of CT for patients with contraindications to the administration of contrast agents, or due to 
other medical reasons, at the same timepoints as CT or, in addition to CT, at the discretion of the 
Investigator (in this case, MRI may be performed as/when appropriate). 
 
 


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Table 12: 
Lugano Classification Criteria for SLL (adapted from Cheson et al., 2014) 
Response 
Site 
CT-Based Response 
CR 
 
Complete remission requires all of the following: 
 
Lymph nodes and extralymphatic 
sites 
Target nodes/nodal masses must regress to ≤ 1.5 cm in LDi 
No extralymphatic sites of disease 
 
Nonmeasured lesions 
Absent 
 
Organ enlargement 
Regress to normal 
 
New lesions 
None 
 
Bone marrow 
Normal by morphology; if indeterminate, IHC negative 
PR 
 
Partial remission requires all of the following: 
 
Lymph nodes and extralymphatic 
sites 
≥ 50% decrease in SPD of up to 6 target nodes and 
extranodal sites 
When a lesion is too small to measure on CT, assign 5 mm 
x 5 mm as the default value 
When no longer visible, 0 x 0 mm 
For a node > 5 mm x 5 mm, but smaller than normal, use 
actual measurement for calculation 
 
Nonmeasured lesions 
Absent/normal, regressed, but no increase 
 
Organ enlargement 
Spleen must have regressed by > 50% in length beyond 
normal (13 cm) 
 
New lesions 
None 
 
Bone marrow 
Normal marrow, persistent infiltration, or no marrow 
obtained 
SD 
 
Stable disease 
 
Target nodes/nodal masses/ 
extranodal lesions 
< 50% decrease from baseline in SPD of up to 6 target 
nodes and extranodal sites; no criteria for progressive 
disease are met 
 
Nonmeasured lesions 
No increase consistent with progression 
 
Organ enlargement 
No increase consistent with progression 
 
New lesions 
None 
 
 
Bone marrow 
Normal marrow, persistent infiltration, or no marrow 
obtained 
PD 
 
Progressive disease requires at least 1 of the following: 
 
Individual target nodes/nodal 
masses 
PPD progression 


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Response 
Site 
CT-Based Response 
PD 
Extranodal lesions 
An individual node/lesion must be abnormal with: 
LDi > 1.5 cm and 
Increase by ≥ 50% from PPD nadir and 
An increase in LDi or SDi from nadir 
0.5 cm for lesions ≤ 2 cm 
1.0 cm for lesions > 2 cm 
In the setting of splenomegaly, the splenic length must 
increase by > 50% of the extent of its prior increase 
beyond baseline (e.g., a 15-cm spleen must increase to 
> 16 cm). If no prior splenomegaly, must increase by 
at least 2 cm from baseline 
New or recurrent splenomegaly 
 
Nonmeasured lesions 
New or clear progression of preexisting nonmeasured 
lesions 
 
New lesions 
Regrowth of previously resolved lesions 
A new node > 1.5 cm in any axis 
A new extranodal site > 1.0 cm in any axis; if < 1.0 cm in 
any axis, its presence must be unequivocal and must 
be attributable to lymphoma 
Assessable disease of any size unequivocally attributable to 
lymphoma 
 
Bone marrow 
New or recurrent involvement 
Abbreviations: CR=complete remission; PR=partial remission; SD=stable disease; PD=progressive disease; 
CT=computed tomography; LDi=longest transverse diameter of a lesion; IHC=immunohistochemistry; 
SPD=sum of the product of the perpendicular diameters for multiple lesions; PPD=cross product of the LDi and 
perpendicular diameter; SDi=shortest axis perpendicular to the LDi. 
 
 
 


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9.3.3.4 Bone Marrow Aspiration and Biopsy 
For patients with CR, a bone marrow aspiration and biopsy has to be performed for confirmation 
of CR at least 8 weeks after the CR criteria for tumor response were first met. The results of the 
CT scan need to be obtained first; if this does not confirm a CR, then a BM aspiration/biopsy 
should not be performed. Histological examination of the bone marrow should be performed 
locally. Furthermore, patients who achieved a PR and PB MRD negativity need also to perform 
a bone marrow aspiration/biopsy. 
9.3.3.5 B-Symptoms 
B-symptoms are defined as any one or more of the disease-related symptoms or signs mentioned 
in Appendix K. Assessment of the presence or absence of B-symptoms will be performed at 
screening and on Day 1 of all cycles, as well as the EOT visit, and at the 30-Day Safety Follow-
up visit. B-Symptoms will also be assessed in case a patient will be followed up for disease 
progression after the EOT visit, as described in the Schedule of Assessments (Table 10). B-
symptoms should not be reported as AEs. Worsening is generally considered a symptom (but not 
an objective criterion) of progression. 
9.3.3.6 Assessment of MRD Response 
New detection technologies such as multicolor flow cytometry and real-time quantitative 
polymerase chain reaction (PCR) have undergone a critical evaluation and either 4-color flow 
cytometry (MRD flow) or allele-specific oligonucleotide PCR is reliably sensitive down to a 
level of approximately one CLL cell in 10,000 leukocytes. 
Patients who develop a PR or CR will be assessed using MRD testing from peripherial blood at 
C1D1, C4D1, C7D1, C13D1, etc. until bone marrow MRD negativity was confirmed. An 
additional PB sample will be obtained from CR patients at the time when CR is confirmed by 
CT outside of the scheduled radiological examinations. Additionally, patients with CR or PR 
will be further assessed for MRD negativity status from bone marrow (aspirate) at least 8 weeks 
after the PB MRD negativity was detected and only after CR was confirmed by CT/MRI scan. 
Further details on MRD methodology will be provided separately in the Laboratory Manual. 
9.3.4 Assessment of Pharmacokinetics 
Concentration-time profiles and PK parameters will be assessed for MOR00208 according to the 
Schedule of Assessments (Table 10). 
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. 
At each sampling timepoint the obtained serum sample should be split into 2 aliquots (a primary 
and a back-up sample). 
9.3.5 Assessment of Immunogenicity 
Serum samples for anti-MOR00208 antibody analysis will be collected according to the 
Schedule of Assessments (Table 10) and 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). 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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9.3.6 Biomarker Assessment 
Explorative biomarkers analyzed at baseline and during the course of the study may include the 
assements listed in Table 13. 
 
Table 13: 
Biomarker Assessment 
 
The patient is asked for his participation in additional Pharmacogenomic analyses. For this 
purpose samples will be stored to analyze tumor DNA, RNA (Cohort A and B) and/or protein 
levels (Cohort B only) of predictive biomarkers. Participation in these optional analyses is 
completely voluntary and will not affect the participation of the patient in this trial. 
Due to the exploratory nature of some assays, the sponsor may decide at any point during the 
study to terminate these assessments, in which case the sites will be informed accordingly. 
 
9.3.7 Disease Risk Assessment 
Disease risk assessment as per IWCLL guideline includes cytogenetics (flourescence in-situ 
hybridization [FISH] for del(17p), del(11q), del(13q), trisomy 12, del(6q), karyotyping, IGHV 
mutational status, analysis of serum markers as β2 microglobulin or CLL cell markers as CD38 
and ZAP-70 (cytometry). 
Additional information on disease risk can be obtained by analysis of TP53, NOTCH1, BTK and 
PLCγ2 mutational status in CLL cells from peripheral blood (Table 14). 
ADCC assessment 
(heparinized blood) 
(exploratory assay) 
ADCC with peripheral blood mononuclear cells 
B-/T-/NK cell count 
(heparinized blood) 
(exploratory assay) 
Absolute cell counts 
CD16 expression on 
peripheral NK cells 
(heparinized blood) 
(exploratory assay) 
CD16 molecules expressed per cell (CD16 antibodies bound per cell) 
CD19 expression on 
peripheral B cells 
(heparinized blood) 
(exploratory assay) 
CD19 molecules expressed per cell (CD19 antibodies bound per cell) 
Analysis of genetic CD19 
alterations (optional) 
(heparinized blood) 
(exploratory assay) 
CD19 mutational status (DNA isolated from tumor cells) 
FcR genotyping (optional) 
(mucosal cheek swabs) 
FcR polymorphism (FcγRII/III genes) 
Abbreviations: ADCC=antibody dependent cell mediated cytotoxicity; CD=cluster of differentiation; CD16=low 
affinity Fc receptor; CD19=B lymphocyte antigen CD19; Fc (fragment crystallizable) gamma receptors; 
NK=natural killer. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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Table 14: 
Disease Risk Assessment 
 
9.3.8 ECOG Performance Status 
The Eastern Cooperative Oncology Group (ECOG) performance status scale will be used by the 
Investigator to assess functional impairment of patients, i.e., how the disease affects their daily 
living abilities (see Appendix L). Patients will be assessed for ECOG performance status at 
screening, on Day 1 of each cycle, and at the EOT visit. 
 
10 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 nonleading 
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 
life-threatening. 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, hospitalization, 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. 
10.1 Definition of Adverse Events, Serious Adverse Events and Adverse 
Events of Special Interest 
An AE is defined as any untoward medical occurrence in a patient administered a medicinal 
product, which does not necessarily have a causal relationship to this treatment. 
An AE can therefore be any unfavorable 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. 
As per IWCLL guideline 
Cytogenetic tests for del(17p), del(11q), del(13q), trisomy 12; 
karyotyping 
β2 microglobulin (serum); 
CD38 and ZAP-70 (cytometry); 
IGHV mutational status (optional) 
In addition (optional) 
Mutational status of e.g., TP53, NOTCH1, BTK and PLCγ2  
Abbreviations: ZAP-70=zeta-chain-associated protein kinase 70; IGHV=immunoglobulin heavy-chain variable; 
TP53=tumor protein p53; BTK=Bruton's tyrosine kinase; PLC=phospholipase C.


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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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 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 MOR00208 dose 
by 30% and/or more than the daily idelalisib or venetoclax dose according to protocol) 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 (CLL/SLL) do not fall under the definition of AEs. 
 
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 
 Severity, i.e., toxicity grade: determined according to the 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.) 
grade 3: 
severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of hospitalization 
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; medication taken; non-drug therapy given; 
hospitalization/prolonged hospitalization) 
 Seriousness: whether it is serious, where an SAE is defined as one that: 
o results in death 
o is life-threatening 
o requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization signifies that the patient was an inpatient for at least one 
overnight stay) unless hospitalization is for: 
 routine treatment or monitoring of the studied indication, not associated with 
deterioration of symptoms related to CLL/SLL 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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EudraCT Number: 2015-002915-14 
 
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 elective or preplanned treatment for a pre-existing condition that is unrelated 
to CLL/SLL 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 
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. 
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 life-threatening or do not result in death or hospitalization 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 (AESIs) for MOR00208 are: TLS, IRRs and allergic reactions to study 
drug ≥ grade 3, cytokine release syndrome and overdoses. 
AEs of special interest (AESIs) for idelalisib are: Diarrhea/colitis ≥ grade 3, pneumonitis 
≥ grade 3 and elevation of hepatic enzymes ≥ grade 3, Pneumocystis jirovecii pneumonia (PJP), 
Cytomegalovirus (CMV) infections, Stevens-Johnson syndrome (SJS), toxic epidermal 
necrolysis (TEN) and overdoses. 
AEs of special interest (AESIs) for venetoclax are: TLS, neutropenia with infection or fever 
≥grade 3, overdoses. 
Unlike routine safety assessments, SAEs and AESIs are monitored continuously and have special 
reporting requirements (see Section 11.2). 
The Investigator should determine the causality (relationship to the study drug) based on his/her 
clinical experience and on the information given in the IB. 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 respectively SmPC or PI, 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. 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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EudraCT Number: 2015-002915-14 
 
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10.2 Methods and Timing for Capturing and Assessing Safety Parameters 
The Investigator is responsible for ensuring that all adverse AEs (for definition, see Section 10.1) 
are recorded on the Adverse Event eCRF and reported to the Sponsor in accordance with 
instructions provided in this section and in Section 10.5. For each AE recorded on the Adverse 
Event eCRF, the Investigator will make an assessment of seriousness, severity and causality (for 
the respective definition, see Section 10.1). 
 
10.3 Diagnosis Versus Signs and Symptoms 
In general, diagnoses rather than individual symptoms should be reported as the event term. If a 
diagnosis has been reported as an AE, 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, 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. 
 
10.4 Safety Review by the Independent Data Monitoring Committee 
The safety run-in phase will be concluded with an evaluation of the safety data of all treated 
patients once 10 patients completed at least one treatment cycle in Cohort A or 5 weeks of 
combination treatment in Cohort B. The first 3 patients of Cohort A will be dosed sequentially, 
at least 48 hours apart. In Cohort B all 10-12 patients will be dosed sequentially, at least one 
week apart.  
In Cohort A there will be two safety evaluations. After completion of the first cycle the safety 
data of the first three patients will be evaluated. This evaluation will be done by the IDMC 
composed of experts in the field of oncology and clinical biostatistics who have no other role in 
the study and do not have an affiliation with the Investigators or the sponsor. After the evaluation 
of the safety data from the first 3 patients for cycle 1 of treatment and a positive recommendation 
from the IDMC the next 7-9 patients may be dosed in parallel. An additional IDMC review will 
take place after 10 patients completed at least 1 cycle of treatment.  
In Cohort B the safety evaluation will be performed by an IDMC after the first 10 patients 
completed at least 5 weeks of combination treatment. The evaluation will be done by the IDMC 
as already described. Importantly, all patients in Cohort B, who participate in the safety run-in 
phase, will be hospitalized on the day of the first two dose escalations (C1D8 and C1D15).  
The criteria for the evaluation of safety of the combination therapy will be defined by the IDMC 
and laid down in the IDMC Charter of the trial.  
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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The review is based on the number and type of AEs occurring during the first cycle and on 
laboratory values (biochemistry and hematology) and other relevant safety data as necessary: 
 TEAEs sorted by SOC and PT 
 TEAEs sorted by frequency 
 TEAEs of Grade 3 and 4 according to NCI CTCAE version 4.03 (or higher) 
 TEAEs by relationship (by SOC and PT and by frequency) 
 Serious adverse events (SAEs) 
 TEAEs that requires discontinuation of the study drug 
 Laboratory data (hematology and biochemistry) 
 Patient deaths 
 Concomitant medications 
Following each meeting, the IDMC will provide a recommendation to the sponsor whether the 
study may continue according to the protocol or may suggest changes to the protocol or may 
recommend stopping the study due to safety reasons. 
A primary analysis in order to check for safety and preliminary efficacy will be based on the 
safety and response assessment data of the enrolled patients up to the time point of 3-18 months 
after last patient started treatment in Cohort B.  
The specific details for decision making are included in the IDMC Charter. 
 
10.5 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 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 SAEs/AESIs 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 AESIs will be recorded on the SAE report form. Study centers and 
Investigators are instructed to report all SAEs and AESIs to the contract research organization 
(CRO) mentioned below within 24 hours, using the study-specific SAE report form. NOTE: FU 
SAEs do also have to be reported within 24 hours to the CRO. 
IRRs and allergic reactions to study drugs grade 3 or higher, cytokine release syndrome or TLS, 
which are AESIs in this study, should be reported as diagnosis along with their respective 
symptoms in one event term (e.g., “IRR with symptoms of hives, chills and fever” for IRRs; 
“TLS with symptom of hyperuricemia” for TLSs). For overdoses, the diagnosis and if applicable 
the accompanying symptoms caused by the overdose should be reported. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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EudraCT Number: 2015-002915-14 
 
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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 the study. All SAEs 
must be followed up for a final outcome until resolution or, if resolution becomes unlikely, until 
stabilization or death.  
Notification of initial or follow-up SAE/AESI information (by using the standard SAE form 
provided by the sponsor) must be sent by fax to the CRO at one of the following numbers, as 
appropriate: 
 
Europe: 
Fax: + XXXXXXXXXX 
E-mail: XXXXXXXXXX 
 
United States: 
Fax: + XXXXXXXXXX 
E-mail: XXXXXXXXXX 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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For any safety-related or protocol related questions, please use the contact numbers below (24/7 
coverage): 
 
24/7 Medical Emergency 
Coverage (out of office 
hours) 
Globally 
Telephone: + XXXXXXXXXX 
  
In a study related medical emergency situation, when assigned 
medical monitors for a study cannot be reached by a caller, an 
on-call physician can be reached 24 hours per day, 7 days per 
week via XXXXXXXXXX. (The telephone number above is a 
chargeable telephone number allowing a global reach from 
both landlines and mobile phones.) 
 
XXXXXXXXXX  
On this internet page a list of country-specific toll-free 
telephone numbers is provided. Note that not all countries 
globally have access to toll-free numbers as indicated on the 
“24/7 Medical Help desk” index. Countries without toll-free 
numbers need to dial the chargeable number as indicated 
above. Furthermore, toll-free numbers are not available from 
mobile phones. 
 
 
Medical Emergency 
Coverage (during Medical 
Monitor office hours) 
Europe 
XXXXXXXXXX  
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX  
United States 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
 
 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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10.6 Pregnancies 
As detailed in the Schedule of Assessments (Table 10) and in Section 9.3.2.1, serum pregnancy 
testing will be carried out at the Screening, and EOT visits. 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 by fax to 
one of the following numbers: 
 
Europe: 
Fax: + XXXXXXXXXX 
 
United States: 
Fax:  + XXXXXXXXXX 
 
Female study patients who become pregnant must be withdrawn from the study treatment period. 
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. 
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. 
 
10.7 Deaths 
Deaths occurring during the protocol-specified AE reporting period that are attributed by the 
Investigator solely to progression of CLL/SLL should not be reported as SAE. All other on-study 
deaths, regardless of relationship to study drug, must be immediately reported to the sponsor as 
SAE (see Section 10.5). 
Death should be considered an outcome and not a distinct event. The event or condition that 
caused or contributed to the fatal outcome should be recorded as the single medical concept on 
the Adverse Event eCRF. Generally, only one such event should be reported. 
If the cause of death is unknown and cannot be ascertained at the time of reporting, "unexplained 
death" should be recorded on the Adverse Event eCRF. The IDMC will monitor the frequency 
of deaths from all causes. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
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11 DATA HANDLING AND ARCHIVING 
11.1 Completing and Signing Case Report Forms 
An eCRF will be used in this study. The Investigator will be responsible for accurate and timely 
data entry into the eCRF. Data entry may be delegated to adequately trained site personnel. Any 
errors should be corrected within the electronic system. In the case of missing data, a reason 
should be given. 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 
Investigators will receive a copy of their eCRF in a readable format after database lock for 
archiving. 
11.2 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 (WHO DDE) 
for medication. 
11.3 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: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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EudraCT Number: 2015-002915-14 
 
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12 STATISTICAL METHODS AND PLANNED ANALYSES 
A Statistical Analysis Plan (SAP) will be prepared after the protocol is approved. This document 
will provide further details regarding the definition of analysis variables and analysis 
methodology to address all study objectives. The SAP will serve as a compliment to the protocol 
and supersedes it in case of differences. 
The statistical evaluation will be performed using the Statistical Analysis Software (SAS®) 
Version 9.3 or higher (SAS Institute, Cary, NC). All data will be listed, and summary tables will 
be provided. For continuous variables, data will be summarized with the number of subjects (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. For categorical variables, data will be tabulated with the frequency and 
percentage of patients/entries for each category. 
Missing values will not be imputed. All statistical evaluations will be based on valid cases except 
for procedures described for calculating response rates or in the 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 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 and finalized prior to database lock. 
12.1 Determination of Sample Size 
The primary endpoint of this study is the incidence and severity of AEs in Cohort A (MOR00208 
combined with idelalisib) and Cohort B (MOR00208 combined with venetoclax) and will be 
analyzed descriptively. In each cohort 12 patients will be enrolled. No formal sample size 
calculation was performed and no formal statistical hypothesis testing is planned. 
12.2 Analysis Sets 
The following analysis populations will be used: 
Full Analysis Set 
The Full analysis set (FAS) will include all subjects who receive at least one dose of MOR00208 
and/or one dose of idelalisib in Cohort A and/or one dose of 100 mg daily dose of venetoclax in 
Cohort B. 
Per-Protocol Set 
The Per-protocol set (PPS) is the subset of subjects in the FAS without any major protocol 
deviations. Patients with no post-baseline assessment of response will be excluded from the PPS. 
Safety Analysis Set 
The Safety analysis set (SAF) will include all subjects who receive at least one dose of 
MOR00208 and/or one dose of idelalisib or venetoclax. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
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IND Number: 114,856 
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PK Analysis Set 
The PK analysis set (PKAS) will include all patients who have at least one quantifiable serum 
MOR00208 concentration. PK parameters will be calculated as data permit. 
Secondary and supportive efficacy parameters will be evaluated using the FAS and PPS, while 
safety parameter evaluations will use the SAF, as well as for evaluations on immunogenicity and 
biomarkers. 
The primary analysis of the secondary 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. 
12.3 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 set and the number of withdrawals with reasons 
for withdrawal. 
12.4 Demographic and Baseline Characteristics 
Demographic information will be summarized using descriptive statistics or counts and 
percentages. 
General medical histories and CLL/SLL-specific medical histories will be summarized 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. 
12.5 Safety Analysis 
All reported AEs will be coded using MedDRA Version 18.0 or higher. Incidence of all AEs by 
System Organ Class (SOC), Preferred Term (PT), and relationship to treatment, severity and 
seriousness will be reported. The incidence of treatment-emergent AEs (TEAEs; events with 
onset dates on or after the start of the study drug) will be included in incidence tables. Events 
with missing onset dates will be included as treatment-emergent. If a patient experiences more 
than 1 occurrence of the same AE, the occurrence with the greatest severity and the closest 
association with the study drug will be used in the summary tables. All AEs will be listed by 
patient, along with information regarding onset, duration, relationship and severity to study drug, 
action taken with study drug, treatment of event, and outcomes. 
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. 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. Details are described in the SAP. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
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12.5.1 Clinical Laboratory Evaluations 
Clinical laboratory data will be summarized using descriptive statistics including mean values 
and mean change from baseline values, as well as numbers of patients with values outside limits 
of the normal range at each timepoint. 
12.5.2 Physical Examination, Vital Signs and Electrocardiogram 
Physical examination results will be summarized by body system and tabulated as counts and 
percentages. New and worsening abnormal physical examination findings during the study will 
be entered as AEs and analyzed within the AE tables in detail. Descriptive summaries of vital 
sign parameters will be calculated. Summary ECG assessments will be tabulated by timepoint 
using frequency tabulations. Results of the 12-lead ECG (PR, QRS, 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. 
12.6 Efficacy Analysis 
12.6.1 Analysis of Secondary Efficacy Endpoint – ORR 
The secondary endpoint is overall response (ORR). ORR is defined for Cohort A as percentage 
of patients achieving a complete response (CR), a partial response (PR) or a partial response with 
lymphocytosis (PRL), and for Cohort B as percentage of patients achieving a CR or a PR based 
on local assessment. CR, PR or a PRL is defined according to the criteria of the IWCLL for CLL 
subjects (Hallek et al., 2008) for patients with CLL, with the modification that treatment-related 
lymphocytosis in the absence of other signs or symptoms of disease progression will not be 
considered as progressive disease (Cheson et al., 2012; Hallek et al., 2012; NCCN NHL 2015 
Guidelines). For patients with SLL, assessments will be performed using the Lugano 
Classification criteria for SLL subjects (Cheson et al., 2014). 
Local response evaluations (CR, PR, PRL, SD and PD) will be tabulated with counts and 
percentages for each available visit. Missing response evaluations will be taken into account, 
with patients with missing responses included in the denominator for calculating rates. The SAP 
will specify further sensitivity and supportive analyses, as well as possible evaluation of further 
response parameters (e.g., best response). 
12.7 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 samples will be tabulated. Further details will be provided in the SAP. 
12.8 Pharmacokinetic Analysis 
Appropriate PK parameters for MOR00208 will be computed based on non-compartmental data 
analysis and summarized using descriptive statistics. Mean concentrations (on original and on 
log-linear scale) will be visualized in figures. Further details of the PK analysis will be specified 
in the SAP. 


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12.9 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, flow cytometry results of CD16 expression on NK cells will be descriptively 
tabulated. 
12.10 Primary Analysis 
The primary analysis of each cohort of the main study to evaluate safety and preliminary efficacy 
will be based on the safety data and response assessment of the enrolled patients up to the time 
point of 3-18 months after last patient started treatment in Cohort B.  
12.11 Final Analysis 
The final analysis of the main study will be conducted at the end of the main study defined as 5 
years after the first patient was enrolled (C1D1) or approximately 30 days after the last patient 
received his/her last treatment, whichever comes first. 
12.12 Independent Data Monitoring Committee 
An IDMC will be established by the sponsor to review the safety run-in phase for each cohort. 
The IDMC will be composed of experts in the field of oncology and clinical biostatistics who 
have no other role in the study and do not have an affiliation with the Investigators or the sponsor. 
Based on the safety data, the IDMC recommends in writing to the sponsor whether the study 
may continue according to the protocol. The IDMC’s specific duties as well as statistical 
monitoring guidelines and procedures will be fully described in an IDMC Charter. 
 
13 STUDY MANAGEMENT 
13.1 Regulatory Requirements and Ethical Considerations 
Prior to initiation of a study site, MorphoSys will obtain favorable 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 favorable 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 favorable opinion/approval of the study protocol and any 
subsequent amendments 


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 Patient informed consent 
 Investigator reporting requirements 
MorphoSys will provide full details of the above procedures, either verbally, in writing, or both. 
13.1.1 Institutional Review Board/Independent Ethics Committee 
Conduct of the study must be approved by an appropriately constituted IRB/IEC. Approval is 
required for the study protocol, IB, protocol amendments, ICFs) and PISs. 
13.1.2 Informed Consent 
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 prior to any protocol-related 
activities. As part of this procedure, the Principal Investigator (PI) or one of his/her associates 
must explain orally and in writing the nature, duration, and purpose of the study, and the action 
of the drug in such a manner that the patient is aware of the potential risks, inconveniences, or 
adverse effects that may occur. The patient should be informed that he/she may withdraw from 
the study at any time, and the patient will receive all information that is required by local 
regulations and International Conference on Harmonisation (ICH) guidelines. The PI will 
provide the sponsor or its representative with a copy of the IRB/IEC-approved ICF template 
prior to the start of the study. The ICF must be signed, with name and date and time noted by the 
patient, before the patient is exposed to any study-related procedure, including screening tests 
for eligibility. The patient should receive a copy of the signed form. 
13.2 Data Handling 
Data reported on the eCRF that are derived from source documents should be consistent with the 
source documents, or the discrepancies must be explained. 
Clinical data will be entered on eCRFs for transmission to the sponsor. Data on eCRFs 
transmitted via the web-based data system must correspond to and be supported by source 
documentation maintained at the study site, unless the study site makes direct data entry to the 
databases for which no other original or source documentation is maintained. In such cases, the 
study site should document which eCRFs are subject to direct data entry and should have in place 
procedures to obtain and retain copies of the information submitted by direct data entry. All study 
forms and records transmitted to the sponsor must carry only coded identifiers such that 
personally identifying information is not transmitted. The primary method of data transmittal is 
via the secure, internet-based electronic data capture (EDC) system maintained by CRO. Access 
to the EDC system is available to authorized users via the study’s Internet web site, where an 
assigned username and password are required for access.  
The eCRFs will be considered complete when all missing and/or incorrect data have been 
resolved. 
13.3 Source Documents 
Source documents are considered to be all information in original records and certified copies of 
original records of clinical findings, observations, data or other activities in a clinical study 
necessary for the reconstruction and evaluation of the study. 


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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. 
The Investigator must accept audits by the sponsor’s Quality Assurance Unit and/or their 
authorized representative(s) and ensure direct access to all source data documents. 
13.4 Use of Computerized Systems 
The following requirements apply to study sites where clinical observations and data are entered 
directly into the hospital information system or medical office information system, i.e., where 
paper records are not used on a routine basis: The electronic record will be accepted as a source 
document, only if the information system has been validated in accordance with health authority 
requirements pertaining to computerized systems used in clinical research. An acceptable 
computerized data collection system allows preservation of the original entry of data. If original 
data are modified, the system should maintain a viewable audit trail that shows the original data 
as well as the reason for the change, name of the person making the change, and the date of 
change. 
13.5 Monitoring 
The study will be monitored to ensure that it is conducted and documented properly according 
to the protocol, GCP, and all applicable regulatory requirements. 
On-site monitoring visits will be made at appropriate times during the study. Clinical monitors 
must have direct access to source documentation in order to check the completeness, clarity, and 
consistency of the data recorded in the eCRFs/CRFs for each patient. 
The Investigator will make available to the clinical monitor source documents and medical 
records necessary to complete eCRFs/CRFs. In addition, the Investigator will work closely with 
the clinical monitor and, as needed, provide them appropriate evidence that the conduct of the 
study is being done in accordance with applicable regulations and GCP guidelines. 
13.6 Quality Control and Quality Assurance 
The sponsor or its designee will perform the quality assurance and quality control activities of 
this study; however, responsibility for the accuracy, completeness, and reliability of the study 
data presented to the sponsor lies with the Investigator generating the data. 
The sponsor will arrange audits as part of the implementation of quality assurance to ensure that 
the study is being conducted in compliance with the protocol, Standard Operating Procedures, 
GCP, and all applicable regulatory requirements. Audits will be independent of and separate 
from the routine monitoring and quality control functions. 
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. 
 
 


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13.7 Protocol Amendment and Protocol Deviation 
13.7.1 Protocol Amendment 
Amendments to the protocol that entail corrections of typographical errors, clarifications of 
confusing wording, changes in study personnel, and minor modifications that have no impact on 
the safety of patients or the conduct of the study will be classed as administrative amendments 
and will be submitted to the IRB/IEC and appropriate Regulatory Authorities for information 
only. The sponsor will ensure that acknowledgement is received and filed. Amendments that are 
classed as substantial amendments must be submitted to the appropriate Regulatory Authorities 
and the IRBs/IECs for approval. 
13.7.2 Protocol Deviations 
Should a protocol deviation occur, the sponsor must be informed as soon as possible. Protocol 
deviations and/or violations and the reasons they occurred will be included in the clinical study 
report. Reporting of protocol deviations to the IRB/IEC and in accordance with applicable 
Regulatory Authority mandates is an Investigator responsibility. 
13.8 Investigator Contract and Insurance 
Prior to the study commencing, the sponsor (or its designee) and the Investigator (or the 
institution, as applicable) will agree on costs necessary to perform the study. This agreement will 
be documented in a financial agreement that will be signed by the Investigator (or the institution 
signatory) and the sponsor (or its designee). 
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. 
13.9 Publication Policy and Disclosure of Data 
Any presentation or publication of data from this study will be intended as a joint publication by 
the Investigator(s)/appropriate study center personnel and appropriate sponsor personnel. 
Authorship will follow the International Committee of Medical Journal Editors (ICMJE) 
Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in 
Medical Journals (http://www.icmje.org/recommendations/) and will be defined prior to the first 
publication. 
For multicenter studies, it is mandatory that the first publication be based on data from all centers, 
and that the data are analyzed 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 multicenter publication is made which covers the data from all centers. The 


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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. 
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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of navitoclax in patients with relapsed or refractory disease. J Clin Oncol. 2012 Feb 
10;30(5):488-96.  
Roberts AW, Ma S, Brander D, Kipps TJ, Barrientos JC, Davids MS, et al., Impact of Adding 
Rituximab to Venetoclax on the Rate, Quality, and Duration of Response in Patients With 
Relapsed/Refractory Chronic Lymphocytic Leukaemia: a Cross-Study Multivariable 
Analysis. Poster #209 EHA 2016. 
Saffran DC, Parolini O, Fitch-Hilgenberg ME, Rawlings DJ, Afar DE, Witte ON, et al. Brief 
report: a point mutation in the SH2 domain of Bruton's tyrosine kinase in atypical X-linked 
agammaglobulinemia. N Engl J Med. 1994;330(21):1488-91. 
Sant M, Allemani C, Tereanu, C, De Angelis R, Capocaccia R, Visser O, et al. Incidence of 
hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE 
project. Blood 2010. 116(19);3724-34. 
Schnaiter A, Paschka P, Rossi M, Zenz T, Bühler A, Winkler D, et al. NOTCH1, SF3B1, and 
TP53 mutations in fludarabine-refractory CLL patients treated with alemtuzumab: results 
from the CLL2H trial of the GCLLSG. Blood. 2013;122(7):1266-70. 
Shanafelt TD, Byrd JC, Call TG, Zent CS, Kay NE. Narrative review: initial management of 
newly diagnosed, early-stage chronic lymphocytic leukemia. Ann Intern Med. 
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Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, et al. ABT-199, a potent 
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2013 Feb;19(2):202-8. 
Stilgenbauer S, Schnaiter A, Paschka P, Zenz T, Rossi M, Döhner K, et al. Gene mutations and 
treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 
2014;123(21):3247-54. 
Stilgenbauer S, Eichhorst B, Schetelig J, Coutre S, Seymour JF, Munir T, et al. Venetoclax in 
relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, 
open-label, phase 2 study. Lancet Oncol. 2016 Jun;17(6):768-78. 
Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. 
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Takei K, Yamazaki T, Sawada U, Ishizuka H, Aizawa S. Analysis of changes in CD20, CD55, 
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Woyach JA, Awan F, Flinn IW, Berdeja JG, Wiley E, Mansoor S, et al. A phase 1 trial of the 
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Zou Y, Xu W, Li J. Chimeric antigen receptor-modified T cell therapy in chronic lymphocytic 
leukemia. J Hematol Oncol. 2018 Nov 20;11(1):130. 


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Other Sources 
Clinical Trial Facilitation Group (CTFG). Recommendations related to contraception and 
pregnancy testing in clinical trials. September 15, 2014. 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), 
version 4.03. 
 


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15 APPENDICES 
 
 
 
 
15.1 Appendix A: Binet and Rai Staging System 
 
Binet Staging 
Stage 
Clinical features 
A 
Lymphocytosis, does not meet criteria for stages B or C 
B 
≥ 3 areas of lymphadenopathy*, does not meet criteria for stage C 
C 
Anemia (Hb < 10 g/dL) or thrombocytopenia (platelets < 100 x109/L) 
* The four lymphadenopathy areas are: cervical, axillary, inguinal, spleen/liver 
Adapted from Binet et al., 1981. 
 
 
Modified Rai Clinical Stage 
Risk category 
Clinical features 
Low 
Lymphocytes > 15 x 109/L 
Intermediate 
As 0 + lymphadenopathy or hepato- or splenomegaly 
High 
Anemia (Hb ≤ 11 g/dL) or thrombocytopenia (platelets ≤ 100 x109/L) 
Adapted from Rai et al., 1987. 
 
 
The Binet clinical staging system and the modified Rai clinical staging system for CLL comprise 
three stages. 
The use of clinical staging systems is recommended in current CLL guidelines, and can guide 
the initiation of treatment. 
 
 
 


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15.2 Appendix B: Information on Investigational and Registered Products 
 
The Investigator’s Brochure for MOR00208, Summary of Product Characteristics (Europe, 
EMA) or Prescribing Information (US FDA) for idelalisib or venetoclax approved in the Clinical 
Trial Application or the updates thereof after they were approved for this study will be supplied 
to the study sites. 
 
 


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15.3 Appendix C: Diagnostic Criteria for CLL and SLL According to the 
IWCLL Guidelines 2008 
The World Health Organization (WHO) classification of hematopoietic neoplasias describes CLL as 
leukemic, lymphocytic lymphoma, being only distinguishable from SLL by its leukemic appearance. In 
the WHO classification, CLL is always a disease of neoplastic B cells, whereas the entity formerly 
described as T-CLL is now called T-cell prolymphocytic leukemia. It is important to verify that the patient 
has CLL and not some other lymphoproliferative disease that can masquerade as CLL, such as hairy cell 
leukemia, or leukemic manifestations of mantle cell lymphoma, marginal zone lymphoma, splenic 
marginal zone lymphoma with circulating villous lymphocytes, or follicular lymphoma. To achieve this, 
it is essential to evaluate the blood count, blood smear, and the immune phenotype of the circulating 
lymphoid cells. 
Blood. The diagnosis of CLL requires the presence of at least 5 x 109 B lymphocytes/L (5000/µL) in the 
peripheral blood. The clonality of the circulating B lymphocytes needs to be confirmed by flow 
cytometry. The leukemia cells found in the blood smear are characteristically small, mature lymphocytes 
with a narrow border of cytoplasm and a dense nucleus lacking discernible nucleoli and having partially 
aggregated chromatin. These cells may be found admixed with larger or atypical cells, cleaved cells, or 
prolymphocytes, which may comprise up to 55% of the blood lymphocytes. Finding prolymphocytes in 
excess of this percentage would favor a diagnosis of prolymphocytic leukemia (B-cell PLL). Gumprecht 
nuclear shadows, or smudge cells, found as cell debris, are other characteristic morphologic features 
found in CLL. 
CLL or SLL might be suspected in otherwise healthy adults who have an absolute increase in the clonal 
B lymphocytes but who have less than 5 x 109/L B lymphocytes in the blood. However, in the absence of 
lymphadenopathy or organomegaly (as defined by physical examination or CT scans), cytopenias, or 
disease-related symptoms, the presence of fewer than 5 x 109 B lymphocytes per liter of blood is defined 
as “monoclonal B-lymphocytosis.” Monoclonal B-lymphocytosis may progress to frank CLL at a rate of 
1% to 2% per year. 
The definition of SLL requires the presence of lymphadenopathy and/or splenomegaly. Moreover, the 
number of B lymphocytes in the peripheral blood should not exceed 5 x 109/L. In SLL, the diagnosis 
should be confirmed by histopathologic evaluation of a lymph node biopsy whenever possible. 
Immunophenotype. CLL cells coexpress the T-cell antigen CD5 and B-cell surface antigens CD19, 
CD20, and CD23. The levels of surface immunoglobulin, CD20, and CD79b are characteristically low 
compared with those found on normal B cells. Each clone of leukemia cells is restricted to expression of 
either kappa or lambda immunoglobulin light chains. 
Variations of the intensity of expression of these markers may exist and do not prevent inclusion of a 
patient in clinical trials for CLL. In contrast, B-cell PLL cells do not express CD5 in half of the cases, 
and typically express high levels of CD20 and surface Ig. In addition, the leukemia cells of mantle cell 
lymphoma, despite also expressing B-cell surface antigens and CD5, generally do not express CD23. 
Marrow examination. A marrow aspirate and biopsy generally are not required for the diagnosis of CLL. 
In CLL, characteristically more than 30% of the nucleated cells in the aspirate are lymphoid. 
 
From: Hallek et al. Blood. 2008;111(12): 5446-7. 
 
 
 


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15.4 Appendix D: Indication of Treatment According to the IWCLL 
Guidelines 2008 
 
Active disease meeting at least 1 of the following IWCLL 2008 criteria for requiring treatment: 
 
1. Evidence of progressive marrow failure as manifested by the development of, or 
worsening of, anemia and/or thrombocytopenia 
2. Massive (ie, at least 6 cm below the left costal margin) or progressive or symptomatic 
splenomegaly 
3. Massive nodes (i.e., at least 10 cm in longest diameter) or progressive or symptomatic 
lymphadenopathy 
4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or 
lymphocyte doubling time (LDT) of less than 6 months. LDT can be obtained by linear 
regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks 
over an observation period of 2 to 3 months. In patients with initial blood lymphocyte 
counts of less than 30 x 109/L (30 000/μL), LDT should not be used as a single parameter 
to define a treatment indication. In addition, factors contributing to lymphocytosis or 
lymphadenopathy other than CLL (e.g., infections) should be excluded. 
5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to 
corticosteroids or other standard therapy  
6. Constitutional symptoms, defined as any one or more of the following disease-related 
symptoms or signs: 
a) unintentional weight loss of 10% or more within the previous 6 months; 
b) significant fatigue (ie, ECOG PS 2 or worse; inability to work or perform usual 
activities); 
c) fevers higher than 100.5°F or 38.0°C for 2 or more weeks without other evidence of 
infection; or 
d) night sweats for more than 1 month without evidence of infection. 
 
From Hallek et al. Blood. 2008;111(12): 5450 
 


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15.5 Appendix E: Cockcroft-Gault Formula 
 
 
Cockcroft-Gault Equation (Cockcroft DW et Gault MH, 1976): 
 
 
 
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. 
 
 
 


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15.6 Appendix F: Definitions of Childbearing Potential and Highly Effective 
Birth Control Methods 
Female of Childbearing Potential 
A female is considered of childbearing potential (FCBP), i.e., fertile, following menarche and 
until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods 
include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. 
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used 
to confirm a post-menopausal state in women not using hormonal contraception or hormonal 
replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient. 
Fertile Male 
A male is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 
Highly Effective Contraception 
Methods that can achieve a failure rate of less than 1% per year when used consistently and 
correctly are considered as highly effective birth control methods. Such methods include: 
 Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
 Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
 Intrauterine device (IUD) 
 Intrauterine hormone-releasing system (IUS) 
 Bilateral tubal occlusion 
 Vasectomized partner 
 Sexual abstinence 
From: Clinical Trial Facilitation Group (CTFG). Recommendations related to contraception 
and pregnancy testing in clinical trials. September 15, 2014 
In the course of this study FCBP, using hormonal contraceptives should add a barrier method 
as a second form of contraception since it is currently unknown whether idelalisib or 
venetoclax may affect the effectiveness of hormonal contraceptives (see inclusion criterion #7).


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15.7 Appendix G: New York Heart Association Functional Classification 
 
 
Criteria for NYHA Functional Classification 
 
NYHA Class 
Criteria 
I 
No symptoms and no limitation in ordinary physical activity; shortness of breath 
when walking, stair climbing, etc. 
II 
Mild symptoms (mild shortness of breath and/or angina pain) and slight limitation 
during ordinary activity 
III 
Marked limitation in activity due to symptoms, even during less-than-ordinary 
activity (e.g., walking short distances, approximately >20–100 meters); 
comfortable only at rest 
IV 
Severe limitations; patient experiences symptoms even while at rest, mostly 
bedbound 
Abbreviation: NYHA = New York Heart Association. 
 
 
 


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15.8 Appendix H: Equivalent Doses for Corticosteroids 
 
 
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 
 
 
 


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15.9 Appendix I: Effect of Idelalisib on Other Medicinal Products that are 
CYP3A Substrates 
 
 
Potential interactions between idelalisib and co-administered medicinal products that are CYP3A 
substrates are listed in the table below (increase is indicated as “↑”) (as per Annex I: Summary 
of Product Characteristics, Section 4.2). This list is not exhaustive and is intended to serve as 
guidance only. In general, the label information for the other product must be consulted for the 
recommendations regarding co-administration with CYP3A4 inhibitors. 
 
 
 
 
 


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15.10 Appendix J: Response Definition for CLL by the IWCLL Guidelines 
2008 
 
 
Parameter 
CR* 
PR* 
PD* 
Group A 
 
 
 
Lymphadenopathy† 
None > 1.5 cm 
Decrease ≥ 50% 
Increase ≥ 50% 
Hepatomegaly 
None 
Decrease ≥ 50% 
Increase ≥ 50% 
Splenomegaly 
None 
Decrease ≥ 50% 
Increase ≥ 50% 
Blood lymphocytes 
< 4000/µL 
Decrease ≥ 50% from 
baseline 
Increase ≥ 50% over 
baseline 
Marrow‡ 
Normocellular, 
< 30% lymphocytes, 
no B-lymphoid 
nodules 
Hypocellular marrow 
defines CRi 
50% reduction in 
marrow infiltrate, 
or B-lymphoid nodules 
-- 
Group B 
 
 
 
Platelet count 
> 100,000/µL 
> 100,000/µL or 
increase ≥ 50% over 
baseline 
Decrease of ≥ 50% 
from baseline 
secondary to CLL 
Hemoglobin 
> 11 g/dL 
> 11 g/dL or 
increase ≥ 50% over 
baseline 
Decrease of > 2 g/dL 
from baseline 
secondary to CLL 
Neutrophils‡ 
> 1500/µL 
> 1500/µL or 
> 50% improvement 
over baseline 
-- 
Group A criteria define the tumor load, group B criteria define the function of the hematopoietic 
system (or marrow). 
*CR (complete remission): all of the criteria have to be met, and patients have to lack disease-
related constitutional symptoms; PR (partial remission): at least two of the criteria of groupA 
plus one of the criteria of group B have to be met; SD is absence of progressive disease (PD) and 
failure to achieve at least a PR; 
PD: at least one of the above criteria of group A or group B has to be met. 
†Sum of the products of multiple lymph nodes (as evaluated by CT scans in clinical trials, or by 
physical examination in general practice). 
‡These parameters are irrelevant for some response categories. 
 
From: Hallek et al. Blood. 2008;111(12):5446-56. 
 
 


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15.11  Appendix K: Criteria for B-Symptoms 
 
 
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. 
 
 
 
 


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15.12 Appendix L: ECOG Performance Status 
 
 
ECOG Performance Status Scale 
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 
 
From: Oken et al. Am J Clin Oncol. 1982;5(6):649-55. 
 
 
 


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15.13 Appendix M: Optional Sub-Study - Collection of Biological Samples 
for Evaluation of CD19 Expression after MOR00208 Treatment 
15.13.1 Sub-Study Purpose/Rationale 
It is of importance and has high clinical value to better understand potential escape mechanisms 
to MOR00208 treatment and to evaluate whether subsequent CD19-targeting therapeutic options 
can be offered to patients after MOR00208 treatment. Subsequent CD19-targeting therapy may 
include novel chimeric antigen receptor (CAR) T-cell therapy, other anti-CD19 targeting 
antibodies than MOR00208, or potential re-challenging with MOR00208 e.g. after drug holiday 
as shown for another antibody (Zou Y et al., 2018; Alici E et al., 2016). 
It is well described that resistance to targeted antibody treatment could potentially be mediated 
by alterations in expression of the target antigen as shown in a preclinical Burkitt's lymphoma 
cell line model where down-modulation of CD20 as well as clonal selection of CD20-negative 
cells was related to the acquired resistance to rituximab (Smith MR, 2003; Takei K et al., 2006). 
For the antigen CD19, emerging data from CD19 targeted CAR T-cell trials in B-cell 
malignancies demonstrate that a common mechanism of resistance to therapy is the emergence 
of tumors with loss or downregulation of CD19 antigen via mechanisms like alternative mRNA 
splicing, CD19 gene deletion and mutation or CD19-negative clonal evolution (Zheng PP et al., 
2018; Zhao Z et al., 2018). A recently published Brief Communication paper (Orlando EJ, 2018) 
underlines that acquired resistance to CD19-targeted CAR T-cell therapy in acute lymphoblastic 
leukaemia can occure through mutations in the CD19 gene, consequently leading to the loss of 
CD19 antigen surface expression on tumor cells. 
In a Phase I trial (NCT01161511), where relapsed/refractory CLL/SLL patients received 
MOR00208 treatment, CD19 expression was evaluated, but due to methodological limitations 
(MOR00208 interference with anti-CD19 detection) the obtained data do not allow proper 
interpretation of CD19 expression levels during and after the treatment period. 
To accurately address CD19 antigen expression during MOR00208 treatment, a validated 
method for quantitative CD19 assessment was implemented in the COSMOS trial to evaluate 
samples collected at Cycle 1 Day 1 (baseline value), during treatment at Cycle 2 Day 1 in Cohort 
A or Cycle 1 Day 8 & 15 in Cohort B, furthermore, at the end of treatment visit (EOT). 
Published data on MOR00208 (Horton et al., 2008) or other anti-CD19 antibody clones 
(Pulczynski et al., 1993; Ghetie, 1997) suggest that CD19 might be downregulated by 
internalization during MOR00208 treatment to a certain extent. However, so far it is unknown 
wheter CD19 level will recover after treatment discontinuation in cases where downregulation 
may occur. 
Therefore, post-treatment long term follow up data captured in this sub-study are essential to 
elucidate changes in CD19 expression level and evaluate the kinetics of CD19 recovery after a 
potential downregulation. Due to unknown kinetics of a potential CD19 recovery in this disease 
setting and the expected decline in MOR00208 serum levels, an investigation of CD19 recovery 
is planned on 4 visits within this sub-study: at the first sub-study visit within approximately 30 
days after end of treatment visit (EoT) of the main study, and approximately 1, 3 and 6 months 
thereafter (see Section 15.13.6). 
 


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15.13.2 Sub-Study Objectives and Endpoints 
15.13.2.1 Study Objectives 
 To assess potential downregulation/loss of CD19 on peripheral B cells (CLL and normal 
B cells) as escape mechanism to MOR00208 treatment   
 To assess the kinetics of CD19 recovery on peripheral B cells (CLL and normal B cells) 
after MOR00208 treatment discontinuation, if applicable  
 To assess MOR00208 serum concentrations as supportive parameter for CD19 
expression analysis 
15.13.2.2 Exploratory Study Endpoints 
 CD19 expression (CD19 ABC (Antibodies bound per cell)  
 CD19 mutational status (DNA isolated from tumor cells) 
 Detection of alternative CD19 splice variants (RNA isolated from tumor cells) 
 MOR00208 serum concentrations 
15.13.3 Sub-Study Design 
15.13.3.1 Description of Sub-Study design 
This is an optional sub-study subsequent to the main study in which biological samples will be 
collected for investigations on biological markers (e.g., CD19 expression) for CLL disease. 
Patients who completed the main study will be invited to participate in this optional sub-study. 
Patients who provided their voluntary consent to participate in the sub-study will have additional 
blood samples collected as detailed in Section 15.13.6 below. During the participation in the sub-
study patients could receive anti-neoplastic therapy for their disease. 
15.13.3.2  Study Periods 
The sub-study will be implemented to collect blood samples at 4 visits during the sub-study 
period as described in Section 15.13.6. Patients who already completed the main study before 
implementation of the sub-study may have less visits than as per regular schedule. No screening, 
treatment and follow up periods are planned. 
15.13.4 Patient Selection Criteria 
15.13.4.1 Inclusion Criteria 
To be eligible for this sub-study, subjects must have been enrolled in the main study and must 
have been exposed to study treatment there. Subjects must provide separate written informed 
consent for this sub-study and should be willing to undergo standard blood collection procedures. 
15.13.4.2 Exclusion Criteria 
Patients who have been exposed to MOR00208 for less than one cycle in the main study. 
15.13.5 End of Sub-Study 
The duration of the sub-study will be up to approximately 3.5 years from sub-study introduction 
until sub-study completion. The end of the sub-study is reached for an individual patient, if 
patient has completed sub-study visit 4, has withdrawn consent, is lost to follow up or death 
occurs. The estimated average study duration per individual patient is up to 7 months.  


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
Confidential 
Page 157 of 160 
The sub-study will be completed once the last patient in the sub-study completed the last visit, 
or approximately 7 months after the first visit of the last patient enrolled in the sub-study, 
whichever comes first.  
The sub-study can be terminated at any time for any reason by the sponsor. For general rules 
applicable for investigator study or site termination please refer to Section 7.3 of the main study 
protocol. For the entire trial study end please refer to Section 7.4 of main study protocol. 
15.13.6 Sub-Study Procedures 
15.13.6.1 Schedule of Procedures and Assessments 
The Schedule of Procedures and Assessments is presented on the following page (Table 15). All 
assessments that need to be performed at a specific visit are indicated with an “X”.  
 
Note: Any visit performed not in the visit window as described in Table 15 will be not considered 
as protocol deviation. 
 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
Confidential 
Page 158 of 160 
Table 15: 
Sub-Study - Schedule of Procedures and Assessments 
Procedure 
Sub-Study Period 
Visit 1 1,2 
Visit 2 2 
Visit 3 2 
Visit 4 2 
~30 days after EoT 
of the Main Study 1
~1 month 
after Visit 1 
±2 weeks 
~3 months 
after Visit 1 
±6 weeks 
~6 months 
after Visit 1 
−6 weeks/+ ≥6 weeks
Informed consent 
  X 3 
(X) 3 
(X) 3 
(X) 3 
CD19 assessment (CD19ABC) (blood) 
X 
X 
X 
X 
Optional analysis of genetic CD19 mutations (blood) 
X 
X 
X 
X 
Optional analysis of alternative CD19 splice variants (blood) 
X 
X 
X 
X 
PK MOR00208 (serum) 
X 
X 
X 
X 
Concommittant anti-tumor therapy 
X 
X 
X 
X 
SAE (Serious Adverse Event) related to blood sampling 
X 
X 
X 
X 
 
1 Patient should return for Visit 1 of the sub-study within approximately 30 days after end of treatment visit (EoT) of the main study. Note: Visit 1 
could be on the same day of the 30 day safety follow-up (SFU) visit of main study. 
2 Alternatively, for those patients who already completed the main study before implementation of the sub-study, the visit(s) will be scheduled after 
~2 months from EoT of the main study for Visit 2, after ~4 months for Visit 3 and after ~7 months for Visit 4 as applicable. Note: These patients may 
have less visits than as per regular schedule (e.g., only 1 visit if patient completed the main study more than 7 months before enrolment in the sub-
study).  
3 Patient must consent to the sub-study before or on first sub-study visit, before blood sample collection of the sub-study. (X) is applicable for those 
patients who already completed the main study before implementation of the sub-study. 
Abbreviations: ABC= Antibodies bound per cell; EoT= End of Treatment visit of the main study 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
Confidential 
Page 159 of 160 
15.13.6.2 Study Assessments 
15.13.6.3 CD19 assessment (CD19 ABC) 
Blood samples for CD19 assessment will be handled as specified in the Laboratory Manual and 
shipped at ambient temperature to an external analytical laboratory. 
15.13.6.3.1 
Analysis of genetic and/or transcriptional CD19 alterations 
During the course of the main study the patient will be asked for his participation in additional  
pharmacogenomic analyses in the sub-study. For this purpose blood samples will be collected, 
shipped at ambient temperature to an external analytical laboratory and stored to analyze the 
CD19 mutational status and detection of potential alternative CD19 splice variants. These 
analyses are optional within the sub-study and participation is completely voluntary. 
15.13.6.3.2 
Assessment of MOR00208 serum concentrations (PK samples) 
Serum samples for PK analysis of MOR00208 will be handled and stored at the sub-study site 
as specified in the Laboratory Manual until shipment on dry ice to an external analytical 
laboratory. At each sampling timepoint the serum sample should be split into 2 aliquots (a 
primary and a back-up sample). 
15.13.7 Safety Monitoring 
For this sub-study, only serious adverse event (SAE) e.g., related to procedural complications 
during blood sampling have to be collected. Study centers and Investigators are instructed to 
report all SAEs to MorphoSys Drug Safety (safety@morphosys.com) within 24 hours, using the 
sub-study specific SAE report form. Note: Follow up of SAEs also have to be reported within 
24 hours. 
For definitions please refer to Section 10 of the study protocol. 
15.13.8 Study Management and Data Handling 
Source documents are considered to be all information within original records and covered on 
certified copies of original records concerning clinical findings, observations, data or other 
activities in the clinical sub-study necessary for the reconstruction and evaluation of the sub-
study. 
The sub-study will be monitored to ensure that it is conducted and documented properly 
according to the protocol, GCP, and all applicable regulatory requirements. 
All patients will be informed that participation is entirely voluntary and will have to sign the 
Informed Consent Form (ICF). Patient must consent to the sub-study before or on first sub-study 
visit, before blood sample collection of the sub-study. The Investigator will inform any patient 
participating in the sub-study that this sub-study protocol explicitly allow to undergo any medical 
treatment including anti-neoplastic therapy for their disease as necessary. 
The required data for the sub-study will be collected on the Sub-Study specific Laboratory 
Requisition Form. These data will not be entered in the eCRF of the main study. Data entered on 
the Laboratory Requisition Form should be consistent with the source documents, or the 
discrepancies must be explained.  
The primary method of data transmission is via the sub-study specific Laboratory Requisition 
Form transferred to Central laboratory together with the laboratory samples collected. The data 
collected on the Laboratory Requisition Form will be transferred to the laboratory database. 


Product Name: MOR00208 
Protocol Number: MOR208C205 
Date: 10 January 2019 
IND Number: 114,856 
CTP Amendment No. 7, Version 11.0 
EudraCT Number: 2015-002915-14 
 
MorphoSys AG 
Confidential 
Page 160 of 160 
The Central laboratory will be responsible for the processing and the quality control of the data 
collected for the sub-study according to standard operating procedures (SOPs) and sub-study 
specific procedures. 
Queries will be handled via paper based Data Clarification Forms. 
All study forms and records transmitted to the Central Laboratory/sponsor must just carry coded 
identifiers such that personally identifying information is not transmitted. 
For further general rules and guidelines applicable regarding study management please refer to 
Section 13 of the study protocol. 
15.13.9 Sub-Study Statistical Methods and Planned Analyses 
The analysis will be conducted after completion of the sub-study and reported as an addendum 
to the Clinical Study Report covering the final analysis of the main study. 
Descriptive statistics summarizing CD19 expression levels on peripheral B cells (CLL and 
normal B cells) will be calculated by visit, respectively. The following will be derived: 
 Absolute levels by visit including sub-study visits. 
 Relative change from baseline of the main study by sub-study visits. 
 Relative change from the “End of Treatment Visit” by sub-study visit.  
Descriptive statistics summarizing genetic CD19 mutations and alternative CD19 splice variants 
in peripheral B cells (CLL and normal B cells) will be calculated by visit, respectively. The 
following will be derived: 
 Proportion of patients with acquired CD19 mutation(s) during the MOR00208 treatment 
period  
 Proportion of patients with detectable alternative CD19 splice variants 
CD19 mutational status and alternative CD19 splice variants will be summarized. No formal 
statistical testing will be conducted. Further details will be specified in the SAP. 

SAP_000.pdf: 
Protocol Number: MOR208C205 
Confidential 
MorphoSys AG 
 
REDACTED STATISTICAL ANALYSIS PLAN 
The information contained in the attached report is the property of MorphoSys AG and should not be shared or used 
for any purpose other than that for which it was provided. Laws require that MorphoSys AG protects patient 
privacy. MorphoSys AG may have legal and contractual obligations not to disclose technical information related to 
vendors. 
 
 
Statistical Analysis Plan 
Protocol Number: 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 
 
IND Number: 
114,856 
EudraCT Number: 
2015-002915-14 
Sponsor: 
MorphoSys AG 
Author: 
XXXXXXXX 
SAP Version: 
Version 2.0 – Addendum Version 1.0 
Version Date: 
27 May 2019 
ClinicalTrials.gov Identifier: 
NCT02639910 
-CONFIDENTIAL- 
This document and its contents are the property of and confidential to MorphoSys AG. 
Any unauthorized copying or use of this document is prohibited. 
 
 
 
Version 2.0 Final, 27 May 2019 
 
 
 
 
 
 
 
Page 1 of 71 


Protocol Number: MOR208C205 
Confidential 
MorphoSys AG 
STATISTICAL ANALYSIS PLAN 2.0 
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Version 2.0 Final, 27 May 2019 
Page 2 of 71 
MorphoSys AG 
Semmelweis-Strasse 7 
D-82152 Planegg 
GERMANY 
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 
Protocol No: MOR208C205 


Protocol Number: MOR208C205 
Confidential 
MorphoSys AG 
ADDENDA AS COMPARED TO THE ORIGINAL SAP VERSION 2.0 
Analyses that were added to the SAP are depicted in the Table below. No analyses that have been 
specified in the original SAP Version 2.0 were changed or removed. 
SAP Section 
Changes 
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Version 2.0 Final, 27 May 2019 
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Protocol Number: MOR208C205 
Confidential 
MorphoSys AG 
Contents 
ABBREVIATIONS................................................................................................................................................................... 12 
1 
RELATED DOCUMENTS ........................................................................................................................................... 15 
2 
DEFINITIONS .............................................................................................................................................................. 15 
COHORTS ............................................................................................................................................................... 15 
DEFINITION OF BASELINE ................................................................................................................................ 15 
DATE OF START OF TREATMENT PERIOD ................................................................................................... 16 
3 
OVERALL STUDY DESIGN AND PLAN ................................................................................................................. 16 
3.1 
STUDY OBJECTIVES AND ENDPOINTS ........................................................................................... 16 
3.2 
DISCUSSION OF STUDY DESIGN ...................................................................................................... 17 
3.3 
STUDY TREATMENTS .......................................................................................................................... 19 
3.3.1 Treatment Period ...................................................................................................... 19 
3.3.2 Treatment administration ......................................................................................... 20 
3.4 
STUDY SCHEDULE ............................................................................................................................... 21 
3.5 
CONCOMITANT MEDICATION .......................................................................................................... 29 
3.6 
STUDY ANALYSIS POPULATIONS ................................................................................................... 29 
3.6.1 Full Analysis Set (FAS) ............................................................................................. 29 
3.6.2 Per Protocol Set (PPS) ............................................................................................. 29 
3.6.3 Safety Analysis Set (SAF) .......................................................................................... 29 
3.6.4 PK Analysis Set (PKAS) ............................................................................................ 29 
3.6.5 Immunogenicity Analysis Set (IAS) ........................................................................... 29 
3.6.6 Other Populations Defined for Tables and Listings ................................................. 29 
3.7 
WITHDRAWN PATIENTS ..................................................................................................................... 30 
3.8 RANDOMIZATION ........................................................................................................................................ 30 
3.9 
BLINDING ............................................................................................................................................... 30 
3.10 SAMPLE SIZE .............................................................................................................................................. 30 
4 
STATISTICAL METHODOLOGY ............................................................................................................................ 31 
4.1 
GENERAL STATISTICAL APPROACHES .......................................................................................... 31 
4.1.1 Descriptive Statistics................................................................................................. 31 
4.1.2 Statistical Significance .............................................................................................. 31 
4.1.3 Subgroup Analyses .................................................................................................... 31 
4.1.4 Visit Window ............................................................................................................. 31 
4.1.5 Exclusion of Data from the Statistical Analysis ....................................................... 31 
4.1.6 Listings ...................................................................................................................... 31 
4.2 
TYPES OF PLANNED ANALYSIS ....................................................................................................... 32 
4.2.1 Primary Analysis....................................................................................................... 32 
4.2.2 Final Analysis ........................................................................................................... 32 
4.3 
DISPOSITION OF PATIENTS ................................................................................................................ 32 
4.4 
BASELINE AND DEMOGRAPHIC CHARACTERISTICS ................................................................. 32 
4.4.1 Demography/Baseline Characteristics ..................................................................... 32 
4.4.2 Disease Staging......................................................................................................... 33 
4.4.3 FcγRII/III Gene Mucosal Cheek Swab ..................................................................... 33 
4.4.4 Cytogenetic Risk ....................................................................................................... 33 
4.5 
MEDICAL HISTORY AND CURRENT MEDICAL CONDITIONS .................................................. 34 
4.6 
PRIOR AND CONCOMITANT MEDICATIONS AND THERAPIES ................................................. 34 
4.7 
STUDY TREATMENT ............................................................................................................................ 35 
4.7.1 Duration of Exposure................................................................................................ 35 
4.7.2 Dose Reduction ......................................................................................................... 35 
Version 2.0 Final, 27 May 2019 
Page 9 of 71 


Protocol Number: MOR208C205 
Confidential 
MorphoSys AG 
Version 2.0 Final, 27 May 2019 
 
Page 10 of 71 
4.7.3 Dose Interruption ................................................................................................. 36 
4.7.4 Treatment Compliance ......................................................................................... 36 
4.8 
EFFICACY ANALYSIS ................................................................................................. 40 
4.8.1 Secondary Endpoint ............................................................................................. 40 
4.9 
ADDITIONAL ANALYSES ............................................................................................ 40 
4.9.1 Immunogenicity Analysis ...................................................................................... 40 
4.9.2 Pharmacokinetic Analysis .................................................................................... 41 
4.9.3 Assessment of MRD Response .............................................................................. 42 
4.9.4 Biomarkers ........................................................................................................... 42 
4.10 
SAFETY ANALYSIS .................................................................................................... 43 
4.10.1 
Adverse Events ................................................................................................. 44 
4.10.2 
Vital Signs ........................................................................................................ 50 
4.10.3 
Physical Examination ....................................................................................... 50 
4.10.4 
12-lead ECG ..................................................................................................... 50 
4.10.5 
Laboratory Findings ........................................................................................ 51 
4.10.6 
ECOG Scores Analyses .................................................................................... 52 
4.10.7 
B-Symptoms ...................................................................................................... 52 
4.11 
OTHER DATA ............................................................................................................. 52 
4.12 
PROTOCOL DEVIATIONS ............................................................................................ 52 
4.13 
INDEPENDENT DATA MONITORING COMMITTEE ....................................................... 53 
4.14 
HANDLING OF MISSING DATA AND OUTLIERS ........................................................... 53 
4.14.1 
Missing Data .................................................................................................... 53 
4.14.2 
Outliers ............................................................................................................. 55 
4.15 
DATA HANDLING FOR LABORATORY DATA .............................................................. 55 
4.16 
DEVIATIONS FROM SAP ............................................................................................ 55 
4.17 
CHANGES IN CONDUCT OR PLANNED ANALYSES FROM THE PROTOCOL .................... 55 
4.18 
OUTPUT FORMAT ...................................................................................................... 55 
4.19 
SOFTWARE ................................................................................................................ 56 
4.20 
QUALITY CONTROL OF OUTPUTS .............................................................................. 56 
4.21 
CONVENTIONS ........................................................................................................... 56 
5 
REFERENCES ............................................................................................................................................................ 58 
6 
APPENDICES .............................................................................................................................................................. 59 
6.1 
APPENDIX A: BINET AND RAI STAGING SYSTEM ....................................................... 59 
6.2 
APPENDIX B: COCKCROFT-GAULT FORMULA ........................................................... 60 
6.3 
APPENDIX C: RESPONSE DEFINITION FOR CLL BY THE IWCLL GUIDELINES 2008 ... 61 
6.4 
APPENDIX D: CRITERIA FOR B-SYMPTOMS ............................................................... 63 
6.5 
APPENDIX E: ECOG PERFORMANCE STATUS ............................................................ 64 
6.6 
APPENDIX F: TABLE OF CONTENTS FOR STATISTICAL TABLES, FIGURES, AND 
LISTINGS ............................................................................................................................... 65 
 
 
 


Protocol Number: MOR208C205 
Confidential 
MorphoSys AG 
Version 2.0 Final, 27 May 2019 
 
Page 11 of 71 
 
List of Tables 
(Excluding those in the appendix) 
Table 1: Overview of Study Objectives and Endpoints 
16 
Table 2: Schedule of Procedures and Assessments 
22 
Table 3: Overview of the Analyses Performed on the Different Study 
Populations 
30 
Table 4: Safety Laboratory Evaluations 
51 
 
List of Figures 
Figure 1: Study Design 
18 
Figure 2: Ramp-up Dosing Schedule for Venetoclax 
21 
 
 
 


Protocol Number: MOR208C205 
Confidential 
MorphoSys AG 
Version 2.0 Final, 27 May 2019 
 
Page 12 of 71 
Abbreviations 
 
ADaM 
Analysis dataset model 
ADCC  
Antibody dependent cell mediated cytotoxicity  
ADS 
Analysis dataset 
AE  
Adverse event  
AESI  
Adverse event of special interest  
ALP  
Alkaline phosphatase  
ALT (SGPT)  
Alanine transaminase (serum glutamic pyruvic transaminase)  
ANC 
Absolute neutrophil count 
ANOVA 
Analysis of variance 
Anti-HBc  
Hepatitis B core antibody  
AST (SGOT)  
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase)  
ATC 
Anatomical Therapeutic Chemical (classification system) 
BID 
bis in diem, twice daily 
BLQ 
Below the limit of quantification 
BM 
Bone marrow 
BTK 
Bruton's tyrosine kinase  
C1D1  
Cycle 1 Day 1  
CD  
Cluster of differentiation  
CLL  
Chronic lymphocytic leukemia  
CMV 
Cytomegalovirus 
CPMP 
Committee for Proprietary Medicinal Products (now: CHMP, Committee 
for Medicinal Products for Human Use) 
CR  
Complete response/remission  
CRi  
Complete response with incomplete marrow recovery  
CSR 
Clinical Study Report 
CT  
Computed tomography  
CTCAE  
Common Terminology Criteria for Adverse Events  
CV 
Coefficient of variation 
DBP 
Diastolic blood pressure 
DNA  
Deoxyribonucleic acid 
eCRF  
Electronic Case Report Form  
ECG  
Electrocardiogram  
ECOG  
Eastern Cooperative Oncology Group  
EDTA  
Ethylenediaminetetraacetic acid  
EMA  
European Medicines Agency  
EOT  
End of Treatment  
EudraCT  
European Clinical Trials Database  
FAS  
Full analysis set  
FCBP  
Females of childbearing potential  
FcγR  
Fc (fragment crystallizable) gamma receptors  
FDA  
Food and Drug Administration  
FISH  
Flourescence in-situ hybridization  
GGT  
Gamma-glutamyltransferase  
HCG  
Human chorionic gonadotropin  
HBsAb  
Hepatitis B surface antibody 
HBsAg  
Hepatitis B surface antigen  
HBV  
Hepatitis B virus  
HCV  
Hepatitis C virus  
HIV  
Human immunodeficiency virus  
HR 
Heart rate (pulse rate) 
IB  
Investigator’s Brochure  
IAS 
Immunogenicity analysis set 
ICF  
Informed Consent Form  
ICH  
International Conference on Harmonization  


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IDMC  
Independent Data Monitoring Committee  
Ig  
Immunoglobulin  
IGHV  
Immunoglobulin heavy-chain variable gene 
IND  
Investigational New Drug application  
IRR 
Infusion-related reaction 
IV  
Intravenous(ly)  
IWCLL  
International Workshop on Chronic Lymphocytic Leukemia  
LDH  
Lactate dehydrogenase  
MedDRA  
Medical Dictionary for Regulatory Activities  
MRD  
Minimal residual disease  
NCCN  
National Comprehensive Cancer Network  
NCI  
National Cancer Institute  
NE 
Not evaluable 
NHL  
Non-Hodgkin’s lymphoma  
NK  
Natural killer (cells)  
o.d. 
Once daily 
ORR  
Overall response rate  
PD  
1. Pharmacodynamic(s), 2. Progressive disease, 3. Protocol deviation  
PDVD 
Programming Development and Validation Document 
PB 
Peripheral Blood 
PE  
Physical examination  
PJP 
Pneumocystis jirovecii pneumonia 
PK  
Pharmacokinetic(s)  
PKAS  
PK analysis set  
PLC  
Phospholipase C  
PLL 
Prolymphocytic leukemia 
PPS  
Per-protocol set  
PR  
Partial response/remission 
PRL  
Partial response with lymphocytosis  
PT  
Preferred Term  
QA 
Quality assurance 
QC 
Quality control 
RBC  
Red blood cell  
RNA  
Ribonucleic acid  
R/R CLL  
Relapsed or refractory chronic lymphocytic leukemia  
R/R SLL  
Relapsed or refractory small lymphocytic lymphoma  
SAE  
Serious adverse event  
SAF  
Safety analysis set  
SAP  
Statistical Analysis Plan  
SAR 
Serious adverse reaction 
SAS 
Statistical Analysis System 
SBP 
Systolic blood pressure 
SD  
Stable disease  
SDTM 
Study data tabulation model 
SJS 
Stevens-Johnson syndrome 
SLL  
Small lymphocytic lymphoma  
SOC  
System Organ Class  
SOP 
Standard operating procedure 
sqrt 
Square root 
StD 
Standard deviation 
T-CLL 
Chronic lymphocytic leukemia of T-cell type (now: T-cell prolymphocytic 
leukemia) 
TEAE  
Treatment-emergent adverse event  
TEN 
Toxic epidermal necrolysis 
TLGO 
Tables, Listings, Graphs and other Output 
TLS  
Tumor lysis syndrome  


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TP53  
Tumor protein p53  
UK 
United Kingdom 
US  
United States of America  
WBC  
White blood cell  
WHO  
World Health Organization  
ZAP-70  
Zeta-chain-associated protein kinase 70  
 
 


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1 
Related Documents 
This document presents the Statistical Analysis Plan (SAP) for MorphoSys AG Protocol No. 
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. 
This SAP is based on the final protocol Amendment No. 6, Version 10.0 dated 25 July 2017. 
The SAP provides the description of the final statistical analysis to be reported in the Clinical Study 
Report (CSR). In case of deviations from the SAP, explanations will be provided in the CSR. 
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 (ICH E9: FDA and CPMP). All 
work planned and reported from this SAP will follow internationally accepted guidelines for statistical 
practice, published by the American Statistical Association (ASA 1999) and the Royal Statistical 
Society (RSS 2014). 
The planned analysis identified in this SAP may be included in clinical study reports (CSRs), 
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 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. 
 
2 
Definitions 
Cohorts 
Statistics will be displayed for the following cohorts, i.e., treatment groups: 
 
MOR00208 + Idelalisib (Cohort A) 
 
MOR00208 + Venetoclax (Cohort B) 
The treatment label “MOR00208 + Idelalisib” and “MOR00208 + Venetoclax” should be displayed 
in the Tables, Listings, Graphs and other Output (TLGO). 
In case that at least one patient has received only one of the treatments of the cohort he/she was 
enrolled to, in addition to the column  containing all patients of the cohort additional columns will be 
generated containing the actual treatment the patients have received as column header. E.g., if a patient 
is enrolled into Cohort B but discontinues the study after only one dose of MOR00208 and before the 
first planned dose of venetoclax then all summaries of safety will also include a column with treatment 
label “Treated with MOR00208 only”, a column with treatment label “Treated with MOR00208 + 
Venetoclax ” and a column with treatment label “Enrolled to MOR00208 + Venetoclax”. Safety 
tables for adverse events will further contain two columns “Overall Combination Treatment” and 
“Overall At Least One Study Drug”. 
Definition of Baseline 
Baseline is defined to be the latest non-missing assessment value for a patient, for that particular 
parameter collected prior to initiation of first dose of either study medication.  
Change from baseline value at each post baseline assessment will be calculated as post baseline value 
– baseline value. 


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Date of Start of Treatment Period 
In general, the date of start of treatment period should coincide with the day one of first study 
medication intake. However, discrepancies between these dates may arise and the most appropriate 
date to be used in such situations requires a case-by-case evaluation. Since many algorithms used in 
the statistical analysis require the start of the treatment period to be identified, an ad-hoc variable 
specifying this date will be defined. The date of start of treatment period will be initially set equal to 
the date of first study medication intake for all patients. The need for deviations from this rule in 
single cases will be evaluated during the data review. 
 
3 
Overall Study Design and Plan 
3.1 
Study Objectives and Endpoints 
 
Objectives and endpoints are identical for both cohorts with one exception regarding the definition of 
the overall response rate. Details are specified in Table 1. 
 
Table 1: Overview of Study Objectives and Endpoints 
Study objective 
Endpoint 
Analysis 
Primary objective: 
 
To determine the safety of 
MOR00208 combined with 
idelalisib or venetoclax 
Primary endpoint: 
 
Incidence, frequency and severity of 
adverse events (AEs) 
 
See section 4.10.1 
Secondary objectives: 
 
To determine the quality of 
the response 
Secondary endpoints: 
 
Best objective response rate (ORR):  
o 
Definition for Cohort A: percentage 
of   patients achieving a complete 
response (CR), a partial response 
(PR) or a partial response with 
lymphocytosis (PRL). 
o 
Definition for Cohort B: percentage 
of patients achieving a CR or a PR. 
 
See section 4.8.1 
 
To assess the potential 
immunogenicity of 
MOR00208 (anti-
MOR00208 antibody 
formation) 
 
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 section 4.9.1 
 
To assess the 
pharmacokinetic (PK) 
profile of MOR00208 
 
Pharmacokinetic analysis for 
MOR00208: plasma concentration-
time profiles of MOR00208 and 
appropriate individual PK parameters 
(e.g., accumulation ratios). 
See section 4.9.2 


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Exploratory objectives: 
 
To assess minimal residual 
disease (MRD) in patients 
achieving a complete or 
partial response 
Exploratory endpoints: 
 
Proportion of patients with MRD- 
negativity 
 
See section 4.9.3 
 
To explore putative 
predictive biomarkers 
 
Absolute and percentage change from 
baseline in measurements for B-, T- and 
natural killer (NK) cell populations 
See section 4.9.4 
 
The exploratory objective “To determine and correlate prognostic factors with efficacy parameters” 
specified in the protocol was not addressed in the present SAP. Due to several protocol amendments 
the primary focus of the study has shifted to address safety-relevant questions. Given the small sample 
size no subgroup analyses could be conducted, which would have been necessary to adequately 
address the objective. 
 
 
3.2 
Discussion of Study Design 
This is a multicenter, two-cohort, open-label phase II study of MOR00208 combined with idelalisib 
(Cohort A) or venetoclax (Cohort B) for the treatment of adult patients with relapsed or refractory 
chronic lymphocytic leukemia (R/R CLL) or relapsed or refractory small lymphocytic lymphoma (R/R 
SLL) pretreated with a BTK inhibitor as a single agent or as part of a combination therapy. 
Recruitment of a patient into Cohort A or B is at the discretion of the Investigator. A total of 10 to 
approximately 12 patients are planned to be enrolled in each cohort in Europe and the US. Figure 1 
illustrates the design of the study. 
 


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Figure 1: Study Design 
Cycle 1 to 3
Cohort A: 
Idelalisib Days 1-28
MOR00208 Days 1,8,15,22*1
(28-day cycles)
Cohort A: 
Idelalisib Days 1-28 
MOR00208 Days 1&15 
(28-day cycles)
EOT
R/R CLL or
R/R SLL
pretreated 
with BTK
inhibitor
(e.g. 
ibrutinib)
Screen-
ing
Cycle 4 to 6
*1 Additional loading dose of 
MOR00208 on Cycle 1 Day 4
30 day 
Follow-
Up Visit
Abbreviations: EOT=end of treatment; BTK=Bruton’s tyrosine kinase; R/R CLL=relapsed or refractory chronic lymphocytic leukemia; 
R/R SLL=relapsed or refractory small lymphocytic lymphoma.
Cohort B: 
Venetoclax Days 1-28*2
MOR00208 Days 1,8,15,22*1
(28-day cycles)
Cohort B:
Venetoclax Days 1-28 
MOR00208 Days 1&15 
(28-day cycles)
*2 Weekly ramp up of Venetoclax starting on Cycle 1 Day 8
(C1D8: 20mg, C1D15: 50mg, C1D22:100mg, C2D1: 200mg). 
Venetoclax dosis 400mg up from Cycle 2 Day 8
Cohort A: 
Idelalisib Days 1-28 
MOR00208 Day 1 
(28-day cycles)
Cycle 7 to 24
Cohort B:
Venetoclax Days 1-28 
MOR00208 Day 1 
(28-day cycles)


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The study will include a safety run-in phase for each cohort enrolling 10- approximately 12 patients 
per combination treatment. MOR00208 will be administered at a dose of 12.0 mg/kg as intravenous 
(IV) infusion, idelalisib in Cohort A as 150 mg oral tablets twice daily and venetoclax in Cohort B as 
400 mg oral tablets daily dose. To mitigate the risk for tumor lysis syndrome (TLS) treatment of 
patients with venetoclax will be initiated after an initial treatment with MOR00208 at 20 mg up from 
C1D8 for 7 days, followed by a weekly ramp-up dosing schedule to the recommended daily dose of 
400 mg. The safety run-in phase will be concluded with an evaluation of the safety data of all treated 
patients once 10 patients completed at least one treatment cycle in Cohort A or at least 5 weeks of 
combination treatment in Cohort B. The first 3 patients in Cohort A will be dosed sequentially at least 
48 hours apart. In Cohort B, all 10- approximately 12 patients will be dosed sequentially, at least one 
week apart. 
In Cohort A there will be two safety evaluations. After completion of the first cycle (4 weeks) the 
safety data of the first three patients will be evaluated. This evaluation will be done by an Independent 
Data Monitoring Committee (IDMC) composed of experts in the field of oncology and clinical 
biostatistics who have no other role in the study and do not have an affiliation with the Investigators or 
the sponsor. After the evaluation of the safety data from the first 3 patients for Cycle 1 of treatment 
and a positive recommendation from the IDMC the next 7- approximately 9 patients may be dosed in 
parallel. An additional IDMC review will take place after 10 patients completed at least 1 cycle of 
treatment. 
In Cohort B the safety evaluation will be performed by the IDMC after the first 10 patients completed 
at least 5 weeks of combination treatment. The evaluation will be done by the IDMC as already 
described. Importantly, all patients in Cohort B, who participate in the safety run-in phase, will be 
hospitalized on the day of the first two dose escalations of venetoclax (C1D8 and C1D15). 
The criteria for the evaluation of safety of the combination therapy will be defined by the IDMC and 
laid down in the Safety Management Plan of the trial. 
During the study, MOR00208 will be administered as infusions 12.0 mg/kg in 28-day cycles. From 
Cycle 1 to 3, each cycle will consist of weekly infusions (on Day 1, Day 8, Day 15 and Day 22). In 
Cycle 1, an additional loading dose will be administered on Day 4. From Cycle 4 to 6, MOR00208 
will be administered on a biweekly basis with infusions on Day 1 and Day 15 of each cycle. 
Thereafter, MOR00208 will be administered on Day 1 of each cycle starting with Cycle 7 Day 1. 
Idelalisib will be self-administered twice daily starting on Day 1 of each cycle. Venetoclax will be 
self-administered (except during hospitalization) starting from Cycle 1 Day 8 and on Day 1 of each 
cycle onwards. Treatment with idelalisib or venetoclax may be modified in a de-escalating fashion or 
discontinued based upon clinical and laboratory findings. In case idelalisib or venetoclax treatment 
was stopped due to side effects suspected to be related to idelalisib or venetoclax, the patient may 
continue MOR00208 treatment. 
Progressive disease will require discontinuation of study medication.  
Patients who benefit from treatment are allowed to continue MOR00208 treatment beyond Cycle 24 at 
Investigator’s discretion. The total duration of the study will be limited to a maximum of 5 years from 
first patient first visit or up to the timepoint of approximately 30 days after last patient received his last 
treatment, whichever comes first.  
 
3.3 
Study Treatments 
3.3.1 
Treatment Period 
The treatment period consists of a total of 24 cycles, each cycle lasting 28 days. 
One to four visits are foreseen for each treatment cycle with one additional loading dose of 
MOR00208 on Day 4 of Cycle 1. Day 1 is the main visit of each cycle, where the largest number of 
examinations and assessments will be performed (see Table 2). Idelalisib or venetoclax tablets will be 
handed to the patients on Day 1 of each cycle.  


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Patients who continue to derive benefit from therapy with MOR00208 can stay on MOR00208-
treatment even beyond Cycle 24. In this case, the patient should be followed up at further visits 
(C25D1, C26D1, etc.) as specified for Cycle 7 to Cycle 24 (see Table 2). Examinations which are not 
performed on every cycle, e.g., radiological and PK examinations, should also be followed up 
according to the specifications made in Schedule of Assessments. Patients who achieved a confirmed 
CR or PR with bone marrow MRD negativity are allowed to stop idelalisib or venetoclax treatment 
and proceed with monthly MOR00208 treatment per discussion between the Investigator and 
sponsor’s medical monitor. 
3.3.2 
Treatment administration 
MOR00208 
MOR00208 will be administered IV at a dose of 12.0 mg/kg. 
For the first 3 months (3 cycles) of the study, each cycle will consist of a MOR00208 infusion on Day 
1, Day 8, Day 15 and Day 22 of the cycle. In addition, a loading dose will be administered on Day 4 of 
Cycle 1. Thereafter, MOR00208 will be administered on a biweekly basis (every 14 days) with 
infusions on Days 1 and 15 of each 28-day cycle from Cycle 4 to 6, and on a monthly basis on Day 1 
of each cycle from Cycle 7 Day 1. 
Idelalisib 
The recommended starting dose for idelalisib is 150 mg orally, twice daily (BID). It may be taken with 
or without food approximately at the same time of the day. Ideally, doses should be taken at ~12-hour 
intervals (e.g., at ~8 AM and at ~8 PM) on a BID schedule beginning ~30 minutes prior to the initial 
MOR00208 infusion. 
Patients will self-administer the dose of 150 mg twice daily orally continuously during the study 
duration. Treatment may be continued up to 24 cycles, or until progression of disease, withdrawal of 
consent, unacceptable toxicity, death or patient is lost to follow-up, whichever occurs first. 
Venetoclax 
Venetoclax dose should be administered according to a weekly ramp-up schedule over 5 weeks to the 
recommended daily dose of 400 mg. 
 
 
 
 
 
 
 
 
Figure 2 illustrates this initial ramp-up. The dosing schedule for ramp-up phase is given as follows, 
daily dose of venetoclax: 20 mg 1st week of combination treatment, 50 mg 2nd week, 100 mg 3rd week, 
200 mg 4th week and 400 mg 5th week and thereafter. The 5-week ramp-up dosing schedule, starting 
on C1D8, is designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS. 
Assessment of patient-specific factors for level of risk of TLS and prophylaxis for TLS should be 
performed prior to first dose of venetoclax (see Section 8.10.1 of the protocol). 
Venetoclax should be taken as scheduled orally once daily up to 24 cycles, or until disease progression 
or unacceptable toxicity is observed. Venetoclax tablets should be taken with a meal and water at 
approximately the same time each day. Tablets should be swallowed whole and not chewed, crushed, 
or broken prior to swallowing. If the patient misses a dose within 8 hours of the time it is usually 
taken, the patient should take the missed dose as soon as possible and resume the normal daily dosing 
schedule. If a patient misses a dose by more than 8 hours, the patient should not take the missed dose 


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and should resume the usual dosing schedule the next day. If the patient vomits following dosing, no 
additional dose should be taken that day. The next prescribed dose should be taken at the usual time. 
 
 
 
 
 
 
 
 
Figure 2: Ramp-up Dosing Schedule for Venetoclax 
 
 
 
3.4 
Study Schedule 
 
Prior to start of any study-related examination the Investigator or designated staff will fully 
explain the study to potential patients, to obtain their written informed consent. 
 
The Screening Period begins on the date when the Informed Consent Form (ICF) is signed; it 
will last for up to 28 days and is followed by Cycle 1 Day 1 (C1D1). 
 
The treatment period consists of a total of maximum 24 cycles of combination therapy (i.e., 
MOR00208 and idelalisib/venetoclax), each cycle lasting 28 days. Patients who continue to 
derive benefit from therapy with MOR00208 can stay on MOR00208-treatment even beyond 
Cycle 24. Study treatment will continue until documented disease progression, intolerable 
toxicity, withdrawal of consent to continue study treatment, death, physician decision, or early 
termination of the study. At that time, an End of Treatment (EOT) visit will be performed. 
 
Follow-up Period: 
30 Day Safety Follow-up Visit: A safety follow-up visit scheduled 30 days after the last dose 
of the study treatment to follow up for adverse events (AEs) and serious adverse events 
(SAEs) that may have occurred after discontinuation from the study treatment regardless of 
the reason for study drug discontinuation. 
Follow-up for Drug Discontinuation/Patient Withdrawal from Study: If a patient 
discontinues study treatment and is withdrawn from the study for any reason he/she will attend 
the EOT visit, if possible, and complete all assessments. In the event that a patient 
discontinues prematurely from the study due to a treatment-emergent adverse event (TEAE) or 
serious TEAE, the TEAE or serious TEAE will be followed until it resolves (returns to normal 
or baseline values) or stabilizes, or until it is judged by the Investigator to be no longer 
clinically significant.  
The study plan and scheduled tests are summarized in Table 2. 


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Table 2: Schedule of Procedures and Assessments 
Evaluation or Procedure 
Screening 
Period 
Treatment Period 
Screening 
≤28 Days 
prior to 
D1 
Cycle 1 
Cycle 2 
Cycle 3 
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 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease risk assessment: 
Cytogenetic testing; 
β2-microglobulin (serum); 
Expression of CD38 and 
ZAP-70 
 
X1 
 
 
 
 
 
 
 
 
 
 
 
 
Optional mutational 
analysis 
(e.g., IGHV, TP53, 
NOTCH1, BTK, PLCγ2) 
 
X1 
 
 
 
 
 
 
 
 
 
 
 
 
Previous/concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete physical 
examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Limited physical 
examination 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
ECOG performance status 
X 
X1 
 
 
 
 
X 
 
 
 
X 
 
 
 
Weight/height 2 
X 
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 
 X1 
 
 
X3 
 
 X3 
 
 
 
 X3 
 
 
 


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Evaluation or Procedure 
Screening 
Period 
Treatment Period 
Screening 
≤28 Days 
prior to 
D1 
Cycle 1 
Cycle 2 
Cycle 3 
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 
Urinalysis 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
HIV testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test 
(FCBP)4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 1,4 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
Pregnancy and risks 
counselling 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
“Emergency laboratory” 1, 5 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Central laboratory (blood) 
Hematology  
X 
X1 
 
 
X1 
 
X1 
 
X1 
 
X1 
 
X1 
 
Central laboratory (blood) 
Serum chemistry  
X 
X1 
 
 
X1 
 
X1 
 
X1 
 
X1 
 
X1 
 
Central laboratory (blood) 
Coagulation  
X 
X1 
 
 
 
 
X1 
 
 
 
X1 
 
 
 
Serology (hepatitis B and 
C) 
  X12 
 
 
 
 
 
 
 
 
 
X12 
 
 
 
CMV testing  
X14 
 
 
 
 
 
X14 
 
 
 
X14 
 
 
 
B-, T- and NK cell (blood) 
1 
 
X 
 
X 
 
 
X17 
 
X16 
 
 
 
 
 
CD19 assessment 
(CD19ABC and % CD19 + 
cells) (blood) 1 
 
X 
 
X16 
X16 
 
X17 
 
 
 
 
 
 
 
Anti-MOR00208 
antibodies 1 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
Optional FcγR 
polymorphism (mucosal 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 


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Evaluation or Procedure 
Screening 
Period 
Treatment Period 
Screening 
≤28 Days 
prior to 
D1 
Cycle 1 
Cycle 2 
Cycle 3 
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 
cheek swab) 1 
CD16 assessment 
(CD16ABC) (blood) 1 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
ADCC (blood) 1 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
MRD (blood) 1 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Disease response 
assessment: 
CT/MRI of neck, chest, 
abdomen, pelvis 7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
MOR00208 administration 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispensation of 
idelalisib/venetoclax tablets 
 
X17 
 
X16 
X16 
X16 
X 
X16 
 
 
X 
 
 
 
Venetoclax ramp-up 18 
 
 
 
20mg 
50mg 
100mg 200mg 400mg 
 
 
 
 
 
 
TLS risk assessment 1,16,18 
X 
 
 
X 
X 
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 
 
 
 
 
 
 


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Schedule of Procedures and Assessments (continued) 
 
Additional Treatment Periods 
 
Follow-up Period 
Evaluation or Procedure 
 
Cycle 4 - Cycle 6 
 
Cycle 7 - Cycle 24 
End of Treatment 
Visit (EOT) 
30-Day Safety 
Follow-up Visit 
Day 
D1 ±2 days 
D15 ±2 days 
 
D1 ±2 days 
Preferably within 
≤30 days of last 
dose of study 
treatment 
±2 days 
Concomitant medication 
X 
X 
X 
X 
X 
Complete physical 
examination 
 
 
 
X 
 
Limited physical 
examination 
X 
X 
X 
 
X 
ECOG performance status 
X 
 
X 
X 
 
Weight 2 
X 
X 
X 
X 
 
Vital signs 
X 
X 
X 
X 
 
B-symptoms 
X 
 
X 
X 
X 
12-lead resting ECG 
X 
 
X 
X 
 
Urinalysis 
X 
 
X 
X 
 
Serum pregnancy test 
(FCBP) 4 
 
 
 
X 
 
Urine pregnancy test 1 
X 
 
X 
 
 
Emergency Laboratory 1, 5 
X 
X 
X 
 
 
Central laboratory (blood) 
Hematology) 
X1 
 
X1 
X 
 
Central laboratory (blood) 
Serum chemistry  
X1 
 
X1 
X 
 
Central laboratory (blood) 
Coagulation 
X1 
 
X1 
X 
 
Anti-MOR00208 
antibodies 
X1, 9 
 
X1, 9 
X 
 
B, T, and NK cell (blood) 
1 
 
X10 
 
X 
 


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Additional Treatment Periods 
 
Follow-up Period 
Evaluation or Procedure 
 
Cycle 4 - Cycle 6 
 
Cycle 7 - Cycle 24 
End of Treatment 
Visit (EOT) 
30-Day Safety 
Follow-up Visit 
Day 
D1 ±2 days 
D15 ±2 days 
 
D1 ±2 days 
Preferably within 
≤30 days of last 
dose of study 
treatment 
±2 days 
Disease response 
assessment: CT/MRI of 
neck, chest, abdomen, 
pelvis 7 
X7 
 
X7 
X7, 8 
 
For CR / PR patients only: 
bone marrow aspiration & 
biopsy, MRD assessment 
X11 
 
X11 
X11 
 
MOR00208 
administration 
X 
X 
X 
 
 
Dispensation of 
idelalisib/venetoclax 
tablets 
X 
 
X 
 
 
(S)AE assessment 
X 
X 
X 
X 
X 
CD19 assessment 
(CD19ABC and % 
CD19+ cells) (blood) 
 
 
 
X 
 
PK MOR00208 
X1, 9 
 
X1, 9 
X 
 
Antineoplastic therapy 
after end of study 
treatment  
 
 
 
 
X 
Serology (hepatitis B and 
C) 
X12 
 
X12 
 
 
MRD (blood) 1 
X13 
 
X13 
 
 
CMV testing 
X14 
 
X14 
 
 


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Abbreviations: ABC=antibodies bound per cell; ADCC=antibody-dependent cell-mediated cytotoxicity; AE=adverse event; β-HCG=beta-human 
chorionic gonadotropin; BTK=Bruton's tyrosine kinase; CMV=Cytomegalovirus; CD19=cluster of differentiation 19; CT=computed 
tomography; ECG=electrocardiogram; ECOG=Eastern Cooperative Oncology Group; FCBP=female of childbearing potential; HIV=human 
immunodeficiency virus; IGHV=immunoglobulin heavy-chain variable gene; MRD=minimal residual disease; MRI=magnetic resonance 
imaging; NK=natural killer; PK=pharmacokinetics; SAE=serious adverse event; TLS=tumor lysis syndrome. 
 
Disease risk assessment as per IWCLL guideline: cytogenetic tests: FISH: Minimum required tests are del (17p), del (11q), del (13q), trisomy 
12, karyotyping. IGHV information can be obtained from previous CLL history; should otherwise be obtained from baseline investigation,  
Β2 microglobulin (serum), CD38 (cytometry), ZAP-70 (cytometry). 
 
1Before study drug administration. 
2Body height will be measured at Cycle 1 Day 1 (C1D1) only. Weight and height should be measured while the patient is without shoes but 
dressed. 
312-lead resting ECG performed 1 hour ±10 minutes post-MOR00208 dosing 
4Pregnancy tests for FCBP: a serum pregnancy test must be performed at screening within 7 days prior to the start of study drug and a local 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 C1D1 dosing.  
A β-HCG pregnancy test should also be performed at the EOT visit. At all other indicated timepoints, a urine pregnancy test for FCBP will be 
performed locally. Pregnancy test must be negative for dosing. 
5Emergency laboratory sample to be collected and evaluated in the local laboratory as indicated 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. 
7Baseline CT/MRI scan has to be performed within 14 days before C1D1. CT scans performed prior to screening as part of the regular clinical 
work-up of the patient will be allowed up to 6 weeks before C1D1. However, a CT scan must be performed within the 14 day period prior to 
C1D1 for those patients with signs of rapidly progressing disease at screening. CLL response assessment according to IWCLL guideline (Hallek 
et al., 2008). SLL response assessment according to the Lugano Classification criteria (Cheson et al., 2014). For CLL and SLL: CTs or MRIs 
will be performed at C4D1, C7D1, C13D1, C19D1, etc. Time window is ±7 days for visits C4D1 and C7D1 and ±14 days for the following 
examinations. A CT/MRI scan has to be performed at least 8 weeks after CR was identified by clinical criteria (and before a BM biopsy is 
obtained for CR confirmation). If a regular CT/MRI scan is scheduled within these 8 weeks according to the schedule of assessment (C4, C7, 
C13, etc.) this examination should be postponed to meet the confirmation timeline. The following regular CT/MRI scan can be 
postponed/skipped, if this examination is within 8 weeks of the CR confirmatory scan. 
8In case the patient is withdrawn from treatment for reasons other than progression of disease, a CT is only required at the EOT visit if this was 
not performed within 28 days before EOT. 
9During Cycles 4 through 24, anti-MOR00208 antibody samples and MOR00208 PK samples (all to be collected pre-dose only) will be collected 
in odd numbered cycles only (i.e., Cycles 5, 7, 9, 11, etc.) 
10B/T/NK cell count only in Cycle 4 of additional treatment period. 


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11For patients with CR: a MRD assessment from bone marrow aspirate and a local analysis of bone marrow aspiration/biopsy has to be 
performed for confirmation of CR at least 8 weeks after the CR criteria for tumor response are first met. The result of the CT scan need to be 
obtained first; if this does not confirm a CR, then a biopsy should not be performed.  
For patients with PR and PB MRD negativity: an MRD assessment from bone marrow aspirate/peripheral blood has to be performed at least 
8 weeks after the PB MRD negativity was detected. 
12If positive for hepatitis B serology needs to be followed up locally every 2 months. 
13Periphal blood sample for MRD assessment has to be taken at C4D1, C7D1, C13D1, C19D1, etc. until BM MRD negativity was confirmed. 
For CR patients only: An additional PB sample needs to be obtained at the time when CR is confirmed by CT. 
14Patients with positive serology or with other evidence of a history of CMV infection at screening should be carefully monitored with PCR  
(a) monthly, if initial PCR result has been negative without associated clinical signs of CMV infection or  
(b) weekly, if significant CMV viremia has been detected. 
15During ramp-up of venetoclax patients will receive 20 mg (C1D8), 50 mg (C1D15), 100 mg (C1D22), 200 mg (C2D1) and 400 mg (C2D8), if 
no contraindications 
16Cohort B –Venetoclax+MOR00208 patients only. 
17Cohort A – Idelalisib+MOR00208 patients only. 
18In cases when an unscheduled visit needs to be performed during ramp-up phase of venetoclax (e.g., due to dosing interruption or reduction of 
venetoclax which leads to changed treatment schedule of venetoclax), no risk reassessment for TLS needs to be performed at respective regular 
visit(s) when MOR00208 is administered. 


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3.5 
Concomitant Medication 
Patients are allowed to continue the medications that they are taking at baseline. Patients may also 
receive concomitant medications that are medically indicated as standard care for the treatment of 
symptoms and intercurrent illnesses. Section 8.13 of the protocol details prohibited concomitant 
medications. 
 
3.6 
Study Analysis Populations 
The following analysis populations are defined: 
3.6.1 
Full Analysis Set (FAS) 
The Full analysis set (FAS) will include all patients who receive at least one dose of MOR00208 
and/or one dose of idelalisib in Cohort A and/or one dose of 100 mg daily dose of venetoclax in 
Cohort B. The FAS will be the primary analysis population for the secondary endpoint Overall 
Response Rate (ORR).  
In the FAS patients will be analyzed according to the cohort they were enrolled (intent-to-treat 
principle). 
3.6.2 
Per Protocol Set (PPS) 
The Per Protocol Set (PPS) consists of all patients in the FAS who did not have any protocol 
deviations that could confound the interpretation of the efficacy analyses conducted on the FAS. 
Patients with no post-baseline assessment of response will be excluded from the PPS. The PPS will be 
used for a sensitivity analysis of the secondary endpoint overall response rate (ORR). 
Decisions about whether a protocol deviation is relevant for the exclusion of a patient from the PPS 
will be made before database closure. In the PPS patients will be analyzed according to the cohort they 
were enrolled. 
3.6.3 
Safety Analysis Set (SAF) 
The Safety Analysis Set (SAF) includes all patients who received at least one dose of any study 
treatment and had at least one post-baseline safety evaluation. A record of death or “no adverse event” 
constitutes a valid safety assessment. Data for patients with no post-baseline safety assessment will 
only be listed in the FAS. Patients will be analyzed according to the study treatment they actually 
received. The SAF will be used for the primary endpoint analysis, i.e., incidence and severity of 
adverse events.  
3.6.4 
PK Analysis Set (PKAS) 
The PK analysis set (PKAS) will include all patients who received at least one dose of study 
medication MOR00208 and have at least one quantifiable serum MOR00208 concentration. PK 
parameters will be calculated as data permit. 
3.6.5 
Immunogenicity Analysis Set (IAS) 
The Immunogenicity Analysis Set (IAS) will include all patients who have at least one anti-
MOR00208 antibody assessment. 
3.6.6 
Other Populations Defined for Tables and Listings 
Two further populations are defined for the case any additional tables and listings will be presented: 
 
All patients 
 
All enrolled patients 
 
Screening failure patients  
The “all patients” population consists of all patients who have signed informed consent. The ‘all 
enrolled patients’ population includes all patients who received at least one dose of any study 
treatment. 


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The following Table 3 summarizes the analyses being performed for each analysis set. 
Table 3: Overview of the Analyses Performed on the Different Study Populations 
Analysis 
All 
patients 
FAS 
PPS 
SAF 
PKAS 
IAS 
Patient disposition 
x 
x 
 
 
 
 
Summary of demographic and 
baseline characteristics 
 
x 
 
x 
 
 
Incidence, frequency and severity 
of adverse events 
 
 
 
x 
 
 
Summary of  vital signs, 12-lead 
ECG,  
laboratory safety evaluations 
 
 
 
x 
 
 
ECOG and B-symptoms 
 
 
 
x 
 
 
Overall response rate 
 
x 
x 
 
 
 
Study 
treatment 
(exposure, 
compliance, dose reductions, dose 
interruptions) 
 
x 
 
x 
 
 
Summary of prior CLL therapies 
 
x 
 
x 
 
 
Summary of pre-medication, prior 
medication, 
concomitant 
medication, 
and 
medical 
history/current medical conditions 
 
x 
 
x 
 
 
Pharmacokinetic analyses 
 
 
 
 
x 
 
Immunogenicity analyses 
 
 
 
 
 
x 
Descriptive biomarker analyses 
 
x 
 
 
 
 
 
3.7 
Withdrawn Patients 
Once a patient is withdrawn from the study, the patient may not re-enter the study. 
 
3.8 
Randomization 
The study is a non-randomized trial. 
 
3.9 
Blinding 
This is an open label study. 
 
3.10 Sample Size 
The primary endpoint of this study is the incidence and severity of AEs in Cohort A (MOR00208 
combined with idelalisib) and Cohort B (MOR00208 combined with venetoclax) and will be analyzed 


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descriptively. In each cohort approximately 12 patients will be enrolled. No formal sample size 
calculation was performed and no formal statistical hypothesis testing is planned. 
 
4 
Statistical Methodology 
4.1 
General Statistical Approaches 
4.1.1 
Descriptive Statistics 
All data will be summarized 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, 95% confidence limits of means will be 
presented. The number and percentage of patients in each category will be presented for categorical 
variables. For categorical variables, the number and percentage of patients with missing data will be 
provided. Data from all sites will be pooled for all analyses. 
4.1.2 
Statistical Significance 
No formal statistical hypothesis testing is planned. 
4.1.3 
Subgroup Analyses 
No subgroup analyses are planned in the study. 
4.1.4 
Visit Window 
 
Analysis Window 
For parameters that will be summarized by visit, the nominal visit as recorded on the eCRF will be 
used. There will be no additional analysis windowing done based on the assessment date. 
Unscheduled visits prior to C1D1 will be included for the calculation of baseline values. 
Unscheduled scans will be used for determination of tumor response efficacy endpoints. 
 
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 1 value per analysis window but rather 1 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: 
 
If more than 1 assessment occurs during the same nominal visit, select the record closest to the 
nominal day for that visit. 
 
If there are 2 assessments that are equidistant from the nominal 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. 
 
4.1.5 
Exclusion of Data from the Statistical Analysis 
No data will be excluded from the analyses, including any outliers. 
4.1.6 
Listings 
All data collected in the CRF will be presented in the listings. 
 


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4.2 
Types of Planned Analysis 
4.2.1 
Primary Analysis 
The primary analysis of each cohort to evaluate safety and preliminary efficacy will be based on the 
safety data and response assessment of the enrolled patients up to the time point of 3-18 months after 
last patient started treatment in Cohort B.  
4.2.2 
Final Analysis 
The final analysis will be conducted at the end of the study defined as 5 years after the first patient was 
enrolled (C1D1) or approximately 30 days after last patient received his last treatment, whichever 
comes first. 
 
4.3 
Disposition of Patients 
The number of patients screened, the number (%) of screen failures and the number of patients with 
each reason for screen failure will be presented (by cohort). All patients will be included. 
The following summaries will be provided by cohort based on the total number of enrolled patients: 
 An overview table will be provided by cohort and will include the number of patients enrolled, 
the number (%) of patients in each analysis set (FAS, PPS, SAF, PKAS and IAS). 
 Number (%) of patients who were treated with study drug (split by MOR00208, 
idelalisib/venetoclax, and treated with both drugs). 
 Number (%) of patients who were enrolled but not treated with study drug (split by 
MOR00208 and idelalisib/venetoclax). 
 Number (%) of patients who discontinued treatment including the reason for discontinuation. 
 Number (%) of patients who are still on any treatment (only for the primary analysis).The 
median time on study will be reported for patients in the FAS, which is defined as follows: 
[(Date of Death/last Visit including the End of Treatment Visit) – (Date of first dosing with 
any study drug) + 1]/30.4375.  
The median time on study will be derived using Kaplan-Meier-Methodology. Patients still on study at 
data cut-off will be censored. 
The individual time on study will be graphically illustrated by a ‘Swimmers Plot’. The graph will 
indicate the point in time the best response is reached, the best response (complete response vs. partial 
response), the number of prior treatment lines, and the reason for BTK inhibitor discontinuation in the 
last BTK inhibitor containing line. Moreover, the point in time MRD negativity is reached will be 
shown (see Section 4.9.3). For MRD negativity it will be differentiated between blood and bone 
marrow assessments, i.e., it will be indicated in the ‘Swimmers Plot’ when MRD negativity is reached 
as assessed in blood vs. bone marrow. 
 
4.4 
Baseline and Demographic Characteristics 
4.4.1 
Demography/Baseline Characteristics 
All summaries will be presented overall and by cohort in the FAS and SAF. For categorical variables, 
the number and percentage of patients with missing data will be provided. Demographic and baseline 
characteristics will include the following: 
 
age (both continuous and categorical, i.e., <65 and ≥65, <70 and ≥70) 
 
sex and race 
 
height and weight 
 
ECOG and disease staging (see section 4.4.2) 


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 
number of prior systemic treatment lines 
 
time since first CLL/SLL diagnosis (i.e., the interval between the date of first CLL/SLL 
diagnosis and the screening visit; reported in months)  
 
time on BTK inhibitor treatment (months) in the most recent prior therapy line containing a 
BTK inhibitor (not necessarily the last line before entering COSMOS). The following terms 
will be considered to find the last BTK-containing therapy line: ‘ibrutinib’, ‘imbruvica’, 
‘ACP-196’, ‘acalabrutinib’, ‘CC-292’, ‘AVL-292’, ‘ONO-40-59’, ‘BGB-3111’. The variable 
will be derived as follows: [(End of treatment date for the BTK inhibitor) – (Treatment start 
date for the BTK inhibitor) + 1]/30.4375. 
 
the number of patients with beta-2 microglobulin levels >3mg/L at baseline  (3 mg/L 
corresponds to 254.45 nmol/L). 
 
the number of patients with: 
o neutrophil count ≤1.5 x 109 cells/L at baseline  
o hemoglobin ≤11 g/dL at baseline 
o platelet count ≤100 x 109 platelets/L at baseline 
 
The last three items will be summarized for the FAS only. For the time on BTK inhibitor treatment in 
the most recent prior therapy line containing a BTK inhibitor the following imputations for missing 
start and stop dates will be made: If the day of the start or stop date is missing but the month is present 
the day will be imputed by the 15th of the month. If the month of the start or stop date is missing no 
imputations  will be done and the time on BTK inhibitor will be considered as missing.  
 
The demography and baseline characteristics assessed will also be listed by patient. 
Note: 
 
Weight recorded at all the cycles will be presented in the summary of vital signs; 
 
Baseline BMI will be calculated as: weight at baseline (kg)/squared height at Cycle 1 Day 1 
(m2). 
4.4.2 
Disease Staging 
The “Binet staging system” and “Modified Rai Clinical Stage” for disease staging information 
collected at baseline will be summarized by cohort. 
The Binet clinical staging system and the modified Rai clinical staging system for CLL/SLL comprise 
three stages (see Section 6.1). 
4.4.3 
FcγRII/III Gene Mucosal Cheek Swab 
Following subgroups will be defined: FcγRIIIa high affinity (FCGR3A-158V homozygosity) vs. 
FcγRIIIa low affinity (FCGR3A-158F homozygosity, or FCGR3A-158F/V heterozygosity). FcγRIIa 
high affinity (FCGR2A-131H homozygosity) vs. FcγRIIa low affinity (FCGR2A-131R homozygosity, 
or FCGR2A-131H/R heterozygosity). The number (%) of patients in each subgroup will be 
summarized by cohort. 
4.4.4 
Cytogenetic Risk 
Listings and tables for the mutational status of genes such as immunoglobulin heavy-chain variable 
gene (IGHV), NOTCH1, tumor protein p53 (TP53), BTK, phospholipase C γ2 (PLCγ2) will be 
presented. The tables will summarize the number and proportion of patients with mutations present in 
the aforementioned genes. 
Similarly, information will be provided for both translocations and deletions associated with 
prognosis. Genetic lesions or translocations will be determined by fluorescence in situ hybridization 


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(FISH).The number and proportion of patients with abnormal FISH results for the genetic regions 
17p13, 11q13, 13q14, 13q34, 14q32, 6q22-q23 will be presented.  The number (%) of patients with 
complex karyotype will be summarized. 
Listings will display detailed information on test results for each individual patient.  
 
4.5 
Medical History and Current Medical Conditions 
Medical History and Current Medical Conditions will be summarized by body system and by toxicity 
grade for each treatment group. Summaries will be produced using the SAF and FAS. 
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. 
 
4.6 
Prior and Concomitant Medications and Therapies 
Prior medications and concomitant medications will be summarized by cohort for the SAF and FAS 
using frequency distributions and percentages by Therapeutic Subgroup (2nd level of the Anatomical 
Therapeutic Chemical [ATC] classification) and Preferred Name. 
The medications will be classified according to the following rules: 
 
Prior medication: start date < date of start of treatment period and stop date ≤ date of start of 
treatment period 
 
Concomitant medication: date of start of treatment period ≤ start date < date of study 
completion/discontinuation 
 
Prior and Concomitant Medication: start date < date of start of treatment period and stop date 
> date of start of treatment period or ongoing 
The prior and concomitant medications will be listed by Therapeutic Subgroup (2nd level of the ATC 
classification) and Preferred Name for each patient. 
CLL/SLL-specific prior therapies: 
The best response and duration of response to the previous regimens patients received will be listed. 
Duration of Response (DoR) to previous regimens is defined as time (in months) from date of 
assessment of initial tumor response (CR or PR/PRL) to date of assessment of tumor progression (PD). 
A partial completion date of initial response and progression will be handled using the algorithm 
specified in section 4.14.1 (handling of missing data). Furthermore, the time since the completion of 
last regimen will be listed. Partial completion dates will be imputed using the algorithm specified in 
section 4.14.1 (handling of missing data). 
The number (%) of patients who received 1, 2, 3, etc. prior regimens will be provided. Descriptive 
statistics will also be provided for the last regimen patients received prior to study entry and the best 
response (n, %) and duration of response to last therapy (in months). The reason for discontinuation of 
prior BTK inhibitor will be listed and summarized. The following terms will be used to identify prior 
BTK inhibitor therapy: 
- ibrutinib and imbruvica 
- acalabrutinib and ACP-196 
- CC-292 and AVL-292 


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- ONO-40-59 
- BGB-3111 
 
Additionally, listings on CLL/SLL-specific surgeries, radiation, and stem cell transplantations will be 
presented. The number and proportion of patients who have experienced these procedures will be 
tabulated.  
4.7 
Study Treatment 
All analyses on study treatment will be conducted on the SAF and the FAS. 
4.7.1 
Duration of Exposure 
Exposure to combination treatment (i.e., both MOR00208 and idelalisib or venetoclax) and each 
individual study drug will be summarized for the FAS and the SAF. 
 
4.7.1.1 
Duration of Exposure to Each Individual Study Drug 
Duration of exposure to an individual study drug (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 in Cycle 4-6 a, and 28 days from Cycle 7 onwards. 
 
For idelalisib and venetoclax, the last date of exposure will be defined as the last date of 
administration. 
 
For idelalisib and venetoclax, temporary dose interruptions will not be considered for calculation. 
 
4.7.1.2 
Duration of Exposure to Combination Treatment (i.e., the combination of both 
MOR00208 and idelalisib/venetoclax at the same time) 
Duration of exposure to combination treatment (days) = (last date of exposure to both MOR00208 and 
idelalisib/venetoclax) – (date of first administration of study treatment) + 1. 
The last date of exposure for each individual drug is specified in Section 4.7.1.1.  
 
4.7.1.3 
Exposure Analysis 
 
The number of patients completing each cycle will be summarized and listed. 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 idelalisib or 
venetoclax if he/she was compliant for idelalisib or venetoclax administration during the cycle. 
 
Duration of exposure will be calculated for the following categories: Week (1-2], (2-4], (4-6], (6-
8], etc. Summaries (i.e., mean, standard deviation, etc.) will be displayed in weeks. 
 
Number of infusions with MOR00208 will be summarized.  
 
4.7.2 
Dose Reduction 
Dose reductions are only possible for venetoclax and idelalisib, but not for MOR00208. The number 
(%) of patients with any (i.e., permanent and transient) dose reduction will be summarized. For 
idelalisib, the number (%) of patients with a permanent reduction to 100 mg BID will be summarized. 
For venetoclax, the number of patient with a permanent reduction to 300 mg, 200 mg, or 100 mg will 


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be summarized. Moreover, the number (%) of patients who underwent no permanent reduction at all 
will be shown per cohort.   
 
4.7.3 
Dose Interruption 
The number (%) of patients with temporary interruptions and the associated reasons will be 
summarized for both study drugs split by cohort. 
 
4.7.4 
Treatment Compliance 
If the ratio (total used dose)/(total planned dose) is between 80% (exclusive) and 120% 
(inclusive) of the assigned dosage during a particular Cycle, then the patient is considered 
compliant for treatment. 
The planned dose and the used dose will be calculated based on information collected on the 
eCRF pages ‘Idelalisib Dosing Record’ or ‘Venetoclax Dosing Record’. As patients may 
change the daily dose, or transiently interrupt treatment, information on dosing will be 
represented differently in the eCRF for different situations: 
 
Patients who changed the Actual Total Daily Dose have two (or more) eCRF log lines for a 
particular Cycle or treatment period (during venetoclax ramp-up), i.e., one separate log line for 
each particular Actual Total Daily Dose. Each eCRF log line will contain information on the 
number of tablets dispensed, and the number of tablets returned. 
 
Patients who interrupted treatment and re-initiated treatment in the same Cycle (or same treatment 
phase during ramp-up) have two (or more) eCRF log lines. The Actual Total Daily Dose in each 
log line will be identical. All eCRF log lines will contain the information on the number of tablets 
dispensed, and the last log line will contain the information on the number of tablets returned. 
 
Patients who interrupted treatment, and only re-initiated treatment at the beginning of the next 
Cycle or next treatment period (during venetoclax ramp-up) will have one eCRF log line 
containing all information on Actual Total Daily Dose, number of tablets dispensed, and number 
of tablets returned. 
 
Compliant patients will display only one eCRF log line for a particular cycle, or treatment phase. 
The number of days on treatment for a particular Actual Total Daily Dose (represented by an 
individual eCRF log line) is calculated as follows: 
(Dosing Stop Date – Dosing Start Date) + 1. 
The number of days on treatment will be derived for every single eCRF log line. 
 


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Idelalisib 
Idelalisib is dispensed in 28-day Cycles. The administration is bi-daily (100 mg BID or 150 
mg BID). Compliance will be calculated based on the total planned dose, and the total dose 
actually used. 
 
The total planned dose per Cycle can be calculated as follows:  
 
o For Cycles with one eCRF log line: 
Actual Total Daily Dose as entered in the eCRF [mg] x Number of days on treatment. 
 
o For Cycles with two or more eCRF log lines (two log lines in case of one dose change, or 
treatment interruption with re-initiation in the same Cycle): 
E.g., for two log lines: 
(Actual Total Daily Dose as entered in the eCRF [mg] in log line 1 x Number of days on 
treatment in log line 1) + (Actual Total Daily Dose as entered in the eCRF [mg] in log line 2) 
x (Number of days on treatment in log line 2). 
 
Note: Actual Total Daily Dose may be identical for different log lines (in case of 
interruption), or different in case of dose change. 
 
 
The total dose used per Cycle can be derived as follows: 
 
o For Cycles with one eCRF log line: 
(Actual Total Daily Dose as entered in the eCRF [mg] / 2) x (Number of tablets dispensed – 
Number of tablets returned). 
 
o For Cycles with two or more eCRF log lines: 
 
 All log lines contain information on the number of tablets dispensed, and number of 
tablets returned (in case of dose change): 
E.g., for two log lines: 
[(Actual Total Daily Dose as entered in the eCRF [mg] in log line 1 / 2) x (Number of 
tablets dispensed in log line 1 – Number of tablets returned in log line 1)] +  
[(Actual Total Daily Dose as entered in the eCRF [mg] in log line 2 / 2) x (Number of 
tablets dispensed in log line 2 – Number of tablets returned in log line 2)]. 
 
 All log lines for a particular Cycle contain the information on the number of tablets 
dispensed, and only the last log line for a particular Cycle contains number of tablets 
returned (in case of treatment interruption and re-initiation of treatment in the same 
Cycle): 
E.g., for two log lines: 
[(Actual Total Daily Dose as entered in the eCRF [mg] in log line 1 / 2) x (Number of 
tablets dispensed in log line 1)] - [(Actual Total Daily Dose as entered in the eCRF [mg] 
in log line 2 / 2) x (Number of tablets returned in log line 2)]. 
 
 
Calculation of compliance for a particular Cycle (%): 


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(sum of total dose used for all log lines pertaining to a particular Cycle) / (sum of total planned 
dose for all log lines pertaining to a particular Cycle) * 100. 
 
Venetoclax 
The planned daily doses of venetoclax in the ramp-up phase and beyond are as follows: 
 
20 mg 1st week (study days 8 to 14) 
 
50 mg 2nd week (study days 15 to 21) 
 
100 mg 3rd week (study days 22 to 28) 
 
200 mg 4th week (study days 29 to 35) 
 
400 mg 5th week and thereafter (study days 36 and above) 
 
Different tablet strengths are being used to target a particular Actual Total Daily Dose: 
 
20 mg daily: 2 x 10 mg tablet (i.e., 14 tablets for 7 days) 
 
50 mg daily: 1 x 50 mg tablet (i.e., 7 tablets for 7 days) 
 
100 mg daily: 1 x 100 mg tablet (i.e., 7 tablets for 7 days) 
 
200 mg daily: 2 x 100 mg tablet (i.e., 14 tablets for 7 days) 
 
300 mg daily: 3 x 100 mg tablet (i.e., 84 tablets for 28 days) 
 
400 mg daily: 4 x 100 mg tablet (i.e., 112 tablets for 28 days, or 84 tablets for 21 days) 
 
For an Actual Total Daily Dose beyond 100 mg, only tablets of strength 100 mg are being 
administered. That is, depending on the Actual Total Daily Dose, multiples of these tablets of strength 
100 mg are used for treatment.  
The fact that different tablet strengths are used to target a particular Actual Total Daily Dose requires a 
correction factor (named Factor X) to derive the correct total dose used (see below): 
 
Factor X = 1: for log lines with an Actual Total Daily Dose of 50 mg or 100 mg. 
 
Factor X = 2: for log lines with an Actual Total Daily Dose of 20 mg or 200 mg. 
 
Factor X= 3: for log lines with an Actual Total Daily Dose of 300 mg. 
 
Factor X=4: for log liens with an Actual Total Daily Dose of 400 mg. 
 
Venetoclax is dispensed weekly during ramp-up, or in 28 days Cycles after ramp-up. Compliance will 
be calculated on the basis of the planned dose and actual total dose used per Cycle. 


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 
The total planned dose for a particular treatment period (e.g., one week treatment with a particular 
dose during ramp up) can be calculated as follows:  
 
o For patients and Cycles with one eCRF log line: 
Actual Total Daily Dose as entered in the eCRF [mg] x Number of days on treatment. 
 
o For patients and Cycles with two or more eCRF log lines (e.g., two log lines in case of one 
dose change, or treatment interruption with re-initiation in the same Cycle): 
E.g., for two log lines: 
[(Actual Total Daily Dose as entered in the eCRF [mg] in log line 1) x (Number of days on 
treatment in log line 1)] + [(Actual Total Daily Dose as entered in the eCRF [mg] in log line 
2) x (Number of days on treatment in log line 2)]. 
 
Note: Actual Total Daily Dose may be identical for different log lines (in case of 
interruption), or different in case of dose change. 
 
 
The total dose used per Cycle can be derived as follows: 
 
o For patients and Cycles with one eCRF log line: 
(Actual Total Daily Dose as entered in the eCRF [mg] / Factor X) x (Number of tablets 
dispensed – Number of tablets returned). 
 
o For patients and Cycles with two or more eCRF log lines: 
 
 All log lines contain information on the number of tablets dispensed, and number of 
tablets returned (in case of dose change): 
[(Actual Total Daily Dose as entered in the eCRF [mg] in log line 1 / Factor X) x (Number 
of tablets dispensed in log line 1 – Number of tablets returned in log line 1)] +  
[(Actual Total Daily Dose as entered in the eCRF [mg] in log line 2 / Factor X) x (Number 
of tablets dispensed in log line 2 – Number of tablets returned in log line 2)]. 
 
 All log lines for a particular Cycle contain the information on the number of tablets 
dispensed, and only the last log line for a particular Cycle contains the information 
on number of tablets returned (in case of treatment interruption and re-initiation of 
treatment in the same Cycle): 
[(Actual Total Daily Dose as entered in the eCRF [mg] in log line 1 / Factor X) x (Number 
of tablets dispensed in log line 1(] - [(Actual Total Daily Dose as entered in the eCRF 
[mg] in log line 2 / Factor X) x (Number of tablets returned in log line 2)]. 
 
Calculation of compliance for a particular Cycle (%): 
(sum of total dose used for all log lines pertaining to a particular Cycle) / (sum of total planned 
dose for all log lines pertaining to a particular Cycle) * 100. 
 
MOR00208 
A patient will be considered compliant with the protocol if the MOR00208 dose administered is >80% 
and ≤120% of the planned dosage per single infusion. Therefore MOR00208 compliance will be 
presented for each infusion.  


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Furthermore, MOR00208 dosage will be summarized by cycle as well. The total administered dose per 
cycle will be divided by the total planned dose per cycle. One MOR00208 dose can be missed between 
Cycles 1-3, between Cycles 4-12 and one dose between Cycles 13-24 without the patient being non-
compliant (skipped doses of MOR00208 due to toxicity will not be considered for calculation of 
compliance). 
A summary displaying the number and percentage of patients in the following categories will also be 
presented for each study drug, and each cycle: 
 
≤80% 
 
>80 – 120% 
 
>120% 
 
4.8 
Efficacy Analysis 
4.8.1 
Secondary Endpoint 
Single efficacy variable analyzed in this study is: Best Objective Response Rate (ORR) 
(Best) ORR is defined for Cohort A as percentage of patients achieving a complete response (CR), a 
partial response (PR) or a partial response with lymphocytosis (PRL) at any time during the study, and 
for Cohort B as percentage of patients achieving a CR or a PR at any time during the study based on 
the local assessment. CR, PR or a PRL is defined according to the criteria of the International 
Workshop on Chronic Lymphocytic Leukemia (IWCLL) for CLL patients (Hallek et al., 2008; see 
Section 6.3), with the modification that treatment-related lymphocytosis in the absence of other signs 
or symptoms of disease progression will not be considered as progressive disease (Cheson et al., 2012; 
Hallek et al., 2012; NCCN NHL 2015 Guidelines). For patients with SLL, assessments will be 
performed using the Lugano Classification criteria for SLL patients (Cheson et al., 2014). The number 
of patients and rates will be reported split by cohort. 
For derivation of the best ORR, response assessments after a patient has started a new anti-neoplastic 
therapy will not be taken into account. 
Response evaluations (CR, PR, PRL, SD and PD) will be tabulated with counts and percentages for 
each available visit. Missing response evaluations, or non-evaluable assessments will be taken into 
account, with patients with missing responses included in the denominator for calculating rates. 
The above summary/analysis will be performed using the FAS and PPS. 
 
4.9 
Additional Analyses 
4.9.1 
Immunogenicity Analysis 
 
1. The results of the anti-MOR00208 antibody assessment will be listed for each anti-
MOR00208 sample analyzed. The analysis will be performed using the IAS. 
 
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. 
Furthermore, the absolute number and percentage of the following categories will be tabulated by 
visit: 
2. Patient has positive anti-MOR00208 antibodies (yes/no/missing):  
 yes, if a titer is available  
 no, if result is reported as negative  
 missing, if anti-MOR00208 measurement is not available  


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3. In addition, the absolute number and percentage of patients who develop anti-MOR00208 
antibodies will be tabulated using the following categories: 
 yes, if the patient has at least one positive post-baseline sample containing 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 
 
4. Results (n, mean, StD, median, minimum, maximum) of semi-quantitative anti-MOR00208 
antibody titer determinations of confirmed positive samples assessments will be tabulated by 
visit. 
4.9.2 
Pharmacokinetic Analysis 
Individual plasma samples for the analysis of MOR00208 PK will be collected on various study days. 
For evaluation of PK metrics, patients will be considered who have at least one quantifiable 
MOR00208 serum concentration (the PK analysis set, PKAS). 
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.  
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, standard deviation, geometric mean, coefficient of variation (CV), median, 
minimum and maximum. The CV will be expressed as a percentage and calculated as follows: 
 
CV of the arithmetic mean (%) = standard deviation/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 ± standard deviation (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 (in days) 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 the average concentration 1 hour post-dose of Cycle 3 Day 1 (i.e. the 10th dose) with the 


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corresponding mean from the previous visit for which MOR00208 concentration data is available 
using analysis of variance (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. 
Furthermore, additional PK sample assessment may be performed to determine bioactive MOR00208 
serum concentrations. These MOR00208 serum concentrations will only be reported in listings and 
none of the above described PK analyses (tables, figures) will be performed using these bioactive 
MOR00208 serum concentrations.  
4.9.3 
Assessment of MRD Response 
Patients who develop a PR or CR will be assessed using MRD testing from peripherial blood (PB) at 
C1D1, C4D1, C7D1, C13D1, etc. until bone marrow (BM) MRD negativity was confirmed. An 
additional PB sample will be obtained from CR patients at the time when CR is confirmed by CT 
outside of the scheduled radiological examinations. Additionally, patients with CR or PR will be 
further assessed for MRD negativity status from bone marrow (aspirate) at least 8 weeks after the PB 
MRD negativity was detected (for patients with CR only after CR has been confirmed by CT/MRI 
scan).  
The results of MRD testing for CR and PR patients (MRD positivity/MRD negativity assessed in PB; 
MRD positivity/MRD negativity assessed in BM) will be tabulated with counts and percentages for 
each available visit and overall. The median time to MRD negativity assessed in PB and BM will be 
calculated for CR and PR patients (including only patients who reached MRD negativity).  
4.9.4 
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. A separate validation plan and standard operating procedures (SOPs) for the flow 
cytometry based biomarkers will be generated that provide details on samples handling, processing 
and methods used for sample analysis. 
Biomarker assessments will be tabulated by descriptive statistics. Summaries for baseline values will 
be provided for the following variables: 
 
CD16 molecules on CD16+CD56+ NK cells (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/µl at baseline (continuous  variable) 
 
Longitudinal analyses:  
Longitudinal analyses will be conducted separately for:  
o Peripheral numbers of NK cells 
o B cells (defined as the sum of the following cell populations: “Abs_B cell_CD5+ 
[T3]” and “Abs_B cell_CD5neg [T3]”) 
o T cells 


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o CD19 
molecules 
on 
CD5-positive 
B 
cells 
(defined 
as 
“CD19mol/CD5+CD19+Bcells_BL” or “CD19mol/CD5+22neg19+_BL” at Cycle 1 
Day 1, and as “CD19mol/CD5+22neg19+_AW” at following visits) 
o CD19 
molecules 
on 
CD5-negative 
B 
cells 
(defined 
as 
“CD19mol/CD5neg22neg19+_BL” 
at 
Cycle 
1 
Day 
1, 
and 
as 
“CD19mol/CD5neg22neg19+_AW” at following visits) 
 
The following summaries and graphs will be produced:  
o Summary statistics per visit (a 95% confidence interval for the median will be derived 
by bootstrapping) 
o Summary for the 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 by treatment 
(without confidence interval) will be shown. 
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 by treatment. 
o Graphical illustration showing boxplots for both absolute values and relative change 
per visit across all patients assessed by treatment. 
 
All biomarker analyses will be conducted on the FAS. 
 
4.10 Safety Analysis 
The analysis of safety assessment in this trial will include summaries of the following categories of 
safety and tolerability data collected for each patient: 
 
Adverse Events (number and severity) 
 
Treatment-emergent adverse events (TEAEs) 
 
Treatment-emergent serious adverse events (SAEs) 
 
TEAEs by maximum toxicity grade 
 
TEAEs by intensity 
 
Drug related TEAEs 
 
TEAEs leading to discontinuation of treatment 
 
TEAEs leading to any action on study medication (i.e., interruption, dose reduction, 
permanent discontinuation) 
 
Treatment-emergent AESI  
 
TEAEs leading to death 
 
Vital signs: systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate, 
pulse rate and temperature 
 
Physical Examination 
 
12-lead ECG parameters: PR, QRS, RR and QT interval values 
 
Laboratory safety evaluations (blood chemistry, hematology, coagulation, urinalysis) 
 
ECOG Performance Status 


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 
B-symptoms 
All safety variables will be summarized using the SAF split by actual treatment. 
 
4.10.1 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. 
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 (CLL/SLL) do not fall under the definition of AEs. 
Each AE will be reported to determine the following: 
 
Relationship to the study drug(s) (suspected/not-suspected) 
 
Duration (start and end date, or if continuing at end of study) 
 
NCI-CTCAE Grade (see 4.10.1.5) 
 
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) 
 
Outcome (i.e., Not Recovered/Not Resolved, Recovered/Resolved, Recovered/Resolved with 
sequelae, Recovering/Resolving, Fatal, Unknown) 
 
Action taken with study drug(s) 
 
no action taken 
 
study drug temporarily interrupted 
 
study drug permanently discontinued due to this AE 
 
Other action taken (medication taken; non-drug therapy given; hospitalisation/ prolonged 
hospitalisation) 
 
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 CLL/SLL 
o Elective or pre-planned treatment for a pre-existing condition that is unrelated to 
CLL/SLL and has not worsened since signing of the ICF 


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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 
 
4.10.1.1 Treatment-emergent adverse events (TEAEs) 
An on-treatment adverse event (or Treatment-emergent Adverse Event – TEAE) is defined as: 
- 
An adverse event that occurred in the following time interval (including the lower and upper 
limits):  
o date of first administration of study treatment 
o until 30 days after last study drug administration 
- 
An adverse event present prior to the study treatment start but increased in severity after 
treatment start. 
- 
An adverse event occurring or worsening later than 30 days after the last treatment if 
suspected to be related to the study drug. 
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 AE present prior to the study treatment start but increased in severity after treatment start, will also 
be included as TEAE. 
The handling of partially of completely missing AE start and end dates/times in the determination of 
the status of the AE is described in detail in Section 4.14.1. 
 
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 highest toxicity 
grade/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. 
 
4.10.1.2 Adverse events of special interest 
AEs of special interest (AESIs) for MOR00208 are: tumor lysis syndrome (TLS), infusion-related 
reactions (IRRs) and allergic reactions to study drug ≥ grade 3, cytokine release syndrome and 
overdoses of MOR00208. 
AEs of special interest (AESIs) for idelalisib are: Diarrhea/colitis ≥ grade 3, pneumonitis ≥ grade 3 
and elevation of hepatic enzymes ≥ grade 3, Pneumocystis jirovecii pneumonia (PJP), 
Cytomegalovirus (CMV) infections, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis 
(TEN) and overdoses. 
AEs of special interest (AESIs) for venetoclax are: TLS, neutropenia with infection or fever ≥ grade 
3 and overdoses. 
Unlike routine safety assessments, SAEs and AESIs are monitored continuously and have special 
reporting requirements. 
 


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4.10.1.3 Relationship to study drug 
The Investigator should determine the causality (relationship to the study drug) based on his/her 
clinical experience and on the information given in the Investigator’s Brochure (IB) for MOR00208 
and the SmPC/prescribing information for idelalisib/venetoclax. 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. 
 
4.10.1.4 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). 
 
4.10.1.5 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: 
 
Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
 
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 
 
Grade 4: life-threatening consequences; urgent intervention indicated 
 
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). 
 
4.10.1.6 General rules for reporting 
4.10.1.6.1 AE tables 
i. 
All safety analyses will be done using the Safety Set and will be presented by cohort, and 
overall across both cohorts 
ii. 
The incidence of treatment-emergent AEs will be summarised in incidence tables.  
iii. 
AEs will be summarised by SOC and PT using the Medical Dictionary for Regulatory 
Activities (MedDRA) version 19.0 and will be updated to the most current version at the end 
of the trial. The SOCs and PTs will be used for tabulation. 
iv. 
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). 


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v. 
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. 
vi. 
If a patient reported more than one AE with the same preferred term, the AE with the 
maximum toxicity grade will be presented.  
vii. 
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.  
viii. 
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.  
ix. 
All safety variables will be summarized using the SAF split by actual treatment. 
 
4.10.1.6.2 AE listings 
i. 
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. 
ii. 
Special AE listings displaying details of the event(s) captured on the eCRF in a compact 
format will be provided for:  
 
Treatment-emergent Serious Adverse Events. 
 
TEAEs suspected to be related to study drug 
 
Treatment-emergent SAEs suspected to be related to study drug 
 
TEAEs of toxicity grade 3 or grade 4. 
 
TEAEs leading to interruption of treatment (split by MOR00208, idelalisib/venetoclax, both 
MOR00208 and idelalisib/venetoclax, and any study drug). 
 
TEAEs leading to discontinuation of treatment (split by MOR00208, idelalisib/venetoclax, 
both MOR00208 and idelalisib/venetoclax, and any study drug). 
 
TEAEs of special interest. 
 
AEs leading to death (i.e., AEs of grade 5). 
 
Pre-treatment AEs (for subjects that were successfully screened but not treated). 
iii. 
All AEs will be listed by patient, along with information regarding onset, end date (if not 
ongoing), relationship to study drugs, intensity, toxicity grade, action taken with study drug, 
and outcomes. This listing will be generated for all patients enrolled. 
 
4.10.1.7 AE summaries 
4.10.1.7.1 TEAEs (serious and non-serious) 
The following summaries will be provided: 
i. 
All TEAEs regardless of study treatment relationship by primary SOC, PT and grade. 
ii. 
All TEAEs regardless of study treatment relationship by primary SOC, PT and 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.  


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vi. 
TEAEs regardless of study treatment relationship starting in Cycle 1 (reported for Cohort A 
only). 
vii. 
TEAEs regardless of study treatment relationship starting before Cycle 2 Day 15 (reported for 
Cohort B only). 
viii. 
TEAEs suspected to be related to the study drug by primary SOC, PT and grade (split by 
MOR00208, idelalisib/venetoclax, both MOR00208 and idelalisib/venetoclax, or any study 
drug). 
ix. 
TEAEs suspected to be related to the study drug by primary SOC, PT, and intensity (split by 
MOR00208, idelalisib/venetoclax, both MOR00208 and idelalisib/venetoclax, or any study 
drug). 
x. 
TEAEs suspected to be related to the study drug of ≥ grade 3 by primary SOC, PT and grade 
(split by MOR00208, idelalisib/venetoclax, both MOR00208 and idelalisib/venetoclax, or any 
study drug). 
xi. 
TEAEs suspected to be related to the study drug of grade 3 or grade 4 by primary SOC, PT 
and 
grade 
(split 
by 
MOR00208, 
idelalisib/venetoclax, 
both 
MOR00208 
and 
idelalisib/venetoclax, or any study drug). 
xii. 
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, idelalisib/venetoclax, both 
MOR00208 and idelalisib/venetoclax, or any study drug). 
xiii. 
TEAEs leading to any action on MOR00208, on idelalisib/venetoclax, on both MOR00208 
and idelalisib/venetoclax, or any study drug regardless of study treatment relationship by 
primary SOC, PT and grade. 
Note: Any Action = Dose reduction/Dose interruption/Permanent discontinuation. 
xiv. 
TEAEs leading to discontinuation of treatment (split by MOR00208, idelalisib/venetoclax, 
both MOR00208 and idelalisib/venetoclax, or any study drug) regardless of study treatment 
relationship by primary SOC, PT and grade. 
xv. 
TEAEs leading to interruption of treatment (split by MOR00208, idelalisib/venetoclax, both 
MOR00208 and idelalisib/venetoclax, or any study drug) regardless of study treatment 
relationship by primary SOC, PT, and grade. 
xvi. 
Most frequent non-serious TEAEs, regardless of study treatment relationship by primary SOC, 
PT and grade (at least 5% incidence). 
 
4.10.1.7.2 Treatment-emergent SAEs 
The following summaries on treatment-emergent SAEs will be provided: 
 
Treatment-emergent SAEs regardless of study treatment relationship, by primary SOC, PT and 
grade.  
 
Most frequent treatment-emergent SAEs (at least in 2% of the patients) regardless of study 
treatment relationship, PT and grade. 
 
Treatment-emergent SAEs starting in Cycle 1 for Cohort A. 
 
Treatment-emergent SAEs starting before Cycle 2 Day 15 for Cohort B. 
 
Treatment-emergent SAEs regardless of study treatment relationship ≥ grade 3 by primary SOC, 
PT and grade.  
 
Treatment-emergent SAEs of grade 3 or grade 4 regardless of study treatment relationship by 
primary SOC, PT and grade.  
 
Treatment-emergent SAEs suspected to be related to the study drug by primary SOC, PT and 
grade (split by MOR00208, idelalisib/venetoclax, both MOR00208 and idelalisib/venetoclax, and 
any study drug). 


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 
Treatment-emergent SAEs suspected to be related to the study drug ≥ grade 3 by primary SOC, 
PT, 
and 
grade 
(split 
by 
MOR00208, 
idelalisib/venetoclax, 
both 
MOR00208 
and 
idelalisib/venetoclax, and any study drug). 
 
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, idelalisib/venetoclax, both MOR00208 and 
idelalisib/venetoclax, and any study drug). 
 
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, idelalisib/venetoclax, both 
MOR00208 and idelalisib/venetoclax, and any study drug). 
 
Treatment-emergent SAEs of grade 5 by primary SOC and PT. 
 
4.10.1.7.3 AESIs 
Treatment-emergent AEs of special interest will be presented by primary SOC, PT and grade. 
 
4.10.1.7.4 Deaths 
All deaths will be summarized as follows: 
 
Deaths related to disease progression as indicated on the ‘End of Treatment’ eCRF page: 
o Any 
entry 
containing 
the 
phrase 
“PROGRESSIVE 
DISEASE” 
or 
“DISEASE 
PROGRESSION” or “LYMPHOMA PROGRESS” in the log line ‘Primary Reason: Death, 
please specify cause of death’ will indicate PD-related deaths. 
 
Deaths unrelated to disease progression as indicated on the ‘End of Treatment’ eCRF page: 
o All other deaths that are not considered as related to disease progression. 
 
4.10.1.7.5 Overall AE summary table 
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 regardless of study treatment relationship. 
 
At least one treatment-emergent SAE regardless of study treatment relationship. 
 
Deaths (split by related to disease progression vs. unrelated to disease progression). 
 
At least one treatment-emergent SAE suspected to be related (split by MOR00208, 
idelalisib/venetoclax, both MOR00208 and idelalisib/venetoclax, or any study drug). 
 
At least one TEAEs suspected to be related to the study drug by grade (split by MOR00208, 
idelalisib/venetoclax, both MOR00208 and idelalisib/venetoclax, or any study drug). 
 
At least one TEAE suspected to be related to the study drug with grade 3 or grade 4 (split by 
MOR00208, idelalisib/venetoclax, both MOR00208 and idelalisib/venetoclax, or any study drug). 
 
At least one TEAE suspected to be related by intensity (split by MOR00208, idelalisib/venetoclax, 
both MOR00208 and idelalisib/venetoclax, or any study drug).  
 
At least one treatment-emergent AESI. 
 
At least one TEAE leading to any action on MOR00208, on idelalisib/venetoclax, on both 
MOR00208 and idelalisib/venetoclax, or on any study drug). 
Note: Any Action = Dose reduction/Dose interruption/Permanent discontinuation. 
 
TEAEs leading to discontinuation of treatment (split by MOR00208, idelalisib/venetoclax, both 
MOR00208 and idelalisib/venetoclax, or any study drug). 


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 
SAEs of grade 5. 
 
At least one TEAE of PT ‘infusion-related reaction (IRRs)’ of ≥ grade 3 by grade. 
 
4.10.2 Vital Signs 
Systolic and diastolic blood pressure (mmHg), heart rate (beats per min), respiratory rate (breaths per 
min) and temperature assessed will be descriptively summarized using the SAF. The vital signs data 
will be listed by patient and date of assessment. Each abnormal value will be flagged to show whether 
it is a value below or above the normal limit. Normal ranges for vital signs will be defined as follows: 
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 
 
4.10.3 Physical Examination 
A complete physical examination (PE) will be performed at screening and at the end of the treatment 
period. 
Limited PEs may be focused on tumor response assessment (lymph nodes, liver, spleen, etc.) and AEs 
(e.g. attention on respiratory signs and symptoms) at the Investigator’s discretion. Such limited PEs 
will be performed as indicated in the Schedule of Assessments (Table 1). Limited PE will be 
performed on Day 1 and 15 of Cycle 1 to 6, and on Day 1 of all further cycles. Symptom-driven full 
PEs may be performed as clinically indicated at any study visit. 
The number and percentage of patients experiencing an abnormal physical examination finding will be 
presented per body system using the SAF. Physical examination assessments will be listed per body 
system by patient and date of assessment.  
 
4.10.4 12-lead ECG 
Summary ECG assessments (normal; abnormal clinically significant; abnormal not clinically 
significant) will be tabulated by time point (visit) using frequencies. 
ECGs will be shown in a listing and overall interpretations will be flagged to show whether the ECG is 
considered normal; abnormal clinically significant; abnormal not clinically significant. Each abnormal 
PR, QRS, RR and QT interval value will be flagged to show whether it is a value below or above the 
normal limit. The following normal ranges will be applied: 
 
PR interval: 110-220 ms  
QRS interval: 60-120 ms 
RR interval: 600-1200 ms  
QT interval: ≤ 400 ms 
Descriptive summaries of actual values and changes from baseline will be presented by visit for ECG 
measures of RR interval, PR interval, QRS interval, and QT interval. The number of patients having a 
QT interval > 500 ms will be summarized by visit. 
 


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4.10.5 Laboratory Findings 
Descriptive statistics for Clinical laboratory data will be summarized. Actual values and the change 
from baseline will also be summarized along with the numbers of patients with values outside limits of 
the normal range at each timepoint. The laboratory analysis tables will be presented using the SAF. 
Shift tables of baseline to the worst post baseline toxicity grade in chemistry and hematology tests will 
be provided. For a given patient, if the toxicity grade is missing for all post baseline assessments for 
one laboratory test, the patient will be counted only once for that laboratory test under the “Missing” 
toxicity grade category.  
Laboratory toxicities will be graded according to National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE), version 4.03 or higher. 
If a patient has both missing and non-missing toxicity grades for one laboratory test, the missing 
toxicity grade of that laboratory test will be treated as the lowest grade. For each test condition, 
percentages are calculated based on the number of patients in the SAF population who have a baseline 
and at least one post-baseline assessment. 
Laboratory tables and listings will be based on the safety analysis set. Pregnancy test results will be 
only listed. 
The laboratory parameters displayed in Table recorded at Screening and during the treatment and 
additional treatment period will be used for listing and table summary. 
Abnormal values will be flagged to indicate whether the value is below or above the reference range 
and whether investigators assessed the abnormal value as clinically significant. A clinically significant 
result can be commented with “Adverse Event”, “Due to primary disease”, “Pre-existing condition and 
not worsened according to CTCAE 4.03” or free text. 
 
Table 4: Safety Laboratory Evaluations 
Evaluation 
Analysis 
“Emergency laboratory” 
(EDTA blood and serum 
sample) 
 
AST, ALT, bilirubin (total, direct and indirect), direct Coombs test, 
hemoglobin, platelets, potassium, serum creatinine, sodium, WBCs, 
including WBC differential (including ANC) 1 
Cohort B only: Additional values to be analyzed: calcium, creatinine,  
inorganic phosphorus (phosphate), potassium and uric acid 
Hematology 
(EDTA blood) 
Direct Coombs test, erythrocyte count (RBC count), hematocrit, 
hemoglobin, mean corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration, mean corpuscular volume, platelet count,  
reticulocytes, WBC with differential count (absolute counts and % of 
leukocytes: basophils, eosinophils, lymphocytes, monocytes, 
neutrophils) 
At screening: should include a peripheral blood smear. 
 
Serum chemistry 
(serum sample) 
ALT, total albumin, ALP, amylase, AST, β2-microglobulin, 
bicarbonate, bilirubin (total, direct and indirect), blood urea nitrogen, 
calcium (total), chloride, cholesterol, creatinine, creatinine kinase, 
GGT, glucose, LDH, lipase, magnesium, phosphate, potassium, 
protein (total), serum CrCl calculated using a standard Cockcroft-
Gault formula2, sodium, triglycerides, uric acid 
 
Coagulation parameters 
(sodium citrate blood) 
 
Activated partial thromboplastin time, prothrombin time, 
international normalized ratio 


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4.10.6 ECOG Scores Analyses 
The analysis of ECOG scores will be performed on the 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. 
Listings showing ECOG scores will be generated. 
4.10.7 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 the SAF. Data listings will be presented. 
 
4.11 Other Data 
All other data collected in the eCRF will be listed. 
 
4.12 Protocol Deviations 
Key protocol deviations will be summarized overall and by center and grouped into the following 
categories prior to database lock:   
 
   Prohibited concomitant medication 
Viral parameters 
(serum or plasma sample) 
Hepatitis B: HBsAg, anti-HBc and HBsAb. HBV DNA if anti-HBc 
positive, optional  
Hepatitis C: HCV antibody (HCV RNA quantification if anti-HCV 
positive) 
CMV: CMV antibody and CMV copy number per mL (PCR based) 
HIV-1/-2 Ag and Ab Screening (HIV-1/-2 Ab differentiation if HIV 
positive) 
Pregnancy test  
(serum sample) 
 
β-HCG serum, females of childbearing potential only 
Pregnancy test  
(urine) 
 
β-HCG urine, females of childbearing potential only 
Urinalysis 
Clarity (clear, slightly cloudy, cloudy, turbid), bilirubin, color, 
glucose, hemoglobin, ketones, leukocyte esterase, nitrite, pH, 
protein, specific gravity, urobilinogen. 
Microscopy will only be performed if clinically indicated. 
 
Abbreviations: ALP= alkaline phosphatase; ALT=alanine transaminase; anti-HBc=hepatitis B core 
antibody;  ANC=absolute neutrophil count; AST=aspartate amino-transferase; β-HCG=beta-human 
chorionic gonadotropin; CMV=Cytomegalovirus; CrCl=creatinine clearance; DNA=deoxyribonucleic 
acid; EDTA=ethylenediaminetetraacetic acid; GGT=gamma-glutamyltransferase; HBsAb=hepatitis B 
surface antibody; HBsAg=hepatitis B surface antigen; HBV=hepatitis B virus; HIV=human 
immunodeficiency virus; LDH=lactate dehydrogenase;  PCR=polymerase chain reaction;  RNA= 
ribonucleic acid; 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. 
2For the Cockcroft-Gault formula, see Appendix B. 


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 
   Informed consent form 
 
   Eligibility criteria 
 
   Laboratory assessment 
 
   Procedure or test 
 
   Study drug and treatment 
 
   Visit schedule and assessment 
   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. 
Protocol deviations leading to exclusion from the PPS will be identified before database lock. Those 
protocol deviations leading to exclusion from the PPS will be tabulated and listed for the FAS. All key 
protocol deviations will be listed. 
 
4.13 Independent Data Monitoring Committee  
An IDMC will be established by the sponsor to review the safety run-in phase and accumulating safety 
data at regular intervals throughout the study and monitor overall study conduct. The IDMC will also 
evaluate results of a futility analysis described in Section 12.10 of the Clinical Study Protocol. The 
IDMC will be composed of experts in the field of oncology and clinical biostatistics who have no 
other role in the study and do not have an affiliation with the Investigators or the sponsor. Based on 
the safety and efficacy data, the IDMC recommends in writing to the sponsor whether or not to stop 
the clinical study or a specific cohort. The IDMC’s specific duties as well as statistical monitoring 
guidelines and procedures will be fully described in an IDMC Charter. 
 
4.14 Handling of Missing Data and Outliers 
4.14.1 Missing Data 
The number of patients with missing data will be presented under a “Missing” category. Missing 
values will be included in the denominator count when computing percentages. 
When continuous data are being summarized, only the non-missing values will be evaluated for 
computing summary statistics. 
Efficacy analyses: 
In the responder analysis (ORR), patients with missing data will be considered as non-responders. 
Analyses on previous and concomitant medications: 
In case of missing or incomplete dates not directly allowing allocation to any of the categories of 
medications, a worst-case allocation will be done according to the available parts of the start and the 
end dates for: 
 
Concomitant medication 
 
Medication maintained during the treatment period 
 
Post-study medication 
 
Previous medication 
 
Safety analyses: 


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In case of missing or incomplete dates not directly allowing allocation to any of the categories of AEs, 
a worst-case allocation will be done according to the available parts of the start and the stop dates. The 
AE will be allocated to the first category allowed by the available data, according to the following 
order: 
 
 Treatment-emergent 
 
 Post-study 
 
 Pre-treatment 
Other critical missing data, if any, will be discussed during the review of the data. Decisions will be 
fully documented. 
The following approach will be taken to impute only partially completed dates 
 
Only for AESI: If the start time of an AESI is missing but the start date is complete, this AESI 
will only be excluded from treatment-emergent AEs if start day is before day of first treatment 
or start day is after end day of treatment-emergent period. 
 
If the start day is missing but the start month is complete, an AE will only be excluded from 
treatment-emergent AEs if start month is before month of first treatment or start month is after 
end month of treatment-emergent period or if stop date (and time in case of an AESI) is before 
start of first treatment. 
 
If start day and month are missing but the start year is complete, an AE will only be excluded 
from treatment-emergent AEs 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 (and time in case of an AESI) is 
before start of first treatment. 
If start date is completely missing, an AE will not be excluded from treatment-emergent AEs unless 
the stop date (and time in case of an AESI) is before start of first treatment. 
Time since first CLL/SLL diagnosis: 
The time since first CLL/SLL diagnosis (reported in months), i.e., the interval between date of first 
diagnosis and Screening Visit, will be summarized.If the date of diagnosis is incomplete, the time 
since first diagnosis will be calculated based on the latest possible date for the date of diagnosis: 
 
If the day is missing but the month is complete for date of diagnosis, the date will be amended 
using day 15 of that month (or the date of screening visit in case this is earlier) 
 
If the day and month are missing but the year is complete for date of diagnosis, the date will 
be amended using June 30 of that year (or the date of screening visit in case this is earlier) 
Duration of response to last previous therapy line: 
Duration of response for the last previous therapy is defined as the elapsed time between the date of 
first documented response (CR or PR) under this therapy and the date of documented progression after 
that.  
 
If day is missing for the date of initial response or the date of progression and month and year 
are present, the following worst case imputation will be done: the last day of the respective 
month will be used to amend the date of initial response and the first day of the respective 
month will be used to amend the date of progression. In case this approach leads to 
contradictive dates which can only happen if month and year are the same for both dates either 
the missing date the duration of response will be set to 1 day.   
 
If day and month for the date of initial response or the date of progression are missing the 
following worst case imputation will be done if it does not lead to contradictive dates: for 
initial response December 31st of the pertaining year will be used and for date of progression 
January 1st of the pertaining year. If a date of best overall response is present and it is before 
the imputed date of initial response this date will be used as a substitute. If the imputed days 
remain contradictive the duration of response will be set to 1 day. If year is missing for the 


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date of progression no imputation will be done and the duration of response will be treated as 
missing. If year is missing for date of initial response but a date of best overall response is (at 
least partially) present this date will be used for the calculation of duration of response. If both 
dates of initial and best overall response are missing no imputation will be done. 
Time since completion of last prior therapy: 
The following algorithm will be used to impute partially completed dates required to calculate the time 
since completion of the last prior therapy: 
 
If day and month are missing but year is available, then the imputed day and month will be 
January 1st or the starting date of the last regimen, whichever is later; 
 
If day is missing but the month and year are available, then the imputed day will be the first 
day of the month, or the starting date of the last regimen, whichever is later; 
 
If year is missing, no imputation will be done and the completion date will be treated as 
missing. 
 
4.14.2 Outliers 
No data will be excluded from the analyses, including any outliers. 
 
4.15 Data Handling for Laboratory Data 
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). 
 
4.16 Deviations from SAP 
Any deviations from the statistical plan will be described and justified in the final clinical study report. 
 
4.17 Changes in Conduct or Planned Analyses from the Protocol 
In the SAP a more detailed information was provided for both the definition of the FAS and the SAF. 
As per SAP the definition for the SAF was extended in a sense that the SAF is based on the treatment 
actually received. This extension of the definition is justified as the SAF will be used for all safety-
relevant analyses, which have to be interpreted in the context of the treatment that has been actually 
received. Moreover, for the SAF as per SAP the restriction that at least one post-baseline safety 
evaluation is required was added. 
 
4.18 Output Format 
All output will be produced using SAS version 9.4 or a higher version. 
In each table/listing, a table/listing number followed by the title of the table/listing will be presented. 
After the title line, optional sub-title or population information can be presented. Horizontal lines will 
appear before and after the column heading of the table/listing. Footnotes will be put under the main 
body of text at the bottom of the page. 
The following header will be used for all tables, listings and figures outlined in this document: 
MOR208C205 – 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 


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The SAS program name, source data, page number, date and time of creation of table/listing and the 
source listing number will be displayed on each table/listing. 
A landscape layout is proposed for both table and listing presentations. 
Tables and listings will be produced in rich text (RTF) format (i.e. they will tabular in format). 
The left and right margins of all tables and listings will be a minimum of 2.0 cm from the left and 2.0 
cm from the right. The top and bottom margins will be a minimum 2.0 cm. Header and footer will 
both be 1.27 cm. 
A 8-point font size for tables and 7or 8-point for listings is proposed using Courier New font. A 
maximum SAS line size=141 and page size=44 for 8-point font size, and line size=161 and page 
size=50 for 7-point will be used so as to fit on both UK and US paper sizes. 
In a listing, in the case that a patient’s record has been continued to the next page, an appropriate 
identification (e.g., the patient ID number) must be presented at the beginning of that page. 
 
4.19 Software 
 
SAS® Software Version 9.4 or a higher version. Institute Inc., Cary, NC, USA 
 
4.20 Quality Control of Outputs 
The following steps will be taking to ensure the quality of the outputs: 
 
The author of each table/listing/figure program will review the programs and will verify that 
no error message is highlighted in the ‘LOG’ file. 
 
Type A or Type B validation will be carried out for validating the TLGO and the datasets. 
Where Type A validation includes, but is not limited to: 
 
Independently writing code to produce a validation output. 
 
Using an electronic means of comparison (for example, SAS Proc Compare or UNIX 
diff command) to compare the data and/or output produced by the production 
programmer to the data and/or output produced by the Independent Validator. 
 
Visually inspecting the output to ensure that the layout, format and other cosmetic 
factors match the requirements and specifications and that the data appear logical and 
correct. 
 
Type B validation includes, but is not limited to:  
 
Review of the code written by the Production Programmer to ensure that the correct 
variables and data were used and all data manipulation was conducted using sound 
programming logic that results in accurate output. 
 
Visual inspection of the output is required to ensure that the layout, format and other 
cosmetic factors match the requirements and specifications and that the data appear 
logical and correct. 
Related outputs will be compared for consistency. The type of validation used for each Analysis 
Datasets (ADS) and/or TLGO is specified in the Programming Development and Validation 
Document (PDVD). 
 
4.21 Conventions 
Wherever possible, data will be decimal aligned. 
Numeric variables will be listed with the same number of decimal places as in the actual data. 


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The following rules on decimal places will be considered for the results of the analyses (if the analyses 
are performed on derived variables, the level of precision of the actual data is derived from the 
previous list): 
 
Minimum, maximum: same as actual data 
 
Mean and its confidence limits (unadjusted and adjusted), adjusted difference between means 
and its confidence limits, median, first and third quartiles: actual data + 1 decimal place, 
standard deviation (StD): actual data + 2 decimal places. For the tabulation of biomarker there 
will be an exception if the measurements represent counts. In this case mean, median and 
quartiles will be displayed without decimal places.  
 
Percentage: 1 decimal place 
 
Kaplan-Meier percentiles estimates and confidence limits: actual data + 1 decimal place 
(3 decimal places for survival probabilities) 
 
Odds ratio/hazard ratio and its confidence limits: 3 decimal places 
Unless otherwise specified frequency tabulations will be presented by number and percentage, where 
the percentage is presented in brackets. 
P-values, if applicable, will be presented to 3 decimal places. If a p-value is less than 0.05 but is 
greater than or equal to 0.01, then an asterisk (*) will be added next to this value. If a p-value is less 
than 0.01 but is greater than or equal to 0.001, then two asterisks (**) will be added next to this value. 
Finally, if the p-value is less than 0.001 then three asterisks (***) will be added next to this value and 
it will be presented as <0.001. If the rounded result is a value of 1.000, it will be displayed as >0.999. 
Unless otherwise stated, listings will be presented by study treatment, and sorted by patient ID. Patient 
ID will be presented on all listings. 
In general, dates will be presented on listings in the format ddmmmyyyy (date9.) and time in the 
format hh:mm (time5.). In case of partial dates or times, missing information will be replaced by 
dashes. 
In the listing, a unit associated with a variable will be presented only once within parentheses either 
below or next to that variable in the heading portion. If a parameter has multiple units, each unit will 
be displayed only once, as applicable. 
All tables will have their source listing referenced in a footnote. Listings should be sorted by 
treatment, patient and visit (unless otherwise specified) and have the study data tabulation model 
(SDTM) and/or analysis dataset model (ADaM) source data referenced in a footnote. 
In stratified tables, each stratum will start on a new page. 
 
 


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5 
References 
American Statistical Association (ASA). Ethical Guidelines for Statistical Practice. Prepared by the 
Committee on Professional Ethics, August 7, 1999. 
Cheson BD, Byrd JC, Rai KR, Kay NE, O'Brien SM, Flinn IW, et al. Novel targeted agents and the 
need to refine clinical endpoints in chronic lymphocytic leukemia. J Clin Oncol. 
2012;30(23):2820-2. 
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for 
initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the 
Lugano classification. J Clin Oncol. 2014;32(27):3059-68. 
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. Guidelines for 
the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International 
Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute –Working 
Group 1996 guidelines. Blood. 2008;111(12):5446-56. 
Hallek M, Cheson BD, Catovsky D, et al. Response assessment in chronic lymphocytic leukemia 
treated with novel agents causing an increase of peripheral blood lymphocytes [letter]. Blood. 
2012;119(23):5348. 
Hillmen P, Diels J, Healy N, Iraqi W, Aschan J, Wildgust M. Real-World Experience of Ibrutinib in 
>2900 Chronic Lymphocytic Leukemia Patients: Data from a Global Named Patient Program. 
Poster #208 EHA 2016. 
International Conference on Harmonization; Guidance on Statistical Principles for Clinical Trials. 
Department of Health and Human Services: Food and Drug Administration [Docket No. 97D-
0174]. Federal Register Volume 63, Number 179, pages 49583-49598. September 16, 1998. 
Mato AR, Nabhan C, Barr PM, Ujjani CS, Hill BT, Lamanna N, et al., Favorable Outcomes in CLL 
Patients with Alternate Kinase Inhibitors Following Ibrutinib or Idelalisib Discontinuation. Oral 
Presentation Abstract 719 ASH 2015 
National Comprehensive Cancer Network (NCCN) Guidelines for Treatment of Cancer by Site. Non-
Hodgkin's Lymphomas; 2015. 
 
https://www.nccn.org/store/login/login.aspx?ReturnURL=http://www.nccn.org/professionals/phy
sician_gls/pdf/nhl.pdf. 
Note for Guidance on Statistical Principles for Clinical Trials (ICH Topic E9, Step 4) adopted by 
CPMP, March 1998; issued as CPMP/ICH/363/96. 
The Royal Statistical Society (RSA). Code of Conduct; 2014 (revision). 
eA phase 1 trial of the Fc-engineered CD19 antibody XmAb5574 (MOR00208) demonstrates safety 
and preliminary efficacy in relapsed CLL. Blood. 2014a;124(24):3553-60. 
 
 


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6 
Appendices 
 
6.1 
Appendix A: Binet and Rai Staging System 
 
Binet Staging Stage  
Clinical features  
A  
Lymphocytosis, does not meet criteria for 
stages B or C  
B  
≥ 3 areas of lymphadenopathy*, does not 
meet criteria for stage C  
C  
Anemia (Hb < 10 g/dL) or thrombocytopenia 
(platelets < 100 x109/L)  
* The four lymphadenopathy areas are: cervical, axillary, inguinal, spleen/liver  
Adapted from: Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J, et al. A new 
prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival 
analysis. Cancer. 1981;48(1):198-206. 
 
 
 
Modified Rai Clinical Stage Risk category  Clinical features  
Low  
Lymphocytes > 15 x 109/L  
Intermediate  
As 0 + lymphadenopathy or hepato- or 
splenomegaly  
High  
Anemia (Hb ≤ 11 g/dL) or thrombocytopenia 
(platelets ≤ 100 x109/L)  
Adapted from: Rai KR. A critical analysis of staging in CLL. In: Gale RP, Rai KR, eds. Chronic 
Lymphocytic Leukemia: Recent Progress and Future Directions. New York: Alan R. Liss; 1987: 253-
64. 
 
The Binet clinical staging system and the modified Rai clinical staging system for CLL comprise three 
stages.  
The use of clinical staging systems is recommended in current CLL guidelines, and can guide the 
initiation of treatment. 
 


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6.2 
Appendix B: Cockcroft-Gault Formula 
 
 
 
 
 
 


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6.3 
Appendix C: Response Definition for CLL by the IWCLL Guidelines 2008 
 
Parameter  
 
CR*  
PR*  
PD*  
Group A  
Lymphadenopathy†  
None > 1.5 cm  
Decrease ≥ 50%  
Increase ≥ 50%  
Hepatomegaly  
None  
Decrease ≥ 50%  
Increase ≥ 50%  
Splenomegaly  
None  
Decrease ≥ 50%  
Increase ≥ 50%  
Blood lymphocytes  
< 4000/μL  
Decrease ≥ 50% from 
baseline  
Increase ≥ 50% over 
baseline  
Marrow‡  
Normocellular, < 30% 
lymphocytes, no B-lymphoid 
nodules 
Hypocellular marrow defines 
CRi  
50% reduction in 
marrow infiltrate, or B-
lymphoid nodules  
--  
Group B  
Platelet count  
> 100,000/μL  
> 100,000/μL or 
increase ≥ 50% over 
baseline  
Decrease of ≥ 50% 
from baseline 
secondary to CLL  
Hemoglobin  
> 11 g/dL  
> 11 g/dL or increase ≥ 
50% over baseline  
Decrease of > 2 
g/dL from baseline 
secondary to CLL  
Neutrophils‡  
> 1500/μL  
> 1500/μL or > 50% improvement over 
baseline  
Group A criteria define the tumor load, group B criteria define the function of the hematopoietic 
system (or marrow).  
*CR (complete remission): all of the criteria have to be met, and patients have to lack disease-related 
constitutional symptoms; PR (partial remission): at least two of the criteria of group A plus one of the 
criteria of group B have to be met; SD is absence of progressive disease (PD) and failure to achieve at 
least a PR; PD: at least one of the above criteria of group A or group B has to be met. 
CRi: complete response with incomplete marrow recovery 
†Sum of the products of multiple lymph nodes (as evaluated by CT scans in clinical trials, or by 
physical examination in general practice).  
‡These parameters are irrelevant for some response categories.  
 
 
The World Health Organization (WHO) classification of hematopoietic neoplasias describes CLL as 
leukemic, lymphocytic lymphoma, being only distinguishable from SLL by its leukemic appearance. 
In the WHO classification, CLL is always a disease of neoplastic B cells, whereas the entity formerly 
described as chronic lymphocytic leukemia of T-cell type (T-CLL) is now called T-cell 
prolymphocytic leukemia. It is important to verify that the patient has CLL and not some other 
lymphoproliferative disease that can masquerade as CLL, such as hairy cell leukemia, or leukemic 
manifestations of mantle cell lymphoma, marginal zone lymphoma, splenic marginal zone lymphoma 
with circulating villous lymphocytes, or follicular lymphoma. To achieve this, it is essential to 
evaluate the blood count, blood smear, and the immune phenotype of the circulating lymphoid cells. 
 
Blood. The diagnosis of CLL requires the presence of at least 5 x 109 B lymphocytes/L (5000/µL) in 
the peripheral blood. The clonality of the circulating B lymphocytes needs to be confirmed by flow 
cytometry. The leukemia cells found in the blood smear are characteristically small, mature 
lymphocytes with a narrow border of cytoplasm and a dense nucleus lacking discernible nucleoli and 
having partially aggregated chromatin. These cells may be found admixed with larger or atypical cells, 
cleaved cells, or prolymphocytes, which may comprise up to 55% of the blood lymphocytes. Finding 
prolymphocytes in excess of this percentage would favor a diagnosis of prolymphocytic leukemia (B-
cell PLL). Gumprecht nuclear shadows, or smudge cells, found as cell debris, are other characteristic 
morphologic features found in CLL. 


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CLL or SLL might be suspected in otherwise healthy adults who have an absolute increase in the 
clonal B lymphocytes but who have less than 5 x 109/L B lymphocytes in the blood. However, in the 
absence of lymphadenopathy or organomegaly (as defined by physical examination or CT scans), 
cytopenias, or disease-related symptoms, the presence of fewer than 5 x 109 B lymphocytes per liter of 
blood is defined as “monoclonal B-lymphocytosis.” Monoclonal B-lymphocytosis may progress to 
frank CLL at a rate of 1% to 2% per year. 
The definition of SLL requires the presence of lymphadenopathy and/or splenomegaly. Moreover, the 
number of B lymphocytes in the peripheral blood should not exceed 5 x 109/L. In SLL, the diagnosis 
should be confirmed by histopathologic evaluation of a lymph node biopsy whenever possible. 
 
Immunophenotype. CLL cells coexpress the T-cell antigen CD5 and B-cell surface antigens CD19, 
CD20, and CD23. The levels of surface immunoglobulin, CD20, and CD79b are characteristically low 
compared with those found on normal B cells. Each clone of leukemia cells is restricted to expression 
of either kappa or lambda immunoglobulin light chains. 
Variations of the intensity of expression of these markers may exist and do not prevent inclusion of a 
patient in clinical trials for CLL. In contrast, B-cell PLL cells do not express CD5 in half of the cases, 
and typically express high levels of CD20 and surface Ig. In addition, the leukemia cells of mantle cell 
lymphoma, despite also expressing B-cell surface antigens and CD5, generally do not express CD23. 
 
Marrow examination. A marrow aspirate and biopsy generally are not required for the diagnosis of 
CLL. In CLL, characteristically more than 30% of the nucleated cells in the aspirate are lymphoid. 
 
From: Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. 
Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the 
International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute –
Working Group 1996 guidelines. Blood. 2008;111(12):5446-56. 
 


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6.4 
Appendix D: Criteria for B-Symptoms 
 
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. 
 
 
 
 
 


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6.5 
Appendix E: ECOG Performance Status 
 
Grade 
Description 
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 self-care but unable to carry out any 
work activities. Up and about more than 50% of waking hours  
3  
Capable of only limited self-care, confined to bed or chair more 
than 50% of waking hours  
4  
Completely disabled. Cannot carry on any self-care. Totally 
confined to bed or chair  
5  
Dead 
 
 
 
 


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6.6 
Appendix F: Table of Contents for Statistical Tables, Figures, and Listings 
 
TLGO 
Table 
Title 
Analysis Set 
Table 
14.1.1 
Patient Disposition 
All Patients 
Table 
14.1.2 
Analysis Populations 
All Patients 
Table 
14.1.3.1 
Summary of Protocol Deviations by Centre and Overall 
SAF 
Table 
14.1.3.2 
Summary of Protocol Deviations Leading to Exclusion from the PPS 
FAS 
Table 
14.1.4.1 
Demographics and Baseline Characteristics 
FAS 
Table 
14.1.4.2 
Demographics and Baseline Characteristics 
SAF 
Table 
14.1.4.3 
Gene Mucosal Cheek Swab for FcgammaRII/III Genotyping 
FAS 
Table 
14.1.4.4 
Cytogenetic Risk 
FAS 
Table 
14.1.4.5 
Baseline Biomarker Assessments 
FAS 
Table 
14.1.5.1 
Medical History 
FAS 
Table 
14.1.5.2 
Medical History 
SAF 
Table 
14.1.5.3 
Current Medical Conditions 
FAS 
Table 
14.1.5.4 
Current Medical Conditions 
SAF 
Table 
14.1.6.1 
Prior Medications 
FAS 
Table 
14.1.6.2 
Prior Medications 
SAF 
Table 
14.1.6.3 
Concomitant Medications 
FAS 
Table 
14.1.6.4 
Concomitant Medications 
SAF 
Table 
14.1.6.5 
Summary of Prior Treatment Regimens 
FAS 
Table 
14.1.6.6 
Summary of Prior Treatment Regimens 
SAF 
Table 
14.2.1.1 
Summary of Objective Response (Local Evaluation) 
FAS 
Table 
14.2.1.2 
Summary of Objective Response (Local Evaluation) 
PPS 
Table 
14.2.2 
Summary of Minimal Residual Disease 
FAS 
Table 
14.2.3 
Summary of Biomarkers - Absolute and Changes from Baseline Values by Visit 
FAS 
Table 
14.2.4.1 
Summary of Anti-MOR00208 Antibody Assessment by Visit  
IAS 
Table 
14.2.4.2 
Summary of Anti-MOR00208 Antibody (Semiquantitative Results by Visit) 
IAS 
Table 
14.3.1.1 
Overall Summary of Adverse Events 
SAF 


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TLGO 
Table 
Title 
Analysis Set 
Table 
14.3.1.2 
Number and Percentage of Patients Experiencing any Treatment-Emergent AEs by SOC, PT and 
Grade 
SAF 
Table 
14.3.1.3 
Number and Percentage of Patients Experiencing any Treatment-Emergent AEs by SOC, PT and 
Intensity 
SAF 
Table 
14.3.1.4 
Most Frequent Treatment-Emergent AEs (at least in 10% of the Patients) by SOC, PT and Grade 
SAF 
Table 
14.3.1.5 
Number and Percentage of Patients Experiencing TEAEs with Grade >=3  by SOC, PT and Grade 
SAF 
Table 
14.3.1.6 
Number and Percentage of Patients Experiencing TEAEs with Grade 3 or 4  by SOC, PT and Grade 
SAF 
Table 
14.3.1.7 
Number and Percentage of Patients Experiencing TEAEs Starting in Cycle 1 by SOC and PT (Cohort 
A) 
SAF 
Table 
14.3.1.8 
Number and Percentage of Patients Experiencing TEAEs Starting Before Cycle 2 Day 15 by SOC 
and PT (Cohort B) 
SAF 
Table 
14.3.1.9 
Number and Percentage of Patients Experiencing  TEAEs Suspected to Be Related to the Study Drug 
by SOC, PT and Grade 
SAF 
Table 
14.3.1.10 
Number and Percentage of Patients Experiencing TEAEs Suspected to Be Related to the Study Drug 
by SOC, PT and Intensity 
SAF 
Table 
14.3.1.11 
Number and Percentage of Patients Experiencing TEAEs Suspected to Be Related to the Study Drug 
with Grade >=3  by SOC, PT and Grade 
SAF 
Table 
14.3.1.12 
Number and Percentage of Patients Experiencing TEAEs Suspected to Be Related to the Study Drug 
with Grade 3 or 4  by SOC, PT and Grade 
SAF 
Table 
14.3.1.13 
Most Frequent Drug-Related TEAEs (at least in 10% of the Patients) by SOC, PT and Grade 
SAF 
Table 
14.3.1.14 
Number and Percentage of Patients Experiencing TEAEs Leading to Any Action on Study Drug by 
SOC, PT and Grade 
SAF 
Table 
14.3.1.15 
Number and Percentage of Patients Experiencing TEAEs Leading to Discontinuation of Treatment 
by SOC, PT and Grade 
SAF 
Table 
14.3.1.16 
Number and Percentage of Patients Experiencing TEAEs Leading to Interruption of Treatment by 
SOC, PT and Grade 
SAF 
Table 
14.3.1.17 
Most Frequent Non-Serious Treatment-Emergent AEs (at Least in 5% of the Patients) by SOC, PT 
and Grade 
SAF 
Table 
14.3.1.18 
Number and Percentage of Patients Experiencing TEAEs of Special Interest by SOC, PT and Grade 
SAF 
Table 
14.3.1.19 
Number and Percentage of Patients Experiencing Treatment-Emergent SAEs by SOC, PT and Grade 
SAF 
Table 
14.3.1.20 
Most Frequent Treatment-Emergent SAEs (at least in 2% of the Patients) by SOC, PT and Grade 
SAF 
Table 
14.3.1.21 
Number and Percentage of Patients Experiencing Treatment-Emergent SAEs Starting in Cycle 1 by 
SAF 


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TLGO 
Table 
Title 
Analysis Set 
SOC and PT  (Cohort A) 
Table 
14.3.1.22 
Number and Percentage of Patients Experiencing Treatment-Emergent SAEs Starting Before Cycle 2 
Day 15 by SOC and PT (Cohort B) 
SAF 
Table 
14.3.1.23 
Number and Percentage of Patients Experiencing Treatment-Emergent SAEs with Grade >=3  by 
SOC, PT and Grade 
SAF 
Table 
14.3.1.24 
Number and Percentage of Patients Experiencing Treatment-Emergent SAEs with Grade 3 or 4  by 
SOC, PT and Grade 
SAF 
Table 
14.3.1.25 
Number and Percentage of Patients Experiencing Treatment-Emergent SAEs with Grade 5  by SOC 
and PT 
SAF 
Table 
14.3.1.26 
Number and Percentage of Patients Experiencing Treatment-Emergent SAEs Suspected to Be 
Related to the Study Drug by SOC, PT and Grade 
SAF 
Table 
14.3.1.27 
Number and Percentage of Patients Experiencing Treatment-Emergent SAEs Suspected to Be 
Related to the Study Drug with Grade >=3  by SOC, PT and Grade 
SAF 
Table 
14.3.1.28 
Number and Percentage of Patients Experiencing Treatment-Emergent SAEs Suspected to Be 
Related to the Study Drug with Grade 3 or 4  by SOC, PT and Grade 
SAF 
Table 
14.3.1.29 
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 
SAF 
Table 
14.3.1.30 
Summary of Deaths 
SAF 
Listing 
14.3.2.1 
Listing of Treatment-Emergent Serious Adverse Events 
SAF 
Listing 
14.3.2.2 
Listing of AEs of Toxicity Grade 3 or 4 
SAF 
Listing 
14.3.2.3 
Listing of AEs Leading to Discontinuation of Treatment 
SAF 
Listing 
14.3.2.4 
Listing of AEs of Special Interest 
SAF 
Listing 
14.3.2.5 
Listing of AEs Leading to Death 
SAF 
Table 
14.3.4.1 
Laboratory Data - Hematology - Absolute and Change from Baseline Values by Visit 
SAF 
Table 
14.3.4.2 
Laboratory Data - Serum Chemistry - Absolute and Change from Baseline Values by Visit 
SAF 
Table 
14.3.4.3 
Laboratory Data - Coagulation - Absolute and Change from Baseline Values by Visit 
SAF 
Table 
14.3.4.4 
Laboratory Data - Urinalysis - Absolute and Change from Baseline Values by Visit 
SAF 
Table 
14.3.4.5 
Laboratory Data - Urinalysis: Categorical Variables - Results by Visit 
SAF 
Table 
14.3.4.6 
Laboratory Data - Hematology - Values Outside the Normal Range by Visit 
SAF 
Table 
14.3.4.7 
Laboratory Data - Serum Chemistry - Values Outside the Normal Range by Visit 
SAF 
Table 
14.3.4.8 
Laboratory Data - Coagulation - Values Outside the Normal Range by Visit 
SAF 


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TLGO 
Table 
Title 
Analysis Set 
Table 
14.3.4.9 
Laboratory Data - Urinalysis - Values Outside the Normal Range  by Visit 
SAF 
Table 
14.3.4.10 
Laboratory Data - Hematology - Shift from Baseline to Worst NCI-CTCAE Toxicity Grade 
SAF 
Table 
14.3.4.11 
Laboratory Data - Serum Chemistry - Shift from Baseline to Worst NCI-CTCAE Toxicity Grade 
SAF 
Table 
14.3.4.12 
Laboratory Data - Coagulation - Shift from Baseline to Worst NCI-CTCAE Toxicity Grade 
SAF 
Listing 
14.3.4.13 
Abnormal Laboratory Values 
SAF 
Table 
14.3.5 
Vital Signs - Absolute and Change from Baseline Values by Visit 
SAF 
Table 
14.3.6.1 
Electrocardiogram - Summary of Overall Interpretations by Visit 
SAF 
Table 
14.3.6.2 
Electrocardiogram - Absolute and Change from Baseline Values by Visit 
SAF 
Table 
14.3.6.3 
Electrocardiogram - Summary of Clinically Notable ECG Values 
SAF 
Table 
14.3.7.1 
Summary of Abnormal Physical Examination Findings 
SAF 
Table 
14.3.7.2 
ECOG Performance Status – Scores by Visit 
SAF 
Table 
14.3.7.3 
ECOG Performance Status – Shift from Baseline to Worst Post-Baseline Score 
SAF 
Table 
14.3.7.4 
B-Symptoms – Assessments by Visit 
SAF 
Table 
14.3.7.5.1 
Exposure and Treatment Compliance 
FAS 
Table 
14.3.7.5.2 
Exposure and Treatment Compliance 
SAF 
Table 
14.4.1 
Summary of MOR00208 PK Concentrations (ug/mL) 
PKAS 
Table 
14.4.2 
Statistical Analysis of MOR00208 Serum Concentration Accumulation 
PKAS 
Listing 
16.2.1.1 
Patient Disposition 
All Patients 
Listing 
16.2.1.2 
Inclusion/Exclusion Criteria 
All Patients 
Listing 
16.2.2 
Protocol Deviations 
All Patients 
Listing 
16.2.3 
Patients Excluded from the Efficacy Analysis 
All Patients 
Listing 
16.2.4.1 
Demographic and Baseline Characteristics 
All Patients 
Listing 
16.2.4.2 
Baseline Disease Staging 
All Patients 
Listing 
16.2.4.3 
Gene Mucosal Cheek Swab for FcgammaRII/III Genotyping 
All Patients 
Listing 
16.2.4.4 
Cytogenetic Risk 
All Patients 
Listing 
16.2.4.5 
Medical History and Current Medical Conditions 
All Patients 
Listing 
16.2.4.6 
Prior and Concomitant Medications 
All Patients 


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TLGO 
Table 
Title 
Analysis Set 
Listing 
16.2.4.7 
Prior and Concomitant Non-Drug Procedures 
All Patients 
Listing 
16.2.4.8 
Pre-medications for MOR00208 Infusion 
SAF 
Listing 
16.2.4.9 
Prior Cancer Therapy for CLL/SLL - Overview 
All Patients 
Listing 
16.2.4.10 
Prior Cancer Therapy for CLL/SLL - Medications 
All Patients 
Listing 
16.2.4.11 
Prior Cancer Therapy for CLL/SLL - Radiation Therapy 
All Patients 
Listing 
16.2.4.12 
Prior Cancer Therapy for CLL/SLL - Surgery 
All Patients 
Listing 
16.2.4.13 
Prior Cancer Therapy for CLL/SLL - Autologous/Allogenic Stem Cell Transplantation 
All Patients 
Listing 
16.2.4.14 
Anti-Neoplastic Therapies Medications after Treatment 
SAF 
Listing 
16.2.4.15 
Anti-Neoplastic Radiation Therapies after Treatment 
SAF 
Listing 
16.2.4.16 
Anti-Neoplastic Surgeries after Treatment 
SAF 
Listing 
16.2.5.1.1 
Drug Administration Records (MOR00208) 
SAF 
Listing 
16.2.5.1.2 
Drug Administration Records (Idelalisib) 
SAF 
Listing 
16.2.5.1.3 
Drug Administration Records (Venetoclax) 
SAF 
Listing 
16.2.5.2.1 
MOR00208 PK Concentrations 
PKAS 
Listing 
16.2.5.2.2 
Bioactive MOR00208 PK Concentrations 
PKAS 
Listing 
16.2.6.1 
Listing of Efficacy Variables  
FAS 
Listing 
16.2.6.2 
Lymphoma Tumour Assessment 
FAS 
Listing 
16.2.6.3 
Bone Marrow Aspiration and Biopsy and Minimal Residual Disease Assessment 
FAS 
Listing 
16.2.6.4 
Bone Marrow Examination - Confirmation of Complete Response 
FAS 
Listing 
16.2.6.5 
Biomarkers Assessment (Including Genotyping and Disease Risk Assessment) 
FAS 
Listing 
16.2.6.6 
Immunogenicity of MOR00208 
IAS 
Listing 
16.2.7.1 
Listing of Adverse Events 
All Enrolled 
Patients 
Listing 
16.2.7.2 
Listing of Pre-Treatment Adverse Events 
All Enrolled 
Patients 
Listing 
16.2.7.3 
Listing of Treatment-emergent Adverse Events Suspected to be Related to Study Drug 
SAF 
Listing 
16.2.7.4 
Listing of Treatment-emergent SAEs Suspected to be Related to Study Drug 
SAF 
Listing 
16.2.7.5 
Listing of Treatment-emergent Adverse  Events Leading to Interruption of Study Drug 
SAF 
Listing 
16.2.7.6 
Cases of Death 
 


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TLGO 
Table 
Title 
Analysis Set 
Listing 
16.2.8.1 
Listing of Laboratory Values - Hematology 
SAF 
Listing 
16.2.8.2 
Listing of Laboratory Values - Serum Chemistry 
SAF 
Listing 
16.2.8.3 
Listing of Laboratory Values - Serology 
SAF 
Listing 
16.2.8.4 
Listing of Laboratory Values - Coagulation 
SAF 
Listing 
16.2.8.5 
Listing of Laboratory Values - Urinalysis 
SAF 
Listing 
16.2.8.6 
Listing of Emergency Local Laboratory Evaluation 
SAF 
Listing 
16.2.8.7 
Listing of Pregnancy Test Results 
SAF 
Listing 
16.2.9.1 
Vital Signs 
SAF 
Listing 
16.2.9.2.1 
ECG Interpretation 
SAF 
Listing 
16.2.9.2.2 
ECG Results 
SAF 
Listing 
16.2.9.3.1 
Physical Examination (Limited and Complete) 
SAF 
Listing 
16.2.9.3.2 
Complete Physical Examination 
SAF 
Listing 
16.2.9.4 
ECOG Performance Status 
SAF 
Listing 
16.2.9.5 
Assessment of B-Symptoms 
SAF 
Listing 
16.2.9.6 
Tumour Lysis Syndrome Risk Assessment 
SAF 
Figure 
14.2.1.1 
Plot of Peripheral Number of NK Cells (Absolute Values) Over Time 
FAS 
Figure 
14.2.1.2 
Plot of Relative Change of Peripheral Number of NK Cells From Baseline Over Time 
FAS 
Figure 
14.2.1.3 
Plot of Median Peripheral Number of NK Cells (Absolute Values) with 95% Bootstrap Confidence 
Interval Over Time 
FAS 
Figure 
14.2.1.4 
Plot of Median Relative Change of Peripheral Number of NK Cells From Baseline with 95% 
Bootstrap Confidence Interval Over Time 
FAS 
Figure 
14.2.1.5 
Boxplots for Peripheral Number of NK Cells (Absolute Values) Over Time 
FAS 
Figure 
14.2.1.6 
Boxplots for Relative Change of Peripheral Number of NK-Cells Over Time 
FAS 
Figure 
14.2.1.7 
Plot of Peripheral Number of B-Cells (Absolute Values) Over Time 
FAS 
Figure 
14.2.1.8 
Plot of Relative Change of Peripheral Number of B-Cells From Baseline Over Time 
FAS 
Figure 
14.2.1.9 
Plot of Median Peripheral Number of B-Cells (Absolute Values) with 95% Bootstrap Confidence 
Interval Over Time 
FAS 
Figure 
14.2.1.10 
Plot of Median Relative Change of Peripheral Number of B-Cells From Baseline with 95% Bootstrap 
Confidence Interval Over Time 
FAS 


Protocol Number: MOR208C205 
Confidential  
MorphoSys AG 
Version 2.0 Final, 27 May 2019 
 
Page 71 of 71 
TLGO 
Table 
Title 
Analysis Set 
Figure 
14.2.1.11 
Boxplots for Peripheral Number of B-Cells (Absolute Values) Over Time 
FAS 
Figure 
14.2.1.12 
Boxplots for Relative Change of Peripheral Number of B-Cells Over Time 
FAS 
Figure 
14.2.1.13 
Plot of Peripheral Number of T-Cells (Absolute Values) Over Time 
FAS 
Figure 
14.2.1.14 
Plot of Relative Change of Peripheral Number of T-Cells From Baseline Over Time 
FAS 
Figure 
14.2.1.15 
Plot of Median Peripheral Number of T-Cells (Absolute Values) with 95% Bootstrap Confidence 
Interval Over Time 
FAS 
Figure 
14.2.1.16 
Plot of Median Relative Change of Peripheral Number of B-Cells From Baseline with 95% Bootstrap 
Confidence Interval Over Time 
FAS 
Figure 
14.2.1.17 
Boxplots for Peripheral Number of T-Cells (Absolute Values) Over Time 
FAS 
Figure 
14.2.1.18 
Boxplots for Relative Change of Peripheral Number of T-Cells Over Time 
FAS 
Figure 
14.2.1.19 
Plot of CD19 molecules on CD5+22neg19+ B cells (Absolute Values) Over Time 
FAS 
Figure 
14.2.1.20 
Plot of Relative Change of CD19 molecules on CD5+22neg19+ B cells From Baseline Over Time 
FAS 
Figure 
14.2.1.21 
Plot of Median CD19 molecules on CD5+22neg19+ B cells (Absolute Values) with 95% Bootstrap 
Confidence Interval Over Time 
FAS 
Figure 
14.2.1.22 
Plot of Median Relative Change of CD19 molecules on CD5+22neg19+ B cells From Baseline with 
95% Bootstrap Confidence Interval Over Time 
FAS 
Figure 
14.2.1.23 
Boxplots for CD19 molecules on CD5+22neg19+ B cells (Absolute Values) Over Time 
FAS 
Figure 
14.2.1.24 
Boxplots for Relative Change of CD19 molecules on CD5+22neg19+ B cells Over Time 
FAS 
Figure 
14.2.1.25 
Plot of CD19 molecules on CD5neg22neg19+ B cells (Absolute Values) Over Time 
FAS 
Figure 
14.2.1.26 
Plot of Relative Change of CD19 molecules on CD5neg22neg19+ B cells From Baseline Over Time 
FAS 
Figure 
14.2.1.27 
Plot of Median CD19 molecules on CD5neg22neg19+ B cells (Absolute Values) with 95% Bootstrap 
Confidence Interval Over Time 
FAS 
Figure 
14.2.1.28 
Figure 14.2.1.28 Plot of Median Relative Change of CD19 molecules on CD5neg22neg19+ B cells 
From Baseline with 95% Bootstrap Confidence Interval Over Time 
FAS 
Figure 
14.2.1.29 
Boxplots for CD19 molecules on CD5neg22neg19+ B cells (Absolute Values) Over Time 
FAS 
Figure 
14.2.1.30 
Boxplots for Relative Change of CD19 molecules on CD5neg22neg19+ B cells Over Time 
FAS 
Figure 
14.4.1 
Plot of Mean (StD) MOR00208 Serum Concentrations (ng/mL) 
PKAS