Conditions: Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-cell Lymphoma Recurrent
Keywords: Loncastuximab tesirine
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 145
Healthy volunteers: no

Brief summary:
The purpose of this Phase 2 study is to evaluate the clinical efficacy and safety of Loncastuximab Tesirine (ADCT-402) in patients with relapsed or refractory Diffuse Large B-Cell Lymphoma.

Detailed description:
This is a Phase 2, multi-center, open-label, single-arm study of the efficacy and safety of loncastuximab tesirine used as monotherapy in patients with relapsed or refractory DLBCL. The study will enroll approximately 140 patients

Loncastuximab Tesirine is an antibody drug conjugate (ADC) composed of a humanized antibody directed against human cluster of differentiation 19 (CD19), stochastically conjugated through a cathepsin-cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Loncastuximab tesirine has been designed to target and kill CD19-expressing malignant B-cells.

A 2-stage design will be used in this clinical study, with an interim analysis for futility on the first 52 patients. If ≥10 patients respond (CR+PR), the study will proceed to complete full enrollment. Enrollment will continue during the interim analysis; however, further enrollment will be halted if futility is confirmed.

For each patient, the study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 3 weeks), and a Follow-up Period (approximately every 12 week visits for up to 3 years after treatment discontinuation).

Patients may continue treatment until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.

Arms:
arm 1: Participants will receive loncastuximab tesirine as an IV infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg Q3W for 2 cycles, then 75 μg/kg Q3W for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.

Interventions: intervention 1: Loncastuximab tesirine
Intervention descriptions: intervention 1: intravenous infusion

Protocol document:
SAP_002.pdf: 
Protocol Number: ADCT-402-201 
 
Oﬃcial Title: Phase 2 Open-Label Single-Arm Study to Evaluate the Eﬃcacy and 
Safety of Loncastuximab Tesirine in PaƟents with Relapsed or Refractory 
Diﬀuse Large B-Cell Lymphoma (DLBCL) 
 
NCT Number: NCT03589469 
 
Document Date: 04 March 2020 


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Statistical Analysis Plan 
 
 
 
 
A Phase 2 Open-Label Single-Arm Study to Evaluate the Efficacy and 
Safety of Loncastuximab Tesirine in Patients with Relapsed or Refractory 
Diffuse Large B-Cell Lymphoma (DLBCL) 
PROTOCOL NO.:  ADCT-402-201  
 
 
 
SAP Version No./ Date: 1.0/ July 10, 2019 
SAP Version No./ Date: 2.0/ Mar 02, 2020 
 
Statistician: 
 
 
 
 
 
  
Confidentiality Statement 
All financial and nonfinancial support for this study will be provided by ADC Therapeutics 
SA. The concepts and information contained in this document or generated during the study 
are considered proprietary and may not be disclosed in whole or in part without the 
expressed, written consent of ADC Therapeutics SA. The study will be conducted according 
to the International Conference on Harmonisation harmonised tripartite guideline E6(R1), 
Good Clinical Practice. 
 




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Table of Contents 
Table of Contents ...................................................................................................................... 3 
1 Introduction ............................................................................................................................ 5 
2 Study Objectives .................................................................................................................... 6 
2.1 Primary Objectives ......................................................................................................6 
2.2 Secondary Objectives ..................................................................................................6 
 
3 Study Design .......................................................................................................................... 7 
3.1 Sample Size Consideration ..........................................................................................7 
3.2 Randomization .............................................................................................................7 
3.3 Modifications to the statistical section of the protocol ................................................7 
4 Statistical methods ................................................................................................................. 8 
4.1 Analysis Populations ...................................................................................................8 
4.1.1 All-Treated Population ....................................................................................8 
4.1.2 Per-Protocol Population ..................................................................................8 
4.1.3 Stem Cell Transplant (SCT) Population .........................................................8 
4.1.4 Patient Reported Outcome (PRO) Population ................................................8 
4.2 Patient Disposition .......................................................................................................8 
4.3 Protocol Deviations .....................................................................................................9 
4.4 Demographic and Baseline Characteristics .................................................................9 
4.5 Cancer History and Medications History ....................................................................9 
4.6 Prior or Concomitant Medications (other than anticancer therapies) ........................10 
4.7 Exposure to Treatment ............................................................................................... 11 
4.7.1 Extent of Loncastuximab Tesirine Exposure ................................................ 11 
4.7.2 Prophylactic Medications for Hypersensitivity ............................................ 11 
4.7.3 Subsequent Anticancer Therapy or Procedure .............................................. 11 
4.8 Safety Analyses ......................................................................................................... 11 
4.8.1 Adverse Events, Serious Adverse Events, and Deaths ..................................12 
4.8.1.1 Analyses of adverse events .......................................................... 12 
4.8.1.2 Deaths .......................................................................................... 14 
4.8.1.3 AE for Transplant patients ........................................................... 14 
4.8.2 Laboratory Data ............................................................................................14 
4.8.3 Electrocardiogram .........................................................................................15 
4.8.4 Vital Signs .....................................................................................................15 


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4.8.5 ECOG Performance Status ...........................................................................16 
4.8.6 Physical Examinations and Body Weight .....................................................16 
4.9 Efficacy Analyses ......................................................................................................16 
4.9.1 Overall Response Rate ..................................................................................16 
4.9.2 Duration of Response ....................................................................................17 
4.9.3 Time to Response: .........................................................................................18 
4.9.4 Complete Response Rate ..............................................................................18 
4.9.5 Relapse-free Survival ....................................................................................18 
4.9.6 Progression-free Survival..............................................................................18 
4.9.7 Overall Survival ............................................................................................19 
4.9.8 Response for CAR-T patients .......................................................................19 
4.10 Health-Related Quality of Life (HRQoL) Questionnaires ......................................19 
4.10.1 European Quality of life (EuroQol)-5 Dimensions-5 Levels (EQ-5D-5L) .19 
4.10.2 Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) .....20 
5 Interim Analyses .................................................................................................................. 22 
6 Final Analysis....................................................................................................................... 23 
7 Data handling conventions ................................................................................................... 24 
7.1 General conventions ..................................................................................................24 
7.1.1 Missing data ..................................................................................................24 
7.1.2 Unscheduled visits ........................................................................................25 
7.1.3 Duplicated visits............................................................................................25 
8 Reference List ...................................................................................................................... 26 
Appendix 1 Glossary of Abbreviations ................................................................................... 27 
Appendix 2 List of Post-Text Tables, Figures, Listings, and Supportive SAS Output 
Appendices ..................................................................................................................... 29 
 
 


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1 Introduction 
This statistical analysis plan (SAP) describes the statistical methods to be used during the 
reporting and analyses of data collected under ADC Therapeutics Protocol ADCT-402-201. 
This SAP should be read in conjunction with the study protocol and case report form (CRF). 
This version of the plan has been developed using the protocol Amendment 4 dated 09 Jul 
2019 and CRF version 4.0 dated 08 Aug 2019. 


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2  Study Objectives 
2.1 Primary Objectives  
Evaluate the efficacy of single agent loncastuximab tesirine in patients with relapsed or 
refractory DLBCL.   
2.2 Secondary Objectives 
 Further evaluate the efficacy of loncastuximab tesirine 
 Characterize the safety profile of loncastuximab tesirine 
 Characterize the pharmacokinetic (PK) profile of loncastuximab tesirine 
 Evaluate the immunogenicity of loncastuximab tesirine 
 Evaluate the impact of loncastuximab tesirine treatment on health-related quality of 
life (HRQoL) 
 
 
 
 
 
 


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3 Study Design 
This is a Phase 2, multi-center, open-label, single-arm study.  The study will enroll 
approximately 140 patients. 
A 2-stage design will be used, with an interim analysis for futility on the first 52 patients.  If 
≥10 patients respond (complete response [CR]+partial response [PR]), the study will proceed 
to complete full enrollment.  Enrollment will continue during the interim analysis; however, 
further enrollment will be halted if futility is confirmed. 
3.1 Sample Size Consideration 
The primary hypothesis is that the overall response rate (ORR) based on central review for 
patients treated with loncastuximab tesirine is significantly greater than 20% (i.e., H0: p ≤0.2 
vs. Ha: p >0.2).  This hypothesis will be tested at type I error of 0.05 (2-sided).   
Using nQuery exact test for single proportion, a sample size of 140 patients has >99% power 
to achieve a 1-sided significance level of 0.025 (2-sided significance level of 0.05).  This 
sample size will provide adequate precision for observed ORR in the expected range and a 
robust population for safety evaluation.   
3.2 Randomization 
This study is not randomized. 
3.3 Modifications to the statistical section of the protocol  
NA. 


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4 Statistical methods  
All analyses use SAS® version 9.4 or higher. All available data will be used in the analyses, 
and important data will be included in data listings, sorted by patient, and by visit within 
patient. Missing data will not be imputed, except via censoring in survival analyses and as 
otherwise specified. 
Unless otherwise noted, categorical data will be presented using counts and percentages, with 
the number of patients in the analysis population as the denominator for percentages. 
Percentages will be rounded to one decimal place, except 100% will be displayed without 
any decimal places and percentages will not be displayed for zero counts. Continuous data, 
unless otherwise noted, will be summarized using the number of observations (n), mean, 
standard deviation (std), median, minimum, and maximum. Minima and maxima will be 
rounded to the precision of the original value, and means, medians, and 95% confidence 
intervals (CIs) if presented will be rounded to 1 decimal place greater than the precision of 
the original value. The std will be rounded to 2 decimal places greater than the precision of 
the original value, up to a maximum of 3 decimal places.  
4.1 Analysis Populations  
4.1.1 All-Treated Population 
All patients who receive at least 1 dose of loncastuximab tesirine.  This population will be 
used in the primary analyses of efficacy and safety. 
4.1.2 Per-Protocol Population 
All patients in the all-treated population who met the inclusion/exclusion criteria, did not take 
a prohibited concomitant treatment, nor had other protocol deviation which have major 
impact on efficacy results.  
4.1.3 Stem Cell Transplant (SCT) Population 
All patients who have responded to loncastuximab tesirine and undergo stem cell transplant 
(either autologous or allogeneic) after permanent discontinuation of loncastuximab tesirine 
treatment without any intervening anticancer therapy. 
4.1.4 Patient Reported Outcome (PRO) Population 
All patients in the all-treated patients with baseline score (at least one instrument) and at least 
1 postbaseline score (in at least one instrument). 
4.2 Patient Disposition 
The number and percentage of patients enrolled and treated in the study will be presented 
along with the number and percentage of patients in each analysis population. In addition, the 
number and percentage of patients who withdrew from study treatment and who discontinued 
the study for each reason will be tabulated. 


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Patient disposition data will be listed.  
4.3 Protocol Deviations 
The number and percentage of patients with any important clinical study report (CSR) 
reportable protocol deviation will be summarized overall and by type of deviation. The pre-
defined important CSR reportable protocol deviations are listed below; in addition, any other 
protocol deviations deemed by ADCT medical to be important CSR reportable deviations 
will be included in the summary.  
1. Patient entered the study even though they did not satisfy the entry criteria 
2. Patient received a prohibited concomitant treatment during the study 
3. Patient who met criteria for mandatory withdrawal of study drug during the study but 
did not have study drug withdrawn 
4. Patient who received the wrong treatment or incorrect dose, specifically: 
- Actual dose of study drug was greater than 15% more or less than protocol defined 
planned dose level. 
- Patient started next cycle less than 18 days after Day 1 of the most recent treatment 
cycle. 
Important protocol deviations will be listed. 
4.4 Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be tabulated for the all-treated population. 
Variables include the following: 
 Sex (female, male) 
 Race (white, black or African American, Asian, American Indian or Alaska native, 
native Hawaiian or other Pacific Islander, other) 
 Ethnicity (Hispanic or Latino, not Hispanic or Latino) 
 Age (years) 
 Age group (< 65, ≥ 65 - < 75, ≥ 75 years) 
 Height (cm) 
 Weight (kg) 
 Body mass index (BMI) (kg/m2) 
 Eastern Cooperative Oncology Group (ECOG) performance status 
Demographic and baseline characteristics data will be listed. 
4.5 Cancer History and Medications History 
Cancer history will be presented for the all-treated population. Cancer history will include the 
following variables: 
 Duration since diagnosis  


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 
Diffuse large B-cell lymphoma subtype (NOS, Primary Mediastinal, and High-grade 
B-cell Lymphoma, with MYC and BCL2 and/or BCL6 rearrangements) 
 DLBCL additional subtype (germinal center B-cell [GCB]/activated B-cell [ABC], 
double/triple hit, transformed, and other additional information)Stage of disease 
(Stage I, II, III, IV; constitutional symptoms A, B; Subtype E, X, S) 
 Cytogenetic analysis (results available yes, t(11;14), t(11q), +12, del(11q), del(13q), 
del(17p), t(14;18), t(8;14), t(8;22), other) 
 
Immunophenotypic analysis (results available yes; IgVH status mutated, unmutated, 
not applicable; CD5, CD10, CD19, CD20, CD21, CD23, CD43, CD79b, BCL1, 
BCL2, BCL6, CYCLIN D1, ZAP70 negative, positive, not done) 
Prior anticancer procedure or therapy will include the following variables: 
 Number of lines of therapy/regimens per patient 
 Response to the first line and/or most recent line of prior systematic therapy 
 Any prior radiotherapy for the current malignancy (yes, no) 
 Any prior surgery for the current malignancy (yes, no) 
 Reason for stopping therapy (progression, toxicity, other) 
 Best response (complete response [CR], partial response [PR], stable disease [SD], 
progressive disease [PD], not evaluable [NE]) 
 Any prior stem cell transplant (yes, no) 
 Type of transplant (allogenic, autologous, both, other) 
 Conditioning therapy (yes, no) 
Medical and cancer history data will be listed. Results of cytogenetic analysis and 
immunophenotypic analysis will be listed. Tumor tissue biopsy collection will not be listed, 
but will be contained in datasets. 
Prior anticancer surgery, radiotherapy, systemic therapy, and stem cell transplant data will be 
listed. 
4.6 Prior or Concomitant Medications (other than anticancer therapies) 
All medications taken from the ICF signature date or within 14 days prior to Cycle 1 Day 1 
(C1D1), whichever is earlier, and until at least 30 days after last dose of study drug are to be 
reported in the CRF pages. 
All medications will be coded using the World Health Organization-Drug Dictionary (WHO-
DD). 
 Prior medications are those the patient used prior to the first dose. Prior medications 
can be discontinued before the first dose or can be ongoing during the treatment 
phase.   
 Concomitant medications are any treatments received by the patient concomitantly to 
any loncastuximab tesirine from the first dose to the last dose + 30 days. A given 
medication can be classified both as a prior medication and as a concomitant 


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medication. Concomitant medications do not include medications started 30 days 
after the last dose.  
Any technical details related to computation, dates, and imputation for missing dates are 
described in Section 7. 
Prior medications will be listed together with concomitant medications. 
4.7 Exposure to Treatment 
4.7.1 Extent of Loncastuximab Tesirine Exposure 
Loncastuximab tesirine exposure will be summarized for the all-treated population. Duration 
of treatment, total number of cycles dosed, total dose received (in µg and µg/kg), average 
dose per cycle (in µg and µg/kg), and relative dose intensity (actual dose taken / planned 
dose) will be tabulated. Patients will receive150 µg/kg every 3 weeks (Q3W) for 2 cycles, 
then 75 µg/kg Q3W for subsequent cycles as planned. When actual weight adjusted dose is 
needed, the last available weight before each infusion will be used. Patients with a BMI ≥35 
kg/m2 will have their dose calculated based on an adjusted body weight as follows: 
Adjusted body weight in kg = 35 kg/m2 * (height in meters)2 
Dose administered at each infusion (µg) is calculated by concentrated investigational product 
(IP) volume (in mL)* 5 mg/mL *1000. For incomplete infusion, adjust the calculated 
prepared dose by multiplying a factor of (1- volume of dosing solution not administered [in 
mL]/ 50 mL) for concentrated solution formulation, or (1- volume of dosing solution not 
administered [in mL]/ [50 + total volume of reconstituted solution] mL) for lyophilized 
formulation. The number of patients who received loncastuximab tesirine at each cycle will 
also be tabulated using frequency counts and percentages. 
Dose delays and dose reductions may also be analyzed if relevant. A cycle is delayed if it 
starts more than 2 days post- scheduled date. 
Relative dose intensity will be additionally presented categorized (<60%, >=60 - <80%, 
>=80 - <90%, >=90 - <110%, >=110%). 
Exposure data and infusion details will be listed together. 
4.7.2 Prophylactic Medications for Hypersensitivity  
Prophylactic medications for hypersensitivity will be listed only. 
4.7.3 Subsequent Anticancer Therapy or Procedure 
Patients’ subsequent anticancer therapies or procedures including systemic therapy, radiation, 
transplant, or other, along with the start date of new anticancer therapy or procedure will be 
collected and listed only. 
4.8 Safety Analyses 
The summary of safety results will be presented.  


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General common rules 
All safety analyses will be performed on the all-treated population, unless otherwise 
specified, using the following common rules: 
 The baseline value is defined as the last non-missing value or measurement taken up 
to the first dose in the study. 
 The analyses of the safety variables will be essentially descriptive and no systematic 
testing is planned. 
 If relevant, selected safety analyses will be summarized by age, sex, racial subgroups, 
and any pertinent subgroups.  
 The toxicity grade according to the Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.0 will be taken into account in the summary. For patients 
with multiple occurrences of the same event, the maximum grade is used. If a patient 
has both missing and non-missing severity grades for treatment-emergent adverse 
events (TEAEs) within the same preferred term (PT), the patient will be counted 
under the non-missing severity grade. 
4.8.1 Adverse Events, Serious Adverse Events, and Deaths 
4.8.1.1 Analyses of adverse events 
The primary focus of adverse event reporting will be on TEAEs. An adverse event (AE) will 
be considered to be a TEAE if it begins or worsens on or after the first dose date and until 30 
days after the last dose date, or start of a new anticancer therapy/procedure, whichever comes 
earlier. 
An AE occurring before the first dose or more than 30 days after the last dose date or after 
the start of a new anticancer therapy/procedure will not be included in TEAE displays, but 
will be listed as non-TEAEs. 
If an AE date/time of onset (occurrence, worsening, or becoming serious) is incomplete, an 
imputation algorithm will be used to classify the AE as pre-treatment, TEAE, or post-
treatment. The algorithm for imputing date/time of onset will be conservative and will 
classify an AE as treatment-emergent unless there is definitive information to determine it is 
a non-TEAE (pre- or post-treatment). Some details on classification of AEs with missing or 
partial onset dates are provided in Section 7. 
Analysis of all TEAE(s):  
The following TEAE summaries will be generated for the all-treatment population. 
 Overview of TEAEs, summarizing number of TEAE and number (%) of patients with 
any 
- 
TEAE 
- 
Related TEAE (including possibly related, probably related, or related) 


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- 
Any TEAE ≥Grade 3  
- 
Serious TEAE  
- 
TEAE leading to death 
- 
TEAE leading to permanent treatment withdrawal 
- 
TEAE leading to loncastuximab tesirine delay or reduction or interruption (if 
applicable) 
- 
TEAE with at least one infusion related reaction 
 All TEAEs ≥Grade 3 by PT, showing number (%) of patients with at least one TEAE, 
sorted by decreasing incidence of PTs 
 All TEAEs by primary System Organ Class (SOC) and PT, showing number (%) of 
patients with at least one TEAE, sorted by SOC in alphabetic agreed order and 
decreasing incidence of PTs within SOC. This sorting order will be applied to all 
other tables, unless otherwise specified. 
 All TEAEs by primary SOC, PT and Maximal CTCAE grade, showing number (%) 
of patients with at least one TEAE, sorted by SOC and PT in alphabetic order. This 
sorting order will be applied to all other tables, unless otherwise specified. 
 All TEAEs ≥Grade 3 by primary SOC, PT and Maximal CTCAE grade 
 All related TEAEs by primary SOC, PT and Maximal CTCAE grade (including 
possibly related, probably related, or related) 
 All TEAEs leading to treatment withdrawal by primary SOC, PT and Maximal 
CTCAE grade 
 All TEAEs leading to dose delay by primary SOC, PT and Maximal CTCAE grade 
 All TEAEs leading to dose reduction by primary SOC, PT and Maximal CTCAE 
grade 
 All TEAEs leading to infusion interruption by primary SOC, PT and Maximal 
CTCAE grade 
 All TEAEs with fatal outcome by primary SOC, PT and Maximal CTCAE grade 
 All Serious TEAEs by primary SOC, PT and Maximal CTCAE grade 
 All infusion related reaction TEAEs by primary SOC, PT and Maximal CTCAE 
grade 
 Summary of grouped TEAEs selected by Standardised MedDRA Query (SMQ), 
ADCT modified SMQ will also be provided by primary Grouped terms, PT and 
Maximal CTCAE grade. These group term include: effusion/edema, hepatic, fatigue, 
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 Summary of TEAEs will also be provided by demographic factors including: sex, age 
group, race, disease subtype if appropriate. 
All TEAEs, all serious adverse events (SAEs), all TEAEs leading to treatment 
withdrawal, all TEAEs leading to dose reduction, all TEAEs leading to dose delay, all 
TEAEs considered infusion related reactions, all TEAEs with fatal outcome and non-
TEAEs will be listed.  
4.8.1.2 Deaths 
The following deaths summaries will be generated on the all-treated population. 
 Number (%) of patients who died during the study and reasons for death 
 Number (%) of patients who died within 30 days after the last dose of study drug 
(excluding those who died after taking any subsequent anticancer therapy/procedure) 
and reasons for death 
4.8.1.3 AE for Transplant patients 
The following analysis will be performed for patients who have responded to loncastuximab 
tesirine and undergo SCT (either autologous or allogeneic) after permanent discontinuation 
of loncastuximab tesirine treatment without any intervening anticancer therapy.  The data 
will include the following information reported until 180 days post-transplant regardless of 
relationship to loncastuximab tesirine. 
 Summary of AEs ≥Grade 3 suggestive of hepatic toxicity, veno-occlusive 
disease/sinusoidal obstruction syndrome, graft-versus-host disease, infectious 
complications, prolonged cytopenia(s), and pulmonary toxicity 
 Serious TEAEs by primary SOC, PT and Maximal CTCAE grade 
 
Number (%) of patients who died after transplant and reasons for death 
Similar analysis will be performed for patients who receive CAR-T therapy after permanent 
discontinuation of loncastuximab tesirine treatment. The data will include the following 
information reported until 90 days after receiving CAR-T therapy regardless of relationship 
to loncastuximab tesirine. 
 Summary of AEs ≥Grade 3 of cytokine release syndrome, encephalopathy, edema or 
effusion, rash, hepatic toxicity 
 Serious TEAEs by primary SOC, PT and Maximal CTCAE grade 
 
Number (%) of patients who died after CAR-T therapy and reasons for death 
4.8.2 Laboratory Data 
Laboratory data of hematology, biochemistry, and coagulation up to 30 days after the last 
dose of study drug or the end of treatment visit date, whichever is later, will be reported in SI 
units. Descriptive statistics (mean, standard deviation, median, and range) will be calculated 
for the raw data and for their changes from baseline at each scheduled assessment. 


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All results will be summarized using shift from baseline. Shifts for clinical laboratory results 
that can be graded according to CTCAE version 4.0 will be summarized by CTCAE grade. 
Summaries by visit will include data from scheduled assessments, and all data will be 
reported according to the nominal visit date for which it was recorded. Unscheduled data will 
be included in “worst case post-baseline” summaries, which will capture a worst case across 
all scheduled and unscheduled visits after the first dose of study treatment. 
Summary analyses will include data up to the start of subsequent anticancer 
therapy/procedure. 
All laboratory data, including urinalysis, will be listed. Pregnancy test results will not be 
listed, but will be included in datasets. 
4.8.3 Electrocardiogram 
Descriptive statistics (mean, standard deviation, median and range) for ECG data will be 
calculated for the raw data and for their changes from baseline at each scheduled assessment. 
The following abnormal QTc (including QTcF and  QTcB) will be reported by a frequency 
table: 
 At any post-baseline with absolute value 
>450 - <=480 ms 
>480 - <=500 ms 
> 500 ms 
Change from Baseline 
 >30 – <=60 ms 
 >60 ms 
Summary analyses will include data up to the start of subsequent anticancer 
therapy/procedure. 
All ECG data will be listed, both for quantitative data and for overall impression. 
4.8.4 Vital Signs 
Descriptive statistics (mean, standard deviation, median, and range) for vital signs data, 
including systolic and diastolic blood pressure, heart rate, respiration rate, and body 
temperature will be calculated for the raw data and for their changes from baseline at each 
scheduled assessment. 
Summary analyses will include data up to the start of subsequent anticancer 
therapy/procedure. 
All vital signs data will be listed together with body weight. 


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4.8.5 ECOG Performance Status 
Descriptive statistics (mean, standard deviation, median and range) will be calculated for the 
raw data and for their changes from baseline at each scheduled assessment. 
Summary analyses will include data up to the start of subsequent anticancer 
therapy/procedure. 
ECOG performance score data will be listed. 
4.8.6 Physical Examinations and Body Weight 
Physical examination will be performed according to protocol. Clinically significant findings 
from the physical examinations will be recorded as medical history (prior to first 
administration of loncastuximab tesirine) or AEs (subsequent to first administration of 
loncastuximab tesirine). 
Body weight will be listed together with vital signs. 
4.9 Efficacy Analyses 
Disease assessment will be performed according to protocol. The endpoints described in this 
section, if not mentioned specifically, use the independent reviewer’s evaluation according to 
the 2014 Lugano Classification criteria before the start of subsequent anticancer therapy or 
procedure.  
Lesion assessment data (target lesions, non-target lesions, and new lesions) and tumor 
response will be listed. A separate listing will contain derived data for duration of response 
(DOR), relapse-free survival (RFS), progression-free survival (PFS), and Overall survival 
(OS). 
4.9.1 Overall Response Rate 
Overall response rate is defined as the proportion of patients who achieve either CR or PR as 
best overall response (BOR) as determined by central review according to the 2014 Lugano 
Classification criteria before the start of subsequent anticancer therapy or procedure. For the 
primary ORR analysis in the all-treated population, patients with a CR or PR will be counted 
as successes and all other patients (including those with missing response information) will 
be counted as failures. 
The order of overall response category is: CR, PR, SD, NE, PD (including disease 
recurrence/ relapse). The overall response category will be derived based on response 
assessment performed on or before the start of subsequent anticancer therapy/procedure. 
Patients without documented subsequent anticancer therapy and/or with missing start date of 
anticancer therapy will be considered as not having received subsequent anticancer therapy. 
A BOR of SD can only be made after the patient is on-study for a minimum of 35 days after 
the first dose of study drug.  Any tumor assessment indicating SD before this time period will 
be considered as NE for BOR if no assessment after this time period is available.   


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The overall response rate and the corresponding 95% two-sided exact confidence interval 
will be presented. Subgroup analysis may be provided for disease subtype, disease stage, 
double/triple hit (yes/no), bulky disease (yes/no), GCB/ABC, transformed (yes/no), age 
group, sex, country, response to the first line and/or most recent line of prior systematic 
therapy (relapse: CR+PR vs. refractory: SD+PD vs. other: NE + missing), and other relevant 
variables. 
Percent change from baseline in the sum of product of the perpendicular diameters (SPD) for 
target lesions will be presented for available data in the all-treated population . These data 
will also be displayed as a waterfall plot, with vertical bars representing the sorted values of 
best percent reduction for each patient.  
A sensitivity analysis of ORR determined by the independent reviewer’s evaluation will be 
conducted for the per-protocol population if relevant. 
A sensitivity analysis of ORR will be conducted in which best overall response is determined 
by investigators. 
4.9.2 Duration of Response 
Duration of response will be defined for patients with CR or PR only as the interval between 
the date of initial documentation of a response and the date of the first documented evidence 
of progressive disease based on independent radiographic assessment or death, whichever 
occurs first. Clinical progression at EOT/EOS without radiographic assessment could be 
considered as an event in a sensitivity analysis. Patients who have the event after the start of 
subsequent anticancer therapy/procedure, or are progression-free and alive at the time of 
clinical cut-off, or have unknown status, will be censored at the last valid tumor assessment 
on or before the start of subsequent anticancer therapy/procedure or clinical cut-off time. 
When a subsequent anticancer therapy is used and progressive disease (based on radiographic 
or clinical progression at EOT/EOS) is observed within 6 days, they will be considered as the 
same visit (within the protocol specified +/-6 days visit window) and the patient will be 
counted as having an event (losing the response). 
Patients with no post-baseline disease assessment will be censored on Day 1. 
Duration of response will be estimated and displayed for the all-treated population using 
Kaplan-Meier methods (SAS® PROC LIFETEST). A Kaplan-Meier plot will be presented. 
A sensitivity analysis of DOR will be conducted in which the DOR for patients undergo SCT 
will not be censored at SCT. 
A sensitivity analysis of DOR per investigator assessments will also be conducted. 
Subgroup analysis may be provided for disease subtype, disease stage, double/triple hit 
(yes/no), bulky disease (yes/no), GCB/ABC, transformed (yes/no), age group, response to the 
first line and/or most recent line of prior systematic therapy (relapse: CR+PR vs. refractory: 
SD+PD vs. other: NE + missing), best response to loncastuximab tesirine (CR/PR), and other 
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4.9.3 Time to Response:  
Time to response (TTR) is defined among patients who achieve either CR or PR as BOR 
before the start of subsequent anticancer therapy or procedure as the time from  the first dose 
to the initial documented response. For this subset of patients, TTR will be summarized using 
descriptive statistics.  
4.9.4 Complete Response Rate 
Complete Response Rate (CRR) will be defined as the proportion of patients with a best 
overall response of CR.  The percentage of CRR with its 95% CI will be presented. 
 
4.9.5 Relapse-free Survival 
Relapse-free survival will be defined among CR patients as the time from the date of the first 
complete response until the date of the first disease relapse based on independent 
radiographic assessment (i.e., disease progression for CR patients) or death, whichever 
occurs first.  The date of disease progression will be defined as the earliest date of disease 
progression based on central review. Clinical progression at EOT/EOS without radiographic 
assessment could be considered as an event in a sensitivity analysis. For patients who have 
the event after the start of subsequent anticancer therapy/procedure, or are progression-free 
and alive at the time of clinical cut-off, or have unknown status, censoring will be performed 
using the date of the last valid disease assessment on or before the start of subsequent 
anticancer therapy/procedure or clinical cut-off time.  When a subsequent anticancer therapy 
is used and progressive disease (based on radiographic or clinical progression at EOT/EOS) 
is observed within 6 days, they will be considered as the same visit (within the protocol 
specified +/-6 days visit window) and the patient will be counted as having an event (losing 
the response).  
Patients with no post-baseline disease assessment will be censored on Day 1. 
RFS will be estimated and displayed for the all-treated population using Kaplan-Meier 
methods (SAS® PROC LIFETEST). A Kaplan-Meier plot will be presented. 
A sensitivity analysis of RFS will be conducted in which RFS for patients undergo SCT will 
not be censored at SCT. 
A sensitivity analysis of RPS per investigator assessments will also be conducted. 
4.9.6 Progression-free Survival 
Progression-free survival is defined as the interval between the date of the first dose and the 
date of the first disease progression based on independent radiographic assessment or death, 
whichever occurs first. Clinical progression at EOT/EOS without radiographic assessment 
could be considered as an event in a sensitivity analysis. Patients who have the event after the 
start of subsequent anticancer therapy/procedure, or who are progression-free and alive at the 
time of clinical cut-off, or have unknown status, will be censored at the time of their last 
valid disease assessment on or before the start of subsequent anticancer therapy/procedure or 


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clinical cut-off. When a subsequent anticancer therapy was used and progressive disease 
(based on radiographic or clinical progression at EOT/EOS) were observed within 6 days, 
they will be considered as the same visit (within the protocol specified +/-6 days window) 
and the patient will be counted as having an event. 
Patients with no post-baseline disease assessment will be censored on Day 1. 
PFS will be estimated and displayed for the all-treated population using Kaplan-Meier 
methods (SAS® PROC LIFETEST). A Kaplan-Meier plot will be presented. 
A sensitivity analysis of PFS will be conducted in which the PFS for patients undergo SCT 
will not be censored at SCT. 
A sensitivity analysis of PFS per investigator assessments will also be conducted. 
4.9.7 Overall Survival 
Overall survival is defined as the interval between the date of the first dose and the date of 
death from any cause. Patients who are known to be alive as of their last known status will be 
censored at their date of last contact. Patients who are lost to follow-up will be censored at 
the date the patient is last known to have been alive. The last confirmed alive date is the 
latest of the following: study visit date, telephone contact date, end of study last confirmed 
alive date, follow-up systemic (anticancer) therapy end date or start date (if ongoing or end 
date is missing), local or central radiologist scan date, or other date in the clinical database. 
OS will be estimated and displayed for the all-treated population using Kaplan-Meier 
methods (SAS® PROC LIFETEST). A Kaplan-Meier plot will be presented. 
4.9.8 Response for CAR-T patients 
Response data collected after CAR-T therapy will be summarized separately. 
4.10 Health-Related Quality of Life (HRQoL) Questionnaires 
Scoring of QoL  data and methods for handling of missing items or missing assessments will 
be based on each questionnaire’s scoring manual. 
4.10.1 European Quality of life (EuroQol)-5 Dimensions-5 Levels (EQ-5D-
5L) 
EQ-5D-5L is designed as an international, standardized, generic instrument for describing 
and evaluating QoL.  The EQ-5D-5L consists of two parts: 
 The descriptive system: QoL is classified according to five dimensions: mobility, self 
care, usual activities, pain/discomfort, and anxiety/depression.  Each dimension 
comprises five levels of perceived problems (e.g., none, slight, moderate, severe, 
extreme). 
 The visual analog scale (VAS): patients are asked to indicate their health state today 
on a VAS with the endpoints labeled ‘the best health you can imagine’ (score 100) 
and ‘the worst health you can imagine’ (score 0).  Patients are asked to mark an “X” 


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on the VAS to indicate their own health and then to report the score in a text box.  If 
there is a discrepancy between where the patient has placed the X and the number 
he/she has written in the box, the number in the box is to be entered in the CRF 
together with a comment indicating the discrepancy. 
Individual dimension responses will be summarized at each scheduled assessment with 
frequency counts and percentage of patients.  
Descriptive statistics (mean, standard deviation, median and range) of actual values and 
changes from baseline will be presented at each scheduled assessment for the EQ-VAS. 
A change of 7 points in VAS from the baseline is considered minimally important difference 
(MID) (Pickard et al., 2007). Patients will be classified as improved/deteriorated based on the 
established MID, i.e., if at least one of the post-baseline scores improves/deteriorates by the 
magnitude of the MID compared to baseline score. Proportion of patients with 
improvement/deterioration will be summaried.   
Completion rate of EQ-5D-5L will be calculated as the number of patients who complete at 
least one question of EQ-5D-5L (e.g., either in descriptive system or VAS) divided by the 
number of patients treated at a visit. Summary of completion rate at each visit will be 
presented. 
Summary analyses will include data up to the start of subsequent anticancer 
therapy/procedure. 
A data listing for each individual dimension response, and the EQ-VAS will be presented for 
each patient at each visit.  
4.10.2 Functional Assessment of Cancer Therapy - Lymphoma (FACT-
Lym) 
FACT-Lym is a lymphoma-specific subscale for the Functional Assessment of Cancer 
Therapy (FACT) questionnaire.  It consists of 15 specific items that are used together with 
the core 27-item questionnaire FACT-G.  The patient is asked to respond to each item with a 
score of 0–4, where 0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, and 4 = very 
much. 
The FACT-Lym questionnaire includes subscales for physical well-being (PWB, 7 items), 
social/ family well-being (SWB, 7 items), emotional well-being (EWB, 6 items), functional 
well-being (FWB, 7 items) and additional concerns (Lymphoma Subscale, LymS, 15 items). 
The FACT-Lym scoring guide identifies those negatively stated items that must be reversed 
before being added to obtain subscale totals. Negatively stated items are reversed by 
subtracting the response from “4”. After reversing proper items, all subscale items are 
summed to a total, which is the subscale score. For all FACT-Lym scales and symptom 
indices, the higher score is associated with the better quality of life. The scores in the 
following items need to be reversed: 

Physical well-being: all individual items


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 Social/family well-being: none 
 Emotional well-being: 5 individual items (except for the second item, “I am satisfied 
with how I am coping with my illness”) 
 Functional well-being: none 
 Additional concerns: all individual items 
The subscale scores will be a summation of each individual item score. If ≤ 50% of item 
scores are missing, the subscale score will be calculated by multiplying the sum of the item 
scores by the number of items in the subscale, then divided by the number of non-missing 
item scores. This imputes the missing scores by the mean of the non-missing scores within a 
subscale. 
Prorated subscale score = [sum of item scores] x [N of items in subscale]/ [N of items 
answered] 
The following composite scores will be derived from the above subscale total scores: 
 FACT_Lym Trial Outcome Index (TOI, score range: 0-116) = PWB + FWB + LymS 
 FACT_G Total Score (score range: 0-108) = PWB + SWB + EWB + FWB 
 FACT_Lym Total Score (score range: 0-168) = PWB + SWB + EWB + FWB + 
LymS 
The TOI, FACT-G, and FACT-Lym Total scores will be set to missing if 20% or more of the 
included items are missing (eg, only calculated if at least 22 of 27 FACT-G items are 
completed) or any of the component subscales are missing. 
The mean and mean change from baseline to each subsequent assessment will be 
summarized for the subscale and composite scores. The best change from baseline during the 
study, defined as the highest positive value among all post-baseline visits minus the baseline 
value, will also be summarized.  
A change of 3 points for LymS and FACT-G Total Score, 6 points for FACT-Lym TOI, and 7 
points for FACT-Lym Total score are considered MID (Carter et al., 2008, Kimberly et al., 
2003). Patients will be classified as improved/deteriorated based on the established MID for 
each measure. Proportion of patients with improvement/deterioration will be summaried.   
Completion rate of FACT-Lym will be calculated as the number of patients with scores to 
calculate at least FACT-Lym TOI or FACT-G Total Score or FACT-Lym Total Score divided 
by the number of patients treated at a visit. Summary of completion rate at each visit will be 
presented. 
Summary analyses will include data up to the start of subsequent anticancer 
therapy/procedure. 
A data listing for each individual item, the subscale scores and the composite scores will be 
presented for each subject at each visit. 


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5 Interim Analyses  
When the first 52 patients dosed have two tumor assessments (approximately 12 weeks after 
start of study drug), an interim analysis will be performed. The overall response rate and the 
corresponding 95% two-sided exact confidence interval will be reported. If <10 patients 
respond, the study enrollment will be halted. 
Other analyses such DOR, PFS, CR rate, RFS, OS, and safety analyses may be performed if 
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6 Final Analysis 
For primary and key secondary endpoints analyses, a database snapshot will be taken when 
all patients who achieve a response have a minimum of 6 months follow up after initial 
documented response.  All efficacy, safety, and PK endpoints will be analyzed and reported 
in the clinical study report (CSR). 
The exact binomial test will be used in the final analyses for the primary endpoint because of 
the practical consideration that accrual cannot be limited to exactly 140 patients and because 
patients included in the interim analysis as non-responding may be included in the final 
analysis as responding if they experience a late response. 
Follow-up analyses will be performed when all the patients complete the study per protocol.  
The results will be reported in a CSR addendum. 
  
 


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7 Data handling conventions 
7.1 General conventions 
7.1.1 Missing data 
Handling of missing/partial dates   
In general, imputation of missing dates will be made for AE onset date, AE resolution date, 
date of death, medication start/end dates, start and end dates of prior and subsequent 
therapies, and date of initial diagnosis for reporting. No imputation should be done at the data 
level. 
 If dates are completely missing, no imputation will be made.  
 For any partial date with missing year, no imputation will be made. 
 For missing initial diagnosis date and subsequent therapies, if only day is missing, 
then the 15th of the month will be used; if only year is present, then June 30th will be 
used. If such imputed date for initial diagnosis is on or after date of first dose, then 
date of first dose - 1 will be used. If such imputed date for subsequent therapies is 
before date of last dose, then date of last dose +1 will be used. 
 If the imputed date is for an AE start date and is in the same year and month as but 
before the first dose date, then the first dose date will be used, or if the imputed AE 
start date is after the AE end date, then the AE end date will be used. If the imputed 
date is for an AE start date and is in the same year and month as but after the last dose 
date + 30 days, then the last dose date + 30 days will be used. 
 If a medication date or time is missing or partially missing, so it cannot be determined 
whether it was taken prior or concomitantly, it will be considered as a prior and 
concomitant medication. 
 If the imputed date is for a date of death and is before the last date that the patient is 
known to be alive, the latter date will be used. 
 If the date part is missing for new anticancer therapy, the month and year will be used 
for comparison with disease assessment. 
Handling of missing relationship to investigational product of TEAEs 
If the assessment of the relationship to IP is missing, then the relationship to IP has to be 
assumed and the TEAE considered as such in the frequency tables of possibly related 
TEAEs, but no imputation should be done at the data level. 
Handling of missing severity/grades of AEs 
If the severity/grade is missing for one of the treatment emergent occurrences of an AE, the 
maximal severity of the remaining occurrences will be considered. If the severity is missing 
for all the occurrences a “missing” category will be added in summary table. 
No other imputation of values for missing data will be performed. 


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7.1.2 Unscheduled visits 
Unscheduled visit measurements of laboratory data, vital signs, and ECG will be used for 
computation of baseline and worst values and/or grades. Re-windowing for unscheduled 
visits will not be performed  
7.1.3 Duplicated visits 
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. 
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 taken on the same 
day. 
 
 


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8 Reference List 
Carter GC, Liepa AM, Zimmerman AH, Morschhauser F. Validation of the functional 
assessment of cancer therapylymphoma (FACT-Lym) in patients with relapsed/refractory 
mantle cell lymphoma. Blood 2008; 112:828 (abstract 2376). 
Kimberly Webster, David Cella and Kathleen Yost. The Functional Assessment of Chronic 
Illness Therapy (FACIT) Measurement System: properties, applications, and interpretation. 
Health and Quality of Life Outcomes 2003; 1:79. 
Pickard AS, Neary MP, Cella D. Estimation of minimally important differences in EQ-5D 
utility and VAS scores in cancer. Health and Quality of Life Outcomes 2007; 5:70. 
 
 




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SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SCT 
Stem cell transplant 
SD 
Stable disease 
SMQ 
Standardised MedDRA Query 
SOC 
System organ class 
SPD 
Sum of product of the perpendicular diameters  
std 
Standard deviation 
TEAE 
Treatment-emergent adverse event 
WHODRUG DD 
World Health Organization Drug Dictionary  
 
 
 


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Appendix 2 List of Post-Text Tables, Figures, Listings, and Supportive SAS Output 
Appendices 
This list of ouputs is for the purpose of programming instruction, the SAP is not required to 
be updated for changes in future list. 
14.1 DISPOSITION DATA TABLES  
 
14.1.1.1 Subject Disposition (All-Treated Population) 
14.1.1.2 Subject Disposition (Per-Protocol Population) 
14.1.1 Subject Analysis Sets (All Enrolled patients) 
 
14.1.2 PROTOCOL DEVIATION DATA TABLE 
 
14.1.2 Important Protocol Deviations (All-Treated Population)  
14.1.3 DEMOGRAPHIC DATA TABLE 
 
14.1.3.1.1 Demographic and Baseline Characteristics (All-Treated Population) 
14.1.3.1.2 Demographic and Baseline Characteristics (Per-Protocol Population)  
14.1.4 CANCER HISTORY DATA TABLE 
 
14.1.4.1 Cancer History (All-Treated Population) 
14.1.5 Prior Anticancer Procedure or Therapy DATA TABLE 
14.1.5.1 Prior Systemic Anti-cancer Therapy, Surgery, Radiotherapy, and Stem Cell Transplant (All-Treated 
Population) 
14.1.6 Medical History DATA TABLE 
14.1.6 Medical History by System Organ Class and Preferred Term (All-Treated Population) 
14.1.7 PRE-TREATMENT DISEASE CHARACTERISTICS DATA TABLE 
14.1.7.1 Pre-treatment Disease Characteristics (All-Treated Population) 
14.1.8 Cytogenetic Analysis DATA TABLE 
14.1.8 Cytogenetic Analysis (All-Treated Population) 
14.1.9 Immunophenotypic Analysis DATA TABLE 
14.1.9 Immunophenotypic Analysis (All-Treated Population) 
14.1.10 prior mdedications DATA TABLE 
14.1.10 Prior Medications (All-Treated Population)                                                                                                                                 
14.2 EFFICACY DATA TABLE 
14.2.1.1.1 Overall Response Rate (All-Treated Population) 
              Note: Including the 95% CI for CR in the table 
14.2.1.1.2 Overall Response Rate (Per-Protocol Population) 
14.2.1.1.3 Overall Response Rate by Investigator (All-Treated Population) 
14.2.1.1.4 Overall Response Rate by Investigator (Per-Protocol Population) 
14.2.1.1.5 Overall Response Rate for CAR-T patients from Response Data Collected after CAR-T Therapy (All-
Treated Population) 
14.2.1.1.6 Overall Response Rate by Sex (All-Treated Population) 
14.2.1.1.7 Overall Response Rate by Age Group (All-Treated Population) 


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14.2.1.1.8 Overall Response Rate by Country (All-Treated Population) 
14.2.1.1.9 Overall Response Rate by Primary Category of Disease Diagnosis (All-Treated Population) 
14.2.1.1.10 Overall Response Rate by Bulky Disease (Yes/No) (All-Treated Population) 
14.2.1.1.11 Overall Response Rate by Double/Triple Hit (Yes/No) (All-Treated Population) 
14.2.1.1.12 Overall Response Rate by First Line Response Category of Prior Systemic Therapies (All-Treated 
Population) 
14.2.1.1.13 Overall Response Rate by Last Line Response Category of Prior Systemic Therapies (All-Treated 
Population) 
14.2.1.1.14 Overall Response Rate by Number of Prior Systemic Therapies Group (All-Treated Population) 
14.2.1.1.15 Overall Response Rate by Transformed and De novo (All-Treated Population) 
14.2.1.1.16 Overall Response Rate by Disease Stage (All-Treated Population) 
14.2.1.1.17 Overall Response Rate by Subtype of Germinal center B-cell and Activated B-cell (All-Treated 
Population) 
14.2.1.1.18 Overall Response Rate by Use of Prior CAR-T Therapy (Yes/No) (All-Treated Population) 
14.2.2.1.1 Best Percent Change from Baseline in Sum of the Product of Perpendicular Diameters (SPD) (All-
Treated Population) 
14.2.2.2.1 Summary of Duration of Response (All-Treated Population) 
14.2.3.1.1 Time to First CR or PR Response (All-Treated Population)                                                                                                    
14.3 EXPOSURE TO TREATMENT DATA AND SAFETY DATA TABLES 
 
14.3.1 EXPOSURE TO TREATMENT DATA TABLES  
14.3.1.1.1 Study Drug Administration and Extent of Exposure (All-Treated Population) 
14.3.1.1.2 Summary of Study Drug Dose Changes by Cycle (All-Treated Population) 
14.3. 2 Concomitant Medications DATA TABLES 
 
14.3.2.1 Concomitant Medications (All-Treated Population) 
14.3.3 ADVERSE EVENT DATA TABLES 
 
 
14.3.3.1.1 Overall Summary of Treatment-emergent Adverse Events (All-Treated Population) 
 
14.3.3.1.2 Overall Summary of Treatment-emergent Adverse Events by Sex (All-Treated Population) 
14.3.3.1.3 Overall Summary of Treatment-emergent Adverse Events by Age Group (All-Treated Population)  
14.3.3.1.4 Overall Summary of Treatment-emergent Adverse Events by Country (All-Treated Population) 
14.3.3.1.5 Overall Summary of Treatment-emergent Adverse Events by Race Group (All-Treated Population) 
14.3.3.1.6 Overall Summary of Treatment-emergent Adverse Events by Primary Category of Disease Diagnosis 
(All-Treated Population) 
 
14.3.3.2.1 Treatment-emergent Adverse Events by Preferred Term (All-Treated Population) 
14.3.3.2.2 Treatment-emergent Adverse Events by Preferred Term for Grade ≥3 (All-Treated Population) 
14.3.3.3.1 Treatment-emergent Adverse Events by System Organ Class and Preferred Term (All-Treated 
Population) 
14.3.3.4.1 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum CTCAE 
Grade (All-Treated Population) 
14.3.3.4.2 Serious Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade (All-Treated Population) 


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14.3.3.4.3 Study Drug Related Treatment-emergent Adverse Events by System Organ Class, Preferred Term, 
and Maximum Severity (All-Treated Population) 
14.3.3.4.4 Treatment-emergent Adverse Events Leading to Dose Delay by System Organ Class, Preferred Term, 
and Maximum Severity (All-Treated Population) 
14.3.3.4.5 Study Drug Related Treatment-emergent Adverse Events Leading to Dose Delay by System Organ 
Class, Preferred Term, and Maximum Severity (All-Treated Population) 
14.3.3.4.6 Treatment-emergent Adverse Events Leading to Dose Reduction by System Organ Class, Preferred 
Term, and Maximum Severity (All-Treated Population) 
14.3.3.4.7 Study Drug Related Treatment-emergent Adverse Events Leading to Dose Reduction by System 
Organ Class, Preferred Term, and Maximum Severity (All-Treated Population) 
14.3.3.4.8 Treatment-emergent Adverse Events Leading to Treatment Withdrawal by System Organ Class, 
Preferred Term, and Maximum Severity (All-Treated Population) 
14.3.3.4.9 Study Drug Related Treatment-emergent Adverse Events Leading to Treatment Withdrawal by 
System Organ Class, Preferred Term, and Maximum Severity (All-Treated Population) 
14.3.3.4.10 Treatment-emergent Adverse Events Leading to Infusion Interruption by System Organ Class, 
Preferred Term, and Maximum Severity (All-Treated Population) 
14.3.3.4.11 Treatment-emergent Adverse Events with Fatal Outcome by System Organ Class, Preferred Term, 
and Maximum Severity (All-Treated Population) 
14.3.3.4.12 Infusion Related Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and 
Maximum Severity (All-Treated Population) 
14.3.3.4.13 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade for Female Patients (All-Treated Population) 
14.3.3.4.14 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade for Male Patients (All-Treated Population) 
14.3.3.4.15 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade for Patients Age <65 years old (All-Treated Population) 
14.3.3.4.16 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade for Patients Age between 65 - 74 years old (All-Treated Population) 
14.3.3.4.17 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade for Patients Age ≥75 years old (All-Treated Population) 
14.3.3.4.18 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade for Patients in USA (All-Treated Population) 
14.3.3.4.19 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade for Patients in United Kingdom (All-Treated Population) 
14.3.3.4.20 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade for Patients in Italy (All-Treated Population) 
14.3.3.4.21 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade for Race = White (All-Treated Population) 
14.3.3.4.22 Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Maximum 
CTCAE Grade for for Race other than White (All-Treated Population) 
14.3.3.4.23 Treatment-emergent Adverse Events with Grade ≥3 by System Organ Class, Preferred Term, and 
Maximum Severity (All-Treated Population) 
14.3.3.4.24 Selected Treatment-emergent Adverse Events by Grouped AE, Preferred Term, and Maximum 
Severity (All-Treated Population) 


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14.3.3.4.25 Summary of Adverse Events ≥Grade 3 suggestive of Selected Conditions for Patients Undergo Stem 
Cell Transplant after Discontinuation of Study Drug (Stem Cell Transplant Population) 
Note: conditions includes hepatic toxicity, veno-occlusive disease/sinusoidal obstruction syndrome, graft-versus-
host disease, infectious complications, prolonged cytopenia(s), and pulmonary toxicity 
14.3.3.4.26 Serious Adverse Events by System Organ Class, Preferred Term, and Maximum CTCAE Grade for 
Patients Undergo Stem Cell Transplant after Discontinuation of Study Drug (Stem Cell Transplant Population) 
14.3.3.4.27 Summary of Adverse Events ≥Grade 3 suggestive of Selected Conditions for Patients Receive CAR-
T Therapy after Discontinuation of Study Drug (All-Treated Population) 
Note: conditions includes cytokine release syndrome, encephalopathy, edema or effusion, rash, hepatic toxicity 
14.3.3.4.28 Serious Adverse Events by System Organ Class, Preferred Term, and Maximum CTCAE Grade for 
Patients Receive CAR-T Therapy after Discontinuation of Study Drug (All-Treated Population) 
14.3.3.5.1RG Non-serious Treatment-emergent Adverse Events by System Organ Class and Preferred Term 
with a Frequency of ≥5% in Any Treatment Group (All-Treated Population) 
14.3.3.5.2RG Serious Treatment-emergent Adverse Events by System Organ Class and Preferred Term (All-
Treated Population) 
14.3.3.5.3RG Study Drug Related Serious Treatment-emergent Adverse Events by System Organ Class and 
Preferred Term (All-Treated Population) 
14.3.3.5.4RG Treatment-emergent Adverse Events with Fatal Outcome by System Organ Class and Preferred 
Term (All-Treated Population) 
14.3.3.5.5RG Study Drug Related Treatment-emergent Adverse Events with Fatal Outcome by System Organ 
Class and Preferred Term (All-Treated Population) 
14.3.3.5.6RG Non-serious Treatment-emergent Adverse Events by System Organ Class and Preferred Term 
(All-Treated Population) 
14.3.3.5.7RG Number of Serious Treatment-emergent Adverse Events by System Organ Class and Preferred 
Term (All-Treated Population) 
14.3.3.5.8RG Number of Study Drug Related Serious Treatment-emergent Adverse Events by System Organ 
Class and Preferred Term (All-Treated Population) 
14.3.3.5.9RG Number of Non-Serious Treatment-emergent Adverse Events by System Organ Class and 
Preferred Term (All-Treated Population) 
14.3.4 LABORATORY DATA TABLES 
 
14.3.4.1.1 Summary of Hematology Results by Visits (All-Treated Population) 
 
14.3.4.2.1 Summary of Biochemistry Results by Visits (All-Treated Population) 
14.3.4.3.1 Summary of Coagulation Results by Visits (All-Treated Population) 
14.3.4.4.1 Shift Summary of Hematology Results by Maximum CTCAE Grade (All-Treated Population) 
14.3.4.4.1a Hematology Shift CTCAE from Baseline Grade ≤2 to Post-baseline Grade ≥3 (All-Treated 
Population) 
14.3.4.5.1 Shift Summary of Biochemistry Results by Maximum CTCAE Grade (All-Treated Population) 
14.3.4.5.1a Biochemistry Shift CTCAE from Baseline Grade ≤2 to Post-baseline Grade ≥3 (All-Treated 
Population) 
14.3.4.6.1 Shift Summary of Coagulation Results by Maximum CTCAE Grade (All-Treated Population) 
14.3.4.7.1 Maximum Post-baseline Hematology CTCAE Grade (All-Treated Population) 
14.3.4.8.1 Maximum Post-baseline Biochemistry CTCAE Grade (All-Treated Population) 
14.3.4.9.1 Maximum Post-baseline Coagulation CTCAE Grade (All-Treated Population) 


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14.3.5 VITAL SIGN DATA TABLE  
14.3.5.1 Summary of Vital Signs by Visit and Time Point (All-Treated Population) 
14.3.6 ELECTROCARDIOGRAM DATA TABLES 
 
14.3.6.1 Summary of ECG for Heart Rate and QTc by Visit and Time Point (All-Treated Population)  
14.3.6.2 Summary of QTc Abnormality (All-Treated Population) 
14.3.6.3 Shift Summary of QTc Interval (All-Treated Population) 
14.3.7 DEATH DATA TABLE 
14.3.7.1 Summary of Death (All-Treated Population) 
14.3.7.2 Summary of Death after Transplant (Stem Cell Transplant Population) 
14.3.7.3 Summary of Death after CAR-T Therapy (All-Treated Population) 
14.3.8 ECOG DATA TABLE 
14.3.8.1 Summary of ECOG Performance Score by Visits (All-Treated Population) 
14.3.9 PRO DATA TABLE 
14.3.9.1.1 Summary of EQ-5D-5L VAS Score by Visits (PRO Population) 
14. 3.9.1.2 Frequency Distribution of the Individual Dimension Response from EQ-5D-5L Descriptive System by 
Visits (PRO Population) 
14. 3.9.1.3 Summary of Patients Classified as Improvement/Deterioration Based on Minimally Clinically 
Important Difference for EQ-5D-5L VAS Score (PRO Population) 
14. 3.9.1.4 Completion Rate for EQ-5D-5L Descriptive System and VAS Score by Visit (PRO Population) 
14. 3.9.2.1 Summary of Subscale and Composite Scores from FACT-Lym by Visits (PRO Population) 
14. 3.9.2.2 Best Change from Baseline in Subscale and Composite Scores from FACT-Lym (PRO Population) 
14. 3.9.2.3 Summary of Patients Classified as Improvement/Deterioration Based on Minimally Clinically 
Important Difference for FACT-Lym Subscale and Composite Scores (PRO Population) 
14. 3.9.2.4 Completion Rate for FACT-Lym Subscale and Composite Scores by Visit (PRO Population) 
                                                                                                                        
14 FIGURES 
 
14.2 EFFICACY FIGURES  
14.2.1.5.1 Waterfall Plot of Best Percent Change from Baseline in Tumor Size (All-Treated Population) 
14.2.1.5.2 Waterfall Plot of Best Percent Change from Baseline in Tumor Size (Per-Protocol Population) 
14. 2.1.6.1 Kaplan-Meier Plot of Progression-free Survival (All-Treated Population) 
14. 2.1.6.2 Kaplan-Meier Plot of Progression-free Survival (Per-Protocol Population) 
14. 2.1.6.3 Kaplan-Meier Plot of Progression-free Survival with Clinical Progression as an Event (All-Treated 
Population) 
14. 2.1.6.4 Kaplan-Meier Plot of Progression-free Survival with Stem Cell Transplant not Censored (All-Treated 
Population)  
14. 2.1.6.5 Kaplan-Meier Plot of Progression-free Survival by Primary Category of Disease Diagnosis (All-
Treated Population) 
14. 2.1.6.6 Kaplan-Meier Plot of Progression-free Survival by Double/Triple Hit (Yes/No) (All-Treated Population) 
14. 2.1.6.7 Kaplan-Meier Plot of Progression-free Survival by First Line Prior Systemic Therapy Response Group 
(All-Treated Population) 


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14. 2.1.6.8 Kaplan-Meier Plot of Progression-free Survival by Number of Prior Systemic Therapy Line Group (All-
Treated Population) 
14. 2.1.6.9 Kaplan-Meier Plot of Progression-free Survival by Last Line Prior Systemic Therapy Response Group 
(All-Treated Population) 
14. 2.1.7.1 Kaplan-Meier Plot of Relapse-free Survival (All-Treated Population) 
14. 2.1.7.2 Kaplan-Meier Plot of Relapse -free Survival (Per-Protocol Population) 
14. 2.1.7.3 Kaplan-Meier Plot of Relapse -free Survival with Clinical Progression as an Event (All-Treated 
Population) 
14. 2.1.7.4 Kaplan-Meier Plot of Relapse -free Survival with Stem Cell Transplant not Censored (All-Treated 
Population)  
14. 2.1.7.5 Kaplan-Meier Plot of Relapse -free Survival by Primary Category of Disease Diagnosis (All-Treated 
Population) 
14. 2.1.7.6 Kaplan-Meier Plot of Relapse -free Survival by Double/Triple Hit (Yes/No) (All-Treated Population) 
14. 2.1.7.7 Kaplan-Meier Plot of Relapse -free Survival by First Line Prior Systemic Therapy Response Group 
(All-Treated Population) 
14. 2.1.7.8 Kaplan-Meier Plot of Relapse -free Survival by Number of Prior Systemic Therapy Line Group (All-
Treated Population) 
14. 2.1.7.9 Kaplan-Meier Plot of Relapse -free Survival by Last Line Prior Systemic Therapy Response Group 
(All-Treated Population) 
14. 2.1.8.1 Kaplan-Meier Plot of Overall Survival (All-Treated Population) 
14. 2.1.8.2 Kaplan-Meier Plot of Overall Survival (Per-Protocol Population) 
14. 2.1.8.3 Kaplan-Meier Plot of Overall Survival by Primary Category of Disease Diagnosis (All-Treated 
Population) 
14. 2.1.9.1 Kaplan-Meier Plot of Duration of Response (All-Treated Population) 
14. 2.1.9.2 Kaplan-Meier Plot of Duration of Response (Per-Protocol Population) 
14. 2.1.9.3 Kaplan-Meier Plot of Duration of Response with Clinical Progression as an Event (All-Treated 
Population) 
14. 2.1.9.4 Kaplan-Meier Plot of Duration of Response with Stem Cell Transplant not Censored (All-Treated 
Population) 
14. 2.1.9.5 Kaplan-Meier Plot of Duration of Response by Primary Category of Disease Diagnosis (All-Treated 
Population) 
14. 2.1.9.6 Kaplan-Meier Plot of Duration of Response by Double/Triple Hit (Yes/No) (All-Treated Population) 
14. 2.1.9.7 Kaplan-Meier Plot of Duration of Response by First Line Prior Systemic Therapy Response Group 
(All-Treated Population) 
14. 2.1.9.8 Kaplan-Meier Plot of Duration of Response by Number of Prior Systemic Therapy Line Group (All-
Treated Population) 
14. 2.1.9.9 Kaplan-Meier Plot of Duration of Response by Last Line Prior Systemic Therapy Response Group 
(All-Treated Population) 
14. 2.1.9.10 Kaplan-Meier Plot of Duration of Response by CR and PR (All-Treated Population) 
14. 2.1.9.11 Kaplan-Meier Plot of Duration of Response by Age Group (All-Treated Population) 
14. 2.1.9.12 Kaplan-Meier Plot of Duration of Response by Transformed and De novo (All-Treated Population)  
14. 2.1.9.13 Kaplan-Meier Plot of Duration of Response by Disease Stage (All-Treated Population)  


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14. 2.1.9.14 Kaplan-Meier Plot of Duration of Response by Bulky Disease (Yes/No) (All-Treated Population)  
14. 2.1.9.15 Kaplan-Meier Plot of Duration of Response by Subtype of Germinal center B-cell/Activated B-cell 
(All-Treated Population) 
14.2.1.10.1 Swimmer Plot (All-Treated Population) 
14.2.1.10.2 Swimmer Plot (Per-Protocol Population) 
14.2.1.11.1 Kaplan-Meier Plot of Time to First AE Leading to Dose Modification (All-Treated Population) 
14.3 SAFETY FIGURES 
 14.3.4.1.1.1 Mean (SE) Plot of Basophils (10^9/L) by Dose Group (All-Treated Population) 
14.3.4.1.1.2 Mean (SE) Plot of Eosinophils (10^9/L) by Dose Group (All-Treated Population) 
 
14.3.4.1.1.3 Mean (SE) Plot of Hematocrit (fraction of 1) by Dose Group (All-Treated Population) 
 
14.3.4.1.1.4 Mean (SE) Plot of Hemoglobin (g/L) by Dose Group (All-Treated Population)  
14.3.4.1.1.5 Mean (SE) Plot of Lymphocytes (10^9/L) by Dose Group (All-Treated Population) 
 
14.3.4.1.1.6 Mean (SE) Plot of Monocytes (10^9/L) by Dose Group (All-Treated Population) 
 
14.3.4.1.1.7 Mean (SE) Plot of Neutrophils (10^9/L) by Dose Group (All-Treated Population) 
 
14.3.4.1.1.8 Mean (SE) Plot of Platelets (10^9/L) by Dose Group (All-Treated Population)  
14.3.4.1.1.9 Mean (SE) Plot of Leukocytes (10^9/L) by Dose Group (All-Treated Population) 
 
14.3.4.1.1.10 Mean (SE) Plot of Basophils/Leukocytes (fraction of 1) by Dose Group (All-Treated Population) 
14.3.4.1.1.11 Mean (SE) Plot of Eosinophils/Leukocytes (fraction of 1) by Dose Group (All-Treated Population) 
14.3.4.1.1.12 Mean (SE) Plot of Lymphocytes/Leukocytes (fraction of 1) by Dose Group (All-Treated Population) 
14.3.4.1.1.13 Mean (SE) Plot of Monocytes/Leukocytes (fraction of 1) by Dose Group (All-Treated Population) 
14.3.4.1.1.14 Mean (SE) Plot of Neutrophils/Leukocytes (fraction of 1) by Dose Group (All-Treated Population) 
14.3.4.2.1.1 Mean (SE) Plot of Albumin (g/L) by Dose Group (All-Treated Population) 
 
 
14.3.4.2.1.2 Mean (SE) Plot of Alanine Aminotransferase (U/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.3 Mean (SE) Plot of Aspartate Aminotransferase (U/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.4 Mean (SE) Plot of Alkaline Phosphatase (U/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.5 Mean (SE) Plot of Bilirubin (umol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.6 Mean (SE) Plot of Gamma Glutamyl Transferase (U/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.7 Mean (SE) Plot of Amylase (U/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.8 Mean (SE) Plot of Bicarbonate (mmol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.9 Mean (SE) Plot of Blood Urea Nitrogen (mmol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.10 Mean (SE) Plot of Calcium (mmol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.11 Mean (SE) Plot of Cholesterol (mmol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.12 Mean (SE) Plot of Creatine Kinase (U/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.13 Mean (SE) Plot of Chloride (mmol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.14 Mean (SE) Plot of Creatinine (umol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.15 Mean (SE) Plot of Creatinine Clearance (mL/min) by Dose Group (All-Treated Population) 
14.3.4.2.1.16 Mean (SE) Plot of Glucose (mmol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.17 Mean (SE) Plot of Potassium (mmol/L) by Dose Group (All-Treated Population) 


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14.3.4.2.1.18 Mean (SE) Plot of Lactate Dehydrogenase (U/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.19 Mean (SE) Plot of Lipase (U/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.20 Mean (SE) Plot of Magnesium (mmol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.21 Mean (SE) Plot of Phosphate (mmol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.22 Mean (SE) Plot of Protein (g/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.23 Mean (SE) Plot of Sodium (mmol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.24 Mean (SE) Plot of Triglycerides (mmol/L) by Dose Group (All-Treated Population) 
14.3.4.2.1.25 Mean (SE) Plot of Urea (mmol/L) by Dose Group (All-Treated Population)  
14.3.5.1.1 Mean (SE) Plot of ECG Heart Rate (beats/min) by Dose Group (All-Treated Population) 
14.3.5.1.2 Mean (SE) Plot of QTc (msec) by Dose Group (All-Treated Population) 
 
 
16 LISTINGS 
16.1.1 Demographic and Baseline Data (All-Treated Population) 
 
16.1.2 Patients Disposition (All-Treated Population) 
 
16.1.3 Number of Prior Therapies and Best Overall Response (All-Treated Population) 
 
16.1.4 Cancer History (All-Treated Population) 
 
16.1.5 Prior and Concomitant Medications (All-Treated Population) 
 
16.1.6 Dosing Pre-Medication (All-Treated Population) 
 
16.1.7 Prior Systemic Anticancer Therapy (All-Treated Population) 
 
16.1.8 Prior Surgery (All-Treated Population)  
16.1.9 Prior Radiotherapy (All-Treated Population) 
 
16.1.10 Prior Stem Cell Transplant (All-Treated Population)  
16.1.11 Medical History (All-Treated Population) 
16.1.12 Subsequent Anticancer Therapy and Procedures (All-Treated Population) 
16.1.13 Cytogenetic Analysis (All-Treated Population) 
16.1.14 Immunophenotypic Analysis (All-Treated Population) 
16.1.15 Important Protocol Deviation (All-Treated Population) 
16.2.1 Tumor Measurements and Evaluations (All-Treated Population) 
16.2.2 Duration of Response (DOR), Progression-free Survival (PFS), Regression-free Survival (RFS) and 
Overall Survival (OS) (All-Treated Population) 
16.3.1 ADCT-402 Exposure and Infusion Details (All-Treated Population) 
16.4.1 Adverse Events (All-Treated Population) 
16.4.2.1 Treatment-emergent Serious Adverse Events (All-Treated Population) 
16.4.2.2 Nontreatment-emergent Serious Adverse Events (All-Treated Population) 
16.4.3 Treatment-Emergent Adverse Events Leading to Treatment Withdrawal (All-Treated Population) 
16.4.4.1 Treatment-emergent Adverse Events Leading to Death (All-Treated Population) 
16.4.4.2 Nontreatment-emergent Adverse Events Leading to Death (All-Treated Population) 
16.4.5 Infusion Related Reaction Treatment-emergent Adverse Events (All-Treated Population) 


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16.4.6 Treatment-emergent Adverse Events Leading to Dose Reduction (All-Treated Population) 
16.4.7 Treatment-emergent Adverse Events Leading to Dose Delay (All-Treated Population) 
16.4.8 Treatment-emergent Adverse Events Leading to Dose Interruption (All-Treated Population) 
16.4.9 All-cause Deaths (All-Treated Population) 
16.4.10 Vital Signs (All-Treated Population) 
16.4.11 Electrocardiogram Results (All-Treated Population) 
16.4.12 Laboratory Analysis Data: Hematology (All-Treated Population) 
16.4.13 Laboratory Analysis Data: Biochemistry Data (All-Treated Population) 
16.4.14 Laboratory Analysis Data: Coagulation (All-Treated Population) 
16.4.15 Laboratory Analysis Data: Urinalysis (All-Treated Population) 
16.4.16 ECOG Performance Status (All-Treated Population) 
16.4.17 EQ-5D-5L Individual Dimension Response and VAS Score (PRO Population) 
16.4.18 FACT-Lym Individual Item, Subscale Scores, and Composite Scores (PRO Population) 

Prot_000.pdf: 
Protocol Number:  ADCT-402-201 
 
Official Title:   Phase 2 Open-Label Single-Arm Study to Evaluate the Efficacy and 
Safety of Loncastuximab Tesirine in Patients with Relapsed or Refractory 
Diffuse Large B-Cell Lymphoma (DLBCL) 
 
NCT Number:  NCT03589469 
 
Document Date:  09 July 2019 


ADC Therapeutics 
Loncastuximab Tesirine 
ADCT-402-201 Clinical Protocol Amendment 4 
 
Date of Protocol Amendment 4: 09 July 2019 
 
 
Page 1 
 
CLINICAL STUDY PROTOCOL 
IND: 126138 
EudraCT Number: 2017-004288-11 
 
A Phase 2 Open-Label Single-Arm Study to Evaluate the Efficacy and 
Safety of Loncastuximab Tesirine in Patients with Relapsed or Refractory 
Diffuse Large B-Cell Lymphoma (DLBCL) 
PROTOCOL NO.: ADCT-402-201 
 
Sponsor: 
ADC Therapeutics SA 
 
 
Sponsor Contact: 
 
 
 
 
 
 
 
Date of Original Protocol:  
Protocol Amendment 1: 
Protocol Amendment 2: 
Protocol Amendment 3: 
Protocol Amendment 4: 
09 March 2018 
05 April 2018 
24 September 2018 
07 June 2019 
09 July 2019 
 
 
 
 
 
 
 
 
Confidentiality Statement 
The concepts and information contained in this document or generated during the study are 
considered proprietary and may not be disclosed in whole or in part without the express 
written consent of ADC Therapeutics SA.   
 




ADC Therapeutics 
Loncastuximab Tesirine 
ADCT-402-201 Clinical Protocol Amendment 4 
 
Date of Protocol Amendment 4: 09 July 2019 
 
 
Page 3 
Declaration of Investigator 
 
I have read and understood all sections of the protocol entitled: “A Phase 2 Open-Label 
Single-Arm Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients 
with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)” and the 
accompanying Investigator’s Brochure (IB).  
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the Protocol, dated 09 July 2019, the current version of International Council 
for Harmonisation (ICH) harmonised tripartite guideline E6: Good Clinical Practice, and all 
applicable governmental regulations.  I will not make changes to the protocol before consulting 
with ADC Therapeutics or implement protocol changes without independent ethics committee 
approval except to eliminate an immediate risk to patients.  I agree to administer the study drug 
only to patients under my personal supervision or the supervision of a sub-Investigator. 
I will not supply the study drug to any person not authorized to receive it.  Confidentiality will 
be protected. Patient identity will not be disclosed to third parties or appear in any study reports 
or publications. 
I will not disclose information regarding this clinical investigation or publish results of the 
investigation without authorization from ADC Therapeutics SA.  
 
 
 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
 
 
 
Printed Name of Principal Investigator 
 
 
 


ADC Therapeutics 
Loncastuximab Tesirine 
ADCT-402-201 Clinical Protocol Amendment 4 
 
Date of Protocol Amendment 4: 09 July 2019 
 
 
Page 4 
Protocol Amendment Summary of Changes  
 
Overall Changes and Rationale from Amendment 2 
 
• Section 6.3 was updated to include text regarding monitoring for extravasation 
during or after study drug infusion because of updated safety information. 
• Section 6.4 was modified to clarify dose delays and modifications for non-
hematologic and hematologic toxicities.  
• Section 8.1 was modified to allow for capture of response information during the 
follow-up period for patients who receive CAR-T therapy after loncastuximab 
tesirine treatment. 
• Section 8.2.2 was modified to add AE/SAE reporting requirements for patients who 
receive CAR-T therapy after study drug discontinuation.  
• Editorial corrections and clarifications were applied throughout. 
 
Note: Amendment 3 was approved internally by ADC Therapeutics but not submitted to any 
trial sites, regulatory agencies, or ethics committees.  All changes from Amendment 2 are 
included in Amendment 4. 
 
 


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ADCT-402-201 Clinical Protocol Amendment 4 
 
Date of Protocol Amendment 4: 09 July 2019 
 
 
Page 5 
Table of Contents 
 
Protocol Amendment Summary of Changes ............................................................................. 4 
Table of Contents ...................................................................................................................... 5 
List of Tables ............................................................................................................................. 8 
List of Figures ........................................................................................................................... 8 
List of Abbreviations................................................................................................................. 9 
Protocol Synopsis.................................................................................................................... 12 
Schedule of Events .................................................................................................................. 18 
1 
Introduction and Background ......................................................................................... 20 
1.1 
Diffuse Large B-Cell Lymphoma ................................................................................20 
1.2 
Description of Investigational Study Drug ..................................................................21 
1.3 
Safety and Efficacy of Loncastuximab Tesirine in Phase 1 Study, ADCT-402-101 ....22 
2 
Study Rationale .............................................................................................................. 24 
2.1 
Rationale for Study Design ..........................................................................................24 
2.2 
Rationale for Dose Selection .......................................................................................24 
3 
Study Objectives and Endpoints ..................................................................................... 26 
4 
Study Design .................................................................................................................. 27 
4.1 
Overview ......................................................................................................................27 
4.2 
Screening Period ..........................................................................................................27 
4.3 
Treatment Period ..........................................................................................................27 
4.4 
End of Treatment..........................................................................................................28 
4.5 
Follow-up Period .........................................................................................................28 
4.6 
End of Study ................................................................................................................28 
5 
Patient Population ........................................................................................................... 29 
5.1 
Inclusion Criteria .........................................................................................................29 
5.2 
Exclusion Criteria ........................................................................................................30 
5.3 
Screening Failures ........................................................................................................31 
6 
Treatment ........................................................................................................................ 32 
6.1 
Study Drug ...................................................................................................................32 
6.2 
Management of Clinical Supplies ................................................................................32 


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6.2.1 
Packaging and Storage ........................................................................................32 
6.2.2 
Preparation and Administration ...........................................................................33 
6.2.3 
Accountability .....................................................................................................33 
6.3 
Loncastuximab Tesirine Dosing ...................................................................................33 
6.4 
Dose Delays and Modifications ...................................................................................33 
6.5 
Overdose Management ................................................................................................34 
6.6 
Premedication and Supportive care .............................................................................34 
6.6.1 
Premedication ......................................................................................................34 
6.6.2 
Treatment of Edema and Pleural Effusion ...........................................................34 
6.6.3 
Treatment and Prophylaxis of Infusion-Related Hypersensitivity Reactions......35 
6.6.4 
Skin Rash .............................................................................................................35 
6.6.5 
Other Supportive Care .........................................................................................35 
6.7 
Concomitant Medications and Procedures ...................................................................35 
6.7.1 
Permitted During Study .......................................................................................36 
6.7.2 
Prohibited During Study ......................................................................................36 
7 
Discontinuation ............................................................................................................... 37 
7.1 
Discontinuation from Study Treatment ........................................................................37 
7.2 
Discontinuation from the Study ...................................................................................37 
7.3 
Loss to Follow-Up .......................................................................................................37 
8 
Study Assessments and Procedures ................................................................................ 38 
8.1 
Efficacy Assessments ...................................................................................................38 
8.2 
Adverse Events ............................................................................................................39 
8.2.1 
Definition of Adverse Events and Serious Adverse Events .................................39 
8.2.2 
Eliciting and Reporting Adverse Events/Serious Adverse Events ......................39 
8.2.3 
Assessment of Severity ........................................................................................40 
8.2.4 
Assessment of Causality ......................................................................................41 
8.2.5 
Regulatory Reporting ..........................................................................................41 
8.2.6 
Pregnancy ............................................................................................................41 
8.2.7 
Overdose ..............................................................................................................41 
8.3 
Safety Assessments ......................................................................................................41 
8.3.1 
Physical Examination ..........................................................................................42 
8.3.2 
ECOG Performance Status ..................................................................................42 
8.3.3 
Height and Weight ...............................................................................................42 
8.3.4 
Vital Signs ...........................................................................................................42 
8.3.5 
Laboratory Tests ..................................................................................................42 
8.3.6 
Pregnancy Test .....................................................................................................43 


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ADCT-402-201 Clinical Protocol Amendment 4 
 
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8.3.7 
ECG .....................................................................................................................43 
8.4 
Pharmacokinetics, Pharmacodynamics, and Immunogenicity .....................................44 
8.4.1 
Pharmacokinetics .................................................................................................44 
8.4.2 
Immunogenicity ...................................................................................................45 
 
 
 
 
 
 
8.5 
Health-Related Quality of Life (HRQoL) Questionnaires ...........................................46 
8.5.1 
EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) ....................................................46 
8.5.2 
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) ..............46 
9 
Statistical Considerations ............................................................................................... 47 
9.1 
Sample Size Calculation ..............................................................................................47 
9.2 
Analysis Populations ....................................................................................................47 
9.3 
Interim Analysis for Futility .........................................................................................47 
9.4 
Final Analysis...............................................................................................................48 
9.5 
Demographics and Baseline Characteristics ................................................................48 
9.6 
Efficacy Analyses .........................................................................................................48 
9.6.1 
Overall Response Rate ........................................................................................48 
9.6.2 
Duration of Response ..........................................................................................49 
9.6.3 
Complete Response Rate .....................................................................................49 
9.6.4 
Relapse-free Survival ..........................................................................................49 
9.6.5 
Progression-Free Survival ...................................................................................49 
9.6.6 
Overall Survival ...................................................................................................49 
9.6.7 
Subgroup analysis ................................................................................................50 
9.7 
Safety Analyses ............................................................................................................50 
9.7.1 
Adverse Events ....................................................................................................50 
9.7.2 
Clinical Laboratory Results .................................................................................50 
9.7.3 
Additional Safety Assessments ............................................................................51 
9.8 
Pharmacokinetic Analyses ...........................................................................................51 
9.9 
Immunogenicity Analyses ............................................................................................51 
 
10 
Data Management and Quality Assurance ..................................................................... 53 
11 
Ethical, Regulatory, and Study Management Considerations ........................................ 54 
11.1 Regulatory and Ethical Conduct of the Study..............................................................54 
11.2 Independent Ethics Committee or Institutional Review Board ...................................54 


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ADCT-402-201 Clinical Protocol Amendment 4 
 
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11.3 Patient Information and Consent .................................................................................54 
11.4 Confidentiality .............................................................................................................55 
11.5 Financial Disclosure and Obligations ..........................................................................55 
11.6 Serious Adverse Events Report Requirements ............................................................55 
11.7 Study Conduct ..............................................................................................................55 
11.8 Protocol Amendments ..................................................................................................55 
11.9 Monitoring of the Study ...............................................................................................56 
11.10 Records Retention ........................................................................................................56 
11.11 Publications ..................................................................................................................56 
12 
Reference List ................................................................................................................. 57 
13 
Appendices ..................................................................................................................... 59 
13.1 Appendix 1. Eastern Cooperative Oncology Group Performance Status ....................59 
13.2 Appendix 2. Response Assessment of Hodgkin and Non-Hodgkin Lymphoma 
(Lugano Classification) ................................................................................................60 
 
List of Tables 
 
Table 1.  
Schedule of Events .............................................................................................. 18 
Table 2. 
Study Objectives and Endpoints .......................................................................... 26 
Table 3. 
Definition of Severity Grades for CTCAE .......................................................... 40 
Table 4. 
Schedule for Triplicate ECG Collection .............................................................. 43 
Table 5. 
Sampling Schedule for PK and ADA .................................................................. 45 
 
 
List of Figures 
 
Figure 1.  Schematic Representation and Chemical Structure of Loncastuximab Tesirine . 21 
Figure 2. 
Anti-drug Antibody Tiered Immunogenicity Testing Strategy ............................ 52 
 
 
 
 


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ADCT-402-201 Clinical Protocol Amendment 4 
 
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List of Abbreviations 
Abbreviation 
Definition 
ABW 
adjusted body weight 
ADA 
anti-drug antibody 
ADC 
antibody drug conjugate 
ADR 
adverse drug reaction 
AE 
adverse event 
AI 
accumulation index 
Ala 
Alanine 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AlloSCT 
allogeneic stem cell transplant 
ANC 
absolute neutrophil count 
ASCT 
autologous stem cell transplant 
AST 
aspartate aminotransferase 
AUC0-∞ 
area under the concentration-time curve from time zero to infinity 
AUC0-last 
area under the concentration-time curve from time zero to the last 
quantifiable concentration 
AUC0-τ 
area under the concentration-time curve from time zero to the end of 
the dosing interval 
BID 
twice daily 
BMI 
body mass index 
BOR 
best overall response 
BP 
blood pressure 
CAR 
chimeric antigen receptor 
CD 
cluster of differentiation 
C1D1 
Cycle 1 Day 1 
CFR 
Code of Federal Regulations 
cfDNA 
circulating cell-free DNA 
CI 
confidence interval 
CL 
Clearance 
Cmax 
maximum concentration 
CNS 
central nervous system 
CR 
complete response 
CRO 
contract research organization 
CRR 
complete response rate 
CSR 
clinical study report 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLBCL 
diffuse large B-cell lymphoma 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 


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ADCT-402-201 Clinical Protocol Amendment 4 
 
Date of Protocol Amendment 4: 09 July 2019 
 
 
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Abbreviation 
Definition 
EOT 
end of treatment 
EQ-5D-5L 
EuroQol–5 Dimensions–5 Levels 
EU 
European Union 
FACT-Lym 
Functional Assessment of Cancer Therapy - Lymphoma 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed paraffin-embedded 
GCP 
Good Clinical Practice 
gDNA 
genomic DNA 
GGT 
gamma glutamyl transferase 
H0 
null hypothesis 
H1 
first hypothesis 
H2 
second hypothesis 
Ha 
alternate hypothesis 
HBV 
hepatitis B virus 
β-HCG 
beta human chorionic gonadotropin 
HCV 
hepatitis C virus 
HD-ASCT 
high-dose chemotherapy and autologous stem cell transplant 
HIV 
human immunodeficiency virus 
hr 
hour 
HRQoL 
health-related quality of life 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
INR 
international normalized ratio 
IRB 
institutional review board 
IRC 
independent review committee 
IV 
intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
mmHg 
millimeters of mercury 
MRI 
magnetic resonance imaging 
MSD-ECL 
Meso-Scale Discovery Electrochemiluminescence 
MTD 
maximum tolerated dose 
NHL 
non-Hodgkin lymphoma 
ORR 
overall response rate 
OS 
overall survival 
PBD 
pyrrolobenzodiazepine 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
Pharmacokinetic(s) 
PO 
per os 
pp 
predicted probability 
PR 
partial response 
PTT 
partial thromboplastin time 


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Abbreviation 
Definition 
QT 
measure between Q wave and T wave in the electrocardiogram 
QTcF 
Fridericia correction of the QT measure 
Q3W 
every 3 weeks 
RBC 
 red blood cell 
RFS 
relapse-free survival 
RR 
respiratory rate 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SCT 
stem cell transplantation 
SD 
stable disease 
SOC 
standard of care 
SoE 
schedule of events 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TEAE 
treatment-emergent adverse event 
TLS 
tumor lysis syndrome 
Tmax 
time to maximum concentration 
µL 
microliter 
ULN 
upper limit of normal 
US 
United States 
Val 
valine 
VAS 
visual analog scale 
WBC 
white blood cell 
WHO 
World Health Organization 
wk 
week 
WOCBP 
woman of childbearing potential 
 
 
 


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Date of Protocol Amendment 4: 09 July 2019 
 
 
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Protocol Synopsis 
 
Protocol Number: 
ADCT-402-201 
Title: 
A Phase 2 Open-Label Single-Arm Study to Evaluate the Efficacy and Safety 
of Loncastuximab Tesirine in Patients with Relapsed or Refractory 
Diffuse Large B-Cell Lymphoma (DLBCL) 
Sponsor: 
ADC Therapeutics SA 
Study Phase: 
Phase 2 
Indication: 
Diffuse Large B-Cell Lymphoma (DLBCL) 
Rationale: 
Non-Hodgkin lymphoma (NHL) is the seventh most common type of cancer 
in the US, and account for an estimated 4.3% of new cancer cases in 2017.  
DLBCL 
accounts 
for 
nearly 
one-third 
(32.5%) 
of 
NHL.  
Chemo-immunotherapy, with or without radiotherapy, is the most common 
initial treatment for DLBCL.  Response to initial treatment is high; however, 
a significant proportion of patients relapse.  The current standard of care for 
relapsed DLBCL is additional chemotherapy, which can be followed by stem 
cell transplantation (SCT).  The poor prognosis for relapsed patients, 
especially those with chemo-refractory disease with a short interval between 
remission and relapse, or those who relapse after high-dose therapy and SCT, 
highlights the unmet needs for patients with relapsed or refractory DLBCL. 
Human CD19 antigen is a 95 kd transmembrane glycoprotein belonging to the 
immunoglobulin superfamily.  In normal human tissue, expression of CD19 
continues through pre-B and mature B-cell differentiation until it is finally 
down-regulated during terminal differentiation into plasma cells; however, 
expression of CD19 is maintained in hematologic B-cell malignancies, 
including DLBCL.  
Loncastuximab tesirine (ADCT-402) is an antibody drug conjugate (ADC) 
that has been designed to target and kill CD19-expressing malignant B-cells.  
Preliminary data from a Phase 1 study of loncastuximab tesirine in relapsed 
or refractory B-cell NHL shows significant activity in patients with DLBCL. 
Objectives: 
Primary Objective 
• Evaluate the efficacy of single agent loncastuximab tesirine in patients 
with relapsed or refractory DLBCL 
Secondary Objectives 
• Characterize the safety profile of loncastuximab tesirine 
• Characterize the pharmacokinetic (PK) profile of loncastuximab tesirine 
• Evaluate the immunogenicity of loncastuximab tesirine 
• Evaluate the impact of loncastuximab tesirine treatment on health-related 
quality of life (HRQoL) 
 
 
 
 
 
   


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ADCT-402-201 Clinical Protocol Amendment 4 
 
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Endpoints: 
Primary Endpoint 
Overall response rate (ORR) according to the 2014 Lugano classification as 
determined by central review in all treated patients; ORR is defined as the 
proportion of patients with a best overall response (BOR) of complete 
response (CR) or partial response (PR) 
Secondary Endpoints 
• Duration of response (DOR) defined as the time from the first 
documentation of tumor response to disease progression or death  
• CR rate defined as the percentage of treated patients with a BOR of CR 
• Relapse-free survival (RFS) defined as the time from the documentation 
of CR to disease progression or death 
• Progression-free survival (PFS) defined as the time between start of 
treatment and the first documentation of recurrence, progression, or death  
• Overall survival (OS) defined as the time between the start of treatment 
and death from any cause 
• Frequency and severity of adverse events (AEs) and serious adverse 
events (SAEs) 
• Changes from baseline of safety laboratory values, vital signs, 
Eastern Cooperative Oncology Group (ECOG) performance status, and 
12-lead electrocardiograms (ECGs) 
• Concentrations and PK parameters of loncastuximab tesirine total 
antibody, pyrrolobenzodiazepine (PBD)-conjugated antibody, and 
unconjugated warhead SG3199 
• Anti-drug antibody (ADA) titers and, if applicable, neutralizing activity 
to loncastuximab tesirine after treatment with loncastuximab tesirine 
• Change from baseline in HRQoL as measured by EuroQol–5 
Dimensions–5 Levels (EQ-5D-5L) and Functional Assessment of Cancer 
Therapy - Lymphoma (FACT-Lym) 
 
 
 
 
 
 
Study Design: 
This is a Phase 2, multi-center, open-label, single-arm study.  The study will 
enroll approximately 140 patients. 
A 2-stage design will be used, with an interim analysis for futility on the first 
52 patients.  If ≥10 patients respond (CR+PR), the study will proceed to 
complete full enrollment.  Enrollment will continue during the interim 
analysis; however, further enrollment will be halted if futility is confirmed. 


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ADCT-402-201 Clinical Protocol Amendment 4 
 
Date of Protocol Amendment 4: 09 July 2019 
 
 
Page 14 
Patient Selection:  
Inclusion Criteria: 
1. Male or female patient aged 18 years or older 
2. Pathologic diagnosis of DLBCL, as defined by the 2016 WHO 
classification, to include: DLBCL not otherwise specified; primary 
mediastinal large B-cell lymphoma; and high-grade B-cell 
lymphoma, with MYC and BCL2 and/or BCL6 rearrangements 
3. Relapsed or refractory disease following two or more multi-agent 
systemic treatment regimens 
4. Patients who have received previous CD19-directed therapy must 
have a biopsy that shows CD19 protein expression after completion 
of the CD19-directed therapy 
5. Measurable disease as defined by the 2014 Lugano Classification 
6. Availability of formalin-fixed paraffin-embedded (FFPE) tumor 
tissue block (or minimum 10 freshly cut unstained slides if block is 
not available) 
Note: Any biopsy since initial diagnosis is acceptable, but if several 
samples are available, the most recent sample is preferred. 
7. ECOG performance status 0-2 
8. Adequate organ function as defined by screening laboratory values 
within the following parameters: 
a. Absolute neutrophil count (ANC) ≥1.0 × 103/µL (off growth 
factors at least 72 hours) 
b. Platelet count ≥75 × 103/µL without transfusion in the prior 
7 days 
c. Alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), and gamma glutamyl transferase (GGT) ≤2.5 × the 
upper limit of normal (ULN) 
d. Total bilirubin ≤1.5 × ULN (patients with known 
Gilbert’s syndrome may have a total bilirubin up to 
≤3 × ULN)  
e. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance 
≥60 mL/min by the Cockcroft and Gault equation 
Note: A laboratory assessment may be repeated a maximum of two 
times during the Screening period to confirm eligibility.  
9. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy 
test within 7 days prior to start of study drug (C1D1) for women of 
childbearing potential 
10. Women of childbearing potential must agree to use a highly effective 
method of contraception from the time of giving informed consent 
until at least 16 weeks after the last dose of loncastuximab tesirine.  
Men with female partners who are of childbearing potential must 
agree that they will use a highly effective method of contraception 
from the time of giving informed consent until at least 16 weeks after 
the patient receives his last dose of loncastuximab tesirine 


ADC Therapeutics 
Loncastuximab Tesirine 
ADCT-402-201 Clinical Protocol Amendment 4 
 
Date of Protocol Amendment 4: 09 July 2019 
 
 
Page 15 
Exclusion Criteria: 
1. Previous treatment with loncastuximab tesirine 
2. Known history of hypersensitivity to or positive serum human ADA 
to a CD19 antibody 
3. Pathologic diagnosis of Burkitt lymphoma 
4. Bulky disease, defined as any tumor ≥10 cm in longest dimension 
5. Active second primary malignancy other than non-melanoma skin 
cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal 
or lobular carcinoma in situ of the breast, or other malignancy that the 
Sponsor’s medical monitor and Investigator agree and document 
should not be exclusionary 
6. Autologous stem cell transplant within 30 days prior to start of study 
drug (C1D1) 
7. Allogeneic stem cell transplant within 60 days prior to start of study 
drug (C1D1) 
8. Active graft-versus-host disease 
9. Post-transplant lymphoproliferative disorders 
10. Active autoimmune disease, including motor neuropathy considered 
of autoimmune origin and other central nervous system (CNS) 
autoimmune disease 
11. Known seropositive and requiring anti-viral therapy for human 
immunodeficiency virus (HIV), hepatitis B virus (HBV), or 
hepatitis C virus (HCV).  Note: Testing is not mandatory to be eligible 
12. History of Stevens-Johnson syndrome or toxic epidermal necrolysis 
13. Lymphoma with active CNS involvement at the time of screening, 
including leptomeningeal disease 
14. Clinically 
significant 
third 
space 
fluid 
accumulation 
(i.e., ascites requiring drainage or pleural effusion that is either 
requiring drainage or associated with shortness of breath) 
15. Breastfeeding or pregnant 
16. Significant medical comorbidities, including but not limited to, 
uncontrolled hypertension (blood pressure [BP] ≥160/100 mmHg 
repeatedly), unstable angina, congestive heart failure (greater than 
New York Heart Association class II), electrocardiographic evidence 
of acute ischemia, coronary angioplasty or myocardial infarction 
within 6 months prior to screening, uncontrolled atrial or ventricular 
cardiac arrhythmia, poorly controlled diabetes, or severe chronic 
pulmonary disease 
17. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic 
therapy within 14 days prior to start of study drug (C1D1), except 
shorter if approved by the Sponsor 
18. Use of any other experimental medication within 14 days prior to start 
of study drug (C1D1) 
19. Planned live vaccine administration after starting study drug (C1D1)  
20. Failure to recover to Grade ≤1 (Common Terminology Criteria for 
Adverse Events [CTCAE] version 4.0) from acute non-hematologic 
toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy 
prior to screening 


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ADCT-402-201 Clinical Protocol Amendment 4 
 
Date of Protocol Amendment 4: 09 July 2019 
 
 
Page 16 
21. Congenital long QT syndrome or a corrected QTcF interval of 
>480 ms at screening (unless secondary to pacemaker or bundle 
branch block) 
22. Any other significant medical illness, abnormality, or condition that 
would, in the Investigator’s judgment, make the patient inappropriate 
for study participation or put the patient at risk 
Estimated Duration 
of Patient 
Participation and 
Study Duration: 
The duration of the study participation for each patient is defined as the time 
from the date of signed written informed consent to the completion of the 
follow-up period, withdrawal of consent, loss to follow-up, or death, 
whichever occurs first. 
The study will include a Screening Period (of up to 28 days), 
a Treatment Period (cycles of 3 weeks), and a Follow-up Period 
(approximately every 12 week visits for up to 3 years after treatment 
discontinuation).  
Patients may continue treatment until disease progression, unacceptable 
toxicity, or other discontinuation criteria, whichever occurs first.  
The end of study occurs at the last visit or last scheduled procedure for the last 
patient, unless the study is terminated earlier by Sponsor.   
Efficacy 
Assessments: 
• Disease assessments: Positron emission tomography - computed 
tomography (PET-CT) 
Note: If disease is not PET-avid at baseline, CT or magnetic resonance 
imaging (MRI) may be used for follow-up disease assessments.  
The assessment method determined to identify sites of disease at baseline 
should be used for all subsequent assessments. 
Safety Assessments: 
• Physical examination 
• ECOG Performance status 
• Height and weight 
• Vital signs 
• Safety laboratories (hematology, chemistry, coagulation, urinalysis) 
• Pregnancy test, if applicable 
• 12 Lead-ECG (triplicate) 
• AEs/SAEs, graded according to CTCAE version 4.0. 
Other Assessments: 
• Blood sampling for PK, ADA, 
 
• 
 
 
 
 
 
 
 
• HRQoL: EQ-5D-5L and FACT-Lym 
Study Drug, Dosage, 
and Mode of 
Administration: 
Loncastuximab tesirine will be administered as an intravenous (IV) infusion 
over 30 minutes on Day 1 of each cycle.  Patients will receive 150 µg/kg every 
3 weeks (Q3W) for 2 cycles, then 75 µg/kg Q3W for subsequent cycles. 
Patients with a body mass index (BMI) ≥35 kg/m2 will have their dose 
calculated based on an adjusted body weight. 
Sample Size: 
Approximately 140 patients. 


ADC Therapeutics 
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ADCT-402-201 Clinical Protocol Amendment 4 
 
Date of Protocol Amendment 4: 09 July 2019 
 
 
Page 17 
Statistical 
Considerations: 
Study Hypotheses:  
H1: ORR based on central review for patients treated with loncastuximab 
tesirine is significantly greater than 20% (i.e., H0: p ≤0.2 vs. Ha: p >0.2). 
Sample Size Justification: 
Using nQuery exact test for single proportion, a sample size of 140 patients 
has >99%power to achieve a 1-sided significance level of 0.025 (2-sided 
significance level of 0.05).  This sample size will provide adequate precision 
for observed ORR in the expected range and a robust population for safety 
evaluation.   
Statistical Analysis: 
ORR and CR rate with 95% CI from all treated patients will be presented.  
DOR, PFS, RFS, and OS will be analyzed by Kaplan-Meier approach. 
Safety analyses will be presented descriptively. 
 
 


ADC Therapeutics 
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ADCT-402-201 Clinical Protocol Amendment 4 
 
 
Date of Protocol Amendment 4: 09 July 2019 
 
Page 18 
Schedule of Events 
Table 1.  
Schedule of Events 
 
Protocol 
Section Screening 
Treatment Period 
Follow-up Period 
(up to 3 years from EOT) 
(1 Cycle = 3 weeks) 
 
 
Cycle 1 and Cycle 2 (C1 and C2) 
C3 and beyond 
EOT 
Every 12 weeks 
Day (D) 
 
-28 to -1 
1 
8 
15 
1 
 
 
Informed consent 
11.3 
X 
 
 
 
 
 
 
Eligibility criteria 
5 
X 
 
 
 
 
 
 
Demography 
9.5 
X 
 
 
 
 
 
 
Medical/Cancer history 
9.5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
8.3.1 
X 
X 
 
 
X 
X 
 
ECOG performance status 
8.3.2 
X 
X 
 
 
X 
X 
 
Height 
8.3.3 
X 
 
 
 
 
 
 
Weight 
8.3.3 
X 
X 
X 
X 
X 
X 
 
Vital signs (BP, HR, RR, Temp) 
8.3.4 
X 
X 
X 
X 
X 
X 
 
Disease assessment2 
8.1 
X 
6 weeks and 12 weeks after C1D1, then every 9 weeks 
X2 
Every 12 weeks until 1 year 
from EOT, then every 
6 months until disease 
progression3 
Hematology and Chemistry 
8.3.5 
X 
X4 
X 
X 
X4 
X 
 
Coagulation and Urinalysis  
8.3.5 
X 
 
 
 
 
 
 
Pregnancy test, if applicable 
8.3.6 
X 
X5 
 
 
X 
X 
 
12-lead ECG 
8.3.7 
Table 4 
X 
X 
(pre-infusion, 
EOI, and 4 h 
post-infusion) 
X 
X 
Every other cycle 
(C3, pre-infusion and EOI; 
C5 and beyond, 
pre-infusion only) 
X 
 
Premedication  
6.6.1 
 
D-1 to D2 
 
 
D-1 to D2 
 
 
Loncastuximab tesirine 
administration 
6.3 
 
X 
 
 
X 
 
 


ADC Therapeutics 
Loncastuximab Tesirine 
ADCT-402-201 Clinical Protocol Amendment 4 
 
 
Date of Protocol Amendment 4: 09 July 2019 
 
Page 19 
 
Protocol 
Section Screening 
Treatment Period 
Follow-up Period 
(up to 3 years from EOT) 
(1 Cycle = 3 weeks) 
 
 
Cycle 1 and Cycle 2 (C1 and C2) 
C3 and beyond 
EOT 
Every 12 weeks 
Day (D) 
 
-28 to -1 
1 
8 
15 
1 
 
 
PK sample 
8.4.1 
Table 5 
 
X 
(pre-infusion, 
EOI, and 4 h 
post-infusion) 
X 
X 
Every other cycle 
(C3, pre-infusion and EOI; 
C5 and beyond, 
pre-infusion only) 
X 
 
ADA sample  
8.4.2 
Table 5 
 
X 
(pre-infusion) 
 
X6 
Every other cycle 
(C3 and beyond, 
pre-infusion only) 
X7 
 
gDNA and cfDNA samples 
8.4.3 
 
X 
 
 
 
X 
X (at disease progression) 
HRQoL 
8.5 
 
X 
 
 
X 
X 
 
Concomitant medications 
6.7 
From ICF signature date or D-14 whichever is earlier, until at least 30 days after last dose of study drug 
Adverse events 
8.2 
CTCAE, Version 4.0 
AE/SAEs from ICF signature date until at least 30 days after last dose of study drug; thereafter related SAEs only 
1st New anticancer treatment 
 
 
 
 
 
 
X 
X 
Survival 
 
 
 
 
 
 
X 
X 
Abbreviations: ADA, anti-drug antibody; AE, adverse event; BP, blood pressure; cfDNA, circulating cell-free DNA; CTCAE, Common Terminology Criteria for Adverse Events; 
ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; EOI, end of infusion; EOT, end of treatment; gDNA, genomic DNA; HR, heart rate; HRQoL, 
health-related quality of life; ICF, informed consent form; PET-CT, Positron emission tomography - computed tomography; PK, pharmacokinetics; RR, respiratory rate; SAE, 
serious adverse event; Temp, temperature. 
1 Tumor tissue should be submitted once all other eligibility criteria have been met. 
2 Screening imaging (PET-CT) must be performed within 4 weeks prior to C1D1 and the same assessment method should be used throughout the study.  Week 6 imaging should be 
performed within 5 days prior to C3D1 and Week 12 imaging should be performed within 5 days prior to C5D1.  All other imaging for disease assessment for patients on study 
drug should be performed within ± 2 weeks of the scheduled timepoint.  Disease assessments should be performed at the timepoints specified even if study drug dosing is delayed.  
If a scan has been performed within 8 weeks of EOT, it does not need to be repeated at EOT. 
3 Disease assessments to be performed in patients having discontinued study drug for reasons other than disease progression. 
4 ≤3 days prior to administration of study treatment, unless more frequent testing is clinically indicated. 
5 Not needed if screening assessment was performed within 7 days prior to C1D1. 
6 Cycle 1 only  
7 Patients who test positive for ADAs will be requested to supply additional ADA samples as per Section 8.4.2. 
Visit Scheduling Windows:   
• Treatment Period: visit day ± 2 days (excluding C1D1 which is the reference day) 
• EOT: as soon as possible after decision to discontinue the study drug, preferably within 30 days after last dose of study drug, and before initiation of any new anticancer 
treatment  
• Follow-up Period: visit day ± 14 days


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ADCT-402-201 Clinical Protocol Amendment 4 
Date of Protocol Amendment 4: 09 July 2019  
 
Page 20 
1 Introduction and Background 
1.1 Diffuse Large B-Cell Lymphoma 
Non-Hodgkin lymphoma (NHL) represents a biologically and clinically diverse group of 
hematologic malignancies arising from precursor and mature B, T, and natural killer cells. 
It is the 7th most common type of cancer in the US and will account for an estimated 4.3% 
(n=72,240) of new cancer cases in 2017 (Siegel et al., 2017).  Diffuse large B-cell lymphoma 
(DLBCL) accounts for an estimated 32.5% of NHL (Al-Hamadani et al., 2015). 
Approximately 30% to 50% of patients with DLBCL are not cured, and most patients who fail 
a rituximab-containing chemotherapy regimen (e.g., R-CHOP) will die from their disease.  
Salvage therapy, including high-dose chemotherapy and autologous stem cell transplant 
(HD-ASCT), can be effective treatment for DLBCL patients with chemotherapy-sensitive 
relapse.  However, over half of the patients treated in this fashion will not have long term 
disease control (Gisselbrecht et al., 2010).  The prognosis of patients whose disease is 
refractory to initial chemotherapy and are therefore not eligible for HD-ASCT, or who relapse 
early after HD-ASCT, is extremely poor.  These patients have a poor response to salvage 
therapy, with an objective response rate (ORR) of 26% (complete response [CR] rate 7%) and 
a median survival of approximately 6 months (Crump et al., 2017).  The management of 
patients with DLBCL who are ineligible for HD-ASCT or who relapse after HD-ASCT is 
difficult.  Palliation, second HD-ASCT, or allogeneic stem cell transplant (AlloSCT) are some 
of the options available for these patients but results are dismal and toxicity significant.  
The poor prognosis for relapsed patients, especially those with chemotherapy-refractory 
disease with a short interval between remission and relapse or those who relapse after 
high-dose therapy and stem cell transplant (SCT), highlights the unmet needs for patients with 
relapsed or refractory DLBCL (Coiffier, 2016; Epperla, 2017). 
In late 2017, the US Food and Drug Administration (FDA) granted approval to the autologous 
anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel (Yescarta®), 
for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two 
or more lines of systemic therapy, including DLBCL not otherwise specified, primary 
mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from 
follicular lymphoma.  While this therapy does provide disease control in a portion of patients 
(51% CR, 21% partial response [PR]), and provides durable responses in patients who achieve 
a CR, the duration of response (DOR) is short for patients who only achieve a PR (2.1 months), 
meaning that a significant fraction of patients (approximately 50%) treated with this therapy 
will not have long-term disease control.  In addition, this therapy has significant toxicity, with 
94% of patients having cytokine release syndrome (13% Grade 3 or higher) and 57% having 
encephalopathy (29% Grade 3 or higher).  It is only available at specialized centers and requires 
substantial lead-time for preparation, with approximately 10% of patients being unable to 
receive the planned therapy.  Thus, the development of more effective salvage treatment 
remains an unmet medical need. 


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Page 21 
1.2 Description of Investigational Study Drug 
Loncastuximab tesirine (ADCT-402) is an antibody drug conjugate (ADC), composed of a 
humanized monoclonal antibody (RB4v1.2) directed against human cluster of differentiation 
19 
(CD19) 
conjugated 
through 
a 
cathepsin-cleavable 
linker 
to 
SG3199, 
a pyrrolobenzodiazepine (PBD) dimer cytotoxin.  The toxin SG3199 attached to the linker is 
designated as SG3249.  
The schematic representation of loncastuximab tesirine is presented in Figure 1. 
 
Figure 1.  
Schematic Representation and Chemical Structure of Loncastuximab 
Tesirine  
Abbreviations: Ala, alanine; PABA, para-aminobenzoic acid; PEG, polyethylene glycol; RB4v1.2, human monoclonal 
antibody being studied; Val, valine.  
Loncastuximab tesirine binds with picomolar affinity to human CD19.  After binding and 
internalization, loncastuximab tesirine traffics to the lysosomes, where the protease-sensitive 
linker is cleaved and unconjugated PBD dimers (SG3199) are released inside the target cell.  
The released PBD dimers bind in the minor groove of DNA and form potent cytotoxic DNA 
interstrand cross-links.  The cross-links result in a stalled DNA replication fork, blocking cell 
division and causing cell death (Hartley, 2011).  The cross-links formed by PBD dimers are 
relatively non-distorting to the DNA structure, making them hidden to repair mechanisms 
(Adair et al., 2012; Beck et al., 2017).  


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1.3 Safety and Efficacy of Loncastuximab Tesirine in Phase 1 Study, 
ADCT-402-101 
ADCT-402-101 (NCT02669017) is a first-in-human Phase 1 dose-escalation study of 
loncastuximab tesirine in relapsed or refractory B-cell NHL patients, who have failed or are 
intolerant to established therapies, or have no other treatment options available.  The study 
design involves a dose escalation phase (Part 1) followed by a dose expansion phase (Part 2).  
The primary objectives for Part 1 were to evaluate the safety and tolerability of loncastuximab 
tesirine and to determine the maximum tolerated dose (MTD) and/or the recommended dose(s) 
to use in Part 2.  The primary objective for Part 2 was to evaluate the safety and tolerability of 
the dose(s) determined in Part 1.  The secondary objectives include evaluating the clinical 
activity of loncastuximab tesirine as measured by ORR, DOR, progression free survival (PFS), 
and overall survival (OS). 
As of data cut-off date of 03 December 2017, a total of 144 patients with relapsed or refractory 
B-cell NHL received at least one infusion of loncastuximab tesirine.  The median age was 
63.5 years (range: 23-86).  The median number of previous chemotherapy regimens was 
3 (range: 1-10) with 24.3% of patients having prior stem cell transplant. 
Treatment-emergent adverse events (TEAEs) were reported in 137 (95.1%) out of 144 patients 
treated with loncastuximab tesirine.  The most common TEAEs (observed in at least in 15% 
of patients), regardless of relationship to study treatment, were fatigue (42.4%); 
nausea (27.1%); gamma-glutamyltransferase (GGT) increased (26.4%); anemia (25.7%); 
edema peripheral (25.0%); dyspnea (18.8%); neutrophil count decreased, platelet count 
decreased, and thrombocytopenia (18.1% each); rash (17.4%); abdominal pain (16.0%); 
neutropenia (16.0%); and constipation (15.3%).  Grade ≥3 TEAEs were reported in 92 (63.9%) 
patients.  The most common Grade ≥3 TEAEs (observed in at least in 5% of patients) were 
neutrophil count decreased (16.0%); GGT increased (14.6%); anemia (12.5%); platelet count 
decreased (11.8%); neutropenia (11.1); and thrombocytopenia (8.3%). 
The following events were considered non-serious adverse drug reactions (ADRs): 
GGT increased, edema (includes peripheral and facial), neutrophil count decreased, 
platelet count decreased, thrombocytopenia, neutropenia, and skin-related events (such as rash, 
maculopapular rash, and erythema). 
TEAEs in 16 (11.1%) patients led to treatment discontinuation.   
Dose-limiting toxicity was reported in 3 patients (2 thrombocytopenia and 1 febrile 
neutropenia). 
Serious adverse events (SAEs) were reported in 54 (37.5%) out of 144 patients.  
Of these, 24 patients experienced an SAE(s) considered at least possibly related to study drug.  
Six of the possibly related events were observed in multiple patients (febrile neutropenia in 
5 patients, pyrexia in 3 patients, dyspnea in 2 patients, lung infection in 2 patients, 
pleural effusion in 2 patients, and sepsis in 2 patients).  Preliminary data indicate an acceptable 
safety profile.  Febrile neutropenia and pleural effusion have been classified as expected 
serious ADRs. 


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Out of 126 evaluable patients, 33 (26.2%) achieved CR and 25 (19.8%) achieved PR, for an 
ORR of 58/126 (46.0%).   
Out of 92 evaluable patients with DLBCL, 22 (23.9%) achieved CR and 16 (17.4%) achieved 
PR, for an ORR of 38/92 (41.3%). 
Additional details may be found in the current loncastuximab tesirine Investigator’s Brochure 
(IB). 
 


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2 Study Rationale 
Human CD19 antigen is a 95 kd transmembrane glycoprotein belonging to the 
immunoglobulin superfamily.  In normal human tissue, expression of CD19 continues through 
pre-B and mature B-cell differentiation until it is finally down-regulated during terminal 
differentiation into plasma cells (Scheuermann, 1995); however, expression of CD19 is 
maintained in hematologic B-cell malignancies, including DLBCL. 
Loncastuximab tesirine is an ADC that has been designed to target and kill CD19-expressing 
malignant B-cells.  Preliminary data from a Phase 1 study of loncastuximab tesirine in relapsed 
or refractory B-cell NHL (Section 1.3) shows significant activity of loncastuximab tesirine 
with an acceptable safety profile in patients with DLBCL. 
2.1 Rationale for Study Design 
This is a Phase 2, open-label, single-arm study and will enroll approximately 140 patients.  
The primary objective will be to evaluate the efficacy of single agent loncastuximab tesirine 
in patients with relapsed or refractory DLBCL who have failed at least 2 multi-agent systemic 
therapy regimens. 
The primary hypothesis is that the ORR based on central review in all patients treated with 
loncastuximab tesirine is significantly greater than 20%. With the null hypothesis that the true 
response rate is 20%, and the alternative hypothesis that the true response rate is significantly 
greater than 20% (40% is used for calculation), the design controls the type I error rate at 0.025 
and yields a power of >99%. 
To enhance patient safety, a 2-stage design will be used, with an interim analysis for futility 
on the first 52 patients.  If ≥10 patients respond, the study will proceed to complete full 
enrollment.  Enrollment will continue during the interim analysis; however, further enrollment 
will be halted if futility is confirmed to minimize exposure of patients in the study.   
Given the encouraging ORR reported with loncastuximab tesirine in the Phase 1 study at dose 
levels below the MTD and the acceptable safety profile to date, loncastuximab tesirine presents 
a positive risk-benefit for further evaluation in relapse and refractory DLBCL. 
2.2 Rationale for Dose Selection 
For patients with relapsed or refractory non-Hodgkin lymphoma, available data support a 
loncastuximab tesirine dosing regimen of 150 µg/kg every 3 weeks (Q3W) × 2 cycles, 
followed by a 50% reduction to 75 µg/kg Q3W for the Phase 2 trial.  For safety, particular 
differences in predicted probabilities (pp) were apparent between the 200 µg/kg Q3W and 
150 µg/kg Q3W doses, respectively, including Grade ≥3 edema (pp=0.2817 vs. 0.1070 in 
patients with prior stem cell transplant), liver function test-related toxicities (pp=0.4018 vs. 
0.1644 in patients with prior relapsed disease; 0.4018 vs. 0.1644 in patients without prior stem 
cell transplant; pp=0.5208 vs. 0.2203 in patients with body mass index [BMI] of 35 kg/m2, and 
pp=0.4018 vs. 0.1644 in patients with baseline Eastern Cooperative Oncology Group [ECOG] 
of 0 or 1, respectively), and neutropenia or neutrophil decrease (pp=0.4383 vs. 0.2865). 


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For efficacy, the decision for initial dosing at the 150 µg/kg dose level is predicated on higher 
observed and predicted ORR as compared to the 120 µg/kg and lower doses.  The decision to 
dose reduce following 2 cycles of treatment was based on the rapid onset of response observed 
in a majority of patients (median 2 cycles), and desire to mitigate onset of late-developing and 
difficult to manage toxicities, such as edema.  Initial dosing for 2 cycles is anticipated to 
optimize the frequency of objective response, while dose reduction in subsequent cycles will 
permit continued exposure with manageable toxicity to optimize the durability of response. 
 


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3 Study Objectives and Endpoints 
Table 2. 
Study Objectives and Endpoints  
Objectives 
Endpoints 
Primary 
Evaluate the efficacy of single agent loncastuximab tesirine in 
patients with relapsed or refractory DLBCL 
ORR according to the 2014 Lugano classification (Cheson et al. 2014) as determined by 
central review in all treated patients; ORR is defined as the proportion of patients with a 
best overall response (BOR) of CR or PR 
Secondary 
Further evaluate the efficacy of loncastuximab tesirine 
• DOR defined as the time from the first documentation of tumor response to disease 
progression or death 
• CR rate defined as the percentage of treated patients with a BOR of CR 
• Relapse-free survival (RFS) defined as the time from the documentation of CR to 
disease progression or death 
• PFS defined as the time between start of treatment and the first documentation of 
recurrence, progression, or death 
• OS defined as the time between the start of treatment and death from any cause 
Characterize the safety profile of loncastuximab tesirine 
• Frequency and severity of adverse events (AEs), and SAEs 
• Changes from baseline of safety laboratory variables, vital signs, ECOG 
performance status, and 12-lead electrocardiograms (ECGs) 
Characterize the pharmacokinetic (PK) profile of loncastuximab 
tesirine 
Concentrations and PK parameters of loncastuximab tesirine total antibody, 
PBD-conjugated antibody, and unconjugated warhead SG3199 
Evaluate the immunogenicity of loncastuximab tesirine 
Anti-drug antibody (ADA) titers and, if applicable, neutralizing activity to 
loncastuximab tesirine after treatment with loncastuximab tesirine 
Evaluate the impact of loncastuximab tesirine treatment on health-
related quality of life (HRQoL) 
Change from baseline in HRQoL as measured by EuroQol–5 Dimensions–5 Levels 
(EQ-5D-5L) and Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) 
 
 
 
 
 


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4 Study Design 
4.1 Overview 
This is a Phase 2, multi-center, open-label, single-arm study of the efficacy and safety of 
loncastuximab tesirine used as monotherapy in patients with relapsed or refractory DLBCL.  
The study will enroll approximately 140 patients. 
A 2-stage design will be used (Simon, 1989), with an interim analysis for futility using the data 
on the first 52 patients (see Section 9.3).  If ≥10 patients respond (CR+PR), the study will 
proceed to complete full enrollment.  Enrollment will continue during the interim analysis; 
however, further enrollment will be halted if futility is confirmed. 
The duration of the study participation for each patient is defined as the time from the date of 
signed written informed consent to the completion of the follow-up period, withdrawal of 
consent, loss to follow-up, or death, whichever occurs first. 
The study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 
3 weeks), and a Follow-up Period (approximately every 12 week visits for up to 3 years after 
treatment discontinuation).  
4.2 Screening Period 
Informed consent must be obtained for each patient and documented with a signed informed 
consent form (ICF) prior to any study procedures.  Procedures that are performed as part of 
standard of care (SOC) may be used to satisfy screening requirements if they are performed in 
the appropriate window. 
The screening period is from 28 days to 1 day prior to the start of the study drug.  The screening 
assessments should be performed within this period in order to assess the eligibility of the 
patient against the inclusion and exclusion criteria (Sections 5.1 and 5.2, respectively). 
See Section 5.3 for the information to be collected on screening failures. 
4.3 Treatment Period 
The treatment period starts on the date when a patient receives the first dose of study drug and 
continues until the date of discontinuation from treatment.   
A treatment cycle is defined as 3 weeks (i.e., 21 days).  Loncastuximab tesirine will be 
administered as an intravenous (IV) infusion over 30 minutes on Day 1 of each cycle.  
Patients will receive 150 µg/kg Q3W for 2 cycles, then 75 µg/kg Q3W for subsequent cycles. 
Patients may continue treatment for up to one year or until disease progression, unacceptable 
toxicity, or other discontinuation criteria (Section 7), whichever occurs first.  
Additionally, patients benefitting clinically at 1 year may continue treatment after a case by 
case review with the Sponsor. 


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4.4 End of Treatment 
End of Treatment visit (EOT) should be performed as soon as possible after the decision to 
discontinue the study drug, preferably within 30 days after last dose of study drug and before 
initiation of any new anticancer treatment. 
When EOT coincides with a scheduled visit, the scheduled visit will become EOT. 
4.5 Follow-up Period 
All patients, regardless of disease status, will be followed every 12 weeks for up to 3 years, 
or until withdrawal of consent, loss to follow-up, or death, whichever occurs first. 
When disease assessments are not planned for a follow-up visit, the visit can be done by phone. 
4.6 End of Study 
The end of study occurs at the last visit or last scheduled procedure for the last patient, 
unless the study is terminated earlier by Sponsor. 
 


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5 Patient Population 
Patients must meet all inclusion criteria and none of the exclusion criteria to be eligible for the 
study.  All criteria have to be assessed at Screening, unless otherwise specified (e.g., criterion 
to be confirmed within 28 days to 1 day prior to the start of study drug on Cycle 1 Day 1 
[C1D1]). 
5.1 Inclusion Criteria 
1. Male or female patient aged 18 years or older. 
2. Pathologic diagnosis of DLBCL, as defined by the 2016 WHO classification, 
to include: DLBCL not otherwise specified; primary mediastinal large B-cell 
lymphoma; and high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 
rearrangements  
3. Relapsed or refractory disease following two or more multi-agent systemic treatment 
regimens 
4. Patients who have received previous CD19-directed therapy must have a biopsy that 
shows CD19 protein expression after completion of the CD19-directed therapy. 
5. Measurable disease as defined by the 2014 Lugano Classification (Appendix 2). 
6. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block 
(or minimum 10 freshly cut unstained slides if block is not available). 
Note: Any biopsy since initial diagnosis is acceptable, but if several samples are 
available, the most recent sample is preferred. 
7. ECOG performance status 0-2. 
8. Adequate organ function as defined by screening laboratory values within the following 
parameters: 
a. Absolute neutrophil count (ANC) ≥ 1.0 × 103/µL (off growth factors at least 
72 hours). 
b. Platelet count ≥75 × 103/µL without transfusion in the prior 7 days. 
c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma 
glutamyl transferase (GGT) ≤2.5 × the upper limit of normal (ULN). 
d. Total bilirubin ≤1.5 × ULN (patients with known Gilbert’s syndrome may have a 
total bilirubin up to ≤3 × ULN). 
e. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the 
Cockcroft and Gault equation. 
Note: A laboratory assessment may be repeated a maximum of two times during the 
Screening period to confirm eligibility. 
9. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days 
prior to start of study drug (C1D1) for women of childbearing potential. 


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10. Women of childbearing potential* must agree to use a highly effective** method of 
contraception from the time of giving informed consent until at least 16 weeks after the 
last dose of loncastuximab tesirine.  Men with female partners who are of childbearing 
potential must agree that they will use a highly effective method of contraception from 
the time of giving informed consent until at least 16 weeks after the patient receives his 
last dose of loncastuximab tesirine. 
* Women of childbearing potential are defined as sexually mature women who have 
not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or 
who have not been postmenopausal (i.e., who have not menstruated at all) for at least 
1 year. 
** Highly effective forms of birth control are methods that achieve a failure rate of less 
than 1% per year when used consistently and correctly.  Highly effective forms of 
birth control include: hormonal contraceptives (oral, injectable, patch, intrauterine 
devices), male partner sterilization, or total abstinence from heterosexual intercourse, 
when this is the preferred and usual lifestyle of the patient.  
Note: The double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap 
with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, 
symptothermal, post-ovulation), withdrawal (coitus interruptus), lactational 
amenorrhea method, and spermicide-only are not acceptable as highly effective 
methods of contraception. 
5.2 Exclusion Criteria 
1. 
Previous treatment with loncastuximab tesirine 
2. 
Known history of hypersensitivity to or positive serum human ADA to a CD19 
antibody 
3. 
Pathologic diagnosis of Burkitt lymphoma 
4. 
Bulky disease, defined as any tumor ≥10 cm in longest dimension 
5. 
Active second primary malignancy other than non-melanoma skin cancers, 
non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in 
situ of the breast, or other malignancy that the Sponsor’s medical monitor and 
Investigator agree and document should not be exclusionary 
6. 
ASCT within 30 days prior to start of study drug (C1D1) 
7. 
AlloSCT within 60 days prior to start of study drug (C1D1) 
8. 
Active graft-versus-host disease 
9. 
Post-transplant lymphoproliferative disorders  
10. Active autoimmune disease, including motor neuropathy considered of autoimmune 
origin and other central nervous system (CNS) autoimmune disease  
11. Known seropositive and requiring anti-viral therapy for human immunodeficiency 
(HIV) 
virus, 
hepatitis 
B 
virus 
(HBV), 
or 
hepatitis 
C 
virus 
(HCV). 
Note: Testing is not mandatory to be eligible 
12. History of Stevens-Johnson syndrome or toxic epidermal necrolysis 


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13. Lymphoma with active CNS involvement at the time of screening, including 
leptomeningeal disease 
14. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or 
pleural effusion that is either requiring drainage or associated with shortness of breath) 
15. Breastfeeding or pregnant 
16. Significant medical comorbidities, including but not limited to uncontrolled 
hypertension (blood pressure [BP] ≥160/100 mmHg repeatedly), unstable angina, 
congestive heart failure (greater than New York Heart Association class II), 
electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial 
infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac 
arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease 
17. Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 
14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor 
18. Use of any other experimental medication within 14 days prior to start of study drug 
(C1D1) 
19. Planned live vaccine administration after starting study drug (C1D1)  
20. Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events 
version 4.0 [CTCAE v4.0]) from acute non-hematologic toxicity (Grade ≤2 neuropathy 
or alopecia) due to previous therapy prior to screening 
21. Congenital long QT syndrome or a corrected QTcF interval of >480 ms at screening 
(unless secondary to pacemaker or bundle branch block) 
22. Any other significant medical illness, abnormality, or condition that would, in the 
Investigator’s judgment, make the patient inappropriate for study participation or put 
the patient at risk 
5.3 Screening Failures 
Patients who signed the ICF but were found not eligible for the study prior to receiving study 
drug are defined as screening failures. 
For these patients, only limited information will be collected in the electronic case report form 
(eCRF): 
- 
Informed consent 
- 
Demographics 
- 
Inclusion/exclusion criteria 
- 
SAE and/or death occurring during the screening period 


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6 Treatment 
6.1 Study Drug 
The study drug is loncastuximab tesirine, which will be provided as a frozen liquid or a 
refrigerated lyophilized formulation.  
• The liquid formulation will be provided in 10 mL glass vials designed to deliver 3.2 mL 
of loncastuximab tesirine at a concentration of 5 mg/mL (16 mg loncastuximab tesirine 
per vial) and stored at -65°C or below.  It is a sterile, frozen liquid formulated in 30 mM 
histidine, 200 mM sorbitol, and 0.02% polysorbate 20, at pH 6.0.  Prior to use, the 
frozen formulation is thawed at ambient temperature, gently swirled to ensure 
homogeneity, and visually inspected. 
• The lyophilized formulation will be provided as a lyophilized white to off-white 
powder in 8 mL glass vials (10 mg loncastuximab tesirine per vial) and stored at 2-8°C.  
The lyophilized loncastuximab tesirine is formulated in 20 mM histidine, 175 mM 
sucrose, and 0.02% polysorbate 20, at pH 6.0.  Prior to use, the study drug is 
reconstituted with 2.2 mL of Sterile Water for Injection to deliver 2.0 mL at a 
concentration of 5 mg/mL, gently swirled to ensure complete dissolution and 
homogeneity, and visually inspected.  Sterile Water for Injection is to be provided by 
study sites.   
Individual patients will receive the same formulation for their entire treatment. 
6.2 Management of Clinical Supplies 
Detailed instructions regarding study drug shipment, handling, storage, and preparation are 
included in the pharmacy manual. 
6.2.1 Packaging and Storage 
The study drug will be supplied by the Sponsor through the designated packaging, labeling, 
and distribution center.  
Once the package arrives at the study site, the receiving site pharmacy will complete the 
enclosed procedures to acknowledge receipt. 
All study drugs must be stored in a secure area. 
• Loncastuximab tesirine liquid formulation: loncastuximab tesirine should be protected 
from light and stored frozen (-65°C or below).  Loncastuximab tesirine should be 
thawed under ambient conditions. 
• Loncastuximab tesirine lyophilized formulation: should be protected from light and 
stored at 2-8°C. 


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6.2.2 Preparation and Administration  
The study drug solution at the concentration of 5 mg/mL will be the basis for the preparation 
of the infusion solution.  The amount of the product to be diluted will depend on the dose level 
and the body mass of the patient. 
Patients will receive a 30 minutes IV infusion of loncastuximab tesirine on Day 1 of each cycle.  
Variations in infusion times due to minor differences in IV bag overfill/underfill and the 
institution’s procedure for flushing chemotherapy lines will not result in protocol deviation. 
6.2.3 Accountability 
The Investigator will maintain accurate records of receipt of all study drugs, including dates of 
receipt.  In addition, accurate records will be kept regarding when and how much study drug 
is dispensed and used by each patient in the study.  Reasons for departure from the expected 
dispensing regimen must also be recorded.  All study drugs will be reconciled and retained or 
destroyed according to applicable regulations. 
6.3 Loncastuximab Tesirine Dosing 
Administration of loncastuximab tesirine will be performed by the Investigator or a qualified 
designee.  
Loncastuximab tesirine will be administered as an IV infusion over 30 minutes on Day 1 of 
each cycle (every 3 weeks) at a dose of 150 µg/kg Q3W for 2 cycles, then 75 µg/kg Q3W.  
Refer to Section 6.6 for premedication and supportive care. 
Patients with a BMI ≥35 kg/m2 will have their dose calculated based on an adjusted body 
weight as follows: 
Adjusted body weight (ABW) in kg = 35 kg/m2 * (height in meters)2 
Dose to administer (mg) = dosage (µg/kg) * ABW / 1000 
Extravasation of loncastuximab tesirine may be associated with local irritation, swelling, pain, 
or tissue damage.  The IV infusion site should be monitored for signs of IV infiltration or drug 
extravasation, and patients should be instructed to report immediately any signs of IV 
infiltration or drug extravasation during or after the infusion.  Suspected extravasation of 
loncastuximab tesirine should be managed according to institutional protocol for management 
of extravasation of cytotoxic chemotherapy.  For patients who have a central line, administration 
of loncastuximab tesirine via this central line should be considered. 
6.4 Dose Delays and Modifications 
If a patient experiences any Grade ≥3 (≥2 for edema, effusion, or increased AST/ALT/GGT) 
non-hematologic toxicity, loncastuximab tesirine must be held until the toxicity resolves to 
Grade ≤1 (Grade 1 or baseline for peripheral neuropathy).  In addition, if a patient experiences 
hematological toxicity of Grade ≥3 neutropenia or thrombocytopenia, loncastuximab tesirine 
must be held until the toxicity resolves to Grade ≤2. 
If loncastuximab tesirine dosing is delayed by more than 3 weeks and the toxicity is considered 
at least possibly related to loncastuximab tesirine, then subsequent doses of loncastuximab 
tesirine will be reduced by 50%.  In addition, the Investigator may reduce the dose of 
loncastuximab tesirine by 50% for any Grade ≥3 (≥2 for edema, effusion, or increased 


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AST/ALT/GGT) toxicity that is possibly related to loncastuximab tesirine, but does not result 
in dosing delay of more than 3 weeks if they feel it is in the best interest of the patients. 
If toxicity requiring dose reduction as described above occurs following the second dose of 
150 µg/kg (C2D1), the patient should receive the per protocol-defined dose of 75 µg/kg for 
Cycle 3. 
If toxicity as described above recurs at the reduced dose, subsequent doses of loncastuximab 
tesirine will be reduced by an additional 50%. 
If toxicity as described above recurs after a second dose reduction, study drug must be 
discontinued permanently. 
If loncastuximab tesirine dosing is delayed by more than 5 weeks and the toxicity is considered 
at least possibly related to loncastuximab tesirine, study drug must be discontinued 
permanently unless continued administration is approved by the Sponsor. 
6.5 Overdose Management 
An overdose is any dose of study drug given to a patient that exceeds the dose described in the 
protocol.  There are no data available to determine what the effects of overdose are and whether 
they can be reversed.  Symptomatic treatment and standard supportive care measures for the 
management of any observed toxicity should be applied. 
6.6 Premedication and Supportive care 
6.6.1 Premedication 
Unless contraindicated, administer dexamethasone 4 mg per os (PO) twice daily (BID) the day 
before loncastuximab tesirine administration (if possible), the day of loncastuximab tesirine 
administration (give at least 2 hours prior to administration when not given the day before; 
otherwise any time prior to administration), and the day after loncastuximab tesirine 
administration. 
Patients who experience an infusion-related hypersensitivity reaction will receive the 
alternative premedication regimen specified in Section 6.6.3. 
6.6.2 Treatment of Edema and Pleural Effusion 
Spironolactone at standard doses should be administered for patients with weight gain greater 
than 1 kg from C1D1, new or worsening edema, and/or new or worsening pleural effusion.  
The dose of spironolactone may be titrated as clinically indicated.  Additional diuretic support 
may be added if there is further increase in weight, edema, or pleural effusion.  
Additionally, patients should be advised to monitor their weight on a daily basis, at around the 
same time (preferably in the morning), and to notify the study site if they gain >1 kg 
(2.2 pounds) over baseline. 


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6.6.3 Treatment and Prophylaxis of Infusion-Related Hypersensitivity 
Reactions 
Medications for the treatment of severe hypersensitivity reactions, including anaphylaxis, 
should be available for immediate use and may be administered according to site standard 
treatment protocols.  
Any patient who experiences an infusion-related hypersensitivity reaction should receive 
prophylactic treatment in subsequent cycles according to the guidelines below or institutional 
standard of care: 
• On Day 1 of each cycle, patients will be instructed to take dexamethasone 20 mg PO 12 and 
6 hours before the start of the loncastuximab tesirine infusion.  When necessary, 12 and 
6 hours before the first infusion may be defined as “immediately before sleeping” and 
“immediately after waking up.” 
• On Day 1 of each cycle, patients will be given diphenhydramine hydrochloride 50 mg IV 
30 minutes before the start of the loncastuximab tesirine infusion. 
• On Day 1 of each cycle, patients will be given ranitidine (or equivalent) 50 mg IV 
30 minutes before the start of the loncastuximab tesirine infusion. 
• For 2 days following administration of loncastuximab tesirine on Day 1, patients are to 
take dexamethasone 4 mg PO BID. 
6.6.4 Skin Rash 
Skin rash has been reported in the ADCT-402-101 study, as well as with another 
investigational agent containing the same PBD warhead (Rudin et al., 2017).  The rash has 
been reported in areas at risk for sun exposure; it is therefore recommended that precautions 
are taken to avoid prolonged exposure of skin to sunlight. 
6.6.5 Other Supportive Care 
• Although the study patient population has a low risk for development of tumor lysis 
syndrome (TLS) compared to patients with acute disease (Cairo et al., 2010), patients 
should be observed for development of TLS and treated according to site standard 
treatment protocols. 
• 
As testing in animals showed testicular toxicity (atrophy with reduced spermatogenesis), 
male patients are advised to consider cryopreservation of sperm prior to treatment with 
loncastuximab tesirine, where applicable. 
6.7 Concomitant Medications and Procedures 
All medications (except for the study drug) and procedures will be recorded in the eCRF 
starting from the ICF signature date or from 14 days prior to C1D1, whichever is earlier, and 
continuing until at least 30 days after last dose of study drug. 


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6.7.1 Permitted During Study 
All medications or procedures for the clinical care of the patient, including management of 
AEs, are permitted during the study, except for those listed in Section 6.7.2.  
Hematopoietic growth factors are permitted as per American Society of Clinical Oncology 
guidelines (Smith et al., 2006). 
6.7.2 Prohibited During Study 
• Other anticancer therapy with the exception of hormonal therapy for maintenance treatment 
of breast and prostate cancer. 
• Other investigational agents. 
• Live vaccines. 


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7 Discontinuation 
The reason for discontinuation and the date of discontinuation will be collected for all patients. 
Note: Once discontinued from the study for any reason, patients are not permitted to be 
re-enrolled. 
7.1 Discontinuation from Study Treatment 
A patient may be discontinued from the study drug for any of the following reasons: 
• Disease progression 
• Unacceptable toxicity 
• Patient decision 
• Major protocol deviation 
• The Investigator determines that it is in the best interest of the patient to discontinue 
study treatment. 
• Discontinuation of the study by the Sponsor 
• Pregnancy 
• Death 
IMPORTANT: Study drug discontinuation is not to be automatically considered as 
withdrawal from the study.  Patients discontinuing the study drug will be asked to perform an 
EOT visit (Section 4.4) and continue with the Follow-up period (Section 4.5) as per protocol.  
The investigational site should make every effort to complete follow-up per protocol.  
If patients are unable to return to the site, patient status, including but not limited to survival 
status, may be obtained by site staff via phone, email, or mail. 
7.2 Discontinuation from the Study  
A patient may be discontinued from the study for any of the following reasons: 
• Withdrawal of consent 
• Investigator/Sponsor decision 
• Death 
• Loss to follow-up 
If a patient withdraws informed consent, no additional data will be collected. 
The Sponsor may continue to use previously collected medical research data prior to the 
withdrawal consistent with the original authorization. 
The study may be terminated at any time, for any reason, by the Sponsor. 
Patients still receiving study drug should have an EOT visit as described in Section 4.4 and 
SoE (Table 1). 
7.3 Loss to Follow-Up 
Patients who fail to return for protocol follow-up are to be contacted by the investigative site.  
Following a minimum of two documented unsuccessful telephone calls, the investigative site 
should send a registered letter to the patient in a final attempt to ensure protocol compliance. 
 


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8 Study Assessments and Procedures 
Informed consent, as documented by a signed and dated ICF, must be obtained prior to 
performing any study procedures.  Results (e.g., from laboratory tests or radiographic 
evaluations, etc.) obtained prior to the date of informed consent but within the allowed 
timeframe for screening may be used for determination of patient eligibility only if obtained 
as part of standard care. 
8.1 Efficacy Assessments 
Disease assessments will occur as per schedule of events (SoE) (Table 1) until progression.  
Disease assessments should take place at the timepoints specified even if study drug dosing is 
delayed.  Additional disease assessments may be obtained, if clinically indicated.  
Imaging and clinical examination for lymphoma will be performed at all disease assessment 
timepoints.  All patients will have positron emission tomography - computed tomography 
(PET-CT) of the neck/chest/abdomen/pelvis and other areas of known or suspected disease 
performed at baseline.  Patients with PET-avid disease at baseline should have PET-CT for all 
subsequent disease assessments.  If disease is not PET-avid at baseline, computed tomography 
(CT) or magnetic resonance imaging (MRI) may be used for subsequent disease assessments.  
Patients whose disease is not PET-avid should have a bone marrow biopsy as part of their 
baseline staging and disease assessment if clinically appropriate. 
Screening (Baseline) imaging must be performed within 4 weeks prior to C1D1. 
During the treatment period, imaging will be performed 6 weeks and 12 weeks after C1D1, 
then every 9 weeks until EOT.  Week 6 imaging should be performed within 5 days prior to 
C3D1 and Week 12 imaging should be performed within 5 days prior to C5D1.  All other 
imaging should be performed within ± 2 weeks of the scheduled time point. 
During the follow-up period, patients who discontinued study drug for reasons other than 
disease progression or initiation of other anti-cancer therapy except stem cell transplant, will 
have imaging performed every 12 (± 2) weeks until 1 year from EOT, then every 6 months 
until disease progression, up to 3 years from EOT. 
Response data will be collected for patients who receive CAR-T therapy until 90 days after 
receiving CAR-T therapy. 
If a scan has been performed within 8 weeks of EOT, it does not need to be repeated at EOT.  
In case of dose delays, disease assessment should be maintained at the frequencies defined 
above. 
The patient’s response to treatment will be determined according to the 2014 Lugano 
Classification Criteria (Appendix 2) as CR, PR, stable disease (SD), or progressive disease 
(PD).  Images will be obtained according to local site imaging protocols and will be submitted 
for central review.  Submission instructions for central review will be provided in a separate 
manual. 
Central imaging review will be performed using two blinded independent reviewers with 
adjudication by a third blinded independent reviewer in cases of discordance.   


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8.2 Adverse Events 
8.2.1 Definition of Adverse Events and Serious Adverse Events 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product, which does not necessarily have to have a 
causal relationship with this treatment.  
Test results collected during the study (e.g., laboratory values, physical examination, ECGs, 
etc.) or identified from review of other documents may constitute AEs if deemed clinically 
significant.  
A SAE is defined as any AE that: 
• results in death. 
• is life threatening. 
• requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization for elective procedures or for protocol compliance is not considered an 
SAE). 
• results in persistent or significant disability/incapacity. 
• is a congenital anomaly/birth defect. 
• important medical events that do not meet the preceding criteria but based on 
appropriate medical judgement may jeopardize the patient or may require medical or 
surgical intervention to prevent any of the outcomes listed above. 
8.2.2 Eliciting and Reporting Adverse Events/Serious Adverse Events 
Patients will be instructed to contact the Investigator at any time after ICF signature if any 
symptoms develop.  At each study visit, patients will be asked a non-leading question to elicit 
any medically related changes in their well-being.  Patients may also report AEs voluntarily 
and they will be instructed to contact the Investigator between visits if any symptoms develop 
or worsen.  
AEs will be reported starting when the patient provides written informed consent.  
Clinically significant medical conditions present at the time of ICF signature will be reported 
as medical history.  Clinically significant medical conditions that start or worsen after ICF 
signature will be reported as AEs. 
All AE/SAEs, regardless of relationship to study drug, will be reported from the time the 
patient signs the ICF until 30 days after the last dose of study drug or start of new anti-cancer 
therapy, whichever is earlier; thereafter, only related SAEs will be reported, with 2 exceptions.   
1. Patients who have responded to loncastuximab tesirine and undergo SCT 
(either autologous or allogeneic) after permanent discontinuation of loncastuximab 
tesirine treatment without any intervening anti-cancer therapy.  These patients will have 
the following safety information reported until 180 days post-transplant regardless of 
relationship to loncastuximab tesirine: 
• Grade ≥3 AEs suggestive of hepatic toxicity, veno-occlusive disease/sinusoidal 
obstruction syndrome, graft-versus-host disease, infectious complications, 
prolonged cytopenia(s), and pulmonary toxicity 
• SAEs 
• Death 


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2. Patients who receive CAR-T therapy after permanent discontinuation of loncastuximab 
tesirine treatment will have the following safety information reported until 90 days after 
receiving CAR-T therapy regardless of relationship to loncastuximab tesirine: 
• Grade ≥3 AEs of cytokine release syndrome, encephalopathy, edema or 
effusion, rash, hepatic toxicity 
• SAEs 
• Death 
Whenever possible, AEs should be reported as a diagnosis rather than individual signs and 
symptoms.  If no diagnosis is available or has been identified, then the primary symptom is 
reported.  
In general, the term ‘disease progression’ should not be used for reporting an AE/SAE.  
However, AEs/SAEs that are complications of disease progression should be reported. 
All AEs reported or observed during the study will be recorded on the AE page of the 
eCRF.  Information to be collected will include event term, date of onset, assessment of 
severity (Section 8.2.3), seriousness (Section 8.2.1), relationship to study drug  (Section 8.2.4), 
action taken with study drug, date of resolution of the event or ongoing (when no resolution 
by the end of the reporting period), any required treatment or evaluations, and outcome. 
New SAEs and any recurrent episodes, progression, or complications of the original SAE must 
be reported to the pharmacovigilance department of the Sponsor or delegate (e.g., contract 
research organization [CRO]) within 24 hours after the time site personnel first learn about the 
event.  Reporting will occur through the electronic data capture (EDC) system. 
8.2.3 Assessment of Severity 
AEs will be graded according to CTCAE v4.0.  For events not included in the CTCAE criteria, 
the severity of the AE is graded on a scale of 1 to 5 as shown in Table 3.  
Table 3. 
Definition of Severity Grades for CTCAE 
Grade 
Definition 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
2 
Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL).a 
3 
Severe or medically significant but not immediately life threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADL.b 
4 
Life-threatening consequences; urgent intervention indicated. 
5 
Death related to adverse event. 
a ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
b Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and 
not bedridden.  
AEs characterized as intermittent do not require documentation of onset and duration of each 
episode. 


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8.2.4 Assessment of Causality 
The Investigator’s assessment of an AE’s relationship to study drug is an important part of 
safety reporting, but is not a factor in determining whether an AE is reported.  An AE will be 
assessed as related to study drug if there is a reasonable possibility of causal relationship with 
the use of the study drug.  For SAEs, whenever possible, the Investigator should provide a 
rationale for the causality assessment.   
8.2.5 Regulatory Reporting 
All SAEs considered at least possibly related to the study drug will be reported as 
Suspected Unexpected Serious Adverse Reactions (SUSARs), unless they have been defined 
as expected in the Reference Safety Information section of the IB.  SUSARs will be reported 
to competent authorities and independent ethics committee (IEC) in accordance with current 
legislation. 
8.2.6 Pregnancy 
Any pregnancy in a participant or partner that occurs during the study must be reported using 
the Pregnancy Report Form.  Pregnancy must be reported within 24 hours after the site 
personnel first learn of the pregnancy.  The pregnancy itself is not considered an AE.  
However, the pregnancy must be followed to determine outcome (including spontaneous 
miscarriage, elective termination, normal birth, or congenital abnormality) and status of mother 
and child, even if the patient discontinued from the study.  Abortions (elective or spontaneous) 
occurring from the time the patient signs the ICF until 90 days after the last dose of study drug 
must be reported as an SAE. 
Any SAE occurring in association with a pregnancy that is brought to the Investigator’s 
attention after the patient has completed the study and considered by the Investigator as 
possibly related to the study drug must be promptly reported in the same manner. 
Once pregnancy is confirmed in a study participant, study drug will be discontinued, 
see Section 8.3.6 for additional information. 
8.2.7 Overdose 
An overdose of the study drug will be considered an AE if the dose administered to the patient 
exceeds the maximum dose described in the protocol by 15% or more.  If such an overdose 
occurs during the study, with or without any signs or symptoms, it must be reported to the 
Sponsor using the SAE Report Form within 24 hours after the time site personnel first learn 
about the event.   
8.3 Safety Assessments  
Safety will be assessed based on the procedures in the subsection below.  AEs/SAEs collection 
and reporting is described in Section 8.2.2. 
Unless otherwise specified, all safety assessments on dosing days will be done prior to study 
drug administration. 


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8.3.1 Physical Examination 
Physical examination will be performed according to institutional standards and will include a 
whole body skin examination. 
8.3.2 ECOG Performance Status 
ECOG performance status grades are presented in Appendix 1 and will be captured as per SoE 
(Table 1).  
8.3.3 Height and Weight 
Height and weight will be measured as per SoE (Table 1). 
Additional measurements will be performed if clinically indicated. 
Patients should monitor their weight at home to mitigate the risks for edema/effusions.  
Refer to Section 6.6.2 for further details. 
8.3.4 Vital Signs 
Vital signs include the measurements of arterial blood pressure (systolic and diastolic), 
heart rate, respiratory rate, and body temperature and will be performed according to the 
institutional standards.  For Day 1 of each cycle, vital signs are to be measured before the start 
of the loncastuximab tesirine infusion and at the end of infusion. 
8.3.5 Laboratory Tests 
Samples will be collected at the time points specified as per SoE (Table 1).  
Any clinically significant abnormal laboratory test results will be recorded as AEs or SAEs. 
Hematology: white blood cells (WBC) with 5-part differential (neutrophils, eosinophils, 
basophils, lymphocytes, and monocytes), platelet count, hemoglobin, and hematocrit.  
Chemistry: ALT, AST, GGT, alkaline phosphatase (ALP), amylase, lipase, total bilirubin 
(conjugated and unconjugated bilirubin only when total bilirubin is abnormal), sodium, 
potassium, chloride, phosphate, calcium, magnesium, blood urea nitrogen or urea, carbon 
dioxide/bicarbonate, creatinine, creatine phosphokinase, total protein, albumin, glucose, and 
lactate dehydrogenase.  
Coagulation: partial thromboplastin time (PTT) and International Normalized Ratio (INR). 
Urinalysis: pH, specific gravity, protein, WBC, red blood cell (RBC), ketones, glucose, and 
bilirubin.   
Urinalysis may be performed by dipstick.  Abnormal findings will be followed up with a 
microscopic evaluation and/or additional assessments as clinically indicated.  A microscopic 
evaluation consists at a minimum of WBC and RBC quantitation per high power field, as well 
as semi-quantitative assessment of other cells and substances, if present, such as epithelial cells, 
bacteria, and crystals (“few,” “moderate,” “many”).  Other evaluations depending on 
microscopic findings may be added. 


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8.3.6 Pregnancy Test 
A highly sensitive β-HCG test in urine or blood β-HCG test will be performed in woman of 
childbearing potential for eligibility (see Section 5.1 Inclusion criterion 10) and throughout the 
study as per SoE.  
The C1D1 pre-dose pregnancy test can be waived if the test for eligibility was done within 
3 days of C1D1.  After starting the study drug, all efforts should be made to keep the interval 
between 2 consecutive pregnancy tests no more than 6 weeks. 
If a pregnancy test is positive, the study drug must be held pending confirmation.  
If the pregnancy is confirmed, treatment will be discontinued permanently for the patient.  
Refer to Section 8.2.6 for the handling of the patient and reporting the event. 
8.3.7 ECG 
Three consecutive (also called triplicate) 12-lead ECGs will be performed at defined 
timepoints throughout the study as per SoE (Table 1).  Refer to Table 4 for the detailed schedule 
of ECGs. 
ECGs will be performed after the patient is resting for at least 5 minutes. 
At timepoints coinciding with blood sample collection including PK, ECGs should be taken 
prior to blood collection. 
If a patient experiences Torsade de Pointes, additional concomitant PK samples 
(i.e., unscheduled) should be collected. 
Table 4. 
Schedule for Triplicate ECG Collection 
Cycle 
Day 
ECG timepoint (window) 
Screening 
- 
Any time within 28 days prior to C1D1 
C1 
D1 
Pre-dose (preferably within 2 h prior to start of infusion) 
EOI (within 10 min prior to EOI) 
Post-dose* 4 h (± 15 min) 
D8 
Post-dose* 168 h (± 48 h; but within 30 min prior to PK sample) 
D15 
Post-dose* 336 h (± 48 h; but within 30 min prior to PK sample) 
C2 
D1 
Pre-dose (within 30 min prior to PK sample) 
EOI (within 10 min prior to EOI) 
Post-dose* 4 h (± 15 min) 
D8 
Post-dose* 168 h (± 48 h; but within 30 min prior to PK sample) 
D15 
Post-dose* 336 h (± 48 h; but within 30 min prior to PK sample) 
C3 
 
D1 
Pre-dose (within 30 min prior to PK sample)  
EOI (within 10 min prior to EOI) 
C5, C7 … 
every other cycle 
D1 
Pre-dose (within 30 min prior to PK sample) 
EOT 
 
Any time (but within 30 min prior to PK sample) 
Unscheduled 
 
Any time 
Abbreviations: ECG, electrocardiogram; EOI, end of infusion; EOT, end of treatment; PK, pharmacokinetics. 
*Post-dose timepoint is counted from start of infusion.  


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ECGs will be submitted for a central review.  Submission instructions for the central review 
will be provided in a separate manual.  Assessments will include determination of heart rate 
and rhythm and the PR, QRS, QT, QTcF, and QTcB intervals. 
8.4 Pharmacokinetics, Pharmacodynamics, and Immunogenicity 
PK, ADA, 
 will be collected as per SoE (Table 1).  Additional biological 
samples may be collected by the Investigator when clinically indicated (e.g., at the time of 
significant AEs that are at least possibly related to the study drug) and may be used for PK, 
pharmacodynamics, 
   
When multiple samples are required at the same timepoint, collection of safety samples should 
be first followed by PK, then ADA, 
 
In order to better understand the disease, metabolic disposition, and pharmacologic behavior 
of loncastuximab tesirine in humans, samples remaining after primary analyses may be utilized 
for further analysis.   
Biological samples may be retained for up to 10 years to further address scientific questions as 
new information in regards to the disease or the study drug becomes available. 
For detailed instructions related to central laboratory sample collection, labeling, processing, 
storage, or shipment refer to the appropriate laboratory manual(s).  
8.4.1 Pharmacokinetics 
The concentration in serum of loncastuximab tesirine (total antibody), PBD-conjugated 
antibody, and unconjugated warhead SG3199 will be assessed by a central laboratory 
designated by the Sponsor using validated bioanalytical methods. 
Approximately 6 mL of whole blood will be collected as per Table 1 and Table 5.  
Blood should be drawn from a vein away from the one used for study drug infusion. 
PK samples must be stored at -70°C.  Please refer to the laboratory manual for detailed 
instructions regarding specimen handling and shipment.  
At timepoints coinciding with ECG collection, PK blood collection should occur immediately 
after the end of the ECG recording and, when applicable, after vital signs.  If a patient 
experiences Torsade de Pointes, additional PK samples (e.g., unscheduled) should be collected.  
 
 


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Table 5. 
Sampling Schedule for PK and ADA  
Cycle 
Day PK timepoint (window) 
ADA timepoint (window) 
C1 
D1 
Pre-dose (preferably within 2 h prior 
to start of infusion) 
EOI (-5 to +10 min) 
Post-dose* 4 h (± 10 min) 
Pre-dose (preferably within 2 h prior 
to start of infusion) 
 
D8 
Post-dose* 168 h (± 48 h)  
- 
D15 Post-dose* 336 h (± 48 h) 
Post-dose* 336 h (± 48 h) 
C2 
D1 
Pre-dose (within 2h prior to start of 
infusion) 
EOI (-5 to +10 min) 
Post-dose* 4 h (± 10 min) 
Pre-dose (within 2 h prior to start of 
infusion) 
D8 
Post-dose* 168 h (± 48 h) 
- 
D15 Post-dose* 336 h (± 48 h) 
- 
C3 
D1 
Pre-dose (within 2 h prior to start of 
infusion)  
EOI (-5 to +10 min) 
Pre-dose (within 2 h prior to start of 
infusion) 
C5, C7, … 
every other cycle 
D1 
Pre-dose (within 2 h prior to start of 
infusion)  
Pre-dose (within 2 h prior to start of 
infusion) 
EOT 
 
At any time during visit day 
At any time during visit day 
Unscheduled 
 
Any time 
Any time (if applicable, close to PK 
sample) 
Abbreviations: ADA, anti-drug antibody; EOI, end of infusion; EOT, end of treatment; PK, pharmacokinetics. 
*Post-dose timepoint is counted from start of infusion.  
To understand the metabolic disposition of loncastuximab tesirine in humans, samples 
remaining after PK analysis is complete may be pooled among patients for potential metabolite 
identification. 
8.4.2 Immunogenicity 
Detection of ADAs will be performed by using a screening assay for identification of antibody 
positive samples/patients, a confirmation assay, and titer assessment, and will be performed 
using the Meso-Scale Discovery Electrochemiluminescence platform (MSD-ECL).  If an ADA 
is confirmed, a functional assay for the assessment of the neutralizing capacity of the ADA 
will be performed.   
Approximately 6 mL of whole blood will be collected as per Table 1 and Table 5.  
Blood should be drawn from a vein away from the one used for study drug infusion. 
For patients who test positive for ADAs, an additional ADA sample will be requested for 
testing every 12 weeks following the EOT visit until the ADA titer falls to a background level. 
ADA samples must be stored at -70°C.  Please refer to the laboratory manual for detailed 
instructions regarding specimen handling and shipment.  


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8.5 Health-Related Quality of Life (HRQoL) Questionnaires 
8.5.1 EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) 
EQ-5D-5L is designed as an international, standardized, generic instrument for describing and 
evaluating QoL (EuroQol Group, 1990).  The EQ-5D-5L consists of two parts: 
• The descriptive system: QoL is classified according to five dimensions: mobility, 
self-care, usual activities, pain/discomfort, and anxiety/depression.  Each dimension 
comprises five levels of perceived problems (e.g., none, slight, moderate, severe, 
extreme). 
• The visual analog scale (VAS): patients are asked to indicate their health state today on 
a VAS with the endpoints labeled ‘the best health you can imagine’ (score 100) and ‘the 
worst health you can imagine’ (score 0).  Patients are asked to mark an “X” on the VAS 
to indicate their own health and then to report the score in a text box.  If there is a 
discrepancy between where the patient has placed the X and the number he/she has 
written in the box, the number in the box is to be entered in the CRF together with a 
comment indicating the discrepancy. 
8.5.2 Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) 
FACT-Lym is a lymphoma-specific subscale for the Functional Assessment of Cancer Therapy 
(FACT) questionnaire (Hlubocky FJ et al, 2013).  It consists of 15 specific items that are used 
together with the core 27-item questionnaire FACT-G.  The patient is asked to respond to each 
item with a score of 0–4, where 0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, and 
4 = very much.  A higher score indicates a worse level of QoL. 
 


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9 Statistical Considerations 
Full details of the analysis plan, including a more technical and detailed elaboration of the 
statistical analyses, will be provided in the statistical analysis plan (SAP).  
 
 
9.1 Sample Size Calculation 
Patients with DLBCL who have failed second line therapy have a very poor prognosis, with 
response to second-line salvage therapy ranging from 14-26%, with a median survival of 
6.1 months (Seshadri et al., 2008; Crump et al., 2017).  A treatment with a response rate of 
20% would be a clinically meaningful option for this patient population.  
The primary hypothesis is that the ORR based on central review for patients treated with 
loncastuximab tesirine is significantly greater than 20% (i.e., H0: p ≤ 0.2 vs. Ha: p >0.2).  
This hypothesis will be tested at type I error of 0.05 (two sided).   
Using nQuery exact test for single proportion, a sample size of 140 patients has >99% power 
to achieve a 1-sided significance level of 0.025 (2-sided significance level of 0.05).  
This sample size will provide adequate precision for observed ORR in the expected range. 
A 2-stage design will be used, with an interim analysis for futility on the first 52 patients.  
If ≥10 patients respond, the study will proceed to complete full enrollment.  Enrollment will 
continue during the interim analysis; however, further enrollment will be halted if futility is 
confirmed to minimize exposure of patients in the study.  With the null hypothesis that the true 
response rate is 0.2, and the alternative hypothesis that the true response rate is significantly 
greater than 20%, (40% is used for calculation), the design controls the type I error rate at 
0.025 and yields a power of >99%. 
9.2 Analysis Populations 
• All Treated Population: All patients who receive at least 1 dose of loncastuximab tesirine.  
This population will be used in the primary analyses of efficacy and safety.  
• Per-Protocol Population: All patients in the all-treated population without major protocol 
deviations, which will be further described in detail in the SAP. 
• PK Population: All patients in the per-protocol population with at least 1 pre- (C1D1) and 
1 post-dose valid assessment. 
• Pharmacodynamics Population: All patients in the per-protocol population with at least 
1 valid pharmacodynamics/
  
9.3 Interim Analysis for Futility 
A single interim analysis is planned using Simon’s 2-stage procedure.  The purpose of this 
interim analysis is solely to determine if there is a sufficient ORR observed early in the study 
to warrant continuing study enrollment to completion.  The interim analysis constitutes a 
futility analysis; it will not be used to stop the trial early for positive efficacy. 
In the first stage of the study, an interim analysis will be performed at the time when the 
52nd patient has two tumor assessments (approximately 12 weeks after start of study drug).  
Enrollment will continue during the interim analysis.  If ≥10 patients respond, the study will 
proceed to the second stage.  If <10 patients respond, study enrollment will be halted.  


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Patients already enrolled may continue treatment for up to 1 year or until disease progression, 
unacceptable toxicity, or other discontinuation criteria (Section 7), whichever occurs first.  
Additionally, patients benefitting clinically at 1 year may continue treatment after a case by 
case review with the Sponsor.   
9.4 Final Analysis 
For primary and key secondary endpoints analyses, a database snapshot will be taken when all 
patients have a minimum of 6 months follow up after initial documented response.  All efficacy, 
safety, and PK endpoints will be analyzed and reported in the clinical study report (CSR).  
Results of the population PK analysis will be reported separately. 
The exact binomial test will be used in the final analyses for the primary endpoint because of 
the practical consideration that accrual cannot be limited to exactly 140 patients and because 
patients included in the interim analysis as non-responding may be included in the final 
analysis as responding if they experience a late response. 
Follow-up analyses will be performed when all the patients complete the study per protocol.  
The results will be reported in a CSR addendum. 
9.5 Demographics and Baseline Characteristics 
The analyses include: 
• Demographic information such as age, gender, ethnicity, and race (to the extent allowed 
by local regulations). 
• Cancer medical history, which includes a complete history of all surgeries and 
significant diagnoses, and all cancer treatment, including surgery, radiation therapy, 
chemotherapy, etc. 
• Any other relevant medical history. 
9.6 Efficacy Analyses 
Primary efficacy analyses will be based on response as determined by central review.  
Response reported by investigators will be used for sensitivity analyses. 
9.6.1 Overall Response Rate 
The ORR will be defined as the proportion of patients with a BOR of CR or PR.  The overall 
response category will be derived based on response assessment performed on or before the 
start of subsequent anti-cancer therapy.  For the primary ORR analysis in the all treated 
population, patients with a CR or PR will be counted as successes and all other patients 
(including those with missing response information) will be counted as failures. 
The percentage of ORR with its 95% confidence interval (CI) will be presented.  In contrast to 
CR, PR, or PD, a BOR of SD can only be made after the patient is on-study for a minimum of 
35 days after the first dose of study drug.  Any tumor assessment indicating SD before this 
time period will be considered as a non-evaluable for BOR if no assessment after this time 
period is available.   


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9.6.2 Duration of Response 
DOR will be defined among responders (CR or PR) as the time from the earliest date of first 
response until the first date of either disease progression or death due to any cause.  The date 
of disease progression will be defined as the earliest date of disease progression based on 
central review.  For patients who have not progressed or died at the time of the analysis, 
censoring will be performed using the date of the last valid disease assessment.  The data will 
be analyzed by the Kaplan-Meier method.  The median duration of response and 95% CI will 
be presented.  DOR will be analyzed by response subgroup (CR, PR).  Further details will be 
outlined in the SAP. 
9.6.3 Complete Response Rate 
Complete Response Rate (CRR) will be defined as the proportion of patients with a best overall 
response of CR.  The percentage of CRR with its 95% CI will be presented. 
9.6.4 Relapse-free Survival 
RFS will be defined among CR patients as the time from the earliest date of first complete 
response until the first date of either disease relapse or death due to any cause.  The date of 
disease progression will be defined as the earliest date of disease progression based on central 
review.  For patients who have not progressed or died at the time of the analysis, censoring 
will be performed using the date of the last valid disease assessment.  The data will be analyzed 
by the Kaplan-Meier method.  The median duration of response and 95% CI will be presented.  
Further details will be outlined in the SAP. 
9.6.5 Progression-Free Survival 
PFS will be defined among all treated patients as the time from first dose of study drug until 
the first date of either disease progression or death due to any cause.  The date of disease 
progression will be defined as the earliest date of disease progression based on central review.  
For patients whose disease has not progressed at the time of the analysis, censoring will be 
performed using the date of the last valid disease assessment.  The data will be analyzed by the 
Kaplan-Meier method.  The median PFS time and 95% CI will be presented.  Further details 
will be outlined in the SAP. 
9.6.6 Overall Survival 
Median OS will be defined as the time from the beginning of study drug treatment until death 
due to any cause.  For patients who have not died at the time of the analysis, censoring will be 
performed using the date the patient was last known to be alive.  The data will be analyzed by 
the Kaplan-Meier method.  The median OS and 95% CI will be presented.  Further details will 
be outlined in the SAP. 


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9.6.7 Subgroup analysis 
Subgroup analyses will be performed for ORR, DOR, CR, RFS, PFS, and OS using the 
following variables if appropriate 
• 
Demographic variables: age group, gender, race, and country 
• 
Baseline disease characteristics: tumor staging, and subtype 
• 
Number of prior systemic therapies and response to prior systemic therapies 
Other subgroup analysis factors may be evaluated as appropriate and the details will be 
provided in SAP. 
9.7 Safety Analyses 
Safety analyses will be presented descriptively.   
9.7.1 Adverse Events 
The focus of AE summarization will be on TEAEs.  A TEAE is defined as an AE that occurs 
or worsens in the period extending from the first dose of study drug to 30 days after the last 
dose of study drug or start of new anti-cancer therapy, whichever is earlier. 
TEAEs will be summarized.  Summary tables will be presented to show the number of patients 
reporting TEAEs by severity grade and corresponding percentages.  A patient who reports 
multiple TEAEs within the same Preferred Term (or System Organ Class) is counted only once 
for that Preferred Term (or System Organ Class) using the worst severity grade.  
Separate summaries will be prepared for TEAEs classified as severe or life-threatening 
(Grade 3 or higher); study drug-related AEs; AEs leading to treatment interruption, 
modification, or discontinuation; serious AEs; and death.  Dose interruptions, reductions, and 
relative dose intensity will also be summarized. 
9.7.2 Clinical Laboratory Results 
Clinical hematology, coagulation panel, biochemistry, and urinalysis data will be summarized 
at each scheduled assessment.  Shifts for clinical laboratory results that can be graded 
according to CTCAE v4.0 (or more recent) will be summarized by CTCAE grade. 
Shifts for other numeric laboratory results will be by high/normal/low flag.  Shifts for all other 
laboratory results will be by normal/abnormal flag. 
Summaries by visit will include data from scheduled assessments, and all data will be reported 
according to the nominal visit date for which it was recorded.  Unscheduled data will be 
included in “worst-case post-Baseline” summaries, which will capture a worst case across all 
scheduled and unscheduled visits after the first dose of study drug.  Further details will be 
provided in the SAP. 


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9.7.3 Additional Safety Assessments 
The results of scheduled assessments of vital signs, physical examinations, ECOG performance 
status, and 12-lead ECGs will be summarized.  All data will be reported according to the 
nominal visit date for which it was recorded (i.e., no visit windows will be applied).  
Unscheduled data will be included in “worst case” summaries, which will capture a worst case 
across all scheduled and unscheduled visits after the first dose of study drug.  All data will be 
listed.  Further details will be provided in the SAP. 
9.8 Pharmacokinetic Analyses 
The PK profile may include, but is not limited to, determination of: maximum concentration 
(Cmax), area under the concentration-time curve from time zero to the end of the dosing interval 
(AUC0-τ), area under the concentration-time curve from time zero to infinity (AUC0-∞), 
clearance (CL), and accumulation index (AI). 
PK parameters will be determined for all PK-evaluable patients using a non-compartmental 
method with Phoenix WinNonlin (Certara USA, Inc., Princeton, NJ, US) or other appropriate 
software.  Supplemental population PK analyses will be undertaken and reported separately to 
characterize the PK parameters for the typical patient and to identify covariate factors which 
influence drug disposition. 
Demographic data for the PK population will be summarized.  Potential correlations of 
PK parameters to baseline characteristics and safety observations will be assessed but may be 
reported separately.  In addition, the influence of loncastuximab tesirine PBD-conjugated 
antibody and unconjugated warhead SG3199 concentrations on the QTc interval will be 
assessed but reported separately. 
9.9 Immunogenicity Analyses 
A tiered immunogenicity strategy (Figure 2) will be undertaken to evaluate ADAs by screening 
and confirmatory assays with titer evaluation, followed by characterization and evaluation of 
neutralizing capacity as needed.  ADA sample collection, banking, and testing in validated and 
to be validated assays will be according to the new FDA Draft Guidance for Industry 
(April 2016): ‘Assay Development and Validation for Immunogenicity testing of Therapeutic 
Protein Products’.   
 


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Figure 2. 
Anti-drug Antibody Tiered Immunogenicity Testing Strategy 
 
 
Abbreviations: ADA, anti-drug antibody; ADC, antibody-drug conjugate; BSA, bovine serum albumin; mAb, 
monoclonal antibody; PK, pharmacokinetics. 
Results from ADA testing will include tabular summarization for number/proportion of 
patients with positive pre-dose ADA response, number of patients with post-dose ADA 
response only, and number of patients with positive ADA response at any time.  
The denominator will be the total number of patients tested for ADAs in the study. 
 
  
 


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10 Data Management and Quality Assurance 
The Investigator will maintain accurate source documentation including patient medical 
records, laboratory reports, ECG strips, and patient diaries. 
Investigative site qualified personnel will enter patient data into an EDC system.  The analysis 
data sets will be a combination of these data and data from other sources. 
Clinical data management will be performed in accordance with applicable standards and data 
cleaning procedures to ensure the integrity of the data (e.g., removing errors and 
inconsistencies in the data).  AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA).  Concomitant medications will be coded using the world health 
organization (WHO) Drug Dictionary. 
After database lock, each study site will receive information about all of their site-specific 
eCRF data as entered into the EDC system for the study, including full discrepancy and audit 
history.  Additionally, a copy of study data from all sites will be created and sent to the Sponsor 
for storage.  The CRO will maintain a duplicate copy for its records.  In all cases, patient initials 
will not be collected or transmitted to the Sponsor. 
For detailed instruction on data entry procedures and timelines, please refer to the eCRF 
Completion Guidelines. 
 


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11 Ethical, Regulatory, and Study Management Considerations 
11.1 Regulatory and Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki, International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP), and all applicable regulations. 
11.2 Independent Ethics Committee or Institutional Review Board 
Federal regulations and ICH guidelines require that approval be obtained from an institutional 
review board (IRB)/IEC before participation of human patients in research studies.  
Before study onset, the protocol, informed consent, advertisements to be used for the 
recruitment of study patients, and any other written information regarding this study intended 
to be provided to the patient or the patient’s legally authorized representative must be approved 
by the IRB/IEC.  Documentation of all IRB/IEC approvals will be maintained by the site and 
will be available for review by the Sponsor or its designee. 
All IRB/IEC approvals should be signed by the IRB/IEC chairman or designee and must 
identify the IRB/IEC name and address, the clinical protocol by title or protocol number or 
both, and the date approval or a favorable opinion was granted. 
The Investigator is responsible for obtaining continued review of the clinical research as 
specified by the IRB/IEC, at intervals not exceeding 1 year.  The Investigator must supply the 
Sponsor or its designee with written documentation of continued review of the clinical research. 
11.3 Patient Information and Consent 
Informed consent in compliance with IRB/IEC and local regulations shall be obtained from 
each patient or their legally authorized representative before performing any study procedures 
and will be documented with a signed IRB/IEC approved ICF.  Before enrollment, each 
prospective patient or his or her legally authorized representative will be given a full 
explanation of the study and be allowed to read the approved ICF.  Once the Investigator is 
assured that the patient/legally authorized representative understands the implications of 
participating in the study, the patient/legally authorized representative will be asked to give 
consent to participate in the study and sign the ICF.  The process for obtaining consent has to 
be documented at the institution. 
If the ICF is revised during the course of the study, all patients on-study, including those in 
follow-up, must sign the revised form, unless otherwise indicated by the IRB/IEC 
(local or global, as applicable).  In such case, the reason for not re-consenting the patient should 
be documented. 


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11.4 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain patient confidentiality.  All records will be kept in a secure 
storage area with limited access.  Clinical information will not be released without the written 
permission of the patient (or the patient’s legal guardian), except as necessary for monitoring 
and auditing by the Sponsor, its designee, regulatory authorities, or the IRB/IEC. 
The Investigator and other study staff may not disclose or use for any purpose other than 
performance of the study any data, record, or other unpublished, confidential information 
disclosed to those individuals for the purpose of the study.  Prior written agreement from the 
Sponsor or its designee must be obtained for the disclosure of any said confidential information 
to other parties. 
11.5 Financial Disclosure and Obligations 
Investigators are required to provide financial disclosure information to allow the Sponsor to 
submit the complete and accurate certification or disclosure statements as required under 
21 CFR 54 and local regulations.  In addition, the Investigator must promptly update this 
information if any relevant changes occur during the course of the investigation and for 1 year 
following the completion of the study. 
11.6 Serious Adverse Events Report Requirements 
The Sponsor will ensure that all relevant safety information (SAEs and SUSARSs) is reported 
to the FDA and competent authorities of European Member States, and to the IRB/IEC, 
in accordance with current legislation. 
11.7 Study Conduct 
The Investigator will conduct all aspects of this study in accordance with the principles of the 
current version of ICH E6 as well as all national, state, and local laws and regulations.  
Study personnel involved in conducting this study will be qualified by education training and 
experience to perform their respective tasks.  Study information from this protocol will be 
posted on publicly available clinical study registers before enrollment of patients begins.  
11.8 Protocol Amendments 
Any change in the study plan requires a protocol amendment.  All amendments to the protocol 
must be reviewed and approved following the same process as the original protocol before the 
amended protocol can be implemented.  The Investigator will inform the governing IRB/IEC 
of all protocol amendments issued by the Sponsor in accordance with established IRB/IEC 
procedure.  Only protocol amendments intended to eliminate an apparent immediate hazard to 
patient(s) may be implemented immediately, i.e., without IRB/IEC approval, but the 
circumstances of the change must be documented and submitted to the IRB/IEC. 


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11.9 Monitoring of the Study 
All aspects of the study will be carefully monitored by the Sponsor or designee for compliance 
with GCP and applicable government regulations. 
Investigators and institutions involved in the study will permit study-related monitoring, audits, 
IRB/IEC review, and regulatory inspections by providing direct access to all study records.  
In the event of an audit, the Investigator agrees to allow the Sponsor, representatives of the 
Sponsor, or a regulatory agency access to all study records. 
The Investigator should promptly notify the Sponsor and the CRO of any inspections scheduled 
by any regulatory authorities and promptly forward copies of any inspection reports received 
to the Sponsor. 
11.10 
Records Retention 
Essential documents should be retained for at least 15 years from the completion of the study 
(last patient last visit) and until at least 2 years after the last approval of a marketing application 
in an ICH region and until there are no pending or contemplated marketing applications in an 
ICH region or at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational study drug.  However, these documents should be retained 
for a longer period if required by the applicable regulatory requirements or by an agreement 
with the Sponsor.  It is the responsibility of the Sponsor to inform the Investigator/institution 
as to when these documents no longer need to be retained. 
11.11 
Publications 
Following completion of the study, the results from the study may be reported publicly by 
making any oral public presentation and/or submitting or presenting a manuscript, abstract, or 
other materials relating to the Study at scientific meetings and/or to a publisher, reviewer, or 
other outside person in scientific journals (“Publication”), provided; however, that Publication 
of the results from an individual site shall not be made before the first multi-site Publication 
by Sponsor.  The Sponsor shall coordinate the drafting, editing, authorship, and other activities 
related to study Publication and shall mutually agree with the Investigator(s) on the number, 
medium, forum, and timing for Publication.  The Sponsor shall solicit input regarding contents 
of the Publication from all Investigators and in consultation with all sites.  The Sponsor 
acknowledges the right of the Investigator(s) to publish the results of this study after the entire 
study has completed, but also reserves the right to a window to review the Publication for 
regulatory compliance as well as for protection of its intellectual property.  In particular, the 
Sponsor may request to remove the Sponsor’s confidential information and suspend 
Publication for a certain period of time to protect the Sponsor’s intellectual property interest, 
as further set forth in the Clinical Trial Agreement with the clinical study site(s) and 
Investigator(s). 
 


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12 Reference List 
Adair JR, Howard PW, Hartley JA, et al. Antibody-drug conjugates - a perfect synergy. 
Expert Opin Biol Ther 2012;12(9):1191-1206. 
Al-Hamadani M, Habermann TM, Cerhan JR, et al. Non-Hodgkin lymphoma subtype 
distribution, geodemographic patterns, and survival in the US: A longitudinal analysis of the 
National Cancer Data Base from 1998 to 2011. Am J Hematol 2015;90(9):790-795. 
Beck A, Goetsch L, Dumontet C, et al. Strategies and challenges for the next generation of 
antibody-drug conjugates. Nat Rev Drug Discov 2017;16(5):315-337. 
Cairo MS, Coiffier B, Reiter A, et al. Recommendations for the evaluation of risk and 
prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: 
An expert TLS panel consensus. Br J Haematol 2010;149(4):578-586. 
Cheson BD, Fisher RI, Barrington SF, 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):3059-3067. 
Coiffier B, Sarkozy C. Diffuse large B-cell lymphoma: R-CHOP failure-what to do? 
Hematology Am Soc Hematol Educ Program 2016(1):366-378. 
Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: 
results from the international SCHOLAR-1 study. Blood 2017;130(16):1800-1808. 
Epperla N, Hamadani M. Hematopoietic cell transplantation for diffuse large B-cell and 
follicular lymphoma: Current controversies and advances. Hematol Oncol Stem Cell Ther 
2017;10(4):277-284. 
Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation 
for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol 2010;28(27):4184-4190. 
Hartley JA. The development of pyrrolobenzodiazepines as antitumour agents. 
Expert Opin Investig Drugs 2011;20(6):733-744. 
Hlubocky FJ, Webster K, Cashy J, et al. The development and validation of a measure of 
health-related Quality of Life for Non-Hodgkin’s Lymphoma: The Functional Assessment of 
Cancer Therapy-Lymphoma (FACT-Lym). Lymphoma 2013:1-9 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the 
Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5(6):649-655. 
Rudin CM, Pietanza MC, Bauer TM, et al. Rovalpituzumab tesirine, a DLL3-targeted 
antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, 
open-label, phase 1 study. Lancet Oncol 2017;18(1):42-51. 
Scheuermann RH, Racila E. CD19 antigen in leukemia and lymphoma diagnosis and 
immunotherapy. Leuk Lymphoma 1995;18(5-6):385-397. 
Seshadri T, Stakiw J, Pintilie M, et al. Utility of subsequent conventional dose chemotherapy 
in relapsed/refractory transplant-eligible patients with diffuse large B-cell lymphoma failing 
platinum-based salvage chemotherapy. Hematology 2008;13(5):261-266. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin 2017;67(1):7-30. 


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Simon R. Optimal two-stage designs for phase II clinical trials. Controlled Clinical Trials 
1989;10(1):1-10. 
Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of 
white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 
2006;24(19):3187-3205. 
 
 


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13 Appendices 
13.1 Appendix 1. Eastern Cooperative Oncology Group Performance 
Status 
Performance status will be assessed using the ECOG performance status grades as indicated 
below: 
Grade 
Definition 
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 
Oken et al., 1982 
 


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13.2 Appendix 2. Response Assessment of Hodgkin and Non-Hodgkin 
Lymphoma (Lugano Classification) 
Response / Site 
PET-CT-Based Response 
CT-Based Response 
Complete 
Complete metabolic response 
Complete radiologic response  
(all of the following) 
Lymph nodes and 
extralymphatic sites 
• Score 1, 2, or 3* with or without a residual 
mass on 5PS** 
Note: Uptake may be greater than normal 
mediastinum and/or liver in Waldeyer’s ring 
or extranodal sites with high physiologic 
uptake or with activation within spleen or 
marrow (e.g., with chemotherapy or myeloid 
colony-stimulating factors). In this 
circumstance, complete metabolic response 
may be inferred if uptake at sites of initial 
involvement is no greater than surrounding 
normal tissue even if the tissue has high 
physiologic uptake 
• Target nodes/nodal masses must regress to 
≤1.5 cm in LD 
• No extralymphatic sites of disease 
Nonmeasured lesion 
• Not applicable 
• Absent 
Organ enlargement 
• Not applicable 
• Regress to normal 
New lesions 
• None 
• None 
Bone marrow 
• No evidence of FDG-avid disease in 
marrow 
• Normal by morphology; if indeterminate, 
IHC negative 
Partial 
Partial metabolic response 
Partial remission  
(all of the following) 
Lymph nodes and 
extralymphatic sites 
• Score 4 or 5** with reduced uptake 
compared with baseline and residual 
mass(es) of any size. 
• At interim, these findings suggest 
responding disease. 
• At end of treatment, these findings indicate 
residual disease. 
• ≥50% decrease in SPD of up to 6 target 
measurable nodes and extranodal sites 
• When a lesion is too small to measure on 
CT, assign 5 mm × 5mm as the default 
value. 
• When no longer visible, 0 × 0 mm 
• For a node >5 mm × 5 mm, but smaller 
than normal, use actual measurement for 
calculation 
Nonmeasured lesion 
• Not applicable 
• Absent/normal, regressed, but no increase 
Organ enlargement 
• Not applicable 
• Spleen must have regressed by >50% in 
length beyond normal 
New lesions 
• None 
• None 
Bone marrow 
• Residual uptake higher than uptake in 
normal marrow but reduced compared with 
baseline (diffuse uptake compatible with 
reactive changes from chemotherapy 
allowed). If there are persistent focal 
changes in the marrow in the context of a 
nodal response, consideration should be 
given to further evaluation with MRI or 
biopsy or an interval scan 
• Not applicable 
No response or stable 
disease 
No metabolic response 
 
Stable disease 


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Response / Site 
PET-CT-Based Response 
CT-Based Response 
Target nodes/nodal 
masses, extranodal 
lesions 
• Score 4 or 5 with no significant change in 
FDG update from baseline at interim or 
end of treatment 
• <50% decrease from baseline in SPD of up 
to 6 dominant, measurable nodes and 
extranodal sites; no criteria for progressive 
disease are met 
Nonmeasured lesions 
• Not applicable 
• No increase consistent with progression 
Organ enlargement 
• Not applicable 
• No increase consistent with progression 
New lesions 
• None 
• None 
Bone marrow 
• No change from baseline 
• Not applicable 
Progressive disease 
Progressive metabolic disease 
Progressive disease  
(requires at least 1 of the following) 
Individual target 
nodes/nodal masses 
• Score 4 or 5 with an increase in intensity of 
uptake from baseline and/or 
• PPD progression 
Extranodal lesions 
• New FDG-avid foci consistent with 
lymphoma at interim or end of treatment 
assessment 
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 
• None 
• New or clear progression of preexisting 
nonmeasured lesions 
New lesions 
• New FDG-avid foci consistent with 
lymphoma rather than another etiology 
(e.g., infection, inflammation). If uncertain 
regarding etiology of new lesions, biopsy 
or interval scan may be considered 
• 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 FDG-avid foci 
• New or recurrent involvement 
Abbreviations: 5PS, 5-point scale; CT, computed tomography; FDG, fluorodeoxyglucose; IHC, immunohistochemistry; 
LDi, longest transverse diameter of a lesion; MRI, magnetic resonance imaging; PET, positron emission tomography; PPD, 
cross product of the LDi and perpendicular diameter; SDi, shortest axis perpendicular to the LDi; SPD, sum of the product 
of the perpendicular diameters for multiple lesions. 
* A score of 3 in many patients indicates a good prognosis with standard treatment, especially if at the time of an interim 
scan. However, in trials involving PET where de-escalation is investigated, it may be preferable to consider a score of 3 as 
inadequate response (to avoid undertreatment). Measured dominant lesions: Up to six of the largest dominant nodes, nodal 
masses, and extranodal lesions selected to be clearly measurable in two diameters. Nodes should preferably be from 
disparate regions of the body and should include, where applicable, mediastinal and retroperitoneal areas. Non-nodal lesions 
include those in solid organs (e.g., liver, spleen, kidneys, lungs), GI involvement, cutaneous lesions, or those noted on 
palpation. Nonmeasured lesions: Any disease not selected as measured, dominant disease and truly assessable disease 
should be considered not measured. These sites include any nodes, nodal masses, and extranodal sites not selected as 
dominant or measurable or that do not meet the requirements for measurability but are still considered abnormal, as well as 
truly assessable disease, which is any site of suspected disease that would be difficult to follow quantitatively with 


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measurement, including pleural effusions, ascites, bone lesions, leptomeningeal disease, abdominal masses, and other 
lesions that cannot be confirmed and followed by imaging. In Waldeyer’s ring or in extranodal sites (e.g., GI tract, liver, 
bone marrow), FDG uptake may be greater than in the mediastinum with complete metabolic response, but should be no 
higher than surrounding normal physiologic uptake (e.g., with marrow activation as a result of chemotherapy or myeloid 
growth factors). 
** PET 5PS: 1, no uptake above background; 2, uptake ≤ mediastinum; 3, uptake > mediastinum but ≤ liver; 4, uptake 
moderately > liver; 5, uptake markedly higher than liver and/or new lesions; X, new areas of uptake unlikely to be related to 
lymphoma. 
Cheson et al., 2014