Clinical trial NCT03582033
Conditions: Multiple Myeloma
Keywords: RRMM Antibodies, monoclonal Antigens, BCMA Immunotherapy Hematologic diseases Myeloma Seattle Genetics
Sponsor: Seagen Inc.
Start date: 2018-11-01; Completion date: 2023-11-09
Enrollment: 83 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This trial will study SEA-BCMA to find out whether it is an effective treatment for multiple myeloma (MM) and what side effects (unwanted effects) may occur.

The study will have several parts. In Parts A and B, participants get SEA-BCMA by itself. This part of the study will find out how much SEA-BCMA should be given for treatment and how often. It will also find out how safe the treatment is and how well it works.

In Part C of the study, participants will get SEA-BCMA and dexamethasone. In Part D, participants will get SEA-BCMA, dexamethasone, and pomalidomide. Dexamethasone and pomalidomide are both drugs that can be used to treat multiple myeloma. These parts of the study will find out whether these drugs are safe when used together.

Detailed description:

Arms: arm 1: SEA-BCMA arm 2: SEA-BCMA + dexamethasone arm 3: SEA-BCMA + dexamethasone + pomalidomide
Interventions: intervention 1: SEA-BCMA intervention 2: dexamethasone intervention 3: pomalidomide
Intervention descriptions: intervention 1: Given into the vein (IV; intravenously) intervention 2: Given by mouth (orally) or by IV intervention 3: Given orally

Protocol documents:
Prot_000.pdf: 
 
This document contains information proprietary to Seagen Inc. The information is being provided to you for the 
purpose of conducting a clinical trial for Seagen Inc. You may disclose the contents of this document to study 
personnel under your supervision and to your Institutional Review Board (IRB) or Ethics Committee (EC) for the 
same purpose. You may not disclose the contents of this document to any other party, unless government regulations 
or laws require such disclosure, without prior written permission from Seagen Inc. Any supplemental information 
that may be added to this document is proprietary to Seagen Inc. and should be handled using the disclosure 
procedure described above. 
Protocol Number: 
SGNBCMA-001 
Version: 
Amendment 9; 03-Jun-2022 
Protocol Title: 
A phase 1 study of SEA-BCMA in patients with relapsed or 
refractory multiple myeloma 
Investigational Product: 
SEA-BCMA 
Brief Title: 
A safety study of SEA-BCMA in patients with multiple myeloma 
Phase: 
1b 
IND Number: 
137671  
Clinicaltrials.gov 
Identifier: 
NCT03582033 
Sponsor: 
Seagen Inc. 
21823 30th Drive SE 
Bothell, WA 98021, USA 
Medical Monitor: 
, MD 
Seagen Inc. 
Tel: 
  
E-mail: 
  
SAE Email or Fax: 
See email or fax number specified on the SAE report form. 
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PROTOCOL SYNOPSIS  
Protocol Number 
SGNBCMA-001 
Version 
Amendment 9, 03-Jun-2022 
Phase 
Phase 1b 
Product Name 
SEA-BCMA 
Sponsor 
Seagen Inc. 
21823 30th Drive SE 
Bothell, WA 98021, USA 
Protocol Title  
A phase 1 study of SEA-BCMA in subjects with relapsed or refractory multiple myeloma 
Study Objectives  
Primary 
• 
Evaluate the safety and tolerability of SEA-BCMA monotherapy in subjects with relapsed or refractory 
multiple myeloma (RRMM) 
• 
Identify the maximum tolerated dose (MTD) and/or optimal dose and schedule of SEA-BCMA 
monotherapy, and in combination with dexamethasone, in subjects with RRMM 
• 
Evaluate the safety and tolerability of SEA-BCMA in combination with standard of care therapies in 
subjects with RRMM 
Secondary 
• 
Identify a recommended single-agent dose and schedule of SEA-BCMA 
• 
Assess the pharmacokinetics (PK) of SEA-BCMA 
• 
Assess the immunogenicity of SEA-BCMA 
• 
Assess the antitumor activity of SEA-BCMA 
Exploratory 
• 
Assess incidence and level of B-cell maturation antigen (BCMA) expression in RRMM and relationship to 
clinical response to SEA-BCMA 
• 
Assess the pharmacodynamic effects and biomarkers of response, toxicity, and resistance to SEA-BCMA 
• 
Assess minimal residual disease (MRD) in subjects with very good partial response (VGPR) or better 
• 
Assess impact of SEA-BCMA in combination with standard of care therapies on health-related quality of 
life (HRQoL) from the subject’s perspective.  
 
 
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Study Population  
Adults 18 years and older are eligible if they have a histologically confirmed diagnosis of multiple myeloma (MM), 
an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤1 and are a candidate for 
SEA-BCMA treatment in the opinion of the treating physician. In Part A, prior lines of therapy must include at least 
a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody. In Parts B and C, 
subjects must not have other therapeutic options known to provide clinical benefit in multiple myeloma available, 
must have received at least 3 prior lines of antimyeloma therapy, and must be refractory to at least 1 agent in each of 
the following classes: PI, IMiD, and an anti-CD38 antibody. In Part D, subjects must have received at least 3 prior 
lines of antimyeloma therapy, including a PI, IMiD, and an anti-CD38 antibody, and must have documented 
International Myeloma Working Group (IMWG) disease progression on or within 60 days of completion of their last 
treatment. There is no requirement for subject selection based on BCMA expression level.  
Number of Planned Subjects  
Up to approximately 131 subjects are expected to be enrolled in this study. This number is based on the following 
assumptions: 
• 
Up to approximately 45 subjects will be evaluated in Part A (monotherapy dose- escalation and expansion; 
every 2 weeks [q2wk] dosing). 
• 
Up to approximately 20 subjects will be evaluated in Part B (monotherapy intensive dosing; once weekly 
[q1wk] for 8 weeks, followed by q2wk dosing). 
• 
Up to approximately 60 subjects total will be evaluated in the Part C dexamethasone combination therapy 
cohorts. Up to 20 subjects will be enrolled in cohort 1 (standard dosing SEA-BCMA). Up to 40 subjects 
will be enrolled in cohort 2 (intensive dosing SEA-BCMA): 20 subjects in each of up to 2 parallel dose 
levels. 
• 
Up to approximately 6 DLT-evaluable subjects will be evaluated in the Part D pomalidomide and 
dexamethasone combination safety run-in cohort.  
Study Design  
This is a phase 1, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, and 
antitumor activity of SEA-BCMA monotherapy and combination in adults with RRMM. The study will be 
conducted in 4 parts: 
• 
Part A: Monotherapy dose-escalation and expansion 
○ 
Dose-escalation: Up to approximately 25 subjects will be treated with SEA-BCMA monotherapy q2wk 
to evaluate the safety and tolerability of SEA-BCMA, and to identify the MTD or optimal dose. 
○ 
Expansion: Up to approximately 20 subjects will be treated with SEA-BCMA monotherapy at dose 
levels not exceeding the MTD or optimal dose to further characterize the safety and antitumor activity 
of SEA-BCMA. 
• 
Part B: Monotherapy intensive dosing. Up to 20 subjects will be treated at the recommended dose in an 
expansion cohort testing weekly induction dosing (q1wk) of SEA-BCMA for 8 weeks, followed by q2wk 
maintenance dosing. This expansion cohort will begin with a 6-subject safety run-in with dose de-
escalation permitted. 
• 
Part C: Dexamethasone combination therapy cohorts. Up to approximately 60 subjects may be enrolled to 
evaluate the safety and antitumor activity of SEA-BCMA in combination with dexamethasone. 
○ 
Cohort 1: The standard dosing combination cohort will combine dexamethasone with SEA-BCMA 
administered q2wk. This expansion cohort will begin with a 6-subject safety run-in with dose de-
escalation permitted. Cohort expansion up to 20 subjects may occur, if permitted after completion of 
the safety run-in.   
○ 
Cohort 2: The intensive dosing combination cohort will combine dexamethasone with SEA-BCMA 
administered q1wk for 8 weeks, followed by q2wk dosing. This expansion cohort will complete a 
6-subject safety run-in at 800 mg SEA-BCMA intensive dosing (dose level –1) and, if deemed 
tolerable, will be followed by a 6-subject run in at 1600 mg SEA-BCMA intensive dosing. Cohort 
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expansion up to a total of 20 subjects may occur in each of up to 2 dose level cohorts, eg, 800 mg and 
1600 mg SEA-BCMA dose levels, if permitted after completion of each safety run-in.   
• 
Part D: Pomalidomide and dexamethasone combination therapy cohort. Up to 6 DLT evaluable subjects 
may be enrolled in this safety run-in cohort to evaluate the safety of SEA-BCMA administered q2wk in 
combination with pomalidomide and dexamethasone. Part D will be conducted in the US only.  
○ 
Cohort 1: The standard dosing combination cohort will combine dexamethasone and pomalidomide 
with SEA-BCMA administered q2wk. This expansion cohort will begin with a 6-subject safety run-in 
with dose de-escalation permitted.  
A Safety Monitoring Committee (SMC) consisting of the study medical monitor, drug safety representative, site 
investigators, and the study biostatistician will monitor the safety of subjects and make dosing recommendations 
throughout dose-escalation, dose-expansion, post-remission treatment, and combination therapy treatment. The 
SMC may recommend investigation of an intermediate dose level or an alternative dosing schedule if warranted by 
cumulative safety and PK/pharmacodynamic data. 
The dose-escalation part of SEA-BCMA monotherapy will be conducted in up to approximately 25 subjects using 
the modified toxicity probability interval (mTPI) method (Ji 2010) to evaluate safety and tolerability, and to identify 
the MTD of SEA-BCMA. If the MTD is not reached, safety, PK, pharmacodynamic, and biomarker analyses, as 
well as preliminary antitumor activity, will be used to determine the optimal dose. De-escalation to a lower dose 
level may be performed at any time by the sponsor in consultation with the SMC. Intrasubject dose-escalation to a 
dose level shown to be safe may be permitted in the event that a subject has not experienced a Grade ≥2 adverse 
event (AE) while on study treatment, has received at least 1 cycle of SEA-BCMA at the current dose level, and 
achieves stable disease (SD) or better.  
Investigational Product, Dose, and Mode of Administration  
SEA-BCMA will be administered at the assigned dose and schedule by IV infusion. 
Combination Products  
Part C 
Dexamethasone will be administered at a dose of 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle as an IV 
infusion or PO. On days when SEA-BCMA is to be administered, dexamethasone should be administered 1 to 
3 hours prior to SEA-BCMA infusion. 
Part D 
Pomalidomide will be administered at a dose of 4 mg once daily on Days 1 to 21 of each 28-day cycle taken PO. On 
Cycle 1 Day 1, pomalidomide will be administered 1 to 3 hours prior to SEA-BCMA infusion. 
Dexamethasone will be administered at a dose of 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle as an IV 
infusion or taken PO. On days when SEA-BCMA is to be administered, dexamethasone should be administered 1 to 
3 hours prior to SEA-BCMA infusion. 
Duration of Treatment  
Subjects in all cohorts may continue on treatment until disease progression, unacceptable toxicity, withdrawal of 
consent, death, or study termination, whichever occurs first. 
Efficacy Assessments  
• 
Best response per the 2016 IMWG uniform response criteria (Kumar 2016) 
○ 
MRD-negative (in subjects with complete response [CR]) 
○ 
Stringent complete response (sCR) 
○ 
CR 
○ 
VGPR 
○ 
Partial response (PR) 
○ 
Minimal response (MR) 
○ 
SD 
○ 
PD 
• 
Duration of response 
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• 
Progression-free survival (PFS) 
• 
Overall survival (OS) 
Pharmacokinetic and Immunogenicity Assessments  
Blood samples will be obtained for PK and immunogenicity evaluation at protocol-defined time points. Serum 
SEA-BCMA levels will be measured. In Parts C and D, additional PK samples will be collected and archived for 
possible analysis of concentrations of combination drugs. PK parameters to be estimated include maximum serum 
concentration and area under the serum concentration-time curve. Immunogenicity will be evaluated with 
measurements of antitherapeutic antibodies (ATA) in serum. 
Pharmacodynamic Assessments  
Peripheral blood and bone marrow (BM) aspirates and biopsies will be collected for pharmacodynamic biomarker 
assessments. Assessments performed with these samples may include, but are not limited to, myeloma cell 
monitoring and profiling, including expression of BCMA and assessments of immune cell populations. Additionally, 
BM samples may be analyzed to identify gene expression profiles, cytogenetic abnormalities, genetic mutations, and 
other tumor and tumor microenvironment-related biomarkers that may define disease risk profiles, predict response 
to SEA-BCMA, and clarify SEA-BCMA mechanisms of action. MRD may be analyzed in selected BM specimens 
using next generation sequencing (NGS). Plasma and serum will also be collected for quantification of biomarkers 
of drug activity, which may include serum free light chain (SFLC), cytokines/chemokines, soluble BCMA, and other 
soluble biomarkers. 
Information from pharmacodynamic and biomarker assessments, including BCMA expression, will not be used for 
subject selection. 
Qualitative Interviews  
Up to a total of 10 subjects in Parts C and D will be interviewed within 1 cycle of their first objective response (PR 
or better) or within 1 cycle of ongoing SD in Cycle 4 (Part C only). See the Interview Guide for additional details. 
Safety Assessments  
Safety assessments will include the surveillance and recording of AEs, including serious adverse events (SAEs); 
recording of concomitant medications; and measurements of protocol-specified physical examination findings and 
laboratory tests. Safety will be monitored over the course of the study by the SMC. 
Statistical Methods  
For SEA-BCMA monotherapy in Part A, dose-escalation and identification of MTD will be guided by the mTPI 
method. The dose-limiting toxicity (DLT)-evaluable (DE) analysis set includes all treated subjects who either 
experienced a DLT or were followed for the full DLT evaluation period and did not receive prohibited treatment. 
The DE analysis set will be used for determination of the MTD. Safety and efficacy endpoints will be summarized 
with descriptive statistics. The All-Treated Subjects analysis set will include all subjects treated with any amount of 
SEA-BCMA. The efficacy-evaluable analysis set includes all treated subjects who had both a baseline and at least 
1 evaluable postbaseline disease assessment according to the IMWG uniform response criteria (Kumar 2016), or per 
investigator claim of clinical progression. 
Binomial exact 95% confidence intervals (CIs) for objective response rate (ORR) will be provided.  
Assuming the observed ORR is between 30 to 70%, the 95% binomial exact CIs are summarized below. 
ORR 
95% CI (N=20) 
30% 
12%, 54% 
40% 
19%, 64% 
50% 
27%, 73% 
60% 
36%, 81% 
70% 
46%, 88% 
Any expansion cohort may also be discontinued at any point at the discretion of the sponsor. 
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TABLE OF CONTENTS 
PROTOCOL SYNOPSIS .............................................................................................................................................. 2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................................................................. 11 
1. 
INTRODUCTION............................................................................................................................................ 14 
1.1. 
Multiple Myeloma ................................................................................................................................ 14 
1.2. 
BCMA .................................................................................................................................................. 15 
1.3. 
SEA-BCMA .......................................................................................................................................... 15 
1.4. 
Summary of Nonclinical Toxicology .................................................................................................... 15 
1.5. 
Summary of Preclinical Activity .......................................................................................................... 16 
1.6. 
Rationale for Study ............................................................................................................................... 16 
1.6.1. 
Rationale for Study Design .................................................................................................. 17 
1.6.2. 
Rationale for Intensive Dosing Schedule (Part B) ............................................................... 17 
1.6.3. 
Rationale for Combination Therapy .................................................................................... 18 
1.6.3.1. 
Rationale for Dexamethasone Combination Therapy (Part C) ................................. 18 
1.6.3.2. 
Rationale for Pomalidomide and Dexamethasone Combination Therapy (Part D) .. 18 
1.6.3.3. 
Patient Input Into Design.......................................................................................... 18 
1.7. 
Benefit-Risk Assessment ...................................................................................................................... 18 
1.7.1. 
Risk Assessment .................................................................................................................. 18 
1.7.2. 
Benefit Assessment.............................................................................................................. 18 
1.7.3. 
Overall Benefit-Risk Assessment ........................................................................................ 19 
2. 
OBJECTIVES .................................................................................................................................................. 20 
3. 
INVESTIGATIONAL PLAN .......................................................................................................................... 22 
3.1. 
Summary of Study Design .................................................................................................................... 22 
3.1.1. 
Part A: Monotherapy Dose-escalation and Expansion ........................................................ 22 
3.1.1.1. 
Monotherapy Dose-Escalation Cohort ..................................................................... 22 
3.1.1.2. 
Monotherapy Expansion Cohort .............................................................................. 24 
3.1.2. 
Part B: Monotherapy Intensive Dosing ............................................................................... 25 
3.1.3. 
Combination Therapy Cohorts ............................................................................................ 25 
3.1.3.1. 
Parts C and D: Combination Therapy Cohorts Safety Run-in .................................. 26 
3.1.3.2. 
Part C: Dexamethasone Combination Therapy Cohorts ........................................... 26 
3.1.3.3. 
Part D: Pomalidomide and Dexamethasone Combination Therapy Cohort ............. 27 
3.1.4. 
Duration of Treatment ......................................................................................................... 27 
3.1.5. 
Dose-Limiting Toxicity ....................................................................................................... 27 
3.1.6. 
Stopping Criteria.................................................................................................................. 28 
3.1.6.1. 
Enrollment Pause at the Cohort Level ...................................................................... 28 
3.1.6.2. 
Enrollment Halt for the Entire Study ....................................................................... 28 
3.1.7. 
Retreatment .......................................................................................................................... 29 
3.1.8. 
End of Study ........................................................................................................................ 29 
3.1.9. 
Safety Monitoring Committee ............................................................................................. 29 
3.1.9.1. 
Part A Dose-escalation Safety Monitoring ............................................................... 29 
3.1.9.2. 
Parts B, C, and D Safety Monitoring........................................................................ 30 
3.2. 
Method of Assigning Subjects to Treatment Groups ............................................................................ 30 
3.2.1. 
Rationale for Selection of Doses ......................................................................................... 31 
3.2.1.1. 
Monotherapy ............................................................................................................ 31 
3.2.2. 
Combination Therapy .......................................................................................................... 32 
3.2.3. 
Blinding and Unblinding ..................................................................................................... 33 
4. 
STUDY POPULATION .................................................................................................................................. 34 
4.1. 
Inclusion Criteria .................................................................................................................................. 34 
4.2. 
Exclusion Criteria ................................................................................................................................. 36 
4.3. 
Childbearing Potential .......................................................................................................................... 38 
4.3.1. 
Subjects Treated with Pomalidomide (Part D) .................................................................... 38 
4.4. 
Removal of Subjects from Therapy or Assessment .............................................................................. 39 
4.4.1. 
Discontinuation of Study Treatment .................................................................................... 39 
4.4.2. 
Subject Withdrawal from Study .......................................................................................... 39 
5. 
TREATMENTS ............................................................................................................................................... 40 
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5.1. 
Treatments Administered ...................................................................................................................... 40 
5.2. 
Investigational Product: SEA-BCMA ................................................................................................... 40 
5.2.1. 
Description .......................................................................................................................... 40 
5.2.2. 
Dose and Administration ..................................................................................................... 40 
5.2.2.1. 
Fixed-Duration Infusion ........................................................................................... 41 
5.2.2.2. 
Fixed Infusion Rate .................................................................................................. 41 
5.2.2.3. 
Divided-Dose Administration .................................................................................. 41 
5.2.3. 
Dose Modifications.............................................................................................................. 42 
5.2.4. 
Storage and Handling .......................................................................................................... 44 
5.2.5. 
Packaging and Labeling ....................................................................................................... 44 
5.2.6. 
Preparation ........................................................................................................................... 44 
5.2.7. 
Continued Access to SEA-BCMA After the End of the Study ............................................ 44 
5.3. 
Dexamethasone ..................................................................................................................................... 44 
5.3.1. 
Description .......................................................................................................................... 44 
5.3.2. 
Method of Procurement ....................................................................................................... 44 
5.3.3. 
Dose and Administration ..................................................................................................... 45 
5.3.4. 
Dose Modifications.............................................................................................................. 46 
5.3.5. 
Storage and Handling .......................................................................................................... 46 
5.3.6. 
Packaging and Labeling ....................................................................................................... 47 
5.3.7. 
Preparation ........................................................................................................................... 47 
5.4. 
Pomalidomide ....................................................................................................................................... 47 
5.4.1. 
Description .......................................................................................................................... 47 
5.4.2. 
Method of Procurement ....................................................................................................... 47 
5.4.3. 
Dose and Administration ..................................................................................................... 47 
5.4.4. 
Dose Modifications.............................................................................................................. 47 
5.4.5. 
Storage and Handling .......................................................................................................... 48 
5.4.6. 
Packaging and Labeling ....................................................................................................... 48 
5.4.7. 
Preparation ........................................................................................................................... 48 
5.5. 
Required Premedication and Postmedication for SEA-BCMA ............................................................ 48 
5.6. 
Concomitant Therapy ........................................................................................................................... 49 
5.6.1. 
Required Concomitant Therapy ........................................................................................... 49 
5.6.2. 
Allowed Concomitant Therapy ............................................................................................ 49 
5.6.3. 
Prohibited Concomitant Therapy ......................................................................................... 50 
5.7. 
Management of Adverse Reactions ...................................................................................................... 50 
5.7.1. 
Management of SEA-BCMA Infusion Reactions ................................................................ 50 
5.8. 
Treatment Compliance .......................................................................................................................... 53 
6. 
STUDY ACTIVITIES ..................................................................................................................................... 54 
6.1. 
Schedule of Events ............................................................................................................................... 54 
6.2. 
Part A (Monotherapy Dose-escalation and Expansion) ........................................................................ 54 
6.2.1. 
Screening Visit (Days –28 to 1) ........................................................................................... 54 
6.2.2. 
Baseline Visit (Days –7 to 1) ............................................................................................... 54 
6.2.3. 
Treatment Period ................................................................................................................. 55 
6.2.3.1. 
Day 1 (–1 day) .......................................................................................................... 55 
6.2.3.2. 
Day 2 ........................................................................................................................ 56 
6.2.3.3. 
Day 4 (±1 day) ......................................................................................................... 57 
6.2.3.4. 
Day 8 (±1 day) ......................................................................................................... 57 
6.2.3.5. 
Day 15 (±1 day) ....................................................................................................... 57 
6.2.3.6. 
Days 16 and 18 ......................................................................................................... 58 
6.2.3.7. 
Day 22 (±1 day) ....................................................................................................... 58 
6.2.3.8. 
Day 29 ...................................................................................................................... 58 
6.3. 
Part B (Monotherapy Intensive Dosing) ............................................................................................... 58 
6.3.1. 
Screening Visit (Days –28 to 1) ........................................................................................... 58 
6.3.2. 
Baseline Visit (Days –7 to Day 1) ....................................................................................... 59 
6.3.3. 
Treatment Period ................................................................................................................. 59 
6.3.3.1. 
Day 1 (–1 day) .......................................................................................................... 59 
6.3.3.2. 
Day 2 ........................................................................................................................ 61 
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6.3.3.3. 
Day 4 ........................................................................................................................ 61 
6.3.3.4. 
Day 8 (±1 day) ......................................................................................................... 61 
6.3.3.5. 
Day 15 (±1 day) ....................................................................................................... 62 
6.3.3.6. 
Day 22 (±1 day) ....................................................................................................... 63 
6.4. 
Part C (SEA-BCMA plus Dexamethasone) .......................................................................................... 64 
6.4.1. 
Screening Visit (Days –28 to 1) ........................................................................................... 64 
6.4.2. 
Baseline Visit (Days –7 to Day 1) ....................................................................................... 64 
6.4.3. 
Treatment Period ................................................................................................................. 65 
6.4.3.1. 
Day 1 (–1 day) .......................................................................................................... 65 
6.4.3.2. 
Day 2 ........................................................................................................................ 66 
6.4.3.3. 
Day 4 ........................................................................................................................ 66 
6.4.3.4. 
Day 8 (±1 day) ......................................................................................................... 66 
6.4.3.5. 
Day 15 (±1 day) ....................................................................................................... 67 
6.4.3.6. 
Day 22 (±1 day) ....................................................................................................... 68 
6.4.4. 
Qualitative Interview ........................................................................................................... 69 
6.5. 
Part D (SEA-BCMA plus Pomalidomide and Dexamethasone) ........................................................... 69 
6.5.1. 
Screening Visit (Days -28 to 1) ........................................................................................... 69 
6.5.2. 
Baseline Visit (Days -10 to Day 1) ...................................................................................... 69 
6.5.3. 
Treatment Period ................................................................................................................. 70 
6.5.3.1. 
Day 1 (–1 day) .......................................................................................................... 70 
6.5.3.2. 
Day 2 ........................................................................................................................ 72 
6.5.3.3. 
Day 4 ........................................................................................................................ 72 
6.5.3.4. 
Day 8 (±1 day) ......................................................................................................... 72 
6.5.3.5. 
Day 15 (±1 day) ....................................................................................................... 72 
6.5.3.6. 
Day 22 (±1 day) ....................................................................................................... 73 
6.5.4. 
Qualitative Interview ........................................................................................................... 73 
6.6. 
Complete Response Assessment ........................................................................................................... 73 
6.7. 
Evaluation of Infusion/Hypersensitivity Reactions (Part A only) ........................................................ 74 
6.8. 
Infusion/Hypersensitivity Reaction Visit (Part A only) ........................................................................ 74 
6.9. 
Infusion/Hypersensitivity Reaction Follow-up Visit (24 to 72 hours; Part A only) ............................. 74 
6.10. 
End of Treatment Visit (30 to 37 days after last dose of study drug) ................................................... 75 
6.11. 
Follow-up (every 12 weeks ±2 weeks) ................................................................................................. 76 
6.12. 
End of Study/End of Follow-up ............................................................................................................ 77 
7. 
STUDY ASSESSMENTS ................................................................................................................................ 78 
7.1. 
Screening/Baseline Assessments .......................................................................................................... 78 
7.2. 
Response/Efficacy Assessments ........................................................................................................... 78 
7.3. 
Qualitative Interviews ........................................................................................................................... 79 
7.4. 
Pharmacokinetic and Immunogenicity Assessments ............................................................................ 79 
7.5. 
Biomarker Studies ................................................................................................................................ 80 
7.5.1. 
Genetic profiling of effector cells ........................................................................................ 80 
7.5.2. 
Serum Free Light Chain and modified SPEP ...................................................................... 80 
7.5.3. 
Peripheral blood immunophenotyping................................................................................. 80 
7.5.4. 
Plasma cytokines/chemokines ............................................................................................. 80 
7.5.5. 
Soluble target and ligands .................................................................................................... 81 
7.5.6. 
Plasma Biomarkers and PBMCs .......................................................................................... 81 
7.5.7. 
Characterization of Tumor Tissue ....................................................................................... 81 
7.5.7.1. 
Bone marrow immunophenotyping .......................................................................... 81 
7.5.7.2. 
Gene Expression Profiling/NGS/FISH ..................................................................... 81 
7.5.7.3. 
MRD ........................................................................................................................ 81 
7.5.7.4. 
Bone marrow plasma ................................................................................................ 81 
7.6. 
Biospecimen Repository ....................................................................................................................... 81 
7.7. 
Safety Assessments ............................................................................................................................... 82 
7.7.1. 
Adverse Events .................................................................................................................... 82 
7.7.1.1. 
Definitions ................................................................................................................ 82 
7.7.2. 
Serious Adverse Events ....................................................................................................... 83 
7.7.3. 
Adverse Event Severity ....................................................................................................... 83 
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7.7.3.1. 
Relationship of the Adverse Event to Study Treatment ........................................... 83 
7.7.3.2. 
Procedures for Eliciting and Recording Adverse Events ......................................... 84 
7.7.4. 
Progression of the Underlying Malignancy ......................................................................... 85 
7.7.5. 
Pregnancy ............................................................................................................................ 85 
7.7.5.1. 
Notification to Drug Safety ...................................................................................... 85 
7.7.5.2. 
Collection of data on the CRF .................................................................................. 85 
7.7.6. 
Potential Drug-Induced Liver Injury ................................................................................... 86 
7.7.6.1. 
Definition ................................................................................................................. 86 
7.7.6.2. 
Reporting Requirements ........................................................................................... 86 
7.7.6.3. 
Follow-up for Abnormal Laboratory Results Suggesting Potential DILI ................ 86 
7.7.7. 
Reporting Periods for Adverse Events, and Serious Adverse Events .................................. 87 
7.7.8. 
Serious Adverse Events Require Immediate Reporting ....................................................... 87 
7.7.9. 
Sponsor Safety Reporting to Regulatory Authorities .......................................................... 87 
7.7.10. 
Vital Signs ........................................................................................................................... 87 
7.7.11. 
Clinical Laboratory Tests .................................................................................................... 87 
7.7.12. 
Physical Examination .......................................................................................................... 88 
7.7.13. 
Pregnancy Testing ............................................................................................................... 88 
7.7.14. 
Electrocardiograms .............................................................................................................. 88 
7.7.15. 
ECOG Performance Status .................................................................................................. 89 
7.8. 
Appropriateness of Measurements ........................................................................................................ 89 
8. 
DATA QUALITY CONTROL AND QUALITY ASSURANCE ................................................................... 90 
8.1. 
Site Training and Monitoring Procedures ............................................................................................. 90 
8.2. 
Data Management Procedures .............................................................................................................. 90 
8.3. 
Access to Source Data .......................................................................................................................... 90 
8.4. 
Accuracy and Reliability of Data .......................................................................................................... 91 
8.5. 
Quality Assurance Procedures .............................................................................................................. 91 
8.6. 
Data Handling and Record Keeping ..................................................................................................... 91 
8.6.1. 
Data Handling ...................................................................................................................... 91 
8.6.2. 
Investigator Record Retention ............................................................................................. 91 
9. 
DATA ANALYSIS METHODS ...................................................................................................................... 93 
9.1. 
Determination of Sample Size .............................................................................................................. 93 
9.2. 
Study Endpoint Definitions .................................................................................................................. 93 
9.2.1. 
Objective Response Rate ..................................................................................................... 93 
9.2.2. 
Complete Response Rate ..................................................................................................... 94 
9.2.3. 
Duration of Objective Response .......................................................................................... 94 
9.2.4. 
Duration of Complete Response .......................................................................................... 94 
9.2.5. 
Progression-free Survival .................................................................................................... 94 
9.2.6. 
Overall Survival ................................................................................................................... 95 
9.2.7. 
MRD-negativity rate ............................................................................................................ 95 
9.3. 
Statistical and Analytical Plans ............................................................................................................. 95 
9.3.1. 
General Considerations ........................................................................................................ 95 
9.3.1.1. 
Randomization and Blinding .................................................................................... 95 
9.3.1.2. 
Adjustments for Covariates ...................................................................................... 95 
9.3.1.3. 
Handling of Dropouts and Missing Data .................................................................. 95 
9.3.1.4. 
Multicenter Studies .................................................................................................. 96 
9.3.1.5. 
Multiple Comparisons and Multiplicity ................................................................... 96 
9.3.1.6. 
Data Transformations and Derivations ..................................................................... 96 
9.3.1.7. 
Analysis Sets ............................................................................................................ 96 
9.3.1.8. 
Examination of Subgroups ....................................................................................... 96 
9.3.1.9. 
Timing of Analyses .................................................................................................. 97 
9.3.2. 
Subject Disposition .............................................................................................................. 97 
9.3.3. 
Subject Characteristics ........................................................................................................ 97 
9.3.4. 
Treatment Compliance ........................................................................................................ 97 
9.3.5. 
Efficacy Analyses ................................................................................................................ 97 
9.3.6. 
Pharmacokinetic and Immunogenicity Analyses ................................................................. 97 
9.3.7. 
Qualitative Interview Analyses ............................................................................................ 98 
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9.3.8. 
Biomarker Analyses ............................................................................................................ 98 
9.3.9. 
Safety Analyses ................................................................................................................... 98 
9.3.9.1. 
Extent of Exposure ................................................................................................... 98 
9.3.9.2. 
Adverse Events......................................................................................................... 98 
9.3.9.3. 
Dose-Limiting Toxicity ............................................................................................ 99 
9.3.9.4. 
Deaths and Serious Adverse Events ......................................................................... 99 
9.3.9.5. 
Clinical Laboratory Results ...................................................................................... 99 
9.3.9.6. 
Other Safety Analyses .............................................................................................. 99 
9.3.10. 
Interim Analyses .................................................................................................................. 99 
10. 
INFORMED CONSENT, ETHICAL REVIEW, AND REGULATORY CONSIDERATIONS .................. 101 
10.1. 
Informed Consent ............................................................................................................................... 101 
10.2. 
Ethical Review .................................................................................................................................... 101 
10.3. 
Regulatory Considerations .................................................................................................................. 102 
10.3.1. 
Investigator Information .................................................................................................... 102 
10.3.2. 
Protocol Amendments and Study Termination .................................................................. 102 
10.4. 
Study Documentation, Privacy and Records Retention ...................................................................... 102 
10.5. 
Clinical Trial Agreement .................................................................................................................... 102 
11. 
REFERENCES ............................................................................................................................................... 103 
APPENDIX A. 
SCHEDULE OF EVENTS ................................................................................................ 106 
APPENDIX B. 
PK, ATA, AND BIOMARKER SAMPLING TIME POINTS.......................................... 114 
APPENDIX C. 
MODIFIED TOXICITY PROBABILITY INTERVAL DESIGN SIMULATION REPORT
 
123 
APPENDIX D. 
PERFORMANCE STATUS SCALES CONVERSION ................................................... 134 
APPENDIX E. 
GUIDANCE ON CONTRACEPTION: PARTS A, B, AND C ........................................ 135 
APPENDIX F. 
GUIDANCE ON CONTRACEPTION: PART D ............................................................. 136 
APPENDIX G. 
NEW YORK HEART ASSOCIATION CLASSIFICATION ........................................... 137 
APPENDIX H. 
PROHIBITED CONCOMINANT MEDICATIONS ........................................................ 138 
APPENDIX I. 
MODIFICATION OF DIET IN RENAL DISEASE EQUATION.................................... 139 
APPENDIX J. 
DEFINITION OF RESPONSE AND PROGRESSION CRITERIA (MODIFIED FROM 
IMWG) 
140 
APPENDIX K. 
INVESTIGATOR SIGNATURE PAGE ........................................................................... 141 
APPENDIX L. 
DOCUMENT HISTORY .................................................................................................. 142 
 
LIST OF TABLES  
Table 1: 
Objectives and corresponding endpoints .............................................................................................. 21 
Table 2: 
Dose-finding spreadsheet for mTPI design ........................................................................................... 24 
Table 3: 
Dose-escalation schema ........................................................................................................................ 24 
Table 4: 
Planned dose levels for Part B .............................................................................................................. 25 
Table 5: 
Recommended dose modifications for toxicity .................................................................................... 43 
Table 6: 
Recommended dose modifications for dexamethasone-related toxicity ............................................... 46 
Table 7: 
Recommended dose modifications for pomalidomide-related toxicity ................................................ 48 
Table 8: 
Management of infusion-related reactions ............................................................................................ 52 
Table 9: 
Dose-finding spreadsheet for mTPI design ......................................................................................... 125 
 
LIST OF FIGURES  
Figure 1: 
Study Design Schema ........................................................................................................................... 22 
 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS  
ADC 
antibody-drug conjugate 
ADCC 
antibody-dependent cellular cytotoxicity 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
ASCT 
autologous stem cell transplant 
AST 
aspartate aminotransferase 
ATA 
antitherapeutic antibodies 
APRIL 
A proliferation-inducing ligand 
BAFF 
B cell-activating factor 
BCMA 
B-cell maturation antigen 
β-hCG 
beta human chorionic gonadotropin  
BM 
bone marrow 
Ceoi 
concentration at the end of infusion 
Cmax 
maximum observed concentration 
Ctrough 
trough concentration 
CAR 
chimeric antigen receptor 
CBC 
complete blood count 
CI 
confidence interval 
CR 
complete response 
CRF 
case report form 
CT 
computed tomography 
CYP 
cytochrome P 
DDI 
drug-drug interaction 
DE 
DLT-evaluable 
DILI 
drug-induced liver injury 
DLT 
dose-limiting toxicity 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic CRF 
ELISA 
enzyme-linked immunosorbent assay  
EOT 
end of treatment 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed, paraffin-embedded 
FISH 
fluorescent in situ hybridization 
FLC 
free light chain 
FSH 
follicle-stimulating hormone 
GFR 
glomerular filtration rate 
GSI 
gamma-secretase inhibitor 
HbA1c 
hemoglobin A1c 
HCV 
hepatitis C-virus 
HNSTD 
highest non-severely toxic dose 
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HRQoL 
health-related quality of life 
IB 
Investigator’s Brochure 
ICH 
International Council for Harmonisation  
IEC 
independent ethics committee 
IgG 
immunoglobulin G 
IHR 
infusion/hypersensitivity reaction 
IL 
interleukin 
IMiD 
immunomodulatory imide drug 
IMWG 
International Myeloma Working Group 
IND 
investigational new drug 
INR 
international normalized ratio 
IRB 
institutional review board 
IRR 
infusion-related reaction 
IUD 
intrauterine device 
IV 
intravenous 
MDRD 
Modification of Diet in Renal Disease [study] 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIP 
macrophage inflammatory protein 
MM 
multiple myeloma 
MR 
minimal response 
MRD 
minimal residual disease 
MTD 
maximum tolerated dose  
mTPI 
modified toxicity probability interval  
NCI-CTCAE 
National Cancer Institute’s Common Terminology Criteria for Adverse Events 
NGS 
next generation sequencing 
NK 
natural killer (cell) 
NSG™ 
NOD scid gamma 
OR 
objective response 
ORR 
objective response rate 
OS 
overall survival 
P-gp 
P-glycoprotein 
PBMCs 
peripheral blood mononuclear cells 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PFS 
progression-free survival 
PI 
proteasome inhibitor 
PK 
pharmacokinetic 
PO 
orally (per os) 
POEMS 
polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes 
Pom/dex 
pomalidomide in combination with low-dose dexamethasone 
PPoS 
predictive probability of success 
PR 
partial response 
PT 
prothrombin time 
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PTT 
partial thromboplastin time 
q1wk 
once per week 
q2wk 
every 2 weeks 
q4wk 
every 4 weeks 
QD 
once a day 
REMS 
Risk Evaluation and Mitigation Strategy 
RNA 
ribonucleic acid 
RRMM 
relapsed or refractory multiple myeloma 
sBCMA 
soluble BCMA 
sCR 
stringent complete response 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
stable disease 
SFLC 
serum free light chain 
SMC 
Safety Monitoring Committee 
SOC 
standard of care 
SPEP 
serum protein electrophoresis 
ULN 
upper limit of normal 
UPCR 
urine protein to creatinine ratio 
UPEP 
urine protein electrophoresis 
UPM 
unit probability mass 
US 
United States 
VGPR 
very good partial response 
 
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1. 
INTRODUCTION  
SEA-BCMA is a non-fucosylated monoclonal antibody directed against B-cell maturation 
antigen (BCMA), a cell surface receptor that is widely expressed on the surface of malignant 
plasma cells in subjects with multiple myeloma (MM). This phase 1 study is designed to 
establish the safety, tolerability, and antitumor activity of SEA-BCMA as monotherapy and in 
combination with standard of care (SOC) therapies in subjects with relapsed or refractory MM 
(RRMM). 
A complete summary of the clinical and nonclinical data relevant to the investigational product 
and its study in human subjects is provided in the Investigator’s Brochure (IB). 
1.1. 
Multiple Myeloma  
MM is a neoplastic disorder of clonally proliferating plasma cells in the bone marrow (BM), 
peripheral blood or other extramedullary sites. Malignant plasma cells exert a direct pathologic 
effect on the marrow microenvironment and adjacent skeletal bone, leading to anemia, osteolytic 
bone lesions, and hypercalcemia. In most cases, malignant plasma cells also produce an 
abnormal monoclonal immunoglobulin known as the M-protein, but in a minority, the myeloma 
cells produce only monoclonal free light chains (FLC). Abnormal levels of either M-protein or 
FLC can contribute to the clinical spectrum of disease that includes renal failure and an increased 
susceptibility to infections (Palumbo 2011; Rollig 2015; Kumar 2017). 
Standard treatments for MM include combination regimens containing proteasome inhibitors 
(PIs) such as bortezomib and carfilzomib, and/or immunomodulatory drugs (IMiDs), such as 
lenalidomide and pomalidomide, together with corticosteroids, and also chemotherapy regimens 
incorporating alkylating agents such as melphalan and cyclophosphamide. Subjects who are free 
from significant comorbidities and considered eligible are often treated with myeloablative 
chemotherapy and/or radiation, followed by autologous stem cell transplant (ASCT) (Rollig 
2015; Rajkumar 2016). More recently, daratumumab, a monoclonal antibody targeting the CD38 
antigen, has been approved for the treatment of RRMM as monotherapy in fourth line and 
subsequently garnered approvals in various combination regimens in earlier lines of therapy. 
Over the past 20 years, the overall survival (OS) of subjects with MM has increased considerably 
due to advances in treatment as well as improvement in supportive care (Kumar 2008). Despite 
recent advances in treatment options, to date MM remains an incurable disease managed with 
sequential lines of treatment that typically yield shorter durations of disease control with each 
subsequent relapse (Kumar 2004). In particular, frail subjects are facing unmet needs, given the 
toxicity profile of newer agents. The unmet medical need is even further pronounced in the late 
relapsed setting in subjects who are refractory to PIs, IMiDs, and anti-CD38 antibodies 
(“triple-class” refractory). In July of 2019, selinexor was granted accelerated approval by the 
FDA in combination with dexamethasone on the basis of 122 subjects with RRMM (fifth line or 
greater) treated on a phase 2b single-arm trial in which the objective response rate (ORR) was 
26%, median progression-free survival (PFS) was 3.7 months, and median OS was 8.4 months 
(Chari 2019). In August of 2020, the BCMA-targeting ADC belantamab mafodotin received 
FDA accelerated approval in a similar population (fifth line or greater, triple-class refractory 
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RRMM) based on the results of an uncontrolled phase 2 trial in which the ORR was 31%, 
highlighting that an unmet medical need remains in this patient population. Subsequently, 
approvals of BCMA CAR-T therapies such as idecabtagene vileucel and ciltacabtagene 
autoleucel were approved on the basis of high ORR, although the toxicity profile of this form of 
cellular therapy limits its usage to subjects with sufficient underlying fitness. 
1.2. 
BCMA  
SEA-BCMA targets BCMA, an established plasmablast and plasma cell-specific protein that 
mediates cell proliferation and survival. BCMA is expressed at moderate to low levels on the 
majority of MM subject tumor cells (Novak 2004; Seckinger 2017). The ligands A 
proliferation-inducing ligand (APRIL) and B cell-activating factor (BAFF) bind to BCMA and 
mediate prosurvival cellular signals (Moreaux 2004; Novak 2004; O'Connor 2004). 
Efforts are ongoing to optimize the effectiveness of therapeutic targeting of BCMA in MM. One 
such strategy is combination with gamma-secretase inhibitors (GSIs); inhibition of gamma-
secretase prevents the cleavage of BCMA from the surface of plasma cells, leading to higher 
BCMA expression on target cells and reducing levels of soluble BCMA (Pont 2019). This 
combination strategy is particularly attractive in subjects who have failed prior BCMA-directed 
therapies, where downregulation of BCMA on plasma cells may be a mechanism of therapeutic 
escape (Timmers 2019). 
1.3. 
SEA-BCMA  
SEA-BCMA is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody 
targeting BCMA. Based on preclinical data, SEA-BCMA acts through 3 mechanisms: 
1) enhanced FcγRIII binding resulting in enhanced antibody dependent cellular cytotoxicity 
(ADCC), 2) antibody dependent cellular phagocytosis, and 3) blocking of BCMA mediated 
proliferative signaling. Preclinical data support this molecule as an active therapeutic with an 
acceptable safety margin. 
1.4. 
Summary of Nonclinical Toxicology  
Human peripheral blood mononuclear cells (PBMCs) co-cultured in vitro with 
BCMA-expressing myeloma cell lines and treated with SEA-BCMA displayed minimal cytokine 
activation. In PBMCs from donors with normal-affinity FcγRIII (representing approximately 
90% of the target patient population), of 29 cytokines tested, SEA-BCMA induced a minimal 
change in interleukin (IL)-8 at 100 μg/mL (corresponding to the maximum observed 
concentration [Cmax] of a dose of approximately 5 mg/kg). In PBMCs from donors with 
high-affinity FcγRIII (representing approximately 10% of the target patient population), 
SEA-BCMA induced minimal to moderate cytokine production. Of 29 cytokines evaluated, IL-8 
and macrophage inflammatory protein (MIP)–1b were the only immune activating cytokines 
consistently induced by treatment with 100 μg/mL of SEA-BCMA. In addition, no proliferation 
of myeloma cells expressing BCMA was observed when treated with 100 μg/mL of 
SEA-BCMA. 
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The BCMA receptor in the cynomolgus monkey does not cross-react with SEA-BCMA; 
therefore, preclinical testing in this model is an indicator of safety only in the absence of target 
ligation. The highest non-severely toxic dose (HNSTD) in the cynomolgus monkey was 
100 mg/kg every 3 weeks for 2 doses. No adverse effects were observed at this dose. 
1.5. 
Summary of Preclinical Activity  
SEA-BCMA shows activity in 7 of 7 tumor xenograft models tested, inducing tumor delays at 
doses as low as 0.03 mg/kg, and generating prolonged survival and durable complete regressions 
with repeat dosing. SEA-BCMA is active on tumor xenografts expressing as few as 2000 surface 
copies of BCMA antigen. Both effector function and ligand blocking contribute to overall in 
vivo activity. In the absence of effector cell recruitment, ligand blocking alone can induce 
prolonged durable regressions. Treatment of human PBMCs co-cultured in vitro with 
BCMA-expressing myeloma cells induces depletion of target MM cells. SEA-BCMA can bind 
MM cells in the presence of soluble BCMA, APRIL, and BAFF in vitro. 
1.6. 
Rationale for Study  
MM is considered an incurable disease. The most active available therapies for MM include PIs 
and IMiDs in combination with corticosteroids, anti-CD38 monoclonal antibody therapy, and 
high-dose alkylating agents and/or radiotherapy followed by consolidative ASCT for subjects 
considered eligible (Kumar 2017). Advances in therapy have enabled subjects to achieve 
responses of greater depth and duration, however most MM subjects relapse and many will 
become resistant to prior therapies. Subjects who experience superior outcomes are often those 
who achieved deeper remissions to earlier lines of therapy (Kumar 2016). Thus, there is a clear 
need for the development of new antimyeloma agents with novel mechanisms of action and the 
potential for inducing rapid and deep remissions. 
Recent data demonstrate that a targeted therapeutic approach using naked monoclonal antibodies 
directed against either the CS–1 or CD38 antigens expressed on myeloma cells can be highly 
effective (Lokhorst 2015; Lonial 2015). 
Multiple BCMA-targeted programs are currently in clinical development. This includes ADCs, 
BCMA-CD3 bispecific antibodies, and several BCMA CAR T programs. These clinical 
programs support BCMA as an attractive therapeutic target in MM. SEA-BCMA targets BCMA 
using an approach distinct from other clinical stage BCMA therapies. Preclinical testing of 
SEA-BCMA in human in vitro culture and in animals shows a favorable safety profile and 
promising antitumor activity. 
It is appropriate to initially evaluate SEA-BCMA monotherapy dosed every 2 weeks (q2wk) in a 
patient population whose disease has relapsed or is refractory to SOC therapies, and for whom 
there remains no treatment options available that have been shown to provide clinical benefit. 
Based on the favorable safety profile and preliminary evidence of clinical activity observed 
during Part A (monotherapy dose-escalation and expansion), investigation of SEA-BCMA in 
combination with approved SOC agents is also warranted. 
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The immunospecificity and antitumor activity of SEA-BCMA have been demonstrated both in 
vitro and in vivo in BCMA-expressing MM models and support further investigation of its 
clinical utility. Safety, pharmacokinetic (PK), and pharmacodynamic data, as well as preliminary 
antitumor activity acquired in this trial will provide the basis for the development of 
SEA-BCMA as a treatment for MM. 
1.6.1. 
Rationale for Study Design  
This is a phase 1, dose-escalation study to evaluate the safety and tolerability of SEA-BCMA, 
and to estimate the maximum tolerated dose (MTD) and/or optimal dose in subjects with 
RRMM. Initial clinical development of SEA-BCMA will involve its evaluation in subjects with 
RRMM that have no other therapeutic options known to provide clinical benefit available and are 
candidates for SEA-BCMA treatment in the opinion of the treating physician. Prior therapies 
must include at least a PI, an IMiD, and an anti-CD38 antibody. Frontline and first relapse SOC 
treatments are expected to have failed in these subjects prior to enrollment. Because BCMA is a 
broadly expressed tumor antigen in subjects with MM (Section 1.2), initial selection of subjects 
based on BCMA expression will not be required, although the relationship between target 
expression and outcome will be explored in this phase 1 study. 
Part A of the study will include dose-escalation in order to estimate the MTD and/or optimal 
dose of SEA-BCMA. Once dose-escalation is complete and safety of the drug is demonstrated, 
an expansion cohort of up to approximately 20 subjects will be enrolled to further evaluate the 
safety and antitumor activity of SEA-BCMA at the standard q2wk dosing schedule. The 
expansion cohort will allow for the collection of additional information about the safety, 
tolerability, and activity of SEA-BCMA. This information will be the basis for determining the 
recommended single-agent dose and schedule for SEA-BCMA. Because maintenance therapy 
has been shown to prolong remissions in subjects with MM, subjects will be permitted to 
continue on treatment until progressive disease (PD) or unacceptable toxicity, whichever occurs 
first. In addition, intrasubject dose-escalation to a dose level shown to be safe may be permitted 
in the event that a subject has not experienced a Grade ≥2 adverse event (AE) while on study 
treatment, has received at least 1 cycle of SEA-BCMA at the current dose, and achieves a 
response of stable disease (SD) or better. 
The modified toxicity probability interval (mTPI) dose-escalation method was chosen for Part A 
dose-escalation because of potential advantages it has over the traditional “3+3” approach for 
dose finding. These advantages include the ability to estimate the MTD with higher accuracy, 
treating fewer subjects above the MTD thereby improving safety, and allowing for flexible 
cohort sizes (Ji 2010). The mTPI also uses information from all subjects treated at all dose levels 
for estimation of the MTD to improve accuracy of estimation. 
1.6.2. 
Rationale for Intensive Dosing Schedule (Part B)  
The major proposed mechanisms of action of SEA-BCMA (blocking of BCMA ligands binding 
and enhancement of ADCC) are expected to be enhanced by full saturation of membrane 
BCMA. This is complicated by the presence of circulating ligands such as APRIL, BAFF, and 
soluble BCMA, which may increase with higher levels of myeloma disease burden. A more 
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frequent initial dosing schedule may facilitate more consistent maintenance of target saturation 
throughout the dosing interval and initiate response. Thus, an intensive dosing schedule (once 
per week [q1wk] dosing for 8 weeks followed by q2wk dosing) of SEA-BCMA will be tested 
after the completion of dose-escalation at the standard q2wk schedule. 
1.6.3. 
Rationale for Combination Therapy  
Standard treatment for MM consists of combinations of therapies with distinct mechanisms of 
action. SEA-BCMA may provide additive or synergistic therapeutic effects when administered 
with SOC therapies. 
1.6.3.1. 
Rationale for Dexamethasone Combination Therapy (Part C)  
Corticosteroids have historically represented the backbone of SOC regimens across lines of 
therapy for MM (Burwick 2019); steroid treatment potentiates the efficacy of a variety of other 
antimyeloma classes of agents including IMiDs, monoclonal antibodies, and the XPO1 inhibitor 
selinexor. SEA-BCMA will be studied in combination with dexamethasone to determine whether 
coadministration of steroid therapy will augment the activity of SEA-BCMA. 
1.6.3.2. 
Rationale for Pomalidomide and Dexamethasone Combination Therapy 
(Part D)  
IMiDs such as lenalidomide and pomalidomide have long been a cornerstone of early lines of 
therapy for myeloma. IMiDs are known to enhance natural killer (NK) cell expansion and 
activity and potentiate ADCC when combined with monoclonal antibodies (Wu 2008), thus 
making IMiD regimens an attractive combination backbone for SEA-BCMA. 
1.6.3.3. 
Patient Input Into Design  
Patients were not involved in the design of this study.  
1.7. 
Benefit-Risk Assessment  
A brief summary of the expected benefits and risks are outlined below. More detailed 
information about the known and expected benefits and risks and reasonably expected AEs of 
SEA-BCMA may be found in the IB. 
1.7.1. 
Risk Assessment  
The nonclinical safety profile of SEA-BCMA has been evaluated in vitro and in vivo in the 
cynomolgus monkey model (Section 1.4), in which no adverse effects were observed at the 
HNSTD. Monoclonal antibodies have the potential to cause infusion-related reactions (IRRs); a 
premedication plan for IRRs is described in Section 5.5, and study stopping criteria include a 
provision that the entire study will be halted if Grade 4 or higher allergic reactions that cannot be 
controlled with standard treatments exceed 15% at any point during the trial.  
1.7.2. 
Benefit Assessment  
Subjects with RRMM who are eligible for this study have disease that has relapsed or is 
refractory to SOC therapies. BCMA is broadly expressed in MM. Based on the evidence of 
preclinical effectiveness and preliminary clinical evidence of monotherapy activity (Hoffman 
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2021), SEA-BCMA has the potential to become a new therapeutic option. Subjects may also 
derive other benefits from participating in this phase 1 trial because of the regimented routine 
that subjects undergo such as routine physical examinations, laboratory testing, and radiological 
examinations. 
For patients with triple-class refractory RRMM, novel BCMA directed therapies which have 
either received recent Health Authority approval, or remain in late-stage development, may 
represent new therapeutic options. Although some of these agents may produce deep and durable 
remissions, multiple myeloma remains incurable. Thus, patients with triple-class refractory MM 
who have failed prior BCMA therapy represent a new area of high unmet medical need. 
Mechanisms of resistance to prior BCMA therapy are varied and remain under active 
investigation, but early studies suggest that loss of BCMA antigen expression at relapse is a rare 
phenomenon (Martin 2020). Additionally, loss of persistence of CAR-T cells, or intolerance of 
ADC toxicity, may also lead to treatment failure independent of BCMA expression. Recent data 
from the BCMA/CD3 bispecific antibody teclistamab demonstrated encouraging response rates 
in a cohort of patients who had received prior BCMA CAR-T or ADC therapy (Touzeau 2022). 
Thus, retreatment with another BCMA-targeted therapy lacking overlapping class-effect toxicity 
may be a promising therapeutic approach in heavily refractory patients, and therapy with prior 
BCMA-directed agents is permitted in Parts B and C of this study. 
1.7.3. 
Overall Benefit-Risk Assessment  
Considering the measures taken to minimize risk to subjects participating in this study, the 
potential risks identified in association with SEA-BCMA are justified by the anticipated benefits 
that may be afforded to subjects with RRMM. 
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2. 
OBJECTIVES  
This study will evaluate the safety and antitumor activity of SEA-BCMA as monotherapy and in 
combination in subjects with RRMM. Specific objectives and corresponding endpoints are 
detailed in Table 1. 
 
 
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Table 1: 
Objectives and corresponding endpoints 
Primary Objectives 
Corresponding Primary Endpoint 
Evaluate the safety and tolerability of SEA-BCMA 
monotherapy in subjects with relapsed or refractory 
multiple myeloma (RRMM) 
Type, incidence, severity, seriousness, and relatedness 
of adverse events (AEs) 
Type, incidence, and severity of laboratory 
abnormalities 
Incidence of dose-limiting toxicities (DLTs) 
Identify the maximum tolerated dose (MTD) and/or 
optimal dose and schedule of SEA-BCMA 
monotherapy, and in combination with dexamethasone,  
in subjects with RRMM 
Evaluate the safety and tolerability of SEA-BCMA in 
combination with SOC therapies in subjects with 
RRMM 
Secondary Objectives 
Corresponding Secondary Endpoints 
Identify a recommended single-agent dose and schedule 
of SEA-BCMA 
Assess the pharmacokinetics (PKs) of SEA-BCMA 
Assess the immunogenicity of SEA-BCMA 
Assess the antitumor activity of SEA-BCMA 
Incidence of DLTs, cumulative safety and activity by 
dose level and schedule 
Maximum serum concentration and area under the 
serum concentration-time curve 
Incidence of SEA-BCMA antitherapeutic antibodies 
(ATA) 
Best response per the International Myeloma Working 
Group (IMWG) uniform response criteria (Kumar 
2016) 
Objective response rate (ORR) 
Duration of objective response (OR) and complete 
response (CR) 
Progression-free survival (PFS) 
Overall survival (OS) 
Exploratory Objectives 
Corresponding Exploratory Endpoints 
Assess incidence and level of BCMA expression in 
RRMM and relationship to clinical response to 
SEA-BCMA 
Assess the pharmacodynamic effects and biomarkers of 
response, toxicity, and resistance to SEA-BCMA 
Assess minimal residual disease (MRD) in subjects with 
very good partial response (VGPR) or better 
Assess impact of SEA-BCMA in combination with 
SOC therapies on health-related quality of life 
(HRQoL) from the subject’s perspective. 
Characterization of BCMA expression on malignant 
plasma cells  
Exploratory biomarkers of SEA-BCMA mediated 
pharmacodynamic effects 
Rate of MRD clearance 
Descriptive outcomes of qualitative interviews 
Maximum serum concentration and area under the 
serum concentration-time curve 
 
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3. 
INVESTIGATIONAL PLAN  
3.1. 
Summary of Study Design  
Figure 1: 
Study Design Schema 
 
3.1.1. 
Part A: Monotherapy Dose-escalation and Expansion  
3.1.1.1. 
Monotherapy Dose-Escalation Cohort  
The monotherapy dose-escalation portion of the trial will be conducted in up to approximately 
25 subjects using the mTPI method (Ji 2010) to evaluate safety and tolerability, and to identify 
the MTD of SEA-BCMA. If the MTD is not reached, safety, PK, and biomarker analyses, as 
well as preliminary antitumor activity, will be used to determine the optimal dose. The mTPI 
design uses a Bayesian statistical framework and a beta/binomial hierarchic model to compute 
the posterior probabilities of 3 intervals that reflect the relative distance between the toxicity rate 
of each dose level to the target DLT rate (see Appendix C). Using a target DLT rate of 25% with 
a 5% margin, the - 3 intervals will be (0%, 20%), (20%, 30%), and (30%, 100%), and the 
corresponding dosing decision rules would be: 
1. 
Escalate if current DLT rate is most likely <20% 
2. 
Continue if current DLT rate is most likely between 20 and 30% 
3. 
De-escalate if current DLT rate is likely >30% 
Dose finding decisions are shown in Table 2. E, S, and D represent escalating the dose, staying at 
the same dose, and de-escalating the dose, respectively. Decision DU means that the current dose 
level is unacceptable because of high toxicity and should be excluded from future dosing in the 
trial. 
Enrollment in this study will occur on a cohort-by-cohort basis. Multiple cohorts may be treated 
at each dose level, with a maximum of 4 subjects treated per cohort. Decisions on 
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dose-escalation and subsequent cohort size will be made by the sponsor in consultation with the 
Safety Monitoring Committee (SMC) after completion of each cohort. Subjects in the current 
cohort must be observed for the full duration of the DLT period before the next cohort of 
subjects is enrolled. In addition, as a precaution, for the first 2 subjects in the study there will be 
a 72-hour observation period before the next subject can be dosed. At dose levels above Dose 
Level 1, a 24-hour observation period is required after the first subject receives their first dose of 
SEA-BCMA prior to dosing subsequent subjects at that dose level. At least 2 DLT-evaluable 
(DE) subjects will be treated per dose level until the first DLT is observed, then a minimum of 
3 DE subjects per dose level will be required before escalation to all higher doses. Subjects who 
are considered not evaluable for DLT during Cycle 1 may be replaced. A minimum of 6 DE 
subjects will be observed at the estimated MTD before the MTD or optimal dose is determined. 
The MTD or optimal dose will be estimated based on data from all subjects across all evaluated 
doses. 
De-escalation to a lower dose level may be performed at any time by the sponsor in consultation 
with the SMC. Intrasubject dose-escalation to a dose level shown to be safe may be permitted in 
the event that a subject has not experienced a Grade ≥2 AE while on study treatment, has 
received at least 1 cycle of SEA-BCMA at the current dose level, and achieves SD or better. 
 
 
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Table 2: 
Dose-finding spreadsheet for mTPI design 
 
Number of DLT-evaluable subjects treated at current dose 
Number of DLTs 
 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
0 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
1 
S 
S 
S 
S 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
2 
DU 
D 
D 
S 
S 
S 
S 
S 
S 
S 
S 
S 
E 
E 
3 
DU 
DU 
DU 
D 
S 
S 
S 
S 
S 
S 
S 
S 
S 
4 
DU 
DU 
DU 
DU 
DU 
D 
S 
S 
S 
S 
S 
S 
5 
DU 
DU 
DU 
DU 
DU 
DU 
D 
S 
S 
S 
S 
6 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
D 
S 
7 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
8 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
9 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
10 
DU 
DU 
DU 
DU 
DU 
DU 
11 
DU 
DU 
DU 
DU 
DU 
12 
DU 
DU 
DU 
DU 
13 
DU 
DU 
DU 
14 
DU 
DU 
15 
DU 
D = de-escalate to the next lower dose, DLT = dose-limiting toxicity, DU = current dose is unacceptably toxic, 
E = escalate to the next higher dose, mTPI = modified toxicity probability interval, S = stay at the current dose 
SEA-BCMA will initially be administered q2wk in 4-week cycles at the planned doses shown in 
Table 3; a dosing interval of every 4 weeks (q4wk) may be explored after consultation with the 
SMC. The SMC may also recommend investigation of intermediate dose levels, in which case 
the mTPI dose-escalation rules will continue to be applied. 
Table 3: 
Dose-escalation schema 
Dose Levela           
Dose (mg) 
1 
100 
2 
200 
3 
400 
4 
800 
5 
1600 
a The SMC may recommend investigation of intermediate dose levels based on emerging clinical data 
SMC = Safety Monitoring Committee 
3.1.1.2. 
Monotherapy Expansion Cohort  
To further characterize the safety and antitumor activity of SEA-BCMA, an expansion cohort of 
up to approximately 20 subjects may be enrolled. The dose and schedule for the expansion 
cohort were determined by the sponsor in consultation with the SMC based on the cumulative 
safety and activity demonstrated during dose-escalation, which was completed without 
exceeding MTD at the doses tested. 
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3.1.2. 
Part B: Monotherapy Intensive Dosing  
Part B will evaluate the safety and tolerability of SEA-BCMA dosed q1wk during an induction 
phase (for 8 doses during the first 2 cycles of therapy); following the completion of the 8 week 
induction phase, subjects who have not yet experienced confirmed disease progression may 
proceed to receive SEA-BCMA dosed q2wk during a maintenance phase (Cycle 3 and beyond, 
dosing at the recommended standard-schedule monotherapy expansion dose determined in 
Part A). 
Part B will include a safety run-in at the recommended SEA-BCMA monotherapy expansion 
dose (1600 mg), administered on the intensive dosing schedule (Day 1, Day 8, Day 15, and 
Day 22 of Cycles 1 and 2, and Day 1 and Day 15 of subsequent cycles). DLTs will be evaluated 
in the first 6 subjects. 
4. 
If 0 or 1 of the first 6 subjects experience DLT, the expansion cohort will proceed to enroll 
up to 20 total subjects with the recommendation of the SMC. 
5. 
If ≥2 DLTs occur in the first 6 subjects, MTD will be considered exceeded and the dose of 
SEA-BCMA will be de-escalated to the next lower dose level (800 mg q1wk x 8 weeks 
during Cycles 1 and 2, followed by 1600 mg q2wk from Cycle 3 and beyond). 
• If 0 or 1 of the first 6 subjects at the lower dose level experience a DLT, the expansion 
cohort will proceed to enroll up to 20 total subjects at this dose level with the 
recommendation of the SMC. 
• If ≥2 DLTs occur in the first 6 subjects at the lower dose level, MTD will be considered 
exceeded, and the Part B Monotherapy Intensive Dosing cohort will be discontinued. 
Subjects who are deemed not evaluable for DLT during dose finding will be replaced. 
Table 4: 
Planned dose levels for Part B 
Dose Level 
Weekly Induction Dose,  
Cycles 1-2 (mg) 
Biweekly Maintenance Dose,  
Cycles 3 and beyond (mg) 
1 
1600 
1600 
–1 (if Dose Level 1 is not tolerated) 
800 
1600 
 
3.1.3. 
Combination Therapy Cohorts  
To characterize the safety and tolerability of SEA-BCMA in combination regimens, subjects 
may be enrolled in each of the following combination therapy Parts/Dose Level Cohorts: 
• Part C: Dexamethasone Combination Therapy Cohorts 
○ Cohort 1: SEA-BCMA standard dosing (up to 20 subjects) 
○ Cohort 2: SEA-BCMA intensive dosing (up to 40 subjects; up to 20 subjects may 
enroll in each of up to 2 dose level cohorts) 
In addition, up to 6 DLT-evaluable subjects may be enrolled in the following combination 
therapy cohort safety run-in: 
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• Part D: Pomalidomide and Dexamethasone Combination Therapy Cohort 
○ Cohort 1: SEA-BCMA standard dosing 
3.1.3.1. 
Parts C and D: Combination Therapy Cohorts Safety Run-in  
The Part C dexamethasone combination therapy cohorts and Part D Pom/dex combination 
therapy cohort will include 6-subject safety run-ins at each dose level tested. 
3.1.3.2. 
Part C: Dexamethasone Combination Therapy Cohorts  
Enrollment into dexamethasone combination therapy cohorts may be initiated upon identification 
of tolerable SEA-BCMA monotherapy doses and schedules as determined by the SMC. 
• In Cohort 1 
○ SEA-BCMA will be administered at 1600 mg (the recommended monotherapy 
expansion dose) on Day 1 and Day 15 of each 28-day cycle (standard dosing). 
○ Dexamethasone will be administered on Day 1, Day 8, Day 15, and Day 22 of each 
28-day cycle. 
• In Cohort 2 
○ SEA-BCMA will be administered 
− at 800 mg (one dose level below the recommended monotherapy expansion dose) 
on Day 1, Day 8, Day 15, and Day 22 of Cycles 1 and 2 (intensive dosing), AND 
− at 1600 mg (the recommended monotherapy expansion dose) on Day 1 and 
Day 15 of Cycle 3 and subsequent cycles 
○ Dexamethasone will be administered on Day 1, Day 8, Day 15, and Day 22 of each 
28-day cycle. 
In Cohort 2, a 3-subject cohort will be evaluated at dose level –1 (Table 4) initially. If 2 or more 
DLTs occur among the first 3 subjects, then Cohort 2 will be discontinued. If 1 DLT occurs 
among the first 3 subjects, the cohort will be expanded to 6 subjects, and only escalated if there 
are fewer than 2 DLTs among the 6 subjects. If 0 DLTs occur among the first 3 subjects, the 
dose will be escalated to 1600 mg q1wk for 2 cycles and then 1600 mg q2wk from Cycle 3 and 
beyond, the 6-subject safety run-in rules outlined below will be applied, and 3 additional subjects 
will be treated at 800 mg to complete the 6-subject safety run-in. 
In Cohort 1 and Cohort 2, DLTs will be evaluated in the first 6 subjects enrolled at each dose 
level tested, in each combination therapy cohort. 
1. 
If 0 or 1 of the first 6 subjects experience DLTs, the expansion cohort will proceed to 
enroll up to 20 subjects with the recommendation of the SMC. 
2. 
If ≥2 DLTs occur in the first 6 subjects, MTD for the combination will be considered 
exceeded and the dose of SEA-BCMA will be de-escalated to the next lower dose level. 
• If 0 or 1 of the first 6 total subjects at the lower dose level have experienced a DLT, the 
lower dose level will be declared MTD. 
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• If ≥2 DLTs occur in the first 6 total subjects at the lower dose level, MTD for the 
combination will be considered exceeded and the SMC will determine whether a further 
de-escalation will be tested, or if the combination cohort will be discontinued. 
Subjects who are deemed not evaluable for DLT during dose finding will be replaced. 
In Cohort 2, following completion of 6-subject safety run-in at both 800 mg and 1600 mg dose 
levels, up to 2 dose level cohorts may be explored in parallel by random allocation up to 
20 subjects each, if both dose levels are deemed tolerable. 
3.1.3.3. 
Part D: Pomalidomide and Dexamethasone Combination Therapy 
Cohort  
Enrollment into the pomalidomide/dexamethasone combination therapy cohort may be initiated 
upon identification of tolerable SEA-BCMA monotherapy doses and schedules as determined by 
the SMC. Part D will be conducted in the US only.  
• In Cohort 1 
○ SEA-BCMA will be administered at 1600 mg (the recommended monotherapy 
expansion dose) on Day 1 and Day 15 of each 28-day cycle (standard dosing). 
○ Dexamethasone will be administered on Day 1, Day 8, Day 15, and Day 22 of each 
28-day cycle. 
○ Pomalidomide will be administered on Days 1 to 21 of each of each 28-day cycle. 
DLTs will be evaluated in 6 subjects enrolled at the 1600 mg dose level. The dose will be 
considered tolerable if ≤1 DLT is observed among the first 6 subjects. Further expansion in 
Part D will be contingent upon review of the data from the 6 subjects in Cohort 1 and a protocol 
amendment. 
Subjects who are deemed not evaluable for DLT during dose finding will be replaced. 
3.1.4. 
Duration of Treatment  
Subjects in all cohorts may continue on treatment until disease progression, unacceptable 
toxicity, withdrawal of consent, death, or study termination, whichever occurs first. 
3.1.5. 
Dose-Limiting Toxicity  
The DLT-evaluation period is the first cycle of treatment. DLTs are graded according to the 
National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE), 
version 4.03, and defined as any of the following events during the DLT-evaluation period: 
• A delay of SEA-BCMA treatment by more than 7 days due to toxicity 
• Any AE ≥ Grade 3, unless deemed by the SMC to be clearly unrelated to SEA-BCMA (in 
Parts A through D) except for the following AEs, which must meet these specified 
criteria to be considered a DLT: 
○ Grade 4 neutropenia lasting more than 5 days 
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○ Thrombocytopenia ≥ Grade 4, or Grade 3 thrombocytopenia with clinically 
significant bleeding  
○ Anemia ≥ Grade 4 unrelated to underlying disease  
○ Any Grade ≥3 tumor lysis syndrome, including associated laboratory evaluations, that 
is not successfully managed clinically and that does not resolve within 7 days without 
end organ damage 
○ Any ≥ Grade 4 IRRs or Grade 3 IRRs that do not resolve to ≤ Grade 2 within 24 
hours with infusion interruption, infusion rate reduction, and/or standard supportive 
measures. In the event of a Grade 3 IRR in ≥20% of subjects (ie, 2 or more in the first 
10 subjects), all subsequent subjects will require premedication and/or modification 
of infusion approach per the recommendation of the SMC. For subjects receiving 
premedication, any ≥ Grade 3 IRR will be considered a DLT. 
○ Any Grade ≥3 asymptomatic laboratory abnormality that does not resolve, with or 
without intervention, to ≤ Grade 1 or the baseline grade within 72 hours 
• Any treatment-related death  
3.1.6. 
Stopping Criteria  
3.1.6.1. 
Enrollment Pause at the Cohort Level  
If a subject’s death is considered by the investigator, in consultation with the SMC, to be related 
to SEA-BCMA, enrollment will be paused within the applicable cohort until: 
1. 
The case is reviewed by the investigator, the SMC, and the sponsor, and 
2. 
The sponsor has notified applicable regulatory authorities of the outcome of the safety 
assessment and justification for restarting enrollment in the affected cohorts, and has 
received approval to resume, if required by local regulations. 
3.1.6.2. 
Enrollment Halt for the Entire Study  
Enrollment in the entire study will be halted by the sponsor if the overall benefit-risk balance is 
considered unfavorable.  
The study will be halted if any of the following occur:  
• Rate of on-study toxic deaths unrelated to underlying disease occurring within 30 days of 
dose exceeds 10% (initially, 2 or more out of up to 20 subjects; then 3 or more out of up 
to 30 subjects; 4 or more out of up to 40 subjects; etc.)  
• Rate of Grade 4 nonhematologic toxicity unrelated to underlying disease exceeds 25% 
(initially, 5 or more out of up to 20 subjects; then 6 or more out of up to 24 subjects; then 
7 or more out of up to 28 subjects; then 8 or more out of up to 32 subjects; then 9 or more 
out of up to 36 subjects; 10 or more out of up to 40 subjects; etc.) 
• Rate of ≥ Grade 4 allergic reactions that cannot be controlled with standard treatments 
exceeds 15% (initially, 3 or more out of up to 20 subjects; then 4 out of up to 26 subjects; 
then 5 or more out of up to 33 subjects; 6 or more out of up to 40 subjects; etc.)  
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Stopping criteria will be continuously monitored throughout the study by the sponsor in 
consultation with the SMC, considering enrollment halt if the incidence and/or the severity of 
toxicity leads to a risk-benefit assessment that is unacceptable to the study population. The 
sponsor will consult the SMC to consider whether to allow subjects already receiving treatment 
to continue, to consider modifying the protocol to continue the trial, or to terminate the study.  
If enrollment is halted due to safety concerns, enrollment can only be restarted after appropriate 
amendments and notifications to Regulatory Authorities, with approval to resume, if required by 
local regulations. 
3.1.7. 
Retreatment  
Retreatment with SEA-BCMA monotherapy or with SEA-BCMA and combination therapy is 
permitted with medical monitor approval, for subjects who achieve clinical benefit (defined as 
stabilization or improvement of disease-related symptoms as assessed by the investigator) 
objective response (OR) (a partial response [PR] or better) on study and then experience disease 
progression after discontinuing initial treatment with SEA-BCMA. Eligibility criteria in 
Section 4.1 and Section 4.2 must be re-evaluated before initiating retreatment. Subjects who 
discontinue SEA-BCMA treatment due to Grade ≥3 toxicity are not eligible for retreatment with 
SEA-BCMA. The retreatment dose level for each subject will not exceed the highest safe dose 
level and will be determined by the medical monitor and the site investigator. 
3.1.8. 
End of Study  
The study will be closed approximately 3 years after the last subject receives the last dose, or 
when no subjects remain in follow-up, whichever occurs first. In addition, the sponsor may 
terminate the study at any time (Section 10.3.2).  
3.1.9. 
Safety Monitoring Committee  
The SMC will monitor safety throughout the study. The SMC is composed of the study medical 
monitor, study biostatistician, drug safety representative, and study site investigators. The 
committee is tasked with monitoring the safety of subjects in this study, through regular or ad 
hoc meetings that include review of data pertaining to dose-escalation decisions and 
treatment-emergent toxicities. 
At a minimum, SMC meetings will be held during Part A (monotherapy dose-escalation) and 
during dose finding in Part B (intensive dosing) and Parts C and D (combination therapy) cohorts 
after all subjects in a safety run-in cohort have completed the DLT evaluation period. The SMC 
will also meet quarterly throughout the study for cumulative subject data review. 
3.1.9.1. 
Part A Dose-escalation Safety Monitoring  
During monotherapy dose-escalation, the SMC will review clinical data from enrolled subjects 
for safety assessment and for DLT determination. The SMC will make recommendations on dose 
level and cohort size in conjunction with the mTPI decision rules chart. A maximum of 
4 subjects are allowed per cohort, with multiple cohorts allowed at each dose level (ie, the SMC 
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may recommend subsequent enrollment of cohorts of 1, 2, 3, or 4 subjects depending on the 
number of DLTs observed and cumulative data review). 
In addition to determination of DLTs and dose-escalation recommendations, the SMC may make 
one or more of the following recommendations during the study, as applicable: 
• Recommendation or requirement of a premedication regimen as prophylaxis against IRRs 
• Further evaluation of safety of SEA-BCMA at a given dose 
• Evaluation of alternative approaches to SEA-BCMA infusion 
• Evaluation of an intermediate SEA-BCMA dose level during dose-escalation 
• Evaluation of longer (eg, q4wk) SEA-BCMA dosing intervals  
• Consideration of postremission dosing (not exceeding tested dose levels deemed 
tolerable) 
• The SEA-BCMA dose and dosing interval to be evaluated in the monotherapy expansion 
cohort based on activity and tolerability of dose levels during escalation 
• The recommended single-agent dose and schedule for SEA-BCMA based on the safety 
and activity data 
The process for dose-escalation decisions and dose-interval recommendations, and the roles and 
responsibilities of the SMC will be detailed in an SMC charter. 
3.1.9.2. 
Parts B, C, and D Safety Monitoring  
During dose finding safety run-in cohorts in Parts B, C, and D, the SMC will review clinical data 
from enrolled subjects for safety assessment and for DLT determination. The SMC will make 
recommendations on the SEA-BCMA dose. 
In addition to determination of DLTs and dose recommendations for the combination, the SMC 
may make 1 or more of the following recommendations during the study, as applicable: 
• Recommendation or requirement of a premedication regimen as prophylaxis against IRRs 
• Further evaluation of safety of SEA-BCMA on intensive dosing schedule and/or in 
combination with dexamethasone  
• Evaluation of alternative approaches to SEA-BCMA infusion  
• Evaluation of an intermediate SEA-BCMA dose on intensive dosing schedule and/or in 
combination cohorts 
• Consideration of postremission dosing (not exceeding tested dose levels deemed 
tolerable) 
• The recommended dose and schedule for SEA-BCMA on intensive dosing schedule 
and/or in combination based on the safety and activity data 
3.2. 
 Method of Assigning Subjects to Treatment Groups  
Subject allocation to a dose level will be determined by mTPI decision rules as illustrated in 
Table 2 and will occur upon approval of subject enrollment by Seagen or their designee. 
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The medical monitor will assess the safety of SEA-BCMA administration throughout the trial 
and, for safety reasons, may override the model’s allocation of a subject to a particular dose 
level. 
The study design allows for concurrent enrollment in multiple cohorts. If 2 or more expansion 
cohorts with identical eligibility criteria are open for enrollment concurrently, allocation will be 
determined by the sponsor or designee prior to informed consent. 
3.2.1. 
Rationale for Selection of Doses  
3.2.1.1. 
Monotherapy  
For adult phase 1 studies of monoclonal antibodies, either body size-based dosing or fixed 
dosing may be considered. Based on an analysis of 12 mAbs, these 2 dosing approaches 
performed similarly across the mAbs in terms of their population and individual PK 
performances (Wang 2009). In addition, the PK variability of mAbs introduced by either dosing 
approach is moderate relative to the variability generally observed in pharmacodynamics, 
efficacy, and safety (Bai 2012). Available data from clinical trials and extensive population PK 
modeling of monoclonal antibodies in oncology also support use of fixed dosing for oncology 
indications (Hendrikx 2017). Fixed dosing could offer advantages in ease of dose preparation, 
and reduced chance of dosing errors. In addition, previous clinical trials of non-fucosylated and 
bivalent antibodies have utilized this approach during phase 1 with no significant safety concerns 
(Sehn 2012; Rosen 2017). Based on the predicted broad therapeutic window for SEA-BCMA, a 
fixed dosing strategy is used. 
The monotherapy starting dose of 100 mg is based on a 1.25 mg/kg starting dose with a nominal 
subject weight of 80 kg. The starting dose was selected based on preclinical studies and 
PK/pharmacodynamic modeling and is expected to provide an adequate safety margin with the 
potential for clinical benefit. Data supporting the proposed starting dose include: 
• Preclinical testing of SEA-BCMA in cynomolgus monkeys indicates a favorable safety 
profile at the proposed starting dose. The BCMA receptor in the cynomolgus monkey 
does not cross-react with SEA-BCMA; therefore, preclinical testing in this model is an 
indicator of safety in the absence of target ligation. The HNSTD in the cynomolgus 
monkey was 100 mg/kg for 2 doses administered at a 3 week interval. No adverse effects 
were observed at this dose. The proposed starting dose of 1.25 mg/kg is lower than 1/6 of 
the monkey HNSTD, using body surface area for animal-to-human dose conversion 
based on body weight, and represents an appropriately conservative starting dose. 
• Human PBMCs co-cultured in vitro in the presence of BCMA-expressing myeloma cells 
and treated with SEA-BCMA displayed minimal cytokine activation. In PBMCs from 
donors with normal-affinity FcγRIII (representing approximately 90% of the target 
patient population), of 29 cytokines tested, SEA-BCMA induced a minimal change in 
IL-8 at 100 μg/mL (corresponding to the Cmax of a dose of approximately 5 mg/kg). In 
PBMCs from donors with high-affinity FcγRIII (representing approximately 10% of the 
target patient population), SEA-BCMA induced minimal to moderate cytokine 
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production. Of 29 cytokines evaluated, IL-8 and MIP–1b were the only immune 
activating cytokines consistently induced by treatment with 100 μg/mL of SEA-BCMA. 
In addition, no proliferation of myeloma cells expressing BCMA was observed when 
treated with 100 μg/mL of SEA-BCMA. 
• SEA-BCMA is active in 7 of 7 tumor xenograft models tested, with a lowest active dose 
of 0.03 mg/kg in the disseminated NCI-H929 luciferase tumor xenograft model in NSG 
mice. In some models, repeat dosing enables ligand blocking to contribute to antitumor 
activity. Soluble factors, including soluble BCMA, are predicted to impact SEA-BCMA 
binding to target cells below 20 μg/mL of antibody, which corresponds to the predicted 
Cmax of a dose of approximately 1 mg/kg. 
• Based on PK simulations, the proposed dosing interval of q2wk will achieve 99% target 
receptor occupancy over the dosing interval after 2 doses of 400 mg assuming a serum 
half-life of 21 days, or 800 mg assuming a serum half-life of 11 days. Ninety-nine 
percent receptor occupancy is desired because ligand blocking by SEA-BCMA is one 
mechanism contributing to its antitumor activity, and full receptor occupancy may be 
required for optimal activity. Alternative dosing intervals may be explored after 
consultation with the SMC. 
The dose-escalation design is reasonable for a monoclonal antibody in which target expression is 
restricted to plasmablasts and plasma cells and is anticipated to have minimal potential for 
toxicity to other organs and tissues. Ninety-nine percent receptor occupancy over the dosing 
interval is expected to induce an optimal antitumor activity. Based on PK simulations, this will 
be achieved at doses ranging from 400 to 1600 mg. The proposed dose-escalation plan consists 
of 2-fold increases per dose level, enabling efficient escalation (2 to 3 dose-escalations) into a 
dose range where optimal antitumor activity is anticipated to be achieved. This plan will preserve 
safety while avoiding exposure of an excessive number of subjects to subtherapeutic doses.  
Alternative dosing strategies, including intermediate doses or longer dosing intervals, may be 
explored upon the recommendation of the SMC following evaluation of PK, pharmacodynamics, 
safety, and activity from the available clinical data.  
During Part A (monotherapy dose-escalation), 6 DE subjects were treated at the highest tested 
dose of 1600 mg q2wk. No DLTs were observed in these 6 subjects; based upon this and 
cumulative safety data from prior dose cohorts, the sponsor, in consultation with the SMC, 
deemed 1600 mg q2wk tolerable and selected this as the monotherapy expansion dose for the 
standard q2wk dosing schedule. 
3.2.2. 
Combination Therapy  
Dexamethasone and IMiDs such as pomalidomide play an important role in SOC combinations 
for MM. Thus, it is important to assess safety and activity of SEA-BCMA in combination with 
such agents. In Part C Cohort 1 and Part D, SEA-BCMA will be administered at the 
recommended monotherapy expansion dose of 1600 mg (Sections 3.1.1 and 3.1.2). In Part C 
Cohort 2, SEA-BCMA will be administered initially at dose level –1 (Table 4). In Part D, 
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pomalidomide and dexamethasone will be administered at their respective standard doses and 
schedules to ensure subjects receive the optimal doses.  
3.2.3. 
Blinding and Unblinding  
This is an open-label study. 
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4. 
STUDY POPULATION  
Subjects must meet all of the enrollment criteria to be eligible for this study and prior to study 
drug administration (within 1 day of dosing) on Cycle 1 Day 1. Eligibility criteria may not be 
waived by the investigator and are subject to review in the event of a good clinical practice audit 
and/or health regulatory authority inspection. 
To be eligible for retreatment as described in Section 3.1.7, subjects must meet all inclusion and 
exclusion criteria outlined in Section 4.1 and Section 4.2. 
4.1. 
Inclusion Criteria  
1. 
Diagnosis of MM requiring systemic therapy as defined by IMWG 2014 criteria (Kumar 
2016). 
2. 
Subjects must have MM that is relapsed or refractory and must be a candidate for 
SEA-BCMA treatment in the opinion of the treating physician.  
a. 
Part A: Subjects must not have other therapeutic options known to provide clinical 
benefit in MM available. Subjects’ prior lines of therapy must include at least a PI, an 
IMiD, and an anti-CD38 antibody in any order during the course of treatment. 
Subjects who could not tolerate a PI, IMiD, or anti-CD38 antibody are allowed. 
b. 
Parts B and C: Subjects must not have other therapeutic options known to provide 
clinical benefit in MM available. Subjects must have received at least 3 prior lines of 
antimyeloma therapy and must be refractory to at least 1 agent in each of the 
following classes: PI, IMiD, and an anti-CD38 antibody. 
Prior BCMA-directed myeloma therapy, excluding prior treatment with SEA-BCMA, 
is permitted (eg, ADC, CAR-T cell therapy, or bispecific antibody targeting BCMA) 
provided that at least 3 months will have elapsed from the last dose of prior BCMA 
targeting therapy and Cycle 1 Day 1 of this study, and that the subject has recovered 
from any clinically significant toxicity of the prior BCMA-targeting therapy.  
c. 
Part D: Subjects must have received at least 3 prior lines of antimyeloma therapy, 
including a PI, IMiD, and an anti-CD38 antibody, and must have documented IMWG 
disease progression on or within 60 days of completion of their last treatment. 
Subjects with a history of ASCT are eligible if the date of transplant was at least 
12 weeks prior to initiation of SEA-BCMA treatment. Part D will be conducted in the 
US only.  
3. 
Measurable disease, as defined by one or more of the following: 
a. 
Serum monoclonal paraprotein (M-protein) level ≥0.5 g/dL; for IgA or IgD myeloma 
subjects, serum IgA or serum IgD ≥0.5 g/dL is acceptable 
b. 
Urine M-protein level ≥200 mg/24 hr 
c. 
Serum immunoglobulin FLC ≥10 mg/dL and abnormal serum immunoglobulin kappa 
lambda FLC ratio 
4. 
Age 18 years or older. 
5. 
An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 (see 
Appendix D for conversion of performance status using Karnofsky and Lansky scales, if 
applicable) 
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6. 
Life-expectancy of >3 months in the opinion of the investigator 
7. 
The following baseline laboratory data (hematologic criteria must be met in the absence of 
growth factor or platelet transfusion support):  
a. 
Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 per the 
Modification of Diet in Renal Disease (MDRD) equation (Appendix I) 
b. 
Absolute neutrophil count ≥1000/µL 
c. 
Platelet count ≥75,000/μL 
8. 
For Parts A, B, and C: Subjects of childbearing potential, as defined in Section 4.3, under 
the following conditions: 
a. 
Must have a negative serum or urine pregnancy test (minimum sensitivity 25 mIU/mL 
or equivalent units of beta human chorionic gonadotropin [β-hCG]) result within 
7 days prior to the first dose of SEA-BCMA. Subjects with false positive results and 
documented verification that the subject is not pregnant are eligible for participation 
b. 
Must agree not to try to become pregnant during the study and for at least 6 months 
after the final dose of any study drug administration 
c. 
Must agree not to breastfeed or donate ova, starting at time of informed consent and 
continuing through 6 months after the final dose of any study drug  
d. 
If sexually active in a way that could lead to pregnancy, must consistently use 
2 highly effective methods of birth control (as defined in Appendix E) starting at time 
of informed consent and continuing throughout the study and for at least 6 months 
after the final dose of any study drug  
9. 
For Parts A, B, and C: Subjects who can father children, under the following conditions: 
a. 
Must agree not to donate sperm starting at time of informed consent and continuing 
throughout the study period and for at least 6 months after the final dose of any study 
drug 
b. 
If sexually active with a person of childbearing potential in a way that could lead to 
pregnancy, must consistently use 2 highly effective methods of birth control (as 
defined in Appendix E) starting at time of informed consent and continuing 
throughout the study and for at least 6 months after the final dose of any study drug  
c. 
If sexually active with a person who is pregnant or breastfeeding, must consistently 
use 1 of 2 contraception options (as defined in Appendix E) starting at time of 
informed consent and continuing throughout the study and for at least 6 months after 
the final dose of study any drug.  
10. 
For Part D, containing pomalidomide: Subjects of childbearing potential, as defined in 
Section 4.3.1 , under the following conditions: 
a. 
Must have 2 negative serum or urine pregnancy tests (minimum sensitivity 
25 mIU/mL or equivalent units of hCG). One 10 to 14 days prior to start of the study 
drug and one 24 hours prior to the start of study drug 
b. 
Must agree not to try to become pregnant during the study and for at least 6 months 
after the final dose of any study drug administration 
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c. 
Must agree not to breastfeed or donate ova, starting at time of informed consent and 
continuing through 6 months after the final dose of study drug. Must agree to not 
donate blood for at least 90 days following completion of study treatment 
d. 
If sexually active in a way that could lead to pregnancy, must consistently use 
2 highly effective methods of birth control (as defined in Appendix F) for 4 weeks 
prior to the start of treatment with study drugs and continuing throughout the study 
and for at least 6 months after the final dose of any study drug  
11. 
For Part D, containing pomalidomide: Subjects who can father children, under the 
following conditions: 
a. 
Must agree not to donate sperm starting at time of informed consent and continuing 
throughout the study period and for at least 6 months after the final dose of study 
drug. Must agree to not donate blood for at least 90 days following completion of 
study treatment  
b. 
If sexually active with a person of childbearing potential in a way that could lead to 
pregnancy, or a person who is pregnant or breastfeeding, must consistently use 
2 highly effective methods of birth control (as defined in Appendix F), one of which 
must be a latex or synthetic condom, starting at time of informed consent and 
continuing throughout the study and for at least 6 months after the final dose of any 
study drug. 
12. 
For Part D, containing pomalidomide: must be willing and able to comply with the 
Pomalyst® Risk Evaluation and Mitigation Strategy (REMS) program. Part D will be 
conducted in the US only.  
13. 
The subject must provide written informed consent.  
4.2. 
Exclusion Criteria  
1. 
Parts A and D: Prior exposure to any other BCMA-directed therapy 
2. 
History of another malignancy within 3 years before the first dose of study drug, or any 
evidence of residual disease from a previously diagnosed malignancy. Exceptions are 
malignancies with a negligible risk of metastasis or death (eg, 5-year OS ≥90%), such as 
adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized 
prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.  
3. 
Active cerebral/meningeal disease related to the underlying malignancy. Subjects with a 
history of cerebral/meningeal disease related to the underlying malignancy are allowed if 
prior central nervous system disease has been treated. 
4. 
Any uncontrolled Grade 3 or higher (per the NCI-CTCAE, v. 4.03) viral, bacterial, or 
fungal infection within 2 weeks prior to the first dose of SEA-BCMA. Routine 
antimicrobial prophylaxis is permitted. 
5. 
Positive for hepatitis B by surface antigen expression. Active hepatitis C infection (positive 
by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 
6 months). Subjects who have been treated for hepatitis C infection are permitted if they 
have documented sustained virologic response of 12 weeks.  
6. 
Known to be positive for human immunodeficiency virus (HIV) 
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7. 
Subjects with previous allogeneic stem cell transplant (SCT)  
8. 
Uncontrolled or severe cardiovascular or pulmonary disease determined by the 
investigator, including documented history of a cerebral vascular event (stroke or transient 
ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent 
with congestive heart failure, Class III to IV, New York Heart Association (see 
Appendix G) within 6 months prior to their first dose of SEA-BCMA (Parts A, B, and C), 
or within 12 months prior to their first dose of SEA-BCMA (Part D) 
9. 
For Part D containing pomalidomide: unable to tolerate thromboembolic prophylaxis while 
on study 
10. 
Current therapy with other systemic antineoplastic or investigational agents 
11. 
Chemotherapy, radiotherapy, biologics, investigational agents, and/or other antitumor 
treatment with immunotherapy that is not completed 4 weeks prior to first dose of 
SEA-BCMA, or 2 weeks if progressing and recovered from clinically significant toxicity 
associated with the treatment. CAR-T-cell therapy that is not completed 8 weeks prior to 
first dose of SEA-BCMA. Palliative radiotherapy to a single site of disease is allowed with 
the approval of the medical monitor. 
12. 
Systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or 
other immunosuppressive medications within 14 days of enrollment. Inhaled or topical 
steroids and adrenal replacement steroid doses ≤10 mg daily prednisone equivalent are 
permitted. Refer to Section 5.6.2 for allowed use of intermittent high-dose corticosteroid 
treatment. 
13. 
Subjects who are breastfeeding, pregnant, or planning to become pregnant from time of 
informed consent until 6 months after final dose of study drug administration. 
14. 
Known hypersensitivity to any excipient contained in the drug formulation of 
SEA-BCMA. 
15. 
Subjects with plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard 
differential), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, 
organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically 
significant amyloidosis. 
16. 
Moderate or severe hepatic impairment, as indicated by any of the following: 
a. 
Serum total bilirubin >1.5 x upper limit of normal (ULN). For subjects with Gilbert’s 
disease, total bilirubin >3 x ULN 
b. 
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x ULN 
17. 
Significant comorbid condition or disease which in the judgment of the investigator would 
place the subject at undue risk or interfere with the proper assessment of safety and toxicity 
of the study drug. 
18. 
Part C and D only: Known intolerance to corticosteroids. 
19. 
Part C and D only: Any uncontrolled psychoses. 
20. 
Part D only: Prior history of hypersensitivity reaction of prior IMiD therapy 
(pomalidomide, thalidomide, or lenalidomide). 
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21. 
Part D only: Grade ≥2 peripheral neuropathy. 
22. 
Part D: Subjects with gastrointestinal conditions that might predispose for drug 
intolerability or poor drug absorption (eg, inability to take oral medication, prior surgical 
procedures affecting absorption (eg, gastric bypass), malabsorption syndrome, and active 
peptic ulcer disease)  
4.3. 
Childbearing Potential  
Subjects of childbearing potential is anyone born female who has experienced menarche and 
who has not undergone surgical sterilization (eg, hysterectomy, bilateral salpingectomy, bilateral 
oophorectomy) or has not completed menopause. Menopause is defined clinically as 12 months 
of amenorrhea in a person born female over age 45 in the absence of other biological, 
physiological, or pharmacological causes. 
Females treated with hormone replacement therapy are likely to have artificially suppressed 
follicle-stimulating hormone (FSH) levels and may require a washout period in order to obtain a 
physiologic FSH level. The duration of the washout period is a function of the type of hormone 
replacement therapy used. The duration of the washout period below are suggested guidelines 
and the investigators should use their judgment in checking serum FSH levels. If the serum FSH 
level is >40 mIU/mL at any time during the washout period, the subject can be considered 
postmenopausal: 
• 1 week minimum for vaginal hormonal products (rings, creams, gels) 
• 4 week minimum for transdermal products 
• 8 week minimum for oral products 
Other products may require a washout period as long as 6 months.  
Subjects who can father children is anyone born male who has testes and who has not undergone 
surgical sterilization (eg, vasectomy followed by a clinical test proving that the procedure was 
effective). 
4.3.1. 
Subjects Treated with Pomalidomide (Part D)  
Women of childbearing potential, as defined by the Pomalyst REMS program, must also include 
all females who are menstruating, amenorrheic from previous medical treatments, under 50 years 
of age, and/or perimenopausal, and do not qualify for the category “females not of reproductive 
potential.” 
Females not of reproductive potential, as defined by Pomalyst REMS program, include females 
who have been in natural menopause for at least 24 consecutive months, or who have had a 
hysterectomy and/or bilateral oophorectomy. 
Part D will be conducted in the US only.  
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4.4. 
Removal of Subjects from Therapy or Assessment  
Seagen or their designee must be notified if a subject is withdrawn from study treatment or from 
the study. The reason(s) for withdrawal must be documented in the subject’s medical records and 
case report form (CRF). 
4.4.1. 
Discontinuation of Study Treatment  
A subject’s study treatment may be discontinued for any of the following reasons: 
• PD 
• AE 
• Pregnancy 
• Investigator decision 
• Subject decision, non-AE  
• Study termination by sponsor 
• Other, non-AE 
In Parts A and B (monotherapy), subjects who discontinue SEA-BCMA will be considered 
discontinued from study treatment. Subjects who discontinue from study treatment will remain 
on study for follow-up until withdrawal of consent, death, or study closure, whichever occurs 
first. 
In Part C, subjects who discontinue SEA-BCMA and dexamethasone will be considered 
discontinued from study treatment. Subjects receiving dexamethasone who discontinue 
corticosteroid therapy may continue to receive SEA-BCMA as monotherapy with medical 
monitor approval. Subjects who discontinue SEA-BCMA will be considered discontinued from 
study treatment. 
In Part D, subjects who discontinue SEA-BCMA, dexamethasone, and pomalidomide will be 
considered discontinued from study treatment. Subjects receiving dexamethasone who 
discontinue corticosteroid therapy may continue to receive SEA-BCMA and pomalidomide with 
medical monitor approval. Subjects who discontinue pomalidomide may continue to receive 
SEA-BCMA and dexamethasone with medical monitor approval. Subjects who discontinue 
SEA-BCMA will be considered discontinued from study treatment. 
4.4.2. 
Subject Withdrawal from Study  
Any subject may be discontinued from the study for any of the following reasons: 
• Subject withdrawal of consent 
• Retreatment  
• Study termination by sponsor 
• Lost to follow-up 
• Death 
• Other 
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5. 
TREATMENTS  
5.1. 
Treatments Administered  
SEA-BCMA is a non-fucosylated monoclonal antibody directed against BCMA. Subjects will 
receive the investigational medicinal product SEA-BCMA as monotherapy or combination 
therapy (Section 3.1). Subjects in combination therapy cohorts will also receive dexamethasone 
or dexamethasone plus pomalidomide.  
Guidance for intrasubject dose-escalation for subjects who have the potential to achieve greater 
benefit at a dose higher than the dose level assigned during dose-escalation is described in 
Section 5.2.3. 
5.2. 
Investigational Product: SEA-BCMA  
Detailed information describing the preparation, administration, and storage of SEA-BCMA is 
located in the Pharmacy Instructions. 
5.2.1. 
Description  
SEA-BCMA is a sterile, preservative-free, colorless to light yellow, clear to slightly opalescent 
solution with no visible particulate matter. SEA-BCMA is supplied by Seagen in single-dose 
glass vials. The drug product solution is diluted in sterile 0.9% sodium chloride injection, US 
Pharmacopeia, or equivalent, for IV administration. 
SEA-BCMA drug product is labeled with a nominal content of 100 mg/vial. Each vial contains 
110 mg of SEA-BCMA, which allows the label quantity to be withdrawn for use. SEA-BCMA 
drug product consists of SEA-BCMA (20 mg/mL), histidine, arginine, trehalose and 
polysorbate 80. The pH of the product is approximately 6.5. 
5.2.2. 
Dose and Administration  
SEA-BCMA will be administered at the assigned dose by IV infusion. SEA-BCMA must not be 
administered as an IV push or bolus. SEA-BCMA should not be mixed with other medications.  
On Cycle 1, Day 1, subjects were closely observed in the clinic for at least 6 hours after 
completion of study treatment administration during dose-escalation. Vital signs will be collected 
as described in Section 6. Monitoring for subsequent cycles was considered upon review of 
safety data with the SMC. The observation period after completion of study treatment 
administration on Cycle 1, Day 1 is reduced to 2 hours during Part A monotherapy dose 
expansion and in all subsequent cohorts following review of data from the dose-escalation 
cohort, in which there were no instances of delayed-onset IRRs.  
Infusion duration will vary depending on the method of infusion administration and the 
SEA-BCMA dose. Please refer to the Pharmacy Instructions for further details. 
The initial approach to SEA-BCMA administration will be stepwise infusion. In a stepwise 
infusion, the infusion rate is increased at set time intervals until a defined maximum rate of 
infusion is reached. The first infusion of SEA-BCMA will be initiated at a rate of 50 mg/hour. If 
the first 30 minutes is well-tolerated, the rate will be incrementally increased (no greater than 
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2-fold increase in rate) every 30 minutes as tolerated until a maximum rate (400 mg/hour) is 
reached. With subsequent infusions, the infusion rate may be increased more rapidly in shorter 
time intervals; eg, after the first 15 minutes, the rate can be incrementally increased (no greater 
than 2-fold increase in rate) every 15 minutes as tolerated until the maximum rate is reached. 
As clinical experience with stepwise infusions evolves, the maximum rate may be increased or 
decreased based on accumulating safety data and/or recommendations of the SMC. In addition, 
alternative approaches to SEA-BCMA administration may be evaluated to manage potential 
safety signals, including IRRs, as recommended by the SMC. These may include systematic 
implementation of the following strategies: extending the planned infusion duration, 
fixed-duration infusion (Section 5.2.2.1), administration at a fixed infusion rate (Section 5.2.2.2), 
divided-dose administration (Section 5.2.2.3), or a change in premedications (Section 5.6.1). 
See the Pharmacy Instructions for additional details. 
5.2.2.1. 
Fixed-Duration Infusion  
If fixed-duration infusion is implemented, the SEA-BCMA infusion duration is defined by the 
sponsor. As clinical experience with SEA-BCMA infusion evolves, the infusion duration may be 
increased or decreased based on accumulating safety data and/or recommendations of the SMC. 
In an individual subject, if the subject is unable to tolerate the infusion, the infusion duration may 
be increased; the infusion duration in subsequent infusions may also be increased per 
investigator discretion with medical monitor approval. Conversely, if a subject does not 
experience an IRR greater than Grade 1 with consecutive infusions, the infusion duration may be 
shortened (ie, administered at a faster rate) at the discretion of the investigator with medical 
monitor approval, the implementation of which may be dose-cohort specific. 
5.2.2.2. 
Fixed Infusion Rate  
If a fixed infusion rate is implemented, the dose is administered at a fixed rate rather than over a 
fixed time. 
For example, for a fixed infusion rate of 50 mg/hour, a dose of 100 mg would be infused over 
2 hours. As clinical experience with administration at a fixed infusion rate evolves, the rate may 
be increased, or decreased, based on accumulating safety data and/or recommendations of the 
SMC. 
In an individual subject, if the subject is unable to tolerate the infusion rate, the infusion rate may 
be decreased in subsequent infusions per investigator discretion with medical monitor approval. 
Conversely, if an individual subject does not experience an IRR greater than Grade 1 with 
consecutive infusions, the infusion rate may be increased at the discretion of the investigator 
with medical monitor approval. 
5.2.2.3. 
Divided-Dose Administration  
If divided-dose administration is implemented, the dose is divided and administered separately 
within a time period. For example, the dose could be divided in 2 parts, in which the first 10% of 
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the dose is infused over approximately 45 minutes, followed by a 30-minute observation period 
as the subject remains in the infusion chair. If the investigator determines that the subject has 
tolerated the initial SEA-BCMA infusion, the remaining 90% is infused over approximately 
45 minutes. 
5.2.3. 
Dose Modifications  
On a per-subject basis, lengthening of dosing intervals for toxicity, including DLT, may be 
allowed upon approval by the medical monitor. Subjects who experience DLT in Cycle 1 should 
not receive further treatment with SEA-BCMA unless clinical benefit is demonstrated with 
adequately managed toxicity and there is approval from the medical monitor. Examples of 
clinical benefit include an OR assessed by imaging, laboratory assessment, or physical 
examination; or SD and clinical improvement in disease-related symptoms per investigator. If 
clinical benefit is demonstrated, the dosing interval may be lengthened by 50 to 100% after 
discussion with the medical monitor. The type and severity of the AE observed will be taken into 
consideration to inform the decision. For subjects treated at the lowest dose level, the dosing 
interval may be lengthened, or the subject may be discontinued from treatment. 
If a subject has a clinically significant, unresolved AE on the planned dosing day, the dose may 
be delayed for up to 7 days. Dosing delays due to other reasons or lasting >7 days must be 
discussed with the medical monitor (see Table 5); during the DLT period, subjects should not 
receive further treatment with SEA-BCMA unless clinical benefit is demonstrated with 
adequately managed toxicity and there is approval from the medical monitor. For subjects 
requiring a dose delay >7 days due to an unresolved AE, the dosing interval may be lengthened 
by 50 to 100% after discussion with the medical monitor. 
In q2wk dosing, if a subject has a clinically significant, unresolved AE on Day 15 that prevents 
dosing, the Day 15 visit may be delayed for ≤7 days. On the seventh day, if a subject cannot 
receive the dose, the second dose of the cycle will be eliminated, the Day 15 visit will be 
skipped, and the Day 22 visit will be performed. If the Day 15 dose is delayed for ≤7 days, study 
assessments required for Day 15 to 28 will be delayed by the same number of days as the dose 
delay, and study drug administration for the next cycle will be delayed by at least the same 
number of days. 
In intensive dosing weekly induction Cycles 1 and 2, if a subject has a clinically significant, 
unresolved AE that prevents dosing on Day 8, 15, or 22, the dose may be delayed for ≤3 days. 
On the third day, if a subject cannot receive the dose, the dose of SEA-BCMA will be eliminated 
and the corresponding visit will be skipped; dosing and visit schedule would resume the 
following week (eg, at Day 22, if Day 15 is skipped). However, if a Day 8, 15, or 22 dose is 
delayed for ≤3 days, subsequent study assessments within the same cycle will be delayed by the 
same number of days as the dose delay, and study drug administration for the next dose will be 
delayed by at least the same number of days. 
During the DLT period (Cycle 1), growth factor and transfusion support is discouraged unless 
medically indicated; subjects who receive growth factor (eg, granulocyte colony-stimulating 
factor or granulocyte-macrophage colony-stimulating factor) or transfusion support (other than 
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red blood cell transfusions for MM-related anemia) during this period for reasons other than 
DLT may not be evaluable for DLT, except in Part D, where granulocyte colony-stimulating 
factor is permitted during Cycle 1 if given as primary or secondary prophylaxis in conjunction 
with pomalidomide. Consideration should be given for growth factor support for prophylaxis or 
treatment of cytopenias in subsequent cycles (Table 5). During dose-escalation, subjects with 
Grade 4 neutropenia must have a follow-up complete blood count (CBC) with differential 
obtained 5 days from the time of assessment for evaluation of DLT. In addition, subjects with 
Grade 3 asymptomatic laboratory abnormalities must have follow-up laboratory evaluation 
obtained 72 hours from the time of assessment for evaluation of DLT. Serum chemistry and 
CBCs should be collected minimally on a weekly schedule during dose delays resulting from 
toxicity. 
Table 5 describes the recommended dose modifications for toxicity. 
Table 5: 
Recommended dose modifications for toxicity 
Toxicity 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Nonhematologic 
(AE or laboratory 
abnormality) 
Continue at 
same dose level 
Continue at 
same dose level 
Withhold dose until 
toxicity is ≤ Grade 1 or 
baselinea, and then 
resume treatment at 
50% of the SEA-BCMA 
dose           
Discontinue study 
treatment  
Hematologic 
(neutropenia, 
thrombocytopenia, 
and anemia) 
Continue at 
same dose level 
Continue at 
same dose level 
First occurrence: Withhold dose until resolution to 
≤ Grade 2 or baseline; for Grade 3 events, resume 
treatment at the same dose level; for Grade 4 
events, either resume treatment at the same dose 
level after discussion with the medical monitor or 
discontinue treatment at the discretion of the 
investigator. Treatment delay of up to 7 days is 
permitteda 
Second occurrence: Withhold dose until toxicity is 
≤ Grade 2 or baselinea. Either resume treatment at 
the same dose level with growth factor support after 
discussion with the medical monitor or discontinue 
study treatment at the discretion of the investigator 
Infusion-related 
reaction  
See Section 5.7.1 
a Treatment delays of >7 days are to be discussed with the medical monitor. 
AE = adverse event, BCMA = B-cell maturation antigen 
 
Intrasubject dose-escalation may be permitted in the event that a subject has not experienced a 
Grade ≥2 AE while on study treatment, has received at least 1 cycle of SEA-BCMA at the 
current dose level, and achieves SD or better. Additional treatment cycles may be administered at 
1 dose level below the currently enrolling dose level for dose-escalation (or at the MTD if it has 
been determined) at the discretion of the investigator and upon approval by the medical monitor. 
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5.2.4. 
Storage and Handling  
Refrigeration should be set at 2 to 8 °C for storage of vials and solutions containing 
SEA-BCMA. The controlled location must be accessible only to the pharmacist, the investigator, 
or a duly designated person. SEA-BCMA does not contain preservatives; therefore, opened and 
reconstituted vials should be used as soon as possible. Please refer to the Pharmacy Instructions 
for further details on storage and handling. 
Drug accountability procedures are provided in the Pharmacy Binder. 
5.2.5. 
Packaging and Labeling  
SEA-BCMA is supplied in clear glass vials. The clinical supplies for open-label studies are 
labeled as SEA-BCMA Injection. A sample label is provided in the Pharmacy Instructions. 
5.2.6. 
Preparation  
Recommended safety measures for handling and preparation include masks, protective clothing, 
gloves (double glove with nitrile gloves), and vertical laminar airflow safety cabinets. 
Detailed drug preparation instructions are provided in the Pharmacy Instructions. 
5.2.7. 
Continued Access to SEA-BCMA After the End of the Study  
A subject deriving clinical benefit from SEA-BCMA at the time the study is completed may be 
permitted to continue to receive SEA-BCMA, provided the investigator considers it to be the 
subject’s best treatment option and the study is not terminated due to safety concerns. Requests 
will be discussed on a subject-by-subject basis with the sponsor. If continued access to 
SEA-BCMA is permitted, sparse data may be collected to monitor the safety and tolerability of 
continued administration. Subjects will not receive SEA-BCMA beyond the protocol definition 
of end of treatment (EOT). 
5.3. 
Dexamethasone  
5.3.1. 
Description  
Corticosteroids, including dexamethasone, are a key component of SOC combination regimens 
in MM (Burwick 2019). Dexamethasone induces apoptosis and suppresses protein synthesis in 
MM cell lines in vitro (Chauhan 2002; Burwick 2017). In clinical trials, dexamethasone has been 
shown to increase the activity of several classes of drugs, including alkylating agents, IMiDs, 
and PIs. In addition, dexamethasone is administered as premedication for monoclonal antibodies 
such as daratumumab and elotuzumab (Darzalex and Empliciti prescribing information).  
5.3.2. 
Method of Procurement  
In the US, dexamethasone will be sourced by study sites from commercial supply. In other 
countries, oral dexamethasone will be provided to the study sites by the sponsor or 
dexamethasone (oral or IV) will be sourced by study sites from commercial supply.  
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5.3.3. 
Dose and Administration  
Dexamethasone will be administered on Days 1, 8, 15, and 22 of each 28-day cycle. 
Dexamethasone is administered as an IV infusion or PO at a dose of 40 mg. The dose of 
dexamethasone is 20 mg for subjects ≥75 years, or with BMI <18.5, or known to be intolerant of 
dexamethasone 40 mg. On days when SEA-BCMA is to be administered, dexamethasone should 
be administered 1 to 3 hours prior to the SEA-BCMA infusion. 
 
 
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5.3.4. 
Dose Modifications  
Suggested dose modifications and supportive care by toxicity are listed in Table 6. 
Table 6: 
Recommended dose modifications for dexamethasone-related toxicity 
NCI-CTCAE 
Category 
Toxicity 
Recommended Dose Modification/Supportive Care 
Gastrointestinal 
Grade 1 to 2 dyspepsia, 
gastric or duodenal ulcer, 
gastritis requiring medical 
management  
Treat with a proton pump inhibitor such as omeprazole. 
If symptoms persist, decrease dexamethasone dose by 
50%. 
 
≥ Grade 3 requiring 
hospitalization or surgery 
Hold dexamethasone until symptoms are adequately 
controlled. Then restart at 50% of current dexamethasone 
dose along with concurrent therapy with a proton pump 
inhibitor such as omeprazole. If symptoms persist, 
discontinue dexamethasone and do not resume. 
 
Acute pancreatitis  
Discontinue dexamethasone and do not resume. 
Cardiovascular 
≥ Grade 3 edema limiting 
function and unresponsive to 
therapy or anasarca 
Diuretics as needed and decrease dexamethasone dose by 
25%. If symptoms persist, decrease dose to 50% of initial 
dose. If symptoms continue to persist, discontinue 
dexamethasone and do not resume. 
Neurology/ 
Psychiatric  
≥ Grade 2 confusion or mood 
alteration interfering with 
function  
Hold dexamethasone until symptoms are adequately 
controlled. Restart at 50% of current dose. If symptoms 
persist, discontinue dexamethasone and do not resume. 
Musculoskeletal 
≥ Grade 2 muscle weakness, 
symptomatic and interfering 
with function but not 
interfering with activities of 
daily living 
Decrease dexamethasone dose by 25%. If weakness 
persists, decrease to 50% of initial dose. If symptoms 
continue to persist, discontinue dexamethasone and do 
not resume. 
> Grade 2 muscle weakness, 
symptomatic and interfering 
with activities of daily living 
Hold dexamethasone until muscle weakness is ≤ Grade 1 
or baseline. Then decrease dexamethasone dose by 25% 
and resume. If weakness persists, decrease dose to 50% 
of initial dose. If symptoms continue to persist, 
discontinue dexamethasone and do not resume. 
Metabolica           
≥ Grade 3 hyperglycemia 
Treatment with insulin or oral hypoglycemic agents as 
needed. If symptoms persist, decrease dose by 25% 
decrements until levels are satisfactory. 
Constitutional  
≥ Grade 2 insomnia 
Decrease dexamethasone dose by 50%. 
a Subjects who enter the study with elevated hemoglobin A1c (HbA1c) (≥6.5%) or fasting glucose (≥126 mg/dL) at 
screening must be referred to an appropriate provider for glucose management prior to or within 1 week of starting 
study treatment in Cycle 1. 
NCI-CTCAE = National Cancer Institute’s Common Terminology Criteria for Adverse Events 
Adverse drug reactions to dexamethasone and dexamethasone infusion/hypersensitivity 
reactions (IHRs) should be managed according to the approved package insert. 
5.3.5. 
Storage and Handling  
Refer to the dexamethasone package insert for storage and handling requirements. 
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5.3.6. 
Packaging and Labeling  
Dexamethasone is commercially available in the US. 
5.3.7. 
Preparation  
Dexamethasone should be prepared per the package insert. 
5.4. 
Pomalidomide  
5.4.1. 
Description  
IMiD agents such as thalidomide, lenalidomide, and pomalidomide are commonly used in early 
lines of therapy for MM. IMiDs enhance NK cell expansion and activity and have been shown to 
potentiate ADCC when combined with monoclonal antibodies. Pomalidomide is a thalidomide 
analogue which is approved for the treatment of RRMM in subjects who have failed prior 
lenalidomide therapy.  
5.4.2. 
Method of Procurement  
In the US, pomalidomide will be sourced by study sites from commercial supply.  
5.4.3. 
Dose and Administration  
Pomalidomide will be administered once daily at a dose of 4 mg PO on days 1 to 21 of each 
28-day cycle. On Cycle 1 Day 1, pomalidomide should be administered 1 to 3 hours prior to 
SEA-BCMA infusion, to allow for appropriate timing of PK analysis. Pomalidomide should 
subsequently be taken at approximately the same time each day, and without food (at least 
2 hours before or 2 hours after each meal). The capsules should be swallowed whole with water 
and not opened, broken, or chewed. 
5.4.4. 
Dose Modifications  
Suggested dose modifications and supportive care by toxicity are listed in Table 7. 
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Table 7: 
Recommended dose modifications for pomalidomide-related toxicity 
NCI-CTCAE 
Category 
Toxicity 
Recommended Dose Modification 
Hematologic 
Grade 4 thrombocytopenia, 
each occurrence  
 
 
Withhold pomalidomide treatment and follow complete 
blood count weekly until thrombocytopenia improves to 
≤ Grade 2, then resume pomalidomide at 1 mg less than 
previous dose PO dailya.  
 
Grade 4 neutropenia or any 
grade febrile neutropenia, 
each occurrence  
 
Withhold pomalidomide treatment and follow complete 
blood count weekly until neutropenia improves to 
≤ Grade 2, then resume pomalidomide at 1 mg less than 
previous dose PO dailya.  
Gastrointestinal  
Grade 1 or higher AST or 
ALT elevation, or elevation 
from baseline CTCAE grade  
Withhold pomalidomide treatment until liver enzymes 
return to normal or baseline. Consider resuming 
pomalidomide at 1 mg less than previous dosea.  
Other  
≥ Grade 3 nonhematologic 
toxicity 
Withhold pomalidomide treatment and follow for 
improvement of toxicity to ≤ Grade 2, then resume 
pomalidomide at 1 mg less than previous dose PO daily.  
Permanently discontinue pomalidomide for angioedema, 
anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or any 
other severe dermatologic reaction. 
a If toxicities occur after dose reduction to 1 mg, discontinue pomalidomide.  
ALT = alanine aminotransferase, AST = aspartate aminotransferase, CYP = cytochrome P, NCI-CTCAE = National 
Cancer Institute’s Common Terminology Criteria for Adverse Events, PO = taken orally 
If necessary to coadminister strong inhibitors of CYP1A2 in the presence of strong inhibitors of CYP3A4/5 and 
P-glycoprotein, consider reducing pomalidomide dose by 50%. 
Dose modification guidance is based on pomalidomide prescribing information, which contains additional guidance 
on pomalidomide dosing. 
5.4.5. 
Storage and Handling  
Refer to the pomalidomide package insert for storage and handling requirements. 
5.4.6. 
Packaging and Labeling  
Pomalidomide is commercially available in the US. 
5.4.7. 
Preparation  
Pomalidomide should be prepared per the package insert. 
5.5. 
Required Premedication and Postmedication for SEA-BCMA  
In Parts B through D, routine premedication for infusion reactions must be administered prior to 
SEA-BCMA infusion per the following regimen, unless contraindicated or recommended 
otherwise by the SMC or medical monitor: 
• Antipyretic + Antihistamine: administer approximately 45 to 90 minutes prior to 
SEA-BCMA infusion (required for all subjects for all doses during Cycle 1 and Cycle 2) 
○ Acetaminophen, oral, 650 to 1000 mg 
○ Diphenhydramine, oral or IV, 25 to 50 mg (or equivalent H1 blocker) 
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If no IRR is experienced during Cycle 1 or Cycle 2: one or both premedications may be omitted 
starting with Cycle 3 Day 1 dose. 
If IRR occurs despite acetaminophen + antihistamine, treat with supportive care based on 
symptoms. 
For monotherapy subjects (not receiving dexamethasone), add: 
• Methylprednisolone, IV, 100 mg (or equivalent dosage intermediate to long-acting 
corticosteroid) as required premedication 1 to 3 hours prior to next SEA-BCMA infusion. 
If this infusion is tolerated without IRR, methylprednisolone dose may be reduced to 
60 mg (or equivalent dosage of intermediate to long-acting corticosteroid), administered 
either oral or IV, prior to subsequent doses. 
• Additional premedications (eg, H2 blockers or leukotriene inhibitors) may be considered. 
For combination subjects (receiving dexamethasone), add: 
• H2 blocker (famotidine 40 mg IV or equivalent) as required premedication 45 to 
90 minutes prior to all subsequent SEA-BCMA doses 
• Additional premedications (eg, leukotriene inhibitors) may be considered. 
For management of IRRs, including recommended concomitant therapy, see Section 5.7.1. 
There are no required postmedications for SEA-BCMA. 
For Parts C and D, refer to the dexamethasone package insert for detailed information on 
premedication and postmedication. 
5.6. 
Concomitant Therapy  
All concomitant medications, blood products, and radiotherapy administered will be recorded 
from Day 1 (predose) through the safety reporting period. Any concomitant medication given for 
a study protocol-related AE should be recorded from the time of informed consent. 
5.6.1. 
Required Concomitant Therapy  
Required premedications (prior to study treatment) are described in Section 5.5. Based on 
emerging safety data, the SMC may modify concomitant therapy requirements. 
For Part D, containing pomalidomide, subjects must receive thromboembolic prophylaxis per 
institutional guidelines or the investigator’s discretion. Examples of commonly used 
thromboembolic prophylaxis medications include aspirin, low molecular weight heparin, and 
vitamin K antagonists. 
5.6.2. 
Allowed Concomitant Therapy  
During the DLT period (Cycle 1), growth factor and transfusion support is discouraged unless 
medically indicated; subjects who receive growth factor or transfusion support during this period 
for reasons other than DLT may not be evaluable for DLT, except for in Part D. After the DLT 
period, growth factors or transfusions may be administered according to the revised ASCO 2015 
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guidelines (Smith 2015) (see Table 5). Subjects may receive all other supportive treatments 
according to institutional standards. 
Prophylactic treatment/measures are strongly recommended for subjects at risk for tumor lysis 
syndrome, per institutional standard (eg, treatment with allopurinol or rasburicase, as well as 
adequate hydration (Coiffier 2008). 
Prophylactic anti-infective agents (antiviral, antifungal, or antibacterial) may also be 
administered according to institutional standard. 
Allowed concomitant therapy to prevent or manage IRRs is described in Section 5.7 and 5.7.1. 
Palliative radiotherapy to a single site of disease is allowed with the approval of the medical 
monitor. 
Concomitant prednisone (or equivalent) may be used at a dose of ≤10 mg/day for 
noncancer-related AEs. The use of intermittent high-dose corticosteroid treatment to prevent or 
manage IRRs, other noncancer-related symptoms, or as premedication for radiocontrast for 
imaging or blood product transfusions is allowed. 
Adjuvant therapy for other malignancies that have been definitively treated is allowed. 
Routine prophylaxis with vaccines is permitted, including novel respiratory virus vaccines which 
are approved or available under Emergency Use Authorization; it is recommended that vaccines 
used do not contain live micro-organisms. 
5.6.3. 
Prohibited Concomitant Therapy  
Subjects may not receive other investigational drugs, immunosuppressive medications, 
radiotherapy, or systemic antineoplastic therapy during the study, or within 28 days of first study 
drug dose administration (exceptions noted in Section 4.2 Numbers 10 and 11, and 
Section 5.6.2). 
For Part D, containing pomalidomide, avoid coadministration of pomalidomide with strong 
inhibitors of CYP1A2 unless medically necessary. Coadministration of pomalidomide with drugs 
that are strong inhibitors of CYP1A2 (eg, ciprofloxacin, enoxacin and fluvoxamine) and 
CYP3A4/5 (eg, ketoconazole) or P-gp (eg, amiodarone) could increase pomalidomide exposure 
and should be avoided, unless medically necessary. 
5.7. 
Management of Adverse Reactions  
5.7.1. 
Management of SEA-BCMA Infusion Reactions  
IRRs may occur during the infusion of monoclonal antibody therapies such as SEA-BCMA. The 
infusion should be administered at a site properly equipped and staffed to manage anaphylaxis 
should it occur. All supportive measures consistent with optimal patient care should be given 
throughout the study according to institutional standards. Supportive measures may include 
extending the infusion time and/or administering medications for IRRs. 
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During dose-escalation, additional mitigation strategies may be explored to manage IRRs. These 
may be implemented upon SMC recommendation, and may include but are not limited to any or 
all of the following: 
• Slowing, interruption, or other adjustments in the administration of SEA-BCMA 
• Potential premedication or postmedication for infusions, for example: 
• Antihistamines, such as diphenhydramine 50 mg IV or equivalent and famotidine 40 mg 
IV or equivalent 
• Antipyretics, such as acetaminophen 500 to1000 mg PO 
• Antiemetics, such as ondansetron  
• IV fluid support, such as normal saline 
• Anti-rigor medication, such as meperidine 
• Vasopressors 
• Corticosteroids, such as hydrocortisone 100 mg IV or equivalent or methylprednisolone 
40 mg IV or equivalent (for subjects not receiving dexamethasone as combination 
therapy) 
Required premedication regimen for Parts B through D is provided in Section 5.5. Based on 
emerging safety data, the SMC may modify or omit the premedication regimen as per 
Section 3.1.9.2. Recommendations for the management of IRRs are detailed in Table 8. IRRs 
should be graded according to NCI-CTCAE, v. 4.03, guidelines and per Section 7.7. 
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Table 8: 
Management of infusion-related reactions 
IRR Gradea           
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Mild transient 
reaction; 
SEA-BCMA 
treatment interruption 
not 
indicated; 
intervention not 
indicated 
SEA-BCMA treatment 
interruption indicated but 
responds promptly to 
symptomatic treatment (eg, 
antihistamines, NSAIDs, 
narcotics, IV fluids); 
prophylactic medications 
indicated for ≤24 hr 
Prolonged (eg, not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms 
following initial improvement; 
hospitalization indicated for 
clinical sequelae 
Life threatening 
consequences; 
urgent intervention 
indicated 
Treatment Recommendations 
Monitor vital signs 
more frequently until 
symptoms have 
resolved and subject 
is medically stable. 
Administer 
symptomatic 
treatment as 
medically indicated. 
Hold SEA-BCMA treatment. 
Monitor vital signs more 
frequently until symptoms have 
resolved and subject is 
medically stable. Administer 
symptomatic treatment as 
medically indicated. 
If subject responds promptly and 
is medically stable in the opinion 
of the investigator, SEA-BCMA 
treatment may be continued at a 
slower rate. 
Stop SEA-BCMA treatment. 
Institute additional medical 
management as indicated. 
Consider hospitalization. 
Stop SEA-BCMA 
treatment 
immediately. 
Hospitalization. 
Dose Modifications 
No intervention 
indicated. 
Additional premedication with 
subsequent SEA-BCMA 
treatment per Section 5.5. 
Consider slower infusion rate. If 
recurrent after the above 
measures, consider dose 
reduction to 50% of current dose 
with medical monitor 
consultation. 
Subjects with an IRR that 
resolves to baseline or Grade 1 
or lower within approximately 
2 hours after intervention may 
continue SEA-BCMA at 50% 
of the dose with additional 
premedications per Section 5.5. 
required prior to all subsequent 
doses, if approved by the 
medical monitor.  
OR 
Permanently discontinue from 
study treatment. 
Permanently 
discontinue from 
study treatment. 
a Per NCI-CTCAE version 4.03 
BCMA = B-cell maturation antigen, IRR = infusion-related reaction, IV = intravenous, NCI-CTCAE = National 
Cancer Institute’s Common Terminology Criteria for Adverse Events, NSAIDs = Nonsteroidal anti-inflammatory 
drugs 
If anaphylaxis occurs, administration of SEA-BCMA should be immediately and permanently 
discontinued. 
All Grade 3 or 4 events of IRR (with onset during infusion or within ≤24 hr after infusion) or 
hypersensitivity reaction (with onset occurring >24 hr after infusion) must be reported to the 
sponsor or designee immediately, regardless of relationship to SEA-BCMA. All Grade 4 events 
are serious adverse events (SAEs) and are to be reported within the SAE reporting timeframe of 
24 hours via the standard SAE forms (see Section 7.7.8). 
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Subjects in Part A experiencing a ≥ Grade 3 IRR or delayed hypersensitivity reaction must have 
an IHR visit and an IHR Follow-up visit for evaluation and collection of blood samples for 
analysis of the mechanism of action of the reaction. 
5.8. 
Treatment Compliance  
Study drug administration will be performed by study site staff and documented in source 
documents and the CRF. In the event of an overdose ≥10%, the site should notify the sponsor or 
designee as soon as they are aware of the overdose. 
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6. 
STUDY ACTIVITIES  
6.1. 
Schedule of Events  
AEs and concomitant medications will be recorded from Day 1 (predose) through the safety 
reporting period (see Section 7.7.7). Any study protocol-related AE (defined in Section 7.7.1.1) 
as well as any concomitant medications given for treatment of the AE, should be recorded from 
the time of informed consent. 
All procedures on dosing days must be performed predose within 1 day prior to study drug 
administration unless otherwise specified. Clinical laboratory assessments (serum chemistry 
panel, CBC with differential (manual differential if clinically indicated, see Section 7.7.11), 
urinalysis (with microscopy if results are abnormal), spot urine, physical exam, weight, and 
performance status may be performed within 1 day prior to administration of study drug. The 
results from all relevant clinical laboratory assessments must be reviewed prior to dosing in order 
to determine whether to proceed with dosing or whether dose modification is required. 
Tumor biopsies performed during the study should be made available to the sponsor or designee 
if feasible (see Section 7.5.7). 
The schedules of events are provided in Appendix A. Study activities are listed by visit in this 
section and descriptions of all study assessments are presented in Section 7. 
6.2. 
Part A (Monotherapy Dose-escalation and Expansion)  
6.2.1. 
Screening Visit (Days –28 to 1)  
• Informed consent (Section 10.1) 
• Study eligibility per inclusion/exclusion criteria (Section 4)  
• Medical history (Section 7.1) 
• Serology (hepatitis B, C); if hepatitis C serology is positive, hepatitis C-virus (HCV) 
ribonucleic acid (RNA) test by polymerase chain reaction (PCR) is required to confirm 
• Plasmacytoma evaluation per institutional standard imaging modality in cases of 
suspected or known plasmacytoma (Section 7.1) 
6.2.2. 
Baseline Visit (Days –7 to 1)  
• Weight and height  
• Electrocardiogram (ECG) in triplicate (Section 7.7.14) 
• Physical examination (Section 7.1) 
• ECOG performance status (Section 7.7.15 and Appendix D) 
• Blood and urine samples for local laboratory assessment (Section 7.7.11) 
○ Serum chemistry panel 
○ CBC with differential 
○ Pregnancy test for subjects of childbearing potential 
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○ Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized 
ratio (INR)  
○ Urinalysis (microscopy required if urinalysis results are abnormal) 
○ Urine protein to creatinine ratio (UPCR) calculation; 24-hour urine collection 
required if UPCR >2 mg/mg 
• Disease assessments by local laboratory (Section 7.2) 
○ BM aspirate, including BM aspirate clot, and biopsy (to also be submitted for central 
assessment) (Window Day –10 to 1) 
○ Serum protein electrophoresis (SPEP)/immunofixation  
○ Urine protein electrophoresis (UPEP)/immunofixation (24-hour urine sample) 
○ Serum free light chain (SFLC)  
○ Quantitative immunoglobulins 
○ Beta-2 microglobulin 
○ Skeletal survey (via whole body plain film radiography, or via whole body computed 
tomography [CT] scan, to assess presence and size of lytic bony lesions)  
• Blood sample for Modified SPEP for subjects with IgG myeloma only 
• Blood samples for biomarkers assessments by central laboratory (Appendix B)  
6.2.3. 
Treatment Period  
The treatment period is Day 1 to 28 of each cycle. 
6.2.3.1. 
Day 1 (–1 day)  
If Baseline visit activities occur the day prior to Cycle 1, Day 1, the following assessments do 
not need to be repeated at Cycle 1, Day 1: 
• Physical examination 
• Weight and height 
• ECOG performance status 
• Serum chemistry panel 
• CBC with differential 
• Urinalysis (microscopy required if urinalysis results are abnormal) 
• UPCR calculation via spot urine test; 24-hour urine collection required if 
UPCR >2 mg/mg 
Results from clinical laboratory assessments must be reviewed prior to study drug dosing. 
Subjects must continue to meet eligibility prior to study drug administration on Cycle 1 Day 1. 
At subsequent cycles, dose modifications should be made in accordance with Section 5.2.3 and 
5.7.1. 
• Physical examination including weight 
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• Vital signs (Section 7.7.10):  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○ After completion of study treatment administration:  
− Within 5 minutes 
− 15 minutes after completion of infusion (Cycle 1 only) 
− 30 minutes after completion of infusion (Cycle 1 only) 
− 60 minutes after completion of infusion (Cycle 1 only) 
− 90 minutes after completion of infusion (Cycle 1 only) 
− 120 minutes after completion of infusion (Cycle 1 only) 
− 240 minutes after completion of infusion (Cycle 1 for dose-escalation) 
− 360 minutes after completion of infusion (Cycle 1 for dose-escalation) 
• ECOG performance status  
• Blood and urine samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation; 24-hour urine collection required if UPC >2 mg/mg 
• SEA-BCMA administration (Section 5.2.2) 
• ECG in triplicate (Cycle 1 only) 
• Predose 
○ 30 minutes after completion of infusion 
○ 2 hours after completion of infusion 
○ For infusions <2 hours, 6 hours after completion of infusion 
• Blood samples for PK/ATA/biomarkers assessments by central laboratory (Appendix B)  
6.2.3.2. 
Day 2  
• ECG in triplicate (Cycle 1 only) 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycles 1, 2 and 3; 
Appendix B) 
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6.2.3.3. 
Day 4 (±1 day)  
• ECG in triplicate (Cycle 1 only) 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycles 1, 2 and 3; 
Appendix B) 
6.2.3.4. 
Day 8 (±1 day)  
• ECG in triplicate (Cycle 1 only)  
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycles 1, 2 and 3; 
Appendix B)  
6.2.3.5. 
Day 15 (±1 day)  
• Blood samples for local laboratory assessment  
• CBC with differential 
• Serum chemistry panel 
• Blood samples for PK/biomarkers assessments by central laboratory (Appendix B) 
Laboratory results must be reviewed prior to study drug administration in order to 
determine whether to proceed with dosing or whether dose modification is required. 
• Physical examination including weight 
• ECOG performance status 
• Vital signs:  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○  After completion of study treatment administration:  
− Within 5 minutes 
• ECG in triplicate (Cycle 1 only)  
○ Predose 
○ 30 minutes after completion of infusion  
○ 2 hours after completion of infusion 
• Urine samples for local laboratory assessment  
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○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation via spot urine test  
• SEA-BCMA administration  
6.2.3.6. 
Days 16 and 18  
• Blood samples for PK assessments by central laboratory (Cycle 1 only, for subjects who 
received SEA-BCMA administration at Day 15; Appendix B) 
6.2.3.7. 
Day 22 (±1 day)  
• Response assessments by local laboratory (Day 22 to 28) 
○ BM aspirate, including BM aspirate clot, and biopsy (to be also submitted for central 
assessment) (Window Day 22 to Day 28) (Cycle 2 and at time of suspected CR) 
○ SPEP/immunofixation  
○ UPEP/immunofixation if screening UPEP >200 mg/24 hours or for assessment of 
very good partial response (VGPR) or better 
○ In cases of suspected or known plasmacytoma, plasmacytoma evaluation per 
institutional standard imaging modality should be performed every 4 cycles or to 
confirm a response of PR or better, or as clinically indicated to confirm PD. 
○ SFLC  
○ Quantitative immunoglobulins 
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood sample for Modified SPEP for subjects with IgG myeloma only 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycles 1, 2, 3, and 
at time of suspected CR; Appendix B). When applicable, blood and BM samples must be 
collected on the same day. 
6.2.3.8. 
Day 29  
• Blood samples for PK assessments by central laboratory only for subjects not starting the 
next cycle on Day 29 and not at the EOT visit (Appendix B) 
6.3. 
Part B (Monotherapy Intensive Dosing)  
6.3.1. 
Screening Visit (Days –28 to 1)  
• Informed consent (Section 10.1) 
• Study eligibility per inclusion/exclusion criteria (Section 4) 
• Medical history (Section 7.1) 
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• Serology (hepatitis B, C); if hepatitis C serology is positive, HCV RNA test by PCR is 
required to confirm 
• Plasmacytoma evaluation per institutional standard imaging modality in cases of 
suspected or known plasmacytoma (Section 7.1) 
6.3.2. 
Baseline Visit (Days –7 to Day 1)  
• Weight and height  
• ECG in triplicate (Section 7.7.14) 
• Physical examination (Section 7.1) 
• ECOG performance status (Section 7.7.15 and Appendix D) 
• Blood and urine samples for local laboratory assessment (Section 7.7.11) 
○ Serum chemistry panel 
○ CBC with differential 
○ Pregnancy test for subjects of childbearing potential 
○ PT/PTT/INR  
○ Urinalysis (microscopy required if urinalysis results are abnormal) 
○ UPCR calculation via spot urine test 
• Disease assessments by local laboratory (Section 7.2) 
○ BM aspirate, including BM aspirate clot, and biopsy (to also be submitted for central 
assessment) (Window Day –10 to 1) 
○ SPEP/immunofixation  
○ UPEP/immunofixation (24-hour urine sample required on all subjects regardless of 
presence of measurable disease) 
○ SFLC 
○ Quantitative immunoglobulins 
○ Beta-2 microglobulin 
○ Skeletal survey (via whole body plain film radiography, or via whole body CT scan, 
to assess presence and size of lytic bony lesions)  
• Blood sample for Modified SPEP for subjects with IgG myeloma only 
• Blood samples for biomarkers assessments by central laboratory (Appendix B). 
6.3.3. 
Treatment Period  
The treatment period is Day 1 to 28 of each cycle. 
6.3.3.1. 
Day 1 (–1 day)  
If Baseline visit activities occur the day prior to Cycle 1, Day 1, the following assessments do 
not need to be repeated at Cycle 1, Day 1: 
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• Physical examination 
• Weight and height 
• ECOG performance status 
• Serum chemistry panel 
• CBC with differential 
• Urinalysis (microscopy required if urinalysis results are abnormal) 
• UPCR calculation via spot urine test 
Results from clinical laboratory assessments must be reviewed prior to study drug dosing. 
Subjects must continue to meet eligibility prior to study drug administration on Cycle 1 Day 1. 
At subsequent cycles, dose modifications should be made in accordance with Sections 5.2.3 and 
5.7.1. 
• Physical examination including weight 
• Vital signs (Section 7.7.10):  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○ After completion of study treatment administration:  
− Within 5 minutes 
− 15 minutes after completion of infusion (Cycle 1 only) 
− 30 minutes after completion of infusion (Cycle 1 only) 
− 60 minutes after completion of infusion (Cycle 1 only) 
− 90 minutes after completion of infusion (Cycle 1 only) 
− 120 minutes after completion of infusion (Cycle 1 only) 
• ECOG performance status  
• Blood and urine samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
○ Urinalysis (microscopy required if urinalysis results are abnormal)  
• UPCR calculation via spot urine test 
• Administer premedication approximately 45 to 90 minutes prior to the infusion of 
SEA-BCMA (Section 5.5) 
• SEA-BCMA administration (Section 5.2.2) 
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• ECG in triplicate (Cycles 1, 2, and 3 only) 
○ Predose 
○ 30 minutes after completion of infusion 
• Blood samples for PK/ATA/biomarkers assessments by central laboratory (Appendix B)  
6.3.3.2. 
Day 2  
• Blood samples for PK/biomarkers assessments by central laboratory (Cycle 1 only; 
Appendix B) 
6.3.3.3. 
Day 4  
• Blood samples for PK assessments by central laboratory (Cycle 1 only; Appendix B) 
6.3.3.4. 
Day 8 (±1 day)  
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycle 1 and 2 only; 
Appendix B)  
Cycles 1 and 2 only:  
Laboratory results must be reviewed prior to study drug administration in order to 
determine whether to proceed with dosing or whether dose modification is required. 
• Physical examination including weight 
• ECOG performance status 
• Vital signs:  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○ After completion of study treatment administration:  
− Within 5 minutes 
• ECG in triplicate 
○ Predose 
○ 30 minutes after completion of infusion  
• Urine samples for local laboratory assessment  
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○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation via spot urine test 
• Administer premedication approximately 45 to 90 minutes prior to the infusion of 
SEA-BCMA (Section 5.5) 
• SEA-BCMA administration (Section 5.2.2) 
6.3.3.5. 
Day 15 (±1 day)  
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycles 1, 2, and 3; 
Appendix B) 
Laboratory results must be reviewed prior to study drug administration in order to 
determine whether to proceed with dosing or whether dose modification is required. 
• Physical examination including weight  
• ECOG performance status 
• Vital signs:  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○ After completion of study treatment administration:  
− Within 5 minutes 
• ECG in triplicate (Cycles 1 and 2 only) 
○ Predose 
○ 30 minutes after completion of infusion  
• Urine samples for local laboratory assessment  
○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation via spot urine test  
• Administer premedication approximately 45 to 90 minutes prior to the infusion of 
SEA-BCMA (Section 5.5). 
• SEA-BCMA administration (Section 5.2.2) 
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6.3.3.6. 
Day 22 (±1 day)  
• Response assessments by local laboratory (Day 22 to 28) 
○ BM aspirate, including BM aspirate clot, and biopsy (to be also submitted for central 
assessment) (Window Day 22 to Day 28) (Cycle 2, Cycle 6, every 6 cycles thereafter, 
and at time of suspected CR) 
○ SPEP/immunofixation  
○ UPEP/immunofixation if screening UPEP >200 mg/24 hours or for assessment of 
VGPR or better 
○ In cases of suspected or known plasmacytoma, plasmacytoma evaluation per 
institutional standard imaging modality should be performed every 4 cycles or to 
confirm a response of PR or better, or as clinically indicated to confirm PD. 
○ SFLC  
○ Quantitative immunoglobulins 
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood sample for Modified SPEP for subjects with IgG myeloma only 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycles 1, 2, 6 and 
every 6 cycles thereafter, and at time of suspected CR; Appendix B). When applicable, 
blood and BM samples must be collected on the same day. 
Cycles 1 and 2 only:  
Laboratory results must be reviewed prior to study drug administration in order to 
determine whether to proceed with dosing or whether dose modification is required. 
• Physical examination including weight 
• ECOG performance status 
• Vital signs:  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○ After completion of study treatment administration:  
− Within 5 minutes 
• ECG in triplicate 
○ Predose 
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○ 30 minutes after completion of infusion  
• Urine samples for local laboratory assessment  
○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation via spot urine test 
• Administer premedication approximately 45 to 90 minutes prior to the infusion of 
SEA-BCMA (Section 5.5). 
• SEA-BCMA administration 
6.4. 
Part C (SEA-BCMA plus Dexamethasone)  
6.4.1. 
Screening Visit (Days –28 to 1)  
• Informed consent (Section 10.1) 
• Study eligibility per inclusion/exclusion criteria (Section 4) 
• Medical history (Section 7.1) 
• Serology (hepatitis B, C); if hepatitis C serology is positive, HCV RNA test by PCR is 
required to confirm 
• Plasmacytoma evaluation per institutional standard imaging modality in cases of 
suspected or known plasmacytoma (Section 7.1) 
6.4.2. 
Baseline Visit (Days –7 to Day 1)  
• Weight and height  
• ECG in triplicate (Section 7.7.14) 
• Physical examination (Section 7.1) 
• ECOG performance status (Section 7.7.15 and Appendix D) 
• Blood and urine samples for local laboratory assessment (Section 7.7.11) 
○ Serum chemistry panel 
○ CBC with differential 
○ HbA1c  
− If HbA1c is elevated (≥6.5%), refer subject to appropriate provider prior to or 
within 1 week of starting study treatment in Cycle 1 for glucose management). 
○ Pregnancy test for subjects of childbearing potential 
○ PT/PTT/INR  
○ Urinalysis (microscopy required if urinalysis results are abnormal) 
○ UPCR calculation via spot urine test 
• Disease assessments by local laboratory (Section 7.2) 
○ BM aspirate, including BM aspirate clot, and biopsy (to also be submitted for central 
assessment) (Window Day –10 to 1) 
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○ SPEP/immunofixation  
○ UPEP/immunofixation (24-hour urine sample) 
○ SFLC 
○ Quantitative immunoglobulins 
○ Beta-2 microglobulin 
○ Skeletal survey (via whole body plain film radiography, or via whole body CT scan, 
to assess presence and size of lytic bony lesions)  
• Blood sample for Modified SPEP for subjects with IgG myeloma only 
• Blood samples for biomarkers assessments by central laboratory (Appendix B)  
6.4.3. 
Treatment Period  
The treatment period is Day 1 to 28 of each cycle. 
6.4.3.1. 
Day 1 (–1 day)  
If Baseline visit activities occur the day prior to Cycle 1, Day 1, the following assessments do 
not need to be repeated at Cycle 1, Day 1: 
• Physical examination 
• Weight and height 
• ECOG performance status 
• Serum chemistry panel 
• CBC with differential 
• Urinalysis (microscopy required if urinalysis results are abnormal) 
• UPCR calculation via spot urine test 
Results from clinical laboratory assessments must be reviewed prior to study drug dosing. 
Subjects must continue to meet eligibility prior to study drug administration on Cycle 1 Day 1. 
At subsequent cycles, dose modifications should be made in accordance with Sections 5.2.3 and 
5.7.1. 
• Physical examination including weight 
• Vital signs (Section 7.7.10):  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○ After completion of study treatment administration:  
− Within 5 minutes 
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− 15 minutes after completion of infusion (Cycle 1 only) 
− 30 minutes after completion of infusion (Cycle 1 only) 
− 60 minutes after completion of infusion (Cycle 1 only) 
− 90 minutes after completion of infusion (Cycle 1 only) 
− 120 minutes after completion of infusion (Cycle 1 only) 
• ECOG performance status  
• Blood and urine samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation via spot urine test 
• Dexamethasone administration (1 to 3 hours prior to SEA-BCMA infusion) 
• Administer premedication approximately 45 to 90 minutes prior to the infusion of 
SEA-BCMA (Section 5.5). 
• SEA-BCMA administration (Section 5.2.2) 
• Blood samples for PK/ATA/biomarkers assessments by central laboratory (Appendix B)  
6.4.3.2. 
Day 2  
• Blood samples for PK/biomarkers assessments by central laboratory (Cycle 1; 
Appendix B) 
6.4.3.3. 
Day 4  
• Blood samples for PK/biomarkers assessments by central laboratory (Cycle 1; 
Appendix B) 
6.4.3.4. 
Day 8 (±1 day)  
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood samples for PK/biomarkers assessments by central laboratory (Cohort 1, Cycle 1 
only; Cohort 2, Cycles 1 and 2 only; Appendix B)  
• Dexamethasone administration (1 to 3 hours prior to SEA-BCMA infusion, if applicable) 
Part C Cohort 2, Cycles 1 and 2 only: 
Laboratory results must be reviewed prior to study drug administration in order to 
determine whether to proceed with dosing or whether dose modification is required. 
• Physical examination  
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• ECOG performance status 
• Vital signs:  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○ After completion of study treatment administration:  
− Within 5 minutes 
• Urine samples for local laboratory assessment  
○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation via spot urine test  
• Administer premedication approximately 45 to 90 minutes prior to the infusion of 
SEA-BCMA (Section 5.5). 
• SEA-BCMA administration (Section 5.2.2) 
6.4.3.5. 
Day 15 (±1 day)  
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycles 1, 2, and 3 
only; Appendix B) 
Laboratory results must be reviewed prior to study drug administration in order to 
determine whether to proceed with dosing or whether dose modification is required. 
• Physical examination including weight 
• ECOG performance status 
• Vital signs:  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○ After completion of study treatment administration:  
− Within 5 minutes 
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• Urine samples for local laboratory assessment  
○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation via spot urine test 
• Dexamethasone administration (1 to 3 hours prior to SEA-BCMA infusion) 
• Administer premedication approximately 45 to 90 minutes prior to the infusion of 
SEA-BCMA (Section 5.5). 
• SEA-BCMA administration (Section 5.2.2) 
6.4.3.6. 
Day 22 (±1 day)  
• Response assessments by local laboratory (Day 22 to 28) 
○ BM aspirate, including BM aspirate clot, and biopsy (to be also submitted for central 
assessment) (Cycle 2, Cycle 6, every 6 cycles thereafter, and at time of suspected CR) 
○ SPEP/immunofixation  
○ UPEP/immunofixation if screening UPEP >200 mg/24 hours or for assessment of 
VGPR or better 
○ In cases of suspected or known plasmacytoma, plasmacytoma evaluation should be 
performed per institutional standard imaging modality every 4 cycles or to confirm a 
response of PR or better, or as clinically indicated to confirm PD. 
○ SFLC  
○ Quantitative immunoglobulins 
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood sample for Modified SPEP for subjects with IgG myeloma only 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycles 1, 2, 3, 6, 
and every 6 cycles thereafter, and at time of suspected CR; (Appendix B). When 
applicable, blood and BM samples must be collected on the same day. 
• Dexamethasone administration (1 to 3 hours prior to SEA-BCMA infusion, if applicable) 
Part C Cohort 2 Cycles 1 and 2 only:  
Laboratory results must be reviewed prior to study drug administration in order to 
determine whether to proceed with dosing or whether dose modification is required. 
• Physical examination  
• ECOG performance status 
• Vital signs:  
○ Predose 
○ During the infusion: 
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− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○ After completion of study treatment administration:  
− Within 5 minutes 
• Urine samples for local laboratory assessment  
○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation via spot urine test 
• Administer premedication approximately 45 to 90 minutes prior to the infusion of 
SEA-BCMA (Section 5.5). 
• SEA-BCMA administration (Section 5.2.2) 
6.4.4. 
Qualitative Interview  
Qualitative interview to be conducted within 1 cycle of the time of first OR (PR or better) or 
within 1 cycle of documentation of ongoing SD at the end of Cycle 4, whichever occurs first. See 
the Interview Guide for additional details. Qualitative interviews will be conducted in up to a 
total of 10 subjects from Part C and Part D.  
6.5. 
Part D (SEA-BCMA plus Pomalidomide and Dexamethasone)  
6.5.1. 
Screening Visit (Days -28 to 1)  
• Informed consent (Section 10.1) 
• Study eligibility per inclusion/exclusion criteria (Section 4) 
• Medical history (Section 7.1) 
• Serology (hepatitis B, C); if hepatitis C serology is positive, HCV RNA test by PCR is 
required to confirm 
• Plasmacytoma evaluation per institutional standard imaging modality in cases of 
suspected or known plasmacytoma (Section 7.1) 
• Pregnancy test for subjects of childbearing potential (10 to 14 days prior to planned 
Cycle 1 Day 1) 
6.5.2. 
Baseline Visit (Days -10 to Day 1)  
• Weight and height  
• ECG in triplicate (Section 7.7.14) 
• Physical examination (Section 7.1) 
• ECOG performance status (Section 7.7.15 and Appendix D) 
• Blood and urine samples for local laboratory assessment (Section 7.7.11) 
○ Serum chemistry panel 
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○ CBC with differential 
○ HbA1c  
− If HbA1c is elevated (≥6.5%), refer subject to appropriate provider prior to or 
within 1 week of starting study treatment in Cycle 1 for glucose management) 
○ Pregnancy test for subjects of childbearing potential (within 24 hours prior to planned 
Cycle 1 Day 1) 
○ PT/PTT/INR  
○ Urinalysis (microscopy required if urinalysis results are abnormal) 
○ UPCR calculation via spot urine test 
• Disease assessments by local laboratory (Section 7.2) 
○ BM aspirate, including BM aspirate clot, and biopsy (to also be submitted for central 
assessment) (Window Day –10 to 1) 
○ SPEP/immunofixation  
○ UPEP/immunofixation (24-hour urine sample) 
○ SFLC 
○ Quantitative immunoglobulins 
○ Beta-2 microglobulin 
○ Skeletal survey (via whole body plain film radiography, or via whole body CT scan, 
to assess presence and size of lytic bony lesions)  
• Blood sample for Modified SPEP for subjects with IgG myeloma only 
• Blood samples for biomarkers assessments by central laboratory (Appendix B)  
6.5.3. 
Treatment Period  
The treatment period is Day 1 to 28 of each cycle. 
6.5.3.1. 
Day 1 (–1 day)  
If Baseline visit activities occur the day prior to Cycle 1, Day 1, the following assessments do 
not need to be repeated at Cycle 1, Day 1: 
• Physical examination 
• Weight and height 
• ECOG performance status 
• Serum chemistry panel 
• CBC with differential 
• Urinalysis (microscopy required if urinalysis results are abnormal) 
• UPCR calculation via spot urine test 
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Results from clinical laboratory assessments must be reviewed prior to study drug dosing. 
Subjects must continue to meet eligibility prior to study drug administration on Cycle 1 Day 1. 
At subsequent cycles, dose modifications should be made in accordance with Sections 5.2.3 and 
5.7.1. 
• Pregnancy test for subjects of childbearing potential  
• Physical examination including weight 
• Vital signs (Section 7.7.10):  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○ After completion of study treatment administration:  
− Within 5 minutes 
− 15 minutes after completion of infusion (Cycle 1 only) 
− 30 minutes after completion of infusion (Cycle 1 only) 
− 60 minutes after completion of infusion (Cycle 1 only) 
− 90 minutes after completion of infusion (Cycle 1 only) 
− 120 minutes after completion of infusion (Cycle 1 only) 
• ECOG performance status  
• Blood and urine samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation via spot urine test 
• Dexamethasone administration (1 to 3 hours prior to SEA-BCMA infusion) 
• Pomalidomide administration (1 to 3 hours prior to SEA-BCMA infusion on Cycle 1 
Day 1), and then daily self-administration thereafter on Days 2 to 21 
• Administer premedication approximately 45 to 90 minutes prior to the infusion of 
SEA-BCMA (Section 5.5) 
• SEA-BCMA administration (Section 5.2.2) 
• Blood samples for PK/ATA/biomarkers assessments by central laboratory (Appendix B)  
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6.5.3.2. 
Day 2  
• Blood samples for PK/biomarkers assessments by central laboratory (Cycle 1; 
Appendix B) 
6.5.3.3. 
Day 4  
• Blood samples for PK/biomarkers assessments by central laboratory (Cycle 1; 
Appendix B) 
6.5.3.4. 
Day 8 (±1 day)  
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycle 1; 
Appendix B) 
• Dexamethasone administration (1 to 3 hours prior to SEA-BCMA administration) 
6.5.3.5. 
Day 15 (±1 day)  
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycles 1, 2, and 3 
only; Appendix B) 
Laboratory results must be reviewed prior to study drug administration in order to 
determine whether to proceed with dosing or whether dose modification is required. 
• Pregnancy test for subjects of childbearing potential  
• Physical examination including weight 
• ECOG performance status 
• Vital signs:  
○ Predose 
○ During the infusion: 
− 15 minutes after start of infusion  
− 30 minutes after start of infusion 
− 30 minute intervals during infusion and after any change in rate of infusion 
○  After completion of study treatment administration:  
− Within 5 minutes 
• Urine samples for local laboratory assessment  
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○ Urinalysis (microscopy required if urinalysis results are abnormal)  
○ UPCR calculation via spot urine test 
• Dexamethasone administration (1 to 3 hours prior to SEA-BCMA infusion) 
• Administer premedication approximately 45 to 90 minutes prior to the infusion of 
SEA-BCMA (Section 5.5). 
• SEA-BCMA administration (Section 5.2.2) 
6.5.3.6. 
Day 22 (±1 day)  
• Response assessments by local laboratory (Day 22 to 28) 
○ BM aspirate, including BM aspirate clot, and biopsy (to be also submitted for central 
assessment) (Cycle 2, Cycle 6, every 6 cycles thereafter, and at time of suspected CR) 
○ SPEP/immunofixation  
○ UPEP/immunofixation if screening UPEP >200 mg/24 hours or for assessment of 
VGPR or better 
○ In cases of suspected or known plasmacytoma, plasmacytoma evaluation should be 
performed per institutional standard imaging modality every 4 cycles or to confirm a 
response of PR or better, or as clinically indicated to confirm PD. 
○ SFLC  
○ Quantitative immunoglobulins 
• Blood samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
• Blood sample for Modified SPEP for subjects with IgG myeloma only 
• Blood samples for PK/biomarkers assessments by central laboratory (Cycles 1, 2, 3, 6, 
and every 6 cycles thereafter, and at time of suspected CR; Appendix B). When 
applicable, blood and BM samples must be collected on the same day. 
• Dexamethasone administration (1 to 3 hours prior to SEA-BCMA administration) 
6.5.4. 
Qualitative Interview  
Qualitative interview to be conducted within 1 cycle of the time of first OR (PR or better). See 
the Interview Guide for additional details. Qualitative interviews will be conducted in up to a 
total of 10 subjects from Part C and Part D.  
6.6. 
Complete Response Assessment  
• BM aspirate (and BM biopsy, if available) in subjects with a negative blood and urine 
M-protein (to be submitted for central assessment of markers of drug activity and 
resistance to SEA-BCMA) 
• Blood samples for biomarkers assessments by central laboratory (Appendix B)  
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• 24-hour urine sample for UPEP/immunofixation 
• Plasmacytoma evaluation, per institutional standard imaging modality, for subjects with 
plasmacytomas at baseline 
6.7. 
Evaluation of Infusion/Hypersensitivity Reactions (Part A only)  
Subjects in Part A experiencing a ≥ Grade 3 infusion reaction or delayed hypersensitivity 
reaction must have an IHR visit and an IHR Follow-up visit. 
6.8. 
Infusion/Hypersensitivity Reaction Visit (Part A only)  
For subjects in Part A, if the IHR occurs on the day of infusion, perform the IHR visit that day. If 
a delayed hypersensitivity reaction occurs, the IHR visit should be performed as soon as 
possible, preferably within 24 hours, but not more than 72 hours after occurrence. 
The following assessments will be performed: 
• Physical exam 
• Vital signs 
• Blood and urine samples by local laboratory  
○ CBC with differential 
○ Serum chemistry panel 
○ Urinalysis (microscopy required if urinalysis results are abnormal)  
• Blood sample collection for PK/biomarkers assessments by central laboratory 
(Appendix B) 
Timing of the IHR visit blood draw may overlap with another protocol-defined blood draw (ie, 2 
or 6 hours postdose, or other PK/biomarkers sampling time points). If this occurs, collect blood 
samples for the IHR visit; lab tests for the protocol-defined blood draw do not need to be 
duplicated if they are collected as part of the IHR visit. For example, if the IHR visit takes place 
2 hours postdose, a separate blood draw for the protocol-defined 2-hour postdose PK/biomarkers 
blood draw is not required, because samples for Biomarker analyses will be collected as part of 
the IHR visit. 
Similarly, a subject may experience a delayed hypersensitivity reaction so that the IHR visit 
takes place on Day 8. If this occurs, collect blood samples for the IHR visit. The 
protocol-defined Day 8 local labs (CBC and chemistry panel) do not need to be duplicated 
because they are collected as part of the IHR visit. The central lab Biomarkers blood tests (PK, 
immunophenotyping, cytokine, soluble target and ligands, PBMCs) do not need to be duplicated 
provided they are collected within the protocol-defined PK/biomarkers blood draw window. 
6.9. 
Infusion/Hypersensitivity Reaction Follow-up Visit (24 to 72 hours; Part 
A only)  
For subjects in Part A, the IHR Follow-up visit is scheduled 24-72 hours after the initial IHR 
visit, and the following assessments are performed: 
• Physical exam 
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• Vital signs 
• Blood and urine samples by local laboratory  
○ CBC with differential 
○ Serum chemistry panel 
○ Urinalysis (microscopy required if urinalysis results are abnormal) 
• Blood sample collection for PK/biomarkers assessment by central laboratory 
(Appendix B) 
Timing of the IHR Follow-up visit blood draw may overlap with another protocol-defined blood 
draw. If this occurs, collect blood samples for the IHR Follow-up visit local and central labs as 
required; lab tests for the protocol-defined blood draw do not need to be duplicated if they are 
collected as part of the IHR Follow-up visit. 
6.10. 
End of Treatment Visit (30 to 37 days after last dose of study drug)  
EOT visits should occur 30 to 37 days after the last dose of study drug unless delayed due to an 
AE. Note: EOT evaluations must be performed before initiation of a new therapy. If EOT 
evaluations are completed before 30 days after the last study treatment, the subject will be 
contacted 30 to 37 days following the last treatment to assess for AEs.  
• ECG in triplicate 
• Physical examination  
• ECOG performance status  
• Vital signs  
• Weight 
• Pregnancy test for subjects of childbearing potential 
• Blood and urine samples for local laboratory assessment  
○ CBC with differential 
○ Serum chemistry panel 
○ Urinalysis (microscopy required if urinalysis results are abnormal) 
○ UPCR calculation via spot urine test (only required if not conducted within 4 weeks 
prior to EOT) 
• Response assessments by local laboratory  
○ SFLC  
○ BM aspirate and biopsy, if collected per SOC, or to confirm CR, to be submitted for 
central assessment of markers of drug activity and resistance to SEA-BCMA 
○ SPEP/immunofixation 
○ UPEP/immunofixation 
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○ In cases of suspected or known plasmacytoma, plasmacytoma evaluation, per 
institutional standard imaging modality, should be performed every 4 cycles or to 
confirm a response of PR or better, or as clinically indicated to confirm PD.  
○ Quantitative immunoglobulins 
• Blood sample for Modified SPEP for subjects with IgG myeloma only 
• Blood samples for PK/ATA/biomarkers assessments by central laboratory (Appendix B) 
6.11. 
Follow-up (every 12 weeks ±2 weeks)  
Subjects who discontinue from treatment with SEA-BCMA will remain on the study for 
follow-up until withdrawal of consent, death, or study closure, whichever occurs first.  
The first follow-up visit will occur 12 weeks (±2 weeks) from the most recent prior response 
evaluation. Subsequent follow-up visits will be scheduled for 12 weeks (±2 weeks) from the 
previous follow-up visit. 
Subjects who discontinue treatment due to PD or who have initiated subsequent therapy will not 
be assessed for response but will be followed for survival. Subjects who discontinue treatment 
will continue to be assessed for response after EOT until PD or initiation of a new therapy. These 
subjects will be followed at this schedule until withdrawal of consent, death, or study closure, 
whichever occurs first.  
The following assessments will be performed until disease progression or initiation of 
subsequent therapy; subjects will be followed for survival thereafter. 
• Blood samples for local laboratory assessment (obtain until disease progression or until 
initiation of subsequent anticancer therapy) 
○ CBC with differential 
○ Serum chemistry panel 
• Response assessments by local laboratory  
○ SFLC 
○ SPEP/immunofixation  
○ UPEP/immunofixation if measurable disease in urine 
○ BM aspirate and biopsy (for confirmation of CR) (to be submitted for central 
assessment of markers of response) 
○ In cases of suspected or known plasmacytoma, plasmacytoma evaluation, per 
institutional standard imaging modality, should be performed every 4 cycles or to 
confirm a response of PR or better, or as clinically indicated to confirm PD.  
• Blood sample for Modified SPEP for subjects with IgG myeloma only (to be collected 
only until subsequent therapy is initiated) 
• Survival status and collection of first subsequent anticancer treatment information until 
death or study closure 
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6.12. 
End of Study/End of Follow-up  
The date the subject met criteria for study discontinuation and the reason for study 
discontinuation will be recorded. 
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7. 
STUDY ASSESSMENTS  
7.1. 
Screening/Baseline Assessments  
Only subjects who meet all inclusion and exclusion criteria specified in Section 4 will be 
enrolled in this study. Assessments will begin after obtaining a signed informed consent from the 
subject. 
Subject medical history includes a thorough review of significant past medical history, current 
conditions, any treatment for prior malignancies and response to prior treatment, and any 
concomitant medications. The number of prior lines of therapy will be determined using the 
criteria established by Rajkumar et al. (Rajkumar 2015). In brief: 
• If a treatment regimen is discontinued for any reason and a different treatment regimen is 
started, it is considered a new line of therapy 
• A new line of therapy is also considered to start when an unplanned substitution or 
addition of 1 or more drugs is made to an existing course of therapy for any reason 
• In subjects undergoing >1 ASCT (except in the case of a planned tandem ASCT), each 
transplant that follows the first one should be considered a new line of therapy 
• A planned course of therapy that has multiple phases, such as induction therapy followed 
by the first ASCT and maintenance therapy, is considered to be a single line of therapy. 
A baseline plasmacytoma scan, per institutional standard imaging modality, is conducted during 
screening only in cases of suspected or known plasmacytoma. During treatment, plasmacytoma 
evaluations can be performed at any time to confirm a response of PR or better, or as clinically 
indicated to confirm PD.  
BM aspirate (including a BM aspirate clot) and biopsy are required as part of the baseline visit 
(Appendix A and Section 7.2). 
Physical examinations should include assessments of the following body parts/systems: 
abdomen, extremities, head, heart, lungs, neck, and neurological. Weight and height will also be 
measured; measurements of height obtained within the prior 12 months may be utilized 
(Section 7.7.12).  
Blood and urine tests will include CBC with differential, serum chemistry panel, serology 
(hepatitis B and C), PT/PTT/INR, HbA1c (for subjects in Part C) and urinalysis. A pregnancy 
test will be conducted for subjects of childbearing potential (Section 4.3). Urinalysis with 
microscopy is required if urinalysis results are abnormal; UPCR calculation is also required. 
Further details of these tests are provided in Section 7.7.11. 
Blood samples will be collected for pharmacodynamic biomarker assessments by the central 
laboratory.  
7.2. 
Response/Efficacy Assessments  
Response assessment includes SPEP/immunofixation, UPEP/immunofixation (in subjects with a 
baseline urine M-protein ≥200 mg/24 hour or for assessment of VGPR or better), SFLC, 
quantitative immunoglobulins, and plasmacytoma evaluation, per institutional standard imaging 
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modality (at baseline, every 4 cycles, and at additional timepoints if clinically indicated). These 
samples will be collected for local assessment at the times provided in Appendix A. In addition, 
blood will be analyzed in the central laboratory using a modified SPEP for subjects with IgG 
myeloma. 
BM aspirate, including a BM aspirate clot, and biopsy are required as part of the baseline visit, 
Day 22 to 28 of Cycle 2, and to confirm CR in subjects negative for blood and urine M-protein. 
In Part B, Part C, and Part D, BM aspirate and biopsy are also required in Cycle 6 and every 6 
cycles thereafter. Both BM aspirate and biopsy samples will be assessed locally at the site for 
clinical evaluation. In addition, biomarker analyses will be performed centrally on these samples 
(see Section 7.5). Any additional BM aspirates and biopsies collected at any other time while on 
the trial may also be submitted for central assessment.  
The BM specimens will be tested centrally for assessment of response/resistance to SEA-BCMA 
and may include but are not limited to: evaluation of BCMA expression, immune activation, 
disease risk profiling, gene expression profiling, and MRD assessment. 
The determination of antitumor activity will be based on response assessments made according 
to the 2016 IMWG Criteria (Kumar 2016) (see Appendix J). Treatment decisions by the 
investigator will be based on these assessments. Clinical response of stringent complete response 
(sCR), CR, VGPR, PR, SD, and PD will be determined at each assessment based on local 
laboratory (and the modified SPEP run by the central laboratory for subjects with IgG MM), 
radiological, and clinical evaluations. PD is based on IMWG 2016 criteria and/or clinical disease 
progression per investigator. All IMWG responses must be confirmed responses. When 
applicable, determination of immunophenotypic CR, MRD status, and minimal response will be 
made per the IMWG 2016 criteria. 
Subjects’ clinical data must be available for CRF source verification. Copies of tumor images 
must be made available for review by the sponsor (or its designee), upon request. 
7.3. 
Qualitative Interviews  
Up to a total of 10 subjects in Parts C and D will be interviewed within 1 cycle of the time of 
first OR (PR or better) or ongoing SD at the end of Cycle 4 (Part C only). See the Interview 
Guide for additional details.  
7.4. 
Pharmacokinetic and Immunogenicity Assessments  
Blood and BM samples for PK and ATA assessment will be collected at time points outlined in 
Appendix B. In Parts C and D, additional PK samples will be collected and archived for possible 
analysis of concentrations of combination drugs. 
Qualified assays will be used to measure concentrations of SEA-BCMA in serum and BM and 
ATA in serum. Remaining PK samples will be archived for possible analysis of SEA-BCMA 
related species. The assays will include enzyme-linked immunosorbent assays (ELISA) assay, as 
well as other assays if further characterization is required.  
A qualified electrochemiluminescence assay will be used to assess ATA. 
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7.5. 
Biomarker Studies  
Peripheral blood and BM samples for biomarker analyses will be collected at time points 
outlined in Appendix B. In addition to protocol-mandated collections of tumor specimens, BM 
specimens collected at the discretion of the investigator may be submitted for central biomarkers 
analysis. For all BM collections, sites will supply BM aspirates as well as BM biopsy specimens 
and BM aspirate clot specimens as formalin-fixed, paraffin-embedded (FFPE) blocks. For 
samples acquired for SOC, unstained slides may be submitted if an FFPE block for the BM 
biopsy or clot are not available. Samples will be sent to the central lab for analysis as described 
in the laboratory manual. 
Samples will be evaluated for expression of BCMA and relevant biomarkers that may be 
associated with the activity of SEA-BCMA and/or change in response to treatment. Analysis of 
tumor tissue and peripheral blood may also include markers associated with prognosis, response, 
or resistance. Changes in peripheral blood immune cell subsets will be measured as potential 
pharmacodynamic and safety markers. 
7.5.1. 
Genetic profiling of effector cells  
Single nucleotide polymorphisms of FcγRIIA and FcγRIIIA, which may influence the response 
to SEA-BCMA, may be determined, including, but not limited to, testing of the following 
polymorphisms: 
• FcγRIIIA – 158V/F 
• FcγRIIA – 131H/R 
7.5.2. 
Serum Free Light Chain and modified SPEP  
Kappa and Lambda FLCs will be quantified in serum of subjects as surrogate markers of 
antitumor activity. 
For subjects with IgG myeloma who have low levels of serum M-protein SPEP, a reflex 
modified SPEP assay will be used to assess for residual serum M-protein in the absence of 
interference from SEA-BCMA. 
7.5.3. 
Peripheral blood immunophenotyping  
Peripheral blood samples will be collected for evaluation of circulating immune cells by flow 
cytometry. Changes in circulating immune cell subsets will be measured as potential 
pharmacodynamic markers of SEA-BCMA activity. Flow cytometry measurements will include, 
but not be limited to, characterizing NK cells, monocytes, T-cells, and B-cells. 
7.5.4. 
Plasma cytokines/chemokines  
The levels of circulating cytokines/chemokines may be assessed by ELISA and/or multiplex 
cytokine/chemokines assays. 
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7.5.5. 
Soluble target and ligands  
The levels of circulating sBCMA, APRIL and BAFF may be assessed by ELISA or other 
methods (eg, LC-MS or flow cytometry). 
7.5.6. 
Plasma Biomarkers and PBMCs  
Plasma and PBMCs will be collected for retrospective analyses of cellular and circulating 
biomarkers associated with response and/or resistance to SEA-BCMA.  
7.5.7. 
Characterization of Tumor Tissue  
Baseline and on-treatment BM aspirates and biopsies will be collected to assess disease relevant 
immune subsets, characterize tumor burden, investigate depth of response and determine 
prognostic signatures and response to treatment. Additional protein, gene expression profiling, as 
well as further molecular characterization of the tumor for myeloma disease relevant risk 
markers, may also be evaluated to identify biomarkers predictive of response or resistance to 
SEA-BCMA. 
7.5.7.1. 
Bone marrow immunophenotyping  
Expression of BCMA on tumor plasma cells, as well as presence and changes of immune 
components in the BM, may be evaluated by flow cytometry and/or immunohistochemistry. 
7.5.7.2. 
Gene Expression Profiling/NGS/FISH  
Baseline and treatment-related changes in gene expression profiles in tumor and tumor 
microenvironment may be assessed by RNA sequencing of tumor (CD138-positive) and 
nontumor (CD138-negative) cells purified from BM aspirates, to determine prognostic 
disease-risk signatures as well as baseline characteristics and on-treatment changes that may 
correlate with response or resistance. Cytogenetic analyses or DNA sequencing of 
CD138-positive plasma cells enriched from BM aspirate collected at Baseline may also be 
carried out to further determine genetic changes that may predict or be associated with response 
to SEA-BCMA. 
7.5.7.3. 
MRD  
MRD evaluation using the Adaptive next generation sequencing (NGS) for MRD assay 
(Martinez-Lopez 2014) may be carried out on relevant specimens to understand the activity of 
SEA-BCMA. 
7.5.7.4. 
Bone marrow plasma  
BM plasma will be collected and may be tested for levels of soluble target, ligands, and/or 
cytokines/chemokines that may influence or correlate with response to SEA-BCMA. 
7.6. 
Biospecimen Repository  
In the US only, for subjects who provide additional consent, remaining de-identified unused 
blood and/or tissue will be retained by Seagen and used for future research, including but not 
limited to the evaluation of targets for novel therapeutic agents, the biology of sensitivity and 
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resistance mechanisms to SEA-BCMA, and the identification of biomarkers of MM disease and 
response/resistance to therapy. Blood, BM, and tissue samples donated for future research will be 
retained for a period of up to 25 years. If additional consent is not provided, any remaining 
biological samples will be destroyed after the study has been completed and all applicable 
regulatory obligations have been met. 
7.7. 
Safety Assessments  
The assessment of safety during the course of this study will consist of the surveillance and 
recording of AEs including SAEs, recording of concomitant medication, and measurements of 
protocol-specified physical examination findings and laboratory tests. 
Safety will be monitored as described in Section 9.3.9 over the course of the study by the SMC. 
7.7.1. 
Adverse Events  
7.7.1.1. 
Definitions  
Adverse Event  
According to the International Council for Harmonisation (ICH) E2A guideline Definitions and 
Standards for Expedited Reporting, and 21 CFR 312.32, IND Safety Reporting, an AE is any 
untoward medical occurrence in a subject or clinical investigational subject administered a 
medicinal product and which does not necessarily have a causal relationship with this treatment. 
The following information should be considered when determining whether or not to record a 
test result, medical condition, or other incident on the Adverse Events CRF: 
• From the time of informed consent through the day prior to study Day 1, only study 
protocol-related AEs should be recorded. A protocol-related AE is defined as an 
untoward medical event occurring as a result of a protocol-mandated procedure. 
• All medical conditions present or ongoing predose on study Day 1 should be recorded. 
• All AEs (regardless of relationship to study drug) should be recorded from study Day 1 
predose through the end of the safety reporting period (see Section 7.7.7). Complications 
that occur in association with any procedure (eg, biopsy) should be recorded as AEs 
whether or not the procedure was protocol-mandated. 
• Changes in medical conditions and AEs, including changes in severity, frequency, or 
character, during the safety reporting period should be recorded. 
• In general, an abnormal laboratory value should not be recorded as an AE unless it is 
associated with clinical signs or symptoms, requires an intervention, results in a SAE, or 
results in study termination or interruption/discontinuation of study treatment. When 
recording an AE resulting from a laboratory abnormality, the resulting medical condition 
rather than the abnormality itself should be recorded (eg, record “anemia” rather than 
“low hemoglobin”). 
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7.7.2. 
Serious Adverse Events  
An AE should be classified as an SAE if it meets one of the following criteria: 
Fatal: 
AE resulted in death 
Life threatening: 
The AEs placed the subject at immediate risk of death. This classification 
does not apply to an AE that hypothetically might cause death if it were more 
severe. 
Hospitalization: 
The AE resulted in hospitalization or prolonged an existing insubject 
hospitalization. Hospitalizations for elective medical or surgical procedures or 
treatments planned before the signing of informed consent in the study or 
routine check-ups are not SAEs by this criterion. Admission to a palliative 
unit or hospice care facility is not considered to be a hospitalization. 
Hospitalizations or prolonged hospitalizations for scheduled therapy of the 
underlying cancer or study target disease need not be captured as SAEs. 
Disabling/ 
incapacitating: 
An AE that resulted in a persistent or significant incapacity or substantial 
disruption of the subject’s ability to conduct normal life functions. 
Congenital anomaly 
or birth defect: 
An adverse outcome in a child or fetus of a subject exposed to the molecule or 
study treatment regimen before conception or during pregnancy. 
Medically significant: 
The AE did not meet any of the above criteria but could have jeopardized the 
subject and might have required medical or surgical intervention to prevent 
one of the outcomes listed above or involves suspected transmission via a 
medicinal product of an infectious agent. Potential drug-induced liver injury 
(DILI) also is considered a medically significant event (see Section 7.7.3.2 for 
the definition of potential DILI) 
AE = adverse event, DILI = drug-induced liver injury, SAE = serious adverse event 
7.7.3. 
Adverse Event Severity  
AE severity should be graded using the NCI-CTCAE, v. 4.03. These criteria are provided in the 
study manual. 
AE severity and seriousness are assessed independently. ‘Severity’ characterizes the intensity of 
an AE. ‘Serious’ is a regulatory definition and serves as a guide to the sponsor for defining 
regulatory reporting obligations (see definition for SAEs above). 
7.7.3.1. 
Relationship of the Adverse Event to Study Treatment  
The relationship of each AE to each study treatment (SEA-BCMA, and/or dexamethasone, 
and/or pomalidomide) should be evaluated by the investigator using the following criteria: 
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Related: 
There is evidence to suggest a causal relationship between the drug and the 
AE, such as: 
• 
A single occurrence of an event that is uncommon and known to be 
strongly associated with drug exposure (eg, angioedema, hepatic 
injury, Stevens-Johnson Syndrome) 
• 
One or more occurrences of an event that is not commonly associated 
with drug exposure, but is otherwise uncommon in the population 
exposed to the drug (eg, tendon rupture) 
Unrelated: 
Another cause of the AE is more plausible (eg, due to underlying disease or 
occurs commonly in the study population), or a temporal sequence cannot be 
established with the onset of the AE and administration of the study treatment, 
or a causal relationship is considered biologically implausible 
7.7.3.2. 
Procedures for Eliciting and Recording Adverse Events  
Investigator and study personnel will report all AEs and SAEs whether elicited during subject 
questioning, discovered during physical examination, laboratory testing and/or other means by 
recording them on the CRF and/or SAE form, as appropriate. 
Eliciting Adverse Events  
An open-ended or nondirected method of questioning should be used at each study visit to elicit 
the reporting of AEs. 
Recording Adverse Events  
The following information should be recorded on the Adverse Events CRF: 
• Description including onset and resolution dates 
• Whether it met SAE criteria 
• Severity 
• Relationship to study treatment or other causality 
• Outcome 
Diagnosis vs Signs or Symptoms  
In general, the use of a unifying diagnosis is preferred to the listing out of individual symptoms. 
Grouping of symptoms into a diagnosis should only be done if each component sign and/or 
symptom is a medically confirmed component of a diagnosis as evidenced by standard medical 
textbooks. If any aspect of a sign or symptom does not fit into a classic pattern of the diagnosis, 
report the individual symptom as a separate AE. 
Adverse reactions associated with the infusion of study drug may occur in this study. For IHRs, 
record the NCI-CTCAE terms of ‘infusion-related reaction,’ ‘allergic or hypersensitivity 
reaction,’ ‘cytokine release syndrome,’ or ‘anaphylaxis’ with an overall level of severity (per 
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NCI-CTCAE v. 4.03). In addition, record each sign or symptom of the reaction as an individual 
AE. If multiple signs or symptoms occur with a given infusion-related event, each sign or 
symptom should be recorded separately with its level of severity. 
Recording Serious Adverse Events  
For SAEs, record the event(s) on both the CRF and an SAE form. 
The following should be considered when recording SAEs: 
• Death is an outcome of an event. The event that resulted in the death should be recorded 
and reported on both an SAE form and CRF. 
• For hospitalizations, surgical, or diagnostic procedures, the illness leading to the surgical 
or diagnostic procedure should be recorded as the SAE, not the procedure itself. The 
procedure should be captured in the narrative as part of the action taken in response to the 
illness. 
7.7.4. 
Progression of the Underlying Malignancy  
Since progression of underlying malignancy is being assessed as an efficacy variable, it should 
not be reported as an AE or SAE. The terms “Disease Progression”, “Progression of Disease” or 
“Malignant disease progression” and other similar terms should not be used to describe an AE or 
SAE. However, clinical symptoms of progression may be reported as AEs or SAEs if the 
symptom cannot be determined as exclusively due to progression of the underlying malignancy 
or does not fit the expected pattern of progression for the disease under study. In addition, 
complications from progression of the underlying malignancy should be reported as AEs or 
SAEs. 
7.7.5. 
Pregnancy  
7.7.5.1. 
Notification to Drug Safety  
Complete a Pregnancy Report Form for all pregnancies that occur from the time of first study 
drug dose until 6 months after the last dose of study drug(s) including any pregnancies that occur 
in the partner of a study subject who is able to father a child. Only report pregnancies that occur 
in a subject’s partner if the estimated date of conception is after the subject’s first study drug 
dose. Email or fax to the sponsor’s Drug Safety Department within 24 hours of becoming aware 
of a pregnancy. As part of the study, all pregnancies will be monitored for the full duration and 
all perinatal and neonatal outcomes should be reported. Infants should be followed for a 
minimum of 8 weeks. 
7.7.5.2. 
Collection of data on the CRF  
All pregnancies (as described above) that occur within 30 days of the last dose of study drug(s) 
will also be recorded on the Adverse Events CRF. 
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Abortion, whether accidental, therapeutic, or spontaneous, should be reported as an SAE. 
Congenital anomalies or birth defects, as defined by the ‘serious’ criterion above (see definitions 
Section 7.7.1.1) should be reported as SAEs. 
7.7.6. 
Potential Drug-Induced Liver Injury  
The observation of the critical importance of altered liver function has been referred to 
informally as Hy’s Law (Reuben 2004). Hy’s Law can be used to estimate severity and the 
likelihood that a study drug may cause an increased incidence of severe hepatotoxicity. 
The absence of hepatotoxicity in clinical trials provides a limited predictive value for potential 
hepatotoxicity in the clinical setting(s) being studied. However, finding 1 Hy’s Law case in 
clinical trials is ominous; finding 2 cases is highly predictive of a potential for severe DILI. 
7.7.6.1. 
Definition  
Briefly, potential Hy’s Law cases include the following 3 components: 
1. 
Aminotransferase (ALT and/or AST) elevation >3 x ULN 
AND 
2. 
Total bilirubin >2 x ULN, without initial findings of cholestasis (ie, elevated serum 
alkaline phosphatase), 
AND 
3. 
No other immediately apparent possible causes of aminotransferase elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, pre-existing chronic or 
acute liver disease, or the administration of other drug(s) known to be hepatotoxic. 
7.7.6.2. 
Reporting Requirements  
Any potential Hy’s Law case should be handled as an SAE associated with the use of the 
drug and reported promptly to the Sponsor. 
Reporting should include all available information and should initiate close follow-up until 
complete resolution of the problem and completion of all attempts to obtain supplementary data. 
7.7.6.3. 
Follow-up for Abnormal Laboratory Results Suggesting Potential DILI  
In general, an increase of serum ALT or AST to >3 x ULN should be followed by repeat testing 
within 48 to 72 hours of serum ALT, AST, alkaline phosphatase, and total bilirubin, to confirm 
the abnormalities and to determine whether they are worsening. 
Appropriate medical assessment should be initiated to investigate potential confounding factors 
and alternative causes of hepatotoxicity. During this investigation, study drug should be 
withheld. 
Regional guidelines should be followed. Additional information is provided in FDA Guidance 
for Industry, DILI: Premarketing Clinical Evaluation, 2009 and Health Canada Guidance 
Document; Pre-market Evaluation of Hepatotoxicity in Health Products, 2012. 
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7.7.7. 
Reporting Periods for Adverse Events, and Serious Adverse Events  
The safety reporting period for all AEs, and SAEs is from study Day 1 (predose) through the 
EOT visit or 30 days after the last study treatment, whichever is later. However, all study 
protocol-related AEs are to be recorded from the time of informed consent. All SAEs that occur 
after the safety reporting period and are considered study treatment-related in the opinion of the 
investigator should also be reported to the sponsor. 
SAEs will be followed until significant changes return to baseline, the event stabilizes 
(recovering/resolving) or is no longer considered clinically significant by the investigator, or the 
subject dies or withdraws consent. All nonserious AEs will be followed through the safety 
reporting period. Certain nonserious AEs of interest may be followed until resolution, return to 
baseline, or study closure. 
7.7.8. 
Serious Adverse Events Require Immediate Reporting  
Within 24 hours of observing or learning of an SAE, investigators are to report the event to the 
sponsor, regardless of the relationship of the event to the study treatment regimen. 
For initial SAE reports, available case details are to be recorded on an SAE form. At a minimum, 
the following should be included: 
• Subject number 
• Date of event onset 
• Description of the event 
• Study treatment, if known 
• Investigator causality assessment 
The completed SAE form and SAE Fax Cover Sheet are to be emailed or faxed to the sponsor’s 
Drug Safety Department within 24 hours (see email or fax number specified on the SAE report 
form) unless otherwise instructed on the sponsor's SAE form.  
Relevant follow-up information is to be submitted to the sponsor as soon as it becomes available. 
7.7.9. 
Sponsor Safety Reporting to Regulatory Authorities  
Investigators are required to report all SAEs to the sponsor (see Section 7.7.8). 
The sponsor will report all SAEs, including suspected unexpected serious adverse reactions 
(SUSARs) to regulatory authorities as required per local regulatory reporting requirements. 
7.7.10. 
Vital Signs  
Vital signs measures are to include heart rate, blood pressure, and temperature. There is a 
5-minute window to perform vital sign collection at the timepoints identified in Section 6. 
7.7.11. 
Clinical Laboratory Tests  
Samples will be drawn for central and local labs. Local laboratory testing will include 
institutional standard tests for evaluating safety and making clinical decisions. The following 
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laboratory assessments will be performed by the local lab to evaluate safety at scheduled time 
points (see Appendix A) during the course of the study: 
• The chemistry panel is to include the following tests: albumin, alkaline phosphatase, 
ALT, AST, blood urea nitrogen, calcium, creatinine, chloride, lactate dehydrogenase, 
phosphorus, potassium, sodium, glucose, total bilirubin, and uric acid.  
• The CBC with differential is to include the following tests: white blood cell count with 
5-part differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), 
platelet count, hemoglobin, and hematocrit.  
• The eGFR should be calculated using the MDRD equation as applicable, with serum 
creatinine (Scr) reported in mg/dL.  
GFR (mL/min/1.73 m2) = 175 x (Scr)–1.154 x (Age)–0.203 x (0.742 if female) x 
(1.212 if African American) 
• Urinalysis 
○ Standard urinalysis (Note: specify ± reflexive microscopy) 
○ Urine protein and urine creatinine for UPCR via spot urine test 
• A serum or urine β-hCG pregnancy test for subjects of childbearing potential 
• PT, PTT, INR 
• Serology will include assessments of Hepatitis B and C status. If hepatitis C serology is 
positive, HCV RNA test by PCR is required to confirm.  
7.7.12. 
Physical Examination  
Physical examinations should include assessments of the following body parts/systems: 
abdomen, extremities, head, heart, lungs, neck, and neurological. Measurements of height 
obtained within the prior 12 months may be utilized. 
7.7.13. 
Pregnancy Testing  
For subjects of childbearing potential, a serum or urine β-hCG pregnancy test with sensitivity of 
at least 25 mIU/mL will be performed at baseline, within 7 days prior to Day 1 of each treatment 
cycle, and at the EOT visit in Parts A, B, and C. In Part D (containing pomalidomide), a 
pregnancy test will be performed 10 to 14 days prior to planned Cycle 1 Day 1, within 24 hours 
prior to planned Cycle 1 Day 1, q2wk during study treatment (prior to Day 1 and Day 15 dosing), 
and at the EOT visit. A negative pregnancy result is required before the subject may receive 
study drug. Pregnancy tests may also be repeated as requested per institutional review 
board/independent ethics committee (IRB/IEC) or if required by local regulations. 
7.7.14. 
Electrocardiograms  
Subjects will be monitored for changes in cardiac repolarization through assessment of ECGs 
conducted in triplicate at times outlined in Appendix A and Section 6. There is a 30-minute 
window to perform ECGs. Waiting periods between replicate ECGs are not required. 
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7.7.15. 
ECOG Performance Status  
ECOG performance status (Appendix D) will be evaluated at protocol-specific time points 
defined in Appendix A and Section 6. 
7.8. 
Appropriateness of Measurements  
The safety measures that will be used in this trial are considered standard procedures for 
evaluating the potential adverse effects of study medications. 
Response will be assessed according to 2016 IMWG, which are standardized criteria for 
evaluating response in MM (Kumar 2016). The intervals of evaluation in this protocol are 
considered appropriate for disease management. 
Immunogenicity is commonly assessed for biologics; therefore, standard tests will be performed 
to detect the possible presence of specific antibodies to SEA-BCMA. PK assessments are also 
common in clinical studies to help characterize dose-exposure-response relationships. 
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8. 
DATA QUALITY CONTROL AND QUALITY ASSURANCE  
8.1. 
Site Training and Monitoring Procedures  
A study manual with instructions for study compliance and CRF completion will be provided. 
Prior to the enrollment of subjects at the site, Seagen or its designated clinical and medical 
personnel will review the following items with the investigator and clinic staff: 
• The protocol, study objectives, eligibility requirements, study procedures, registration 
and withdrawal processes 
• Current IB/package insert 
• Recording and reporting AEs and SAEs 
• Enrollment goals and study timelines 
• The CRF completion process and source documentation requirements 
• Monitoring requirements 
• IRB/IEC review and approval process 
• Informed consent process 
• Good clinical practice guidelines and related regulatory documentation requirements 
• Key study team roles and responsibilities 
• Investigational product storage, accountability, labeling, dispensing and record keeping 
• Subject coding and randomization (if applicable) 
• Study samples/specimen collection, handling and shipping 
• Protocol compliance 
• Clinical study record keeping, document retention, and administrative requirements 
Monitoring visits will occur periodically, with frequency dependent on the rate of enrollment and 
workload at each site. During monitoring visits, the Seagen representative will typically review 
regulatory documentation, CRFs, source documentation, and investigational product storage, 
preparation, and accountability. The CRFs will be reviewed for completeness, adherence to the 
provided guidelines, and accuracy compared to the source documents. The investigators must 
ensure that the monitor is allowed to inspect all source documents pertinent to study subjects and 
must cooperate with the monitor to ensure that any problems noted in the course of the trial are 
resolved. The investigator must maintain a comprehensive and centralized filing system of all 
study-related documentation that is suitable for inspection by Seagen or its designated monitors 
and by quality assurance auditors, or representatives of regulatory authorities. 
8.2. 
Data Management Procedures  
Seagen will provide CRF Completion Guidelines for eCRF data entry. Study specific data 
management procedures will be maintained in the data management plan. Queries resulting from 
edit checks and/or data verification procedures will be posted electronically in the eCRF. 
8.3. 
Access to Source Data  
The investigator will permit the sponsor’s representatives to monitor the study as frequently as 
the sponsor deems necessary to determine that protocol adherence and data recording are 
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satisfactory. Appropriate measures to protect subject confidentiality are to be employed during 
monitoring. The CRFs and related source documents will typically be reviewed in detail by the 
monitor at each site visit. Original source documents or certified copies are needed for review. 
This review includes inspection of data acquired as a requirement for participation in this study 
and other medical records as required to confirm that the information contained in the CRFs, 
such as disease assessments, AEs, and concomitant medications, is complete and correct. Other 
study records, such as correspondence with the sponsor or its designee and the IRB/IEC and 
screening and drug accountability logs will also be inspected. All source data and study records 
must also be available for inspection by representatives of regulatory authorities and the 
IRB/IEC. 
8.4. 
Accuracy and Reliability of Data  
Steps to be taken to assure the accuracy and reliability of data include: 
• The selection of qualified investigators and appropriate study centers. 
• Review of protocol procedures with the investigators and associated personnel prior to 
the study. 
• Periodic monitoring visits by the designated monitor(s). 
• CRFs will be reviewed for accuracy and completeness during monitoring visits to the 
study centers and/or by centralized monitoring. Any discrepancies will be resolved with 
the investigator or designees as appropriate. 
8.5. 
Quality Assurance Procedures  
The Research and Development Quality group or its designee may conduct audits at the clinical 
site or other study-related facilities and organizations. Audit reports will be retained by the 
Research and Development Quality group of Seagen as part of the written record. 
8.6. 
Data Handling and Record Keeping  
8.6.1. 
Data Handling  
It is the investigator’s responsibility to ensure the accuracy, completeness, legibility, and 
timeliness of the data reported to the sponsor in the CRFs and in all required reports. Data 
reported on the CRF that is derived from source documents should be consistent with the source 
documents or the discrepancies should be explained. 
Any change or correction to a CRF will be maintained in an audit trail within the electronic data 
capture system. Data changes may only be made by those individuals so authorized. The 
investigator should retain records of the changes and corrections, written and/or electronic. 
8.6.2. 
Investigator Record Retention  
The investigator shall retain study drug disposition records and all source documentation (such 
as original ECG tracings, laboratory reports, inpatient or office patient records) for the maximum 
period required by the country and institution in which the study will be conducted, or for the 
period specified by Seagen, whichever is longer. The investigator must contact Seagen prior to 
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destroying any records associated with the study. If the investigator withdraws from the study 
(due to relocation, retirement, etc.), the records shall be transferred to a mutually agreed upon 
designee, such as another investigator or IRB/IEC. Notice of such transfer will be provided in 
writing to Seagen. 
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9. 
DATA ANALYSIS METHODS  
9.1. 
Determination of Sample Size  
Up to approximately 131 subjects are expected to be enrolled in this study. This number is based 
on the following assumptions: 
• Up to approximately 45 subjects will be evaluated in Part A (monotherapy dose- 
escalation and expansion; q2wk dosing). 
With the mTPI study design, the exact number of subjects needed to complete the 
dose-escalation portion of the phase 1 study is unknown because it depends on the 
number of cohorts required to reach MTD and the number of subjects enrolled in each 
cohort. This number is based on the assumption that approximately 25 subjects will be 
evaluated in dose-escalation and that approximately 20 subjects will be evaluated in an 
expansion cohort at the MTD or optimal dose to further define the safety and antitumor 
activity of SEA-BCMA. 
Operating characteristics of the dose-escalation part of the study, including the average 
number of subjects allocated to each dose across a variety of toxicity scenarios are 
presented in the simulation report (Appendix C). 
• Up to approximately 20 subjects will be evaluated in Part B, up to 60 subjects will be 
evaluated in Part C (up to 20 subjects in Cohort 1; up to 20 subjects in each dose level in 
Cohort 2) and up to 6 subjects will be evaluated in Part D.  
No formal hypothesis is planned. The sample size is selected by providing a reasonable 
estimation precision. Assuming the observed ORR is between 30 to 70%, the 95% binomial 
exact CIs are summarized below. 
ORR 
95% CI (N=20) 
30% 
12%, 54% 
40% 
19%, 64% 
50% 
27%, 73% 
60% 
36%, 81% 
70% 
46%, 88% 
9.2. 
Study Endpoint Definitions  
Study endpoints are presented in Section 2. Endpoint definitions are presented in this section. 
9.2.1. 
Objective Response Rate  
A subject is determined to have an OR if, based on the 2016 IMWG uniform response criteria, 
they achieve a sCR, CR, VGPR, or a PR. The ORR is defined as the proportion of subjects with 
an OR per investigator. Subjects whose disease response cannot be evaluated per the 2016 
IMWG uniform response criteria will be scored as Not Evaluable for calculating the ORR. 
Subjects who do not have postbaseline response assessment, or the response is Not Evaluable per 
IMWG criteria will be counted as non-responders in calculation of ORR. 
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9.2.2. 
Complete Response Rate  
A subject is determined to have a CR if, based on the 2016 IMWG uniform response criteria they 
achieve a sCR or CR. The CR rate is defined as the proportion of subjects with a CR per 
investigator. Subjects whose disease response cannot be evaluated per the IMWG uniform 
response criteria will be scored as Not Evaluable for calculating the CR rate. 
9.2.3. 
Duration of Objective Response  
Duration of OR is defined as the time from first documentation of OR (sCR, CR, VGPR, or PR) 
to the first documentation of disease progression or to death due to any cause, whichever comes 
first. Disease progression includes objective evidence of tumor progression (based on serum, 
urine, or BM assessments) and/or clinical progression per investigator. Duration of response will 
be censored on the date of the last disease assessment documenting absence of PD for subjects 
who do not have disease progression and are still on study at the time of an analysis, or are 
removed from study prior to documentation of tumor progression. Subjects who have started a 
new antitumor treatment prior to documentation of PD will be censored at the last disease 
assessment prior to start of new treatment.  
Duration of response will only be calculated for the subgroup of subjects achieving a sCR, or 
CR. 
9.2.4. 
Duration of Complete Response  
Duration of CR is defined as the time from first documentation of complete response (sCR, CR) 
to the first documentation of disease progression or to death due to any cause, whichever comes 
first. Disease progression includes objective evidence of tumor progression (based on serum, 
urine or BM assessments) and/or clinical progression per investigator. Duration of CR will be 
censored on the date of the last disease assessment documenting absence of PD for subjects who 
do not have disease progression and are still on study at the time of an analysis, or are removed 
from study prior to documentation of tumor progression. Subjects who have started a new 
antitumor treatment prior to documentation of PD will be censored at the last disease assessment 
prior to start of new treatment.  
Duration of CR will only be calculated for the subgroup of subjects achieving a sCR or CR. 
9.2.5. 
Progression-free Survival  
PFS is defined as the time from the start of any study treatment to first documentation of disease 
progression or to death due to any cause, whichever comes first. Disease progression includes 
objective evidence of tumor progression (based on serum, urine or BM assessments) and/or 
clinical progression per investigator. PFS will be censored on the date of the last disease 
assessment documenting absence of PD for subjects who do not have disease progression and are 
still on study at the time of an analysis, or discontinuation of study prior to documentation of 
tumor progression. Subjects who have started a new antitumor treatment prior to documentation 
of PD will be censored at the last disease assessment prior to start of new treatment. Subjects 
lacking an evaluation of tumor response after their first dose will have their event time censored 
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at 1 day. A detailed censoring scheme will be described in the statistical analysis plan (SAP) for 
the study. 
9.2.6. 
Overall Survival  
OS is defined as the time from the start of any study treatment to the date of death due to any 
cause. Specifically, 
 
OS = date of death - date of first dose of any study treatment + 1. 
OS for subjects who are alive at their date of last contact, including those lost to follow-up, will 
be censored at the date of last contact. If the last recorded date where a subject is known to be 
alive is the date of first dose of any study treatment, survival time will be censored on the date of 
first dose of any study treatment (ie, OS duration of 1 day).  
9.2.7. 
MRD-negativity rate  
The rate of MRD negativity will be reported among subjects who achieved VGPR or better. 
9.3. 
Statistical and Analytical Plans  
The statistical and analytical plans presented below summarize the more complete plans to be 
detailed in the SAP. A change to the data analysis methods described in the protocol will require 
a protocol amendment only if it alters site conduct (eg, adding baseline assessments to define a 
subgroup). The SAP will be finalized prior to database lock. Any changes to the methods 
described in the final SAP will be described and justified in the clinical study report. 
9.3.1. 
General Considerations  
This is a phase 1 dose-escalation study with subsequent expansion cohort and combination 
cohort. All analyses will be descriptive. 
Descriptive statistics (mean, median, standard deviation, minimum, maximum) will be used to 
describe continuous variables. Frequencies and percentages will be used to describe categorical 
variables.  
9.3.1.1. 
Randomization and Blinding  
This is a phase 1 dose-escalation and expansion, nonrandomized study. Blinding will not be 
performed. 
9.3.1.2. 
Adjustments for Covariates  
Adjustments for covariates are not planned. 
9.3.1.3. 
Handling of Dropouts and Missing Data  
Missing data will not be imputed, with the exception of AE dates while calculating duration of 
events and treatment-emergent status; details will be provided in the SAP. For time-related 
endpoints, eg, PFS, subjects who have no specified event will be censored at the time of the last 
valid assessment of the endpoint(s). 
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9.3.1.4. 
Multicenter Studies  
There are multiple centers in this study; however, it is not anticipated that any center will accrue 
enough subjects to warrant an analysis by center. 
9.3.1.5. 
Multiple Comparisons and Multiplicity  
No multiple comparisons are planned, and no alpha adjustment is needed in this phase 1 study. 
9.3.1.6. 
Data Transformations and Derivations  
Time variables based on 2 dates (eg, start date and end date) will be calculated as (end date - start 
date +1 [in days]) unless otherwise specified in the planned analysis section. 
Baseline values used in all statistical analyses will be the most recent non-missing measurement 
prior to the first dose of SEA-BCMA unless otherwise specified in the analysis plan. 
9.3.1.7. 
Analysis Sets  
9.3.1.7.1. All Treated Subjects Analysis Set  
The All Treated Subjects set includes all subjects who receive any amount of SEA-BCMA. The 
All Treated Subjects set will be used for presentation of safety data and efficacy endpoints. 
9.3.1.7.2. Efficacy-Evaluable Analysis Set  
The efficacy-evaluable analysis set includes all treated subjects who had both a baseline and at 
least 1 postbaseline disease assessment per IMWG uniform response criteria, or per investigator 
claim of clinical progression. 
9.3.1.7.3. DLT-Evaluable Analysis Set  
The DE Analysis Set includes All Treated Subjects who either experienced a DLT, or were 
followed for the full DLT evaluation period and received a minimum 75% of the intended total 
Cycle 1 SEA-BCMA dose, and did not receive prohibited treatment (see Section 5.6.2 and 
Section 5.6.3). The DE analysis set will be used for determination of the MTD. 
Additional details of analyses and analysis sets of subjects may be defined in the SAP. 
9.3.1.8. 
Examination of Subgroups  
All analyses will be presented by dose level and total. Details will be defined in the SAP. 
As exploratory analyses, subgroup analyses may be conducted for selected endpoints. Subgroups 
may include but are not limited to the following: 
• Age (<65 vs ≥65 years old) 
• Cytogenetic risk group (high, intermediate, normal) 
• Refractory to prior therapies (refractory to IMiDs and PIs vs not) 
• Number of prior therapies (<5 vs ≥5) 
• Baseline beta-2 microglobulin (<3.5 vs ≥3.5) 
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• BCMA expression levels 
Detailed methodology will be provided in the SAP.  
9.3.1.9. 
Timing of Analyses  
The final analysis for this study will occur after all subjects have completed their treatment and 
the follow-up period or following study termination by the sponsor. 
For timing of interim analysis, see Section 9.3.10. 
9.3.2. 
Subject Disposition  
An accounting of study subjects by disposition will be tabulated and the number of subjects in 
each analysis set will be summarized. Subjects who discontinue study treatment and subjects 
who withdraw from the study will be summarized with reason for discontinuation or withdrawal. 
9.3.3. 
Subject Characteristics  
Demographics and other baseline characteristics will be summarized. Details will be provided in 
the SAP. 
9.3.4. 
Treatment Compliance  
The dose administered at each cycle, dose intensity, and dose modifications will be summarized. 
Details will be provided in the SAP. 
9.3.5. 
Efficacy Analyses  
All efficacy analyses will be presented using the All Treated Subjects set. Selected efficacy 
endpoints will also be presented using the efficacy-evaluable analysis set. The observed ORR 
and CR rate and corresponding 95% CIs will be presented. Subjects whose disease response 
cannot be assessed will be counted as non-responders. Subjects with intrasubject dose-escalation 
prior to achieving a response will be counted as non-responders at their initial dose. 
Duration of response, PFS and OS will be estimated using Kaplan-Meier methodology, and 
Kaplan-Meier plots will be provided. Medians will be calculated, where possible. The 95% CIs 
may also be calculated, as appropriate.  
Detailed methodology will be provided in the SAP. 
9.3.6. 
Pharmacokinetic and Immunogenicity Analyses  
The PK of SEA-BCMA will be evaluated by noncompartmental analysis. The following PK 
parameters will be determined where data allow: 
• Area under the curve 
• Concentration at the end of infusion (Ceoi) or Cmax 
• Trough concentration (Ctrough) 
• Terminal or apparent terminal half-life (t1/2) 
• Systemic clearance and volume of distribution at steady state 
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• Accumulation ratio 
The incidence of ATA will be summarized by descriptive statistics. 
9.3.7. 
Qualitative Interview Analyses  
No formal statistical analysis will be performed on the qualitative interviews. 
9.3.8. 
Biomarker Analyses  
Peripheral blood and BM aspirates and biopsies will be collected for biomarker assessments. 
Assessments performed with these samples may include, but are not limited to, myeloma cell 
monitoring and profiling, including expression of BCMA and assessments of immune cell 
populations. Additionally, BM samples may be analyzed to identify gene expression profiles, 
cytogenetic abnormalities, genetic mutations, and other tumor and tumor 
microenvironment-related biomarkers that may define disease risk profiles, predict response to 
SEA-BCMA, and clarify SEA-BCMA mechanisms of action. MRD will be analyzed in selected 
BM specimens using NGS. Plasma and serum will also be collected for quantification of 
biomarkers of drug activity, which may include SFLC, cytokines/chemokines, soluble BCMA, 
and other soluble biomarkers. 
Relationships of biomarker and pharmacodynamic parameters (eg, baseline values, absolute and 
relative changes from baseline) to efficacy, safety and PK parameters will be explored. 
Relationships and associated data that are determined to be of interest will be summarized. These 
exploratory analyses will be described in a separate analysis plan (eg, the SAP or Biomarker 
Analysis Plan); clinically relevant findings may be described in the clinical study report or 
reported separately (eg, in an Exploratory Studies Report). 
9.3.9. 
Safety Analyses  
9.3.9.1. 
Extent of Exposure  
Duration of treatment will be summarized and listed. 
Duration of treatment, number of cycles, total dose and dose intensity will be summarized. Dose 
modifications will also be summarized. Details will be provided in the SAP. 
9.3.9.2. 
Adverse Events  
An overview of AEs will provide a tabulation of the incidence of all AEs, treatment-emergent 
AEs, treatment-related AEs, Grade 3 and higher AEs, SAEs, treatment-related SAEs, deaths, 
AEs leading to study treatment discontinuation, treatment‑related TEAEs leading to study 
treatment discontinuation, TEAEs and treatment-related TEAEs leading to dose reduction and 
interruption. AEs will be defined as treatment-emergent if they are newly occurring or worsen 
following study treatment. 
AEs will be listed and summarized by Medical Dictionary for Regulatory Activities (MedDRA), 
preferred term, SOC, severity, and relationship to study drug. In the event of multiple 
occurrences of the same AE with the same preferred term in 1 subject, the AE will be counted 
once as the occurrence. The incidence of AEs will be tabulated by preferred term and treatment 
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group. AEs leading to premature discontinuation of study drug will be summarized and listed in 
the same manner. 
9.3.9.3. 
Dose-Limiting Toxicity  
The observed number and proportion of subjects experiencing a DLT will be reported for the 
dose-escalation part.  
9.3.9.4. 
Deaths and Serious Adverse Events  
All SAEs will be listed and summarized in the same manner as all AEs. Events with a fatal 
outcome will be listed. 
9.3.9.5. 
Clinical Laboratory Results  
Laboratory values (eg, chemistry, hematology, urinalysis, and pulmonary function tests) may be 
presented graphically by visit. Summary statistics may be tabulated as appropriate by scheduled 
visit. Laboratory values will be listed with grade per NCI-CTCAE v. 4.03 and flagged when 
values are outside the normal reference range. 
9.3.9.6. 
Other Safety Analyses  
Vital Signs  
Vital signs will be listed for each vital sign by scheduled visit. Summary statistics may be 
tabulated where appropriate. 
ECOG Status  
ECOG status will be summarized for each visit. Shifts from baseline to the best and worst 
postbaseline score may be tabulated. 
ECG  
ECG status (normal, abnormal clinically significant, or abnormal not clinically significant) may 
be summarized for each scheduled ECG and shifts from baseline may be tabulated. 
Infusion-Related Reactions and Hypersensitivity Reactions  
Subject incidence of IRRs and hypersensitivity reactions and associated signs and symptoms will 
be presented. Additional analyses may be done, including incidence of serious IRRs and 
hypersensitivity reactions as well as IRRs and hypersensitivity reactions that lead to treatment 
discontinuation. 
9.3.10. 
Interim Analyses  
Data will be evaluated after each dose cohort to determine DLTs and inform dose-escalation 
decisions. The SMC will monitor the trial for safety and DLTs on an ongoing basis. The process 
for SMC decisions and the roles and responsibilities of the SMC will be detailed in a separate 
document. 
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Interim data from the study may be presented at scientific meetings such as annual meetings of 
the American Society of Hematology or the American Society of Clinical Oncology. 
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10. 
INFORMED CONSENT, ETHICAL REVIEW, AND REGULATORY 
CONSIDERATIONS  
This study will be conducted in accordance with the Note for Guidance on Good Clinical 
Practice (ICH Harmonised Tripartite Guideline E6 (R2); FDA CFR [21 CFR § 50, 56, 312]), 
Declaration of Helsinki (Brazil 2013), and all applicable regulatory requirements. 
10.1. 
Informed Consent  
The investigator is responsible for presenting the risks and benefits of study participation to the 
subject in simple terms using the IRB/IEC approved informed consent document and for 
ensuring subjects are reconsented when the informed consent document is updated during the 
study, if required. The investigator will ensure that written informed consent is obtained from 
each subject, or legally acceptable representative, if applicable to this study, by obtaining the 
signature and date on the informed consent document prior to the performance of protocol 
evaluations or procedures. 
For phase 1 studies, it is preferable for a subject to provide consent themselves. If informed 
consent is obtained from a legally acceptable representative for a subject who is unable to 
provide informed consent at study entry (if applicable), but the subject is later able to provide 
informed consent, the investigator must obtain written informed consent from the subject. 
10.2. 
Ethical Review  
The investigator will provide the sponsor or its designee with documentation of the IRB/IEC 
approval of the protocol and the informed consent document before the study may begin at the 
investigative site(s). The name and address of the reviewing ethics committee are provided in the 
investigator file. 
The investigator will supply the following to the investigative site’s IRB/IEC: 
• Protocol and amendments 
• Informed consent document and updates 
• Clinical IB and updates 
• Relevant curricula vitae, if required 
• Required safety and SAE reports 
• Any additional submissions required by the site’s IRB/IEC 
The investigator must provide the following documentation to the sponsor or its designee: 
• The IRB/IEC periodic (eg, quarterly, annual) reapproval of the protocol. 
• The IRB/IEC approvals of any amendments to the protocol or revisions to the informed 
consent document. 
• The IRB/IEC receipt of safety and SAE reports, as appropriate. 
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10.3. 
Regulatory Considerations  
This study will be conducted in accordance with the protocol and ethical principles stated in the 
applicable guidelines on good clinical practice, and all applicable local and/or regional laws, 
rules, and regulations. 
10.3.1. 
Investigator Information  
The contact information and qualifications of the principal investigator and subinvestigators and 
name and address of the research facilities are included in the investigator file. 
10.3.2. 
Protocol Amendments and Study Termination  
Any investigator-initiated changes to the protocol (with the exception of changes to eliminate an 
immediate hazard to a study subject) must be approved by the sponsor or its designee prior to 
seeking approval from the IRB/IEC, and prior to implementing. The investigator is responsible 
for enrolling subjects who have met protocol eligibility criteria. Protocol deviations must be 
reported to the sponsor or its designee and the local IRB/IEC in accordance with IRB/IEC 
policies. 
The sponsor may terminate the study at any time. The IRB/IEC must be advised in writing of 
study completion or early termination. 
10.4. 
Study Documentation, Privacy and Records Retention  
To protect the safety of subjects in the study and to ensure accurate, complete, and reliable data, 
the investigator will keep records of laboratory tests, clinical notes, and subject medical records 
in the subject files as original source documents for the study. If requested, the investigator will 
provide the sponsor, its licensees and collaborators, applicable regulatory agencies, and 
applicable IRB/IEC with direct access to original source documents or certified copies. 
Records containing subject medical information must be handled in accordance with local and 
national laws, rules, and regulations and consistent with the terms of the subject authorization 
contained in the informed consent document for the study (the Authorization). Care should be 
taken to ensure that such records are not shared with any person or for any purpose not 
contemplated by the Authorization. Furthermore, CRFs and other documents to be transferred to 
the sponsor should be completed in strict accordance with the instructions provided by the 
sponsor, including the instructions regarding the coding of subject identities. 
In compliance with local and/or regional regulations, this trial may be registered and trial results 
may be posted on public registries, such as ClinicalTrials.gov. 
10.5. 
Clinical Trial Agreement  
Payments by the sponsor to investigators and institutions conducting the trial, requirements for 
investigators’ insurance, the publication policy for clinical trial data, and other requirements are 
specified in the clinical trial agreement. 
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11. 
REFERENCES  
Bai S, Jorga K, Xin Y, et al. A guide to rational dosing of monoclonal antibodies. Clin 
Pharmacokinet. 2012;51(2):119-35. 
 
Burwick N, Sharma S. Glucocorticoids in multiple myeloma: past, present, and future. Ann 
Hematol. 2019;98(1):19-28. 
 
Burwick N, Zhang MY, de la Puente P, et al. The eIF2-alpha kinase HRI is a novel therapeutic 
target in multiple myeloma. Leuk Res. 2017;55:23-32. 
 
Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class 
refractory multiple myeloma. N Engl J Med. 2019;381(8):727-38. 
 
Chauhan D, Catley L, Hideshima T, et al. 2-Methoxyestradiol overcomes drug resistance in 
multiple myeloma cells. Blood. 2002;100(6):2187-94. 
 
Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the management of pediatric 
and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol. 
2008;26(16):2767-78. 
 
Hendrikx J, Haanen J, Voest EE, et al. Fixed dosing of monoclonal antibodies in oncology. 
Oncologist. 2017;22(10):1212-21. 
 
Hoffman JE, Lipe B, Melear J, et al. SEA-BCMA, an investigational nonfucosylated monoclonal 
antibody: ongoing results of a phase 1 study in patients with relapsed/refractory multiple 
myeloma (SGNBCMA-001). Blood. 2021;138(Suppl 1):Abstract 2740. 
 
Ji Y, Liu P, Li Y, Bekele BN. A modified toxicity probability interval method for dose-finding 
trials. Clin Trials. 2010;7(6):653-63. 
 
Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus 
criteria for response and minimal residual disease assessment in multiple myeloma. 
Lancet Oncol. 2016;17(8):e328-46. 
 
Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the 
impact of novel therapies. Blood. 2008;111(5):2516-20. 
 
Kumar SK, Rajkumar V, Kyle RA, et al. Multiple myeloma. Nat Rev Dis Primers. 
2017;3:17046. 
 
Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple 
myeloma. Mayo Clin Proc. 2004;79(7):867-74. 
 
Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the 
modification of diet in renal disease study equation for estimating glomerular filtration 
rate. Ann Intern Med. 2006;145(4):247-54. 
 
Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab monotherapy in 
multiple myeloma. N Engl J Med. 2015;373(13):1207-19. 
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Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab Therapy for Relapsed or Refractory 
Multiple Myeloma. N Engl J Med. 2015;373(7):621-31. 
 
Martin N, Thompson E, Dell'Aringa J, et al. Correlation of tumor BCMA expression with 
response and acquired resistance to idecabtagene vicleucel in the KarMMa study in 
relapsed and refractory multiple myeloma. HemaSphere. 2020;4:450. 
 
Martinez-Lopez J, Lahuerta JJ, Pepin F, et al. Prognostic value of deep sequencing method for 
minimal residual disease detection in multiple myeloma. Blood. 2014;123(20):3073-9. 
 
Moreaux J, Legouffe E, Jourdan E, et al. BAFF and APRIL protect myeloma cells from 
apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood. 
2004;103(8):3148-57. 
 
Novak AJ, Darce JR, Arendt BK, et al. Expression of BCMA, TACI, and BAFF-R in multiple 
myeloma: a mechanism for growth and survival. Blood. 2004;103(2):689-94. 
 
O'Connor BP, Raman VS, Erickson LD, et al. BCMA is essential for the survival of long-lived 
bone marrow plasma cells. J Exp Med. 2004;199(1):91-8. 
 
Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046-60. 
 
Rajkumar SV, Kumar S. Multiple Myeloma: Diagnosis and Treatment. Mayo Clin Proc. 
2016;91(1):101-19. 
 
Rajkumar SV, Richardson P, San Miguel JF. Guidelines for determination of the number of prior 
lines of therapy in multiple myeloma. Blood. 2015;126(7):921-2. 
 
Reuben A. Hy's law. Hepatology. 2004;39(2):574-8. 
 
Rollig C, Knop S, Bornhauser M. Multiple myeloma. Lancet. 2015;385(9983):2197-208. 
 
Rosen LS, Goldman JW, Algazi AP, et al. A first-in-human phase I study of a bivalent MET 
antibody, emibetuzumab (LY2875358), as monotherapy and in combination with 
erlotinib in advanced cancer. Clin Cancer Res. 2017;23(8):1910-9. 
 
Seckinger A, Delgado JA, Moser S, et al. Target expression, generation, preclinical activity, and 
pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma 
treatment. Cancer Cell. 2017;31(3):396-410. 
 
Sehn LH, Assouline SE, Stewart DA, et al. A phase 1 study of obinutuzumab induction followed 
by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies. 
Blood. 2012;119(22):5118-25. 
 
Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC Growth Factors: 
American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol. 
2015;33(28):3199-212. 
 
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Timmers M, Roex G, Wang Y, et al. Chimeric antigen receptor-modified T cell therapy in 
multiple myeloma: beyond B cell maturation antigen. Front Immunol. 2019;10(6 pt 
1):1613. 
 
Touzeau C, Krishnan AY. Efficacy and safety of teclistamab (tec), a B-cell maturation antigen 
(BCMA) x CD3 bispecific antibody, in patients (pts) with relapsed/refractory multiple 
myeloma (RRMM) after exposure to other BCMA-targeted agents. Proceedings of the 
Annual Meeting of the American Society of Clinical Oncology. 2022:Abstract 8013. 
 
Wang DD, Zhang S, Zhao H, Men AY, Parivar K. Fixed dosing versus body size-based dosing 
of monoclonal antibodies in adult clinical trials. J Clin Pharmacol. 2009;49(9):1012-24. 
 
Wu L, Adams M, Carter T, et al. Lenalidomide enhances natural killer cell and monocyte-
mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor 
cells. Clin Cancer Res. 2008;14(14):4650-7. 
 
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APPENDIX A. 
SCHEDULE OF EVENTS  
Schedule of Events: Part A (SEA-BCMA Monotherapy Dose-escalation and Expansion)  
Assessment 
Type 
Day 
Screening/ 
Baseline 
Enrollment 
Treatment Cycles 
IHR 
VisitW 
IHR 
Follow-up 
VisitW 
EOT 
Long-
Term 
F/U 
D -28 
to 1 
D -7 
to 1 
D -7 to 1 
D1 
D2 
D4 
D8 
D15 
D22 
 
24 to 72 
hr post 
IHR Visit 
30 to 37 
days post 
last doseX 
Every 
12 weeks 
Visit window 
–1 
±1 
±1 
±1 
±1 
 
 
±2 weeks 
Baseline 
and Safety 
Assessments 
Informed consent 
X 
 
Eligibility documentation submitted to sponsor or 
designee prior to study start 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
 
X 
XC 
 
 
 
X 
 
X 
X 
X 
 
Vital signs 
 
 
XS 
 
 
 
XS 
 
X 
X 
X 
 
Weight and height M 
 
X 
XC 
 
 
 
X 
 
 
 
X 
 
ECG in triplicate 
 
X 
XA,B 
XB 
XB 
XB 
XA,B 
 
 
 
X 
 
ECOG performance status 
 
X 
XC 
 
 
 
X 
 
 
 
X 
 
Serum chemistryD 
 
X 
XC 
 
 
X 
X 
X 
X 
X 
X 
XF 
CBC with differentialD 
 
X 
XC 
 
 
X 
X 
X 
X 
X 
X 
XF 
Pregnancy test E 
 
X 
 
 
 
 
 
 
 
 
X 
 
Serology (hepatitis B, C)P 
X 
 
 
 
 
 
 
 
 
 
 
 
PT/PTT/INR 
 
X 
 
 
 
 
 
 
 
 
 
 
UrinalysisQ 
 
X 
XC 
 
 
 
X 
 
X 
X 
X 
 
UPCR calculationR 
 
XZ 
XC,Z 
 
 
 
X 
 
 
 
XG 
 
Concomitant medications and 
AEs 
Collect any related to study 
protocol procedures 
Collect from Day 1 (predose) through 30 days post last dose or through EOT visit, whichever is 
later 
Treatment 
SEA-BCMA administration 
 
X 
 
 
 
XY 
 
 
 
 
 
PK/ATA 
Blood samples for PK 
 
See PK/ATA/Biomarkers table – Note visits at D16 and D18 in Cycle 1 with study drug administration at Day 15. 
Perform Day 29 visit for sample collection if subject is not starting a cycle on Day 29. 
Blood samples for ATA 
 
Biomarkers 
BM for biomarkersI 
 
Blood sample for biomarkers 
 
Response 
Assessments 
BM aspirateI 
 
XT 
 
 
 
 
 
 
XK,L 
 
 
XU,V 
XF,U,V 
BM biopsyI 
 
XT 
 
 
 
 
 
 
XK,L 
 
 
XU,V 
XF,U,V 
Plasmacytoma evaluationN 
X 
 
 
 
 
 
 
 
XL 
 
 
X 
XF 
SPEP/Immunofixation 
 
X 
 
 
 
 
 
 
XL 
 
 
X 
XF 
UPEP/Immunofixation J 
 
X 
 
 
 
 
 
 
XL 
 
 
X 
XF 
Serum free light chain 
 
X 
 
 
 
 
 
 
XL 
 
 
X 
XF 
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Assessment 
Type 
Day 
Screening/ 
Baseline 
Enrollment 
Treatment Cycles 
IHR 
VisitW 
IHR 
Follow-up 
VisitW 
EOT 
Long-
Term 
F/U 
D -28 
to 1 
D -7 
to 1 
D -7 to 1 
D1 
D2 
D4 
D8 
D15 
D22 
 
24 to 72 
hr post 
IHR Visit 
30 to 37 
days post 
last doseX 
Every 
12 weeks 
Visit window 
–1 
±1 
±1 
±1 
±1 
 
 
±2 weeks 
Quantitative immunoglobulins 
 
X 
 
 
 
 
 
 
XL 
 
 
X 
 
Beta-2 microglobulin 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Skeletal surveyO 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Survival status 
 
 
 
 
 
 
 
 
 
 
 
 
XH 
AE = adverse event; ATA = antitherapeutic antibody; BCMA = B-cell maturation antigen; BM = bone marrow; CBC = complete blood count; CR = complete response; D = day;  
ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = end of treatment; F/U = follow-up; HCV = hepatitis C-virus; IHR = infusion/hypersensitivity reaction;  
PCR = polymerase chain reaction; PD = progressive disease; PK = pharmacokinetic; PR = partial response; PT/PTT/INR = prothrombin time/partial thromboplastin time/ 
international normalized ratio; RNA = ribonucleic acid; SPEP = serum protein electrophoresis; UPCR = urine protein to creatinine ratio;  
UPEP = urine protein electrophoresis; VGPR = very good partial response 
 
A 
Multiple ECG timepoints. See requirements detailed in Section 6.2.3.1 (Day 1), 6.2.3.5 (Day 15), and 7.7.14 (global). 
B 
Cycle 1 only 
C 
Not required in Cycle 1 if baseline is within 1 day of Day 1 
D 
Serum chemistry and CBC with differential must be performed at least weekly during dose delays 
E 
For subjects of childbearing potential 
F 
Obtain until disease progression or until initiation of subsequent anticancer therapy, whichever occurs first.  
G 
Only required if not conducted within 4 weeks prior to EOT 
H 
Contact subject for survival status and collection of first subsequent anticancer treatment information until death or study closure 
I 
Bone marrow aspirate and biopsy required at baseline, Cycle 2 Day 22 to 28, and to confirm CR in subjects with negative blood and urine M-protein. If a nonprotocol-mandated BM examination is 
conducted at any time, submit BM sample (aspirate and/or biopsy) for central assessment  
J 
Obtain urine for UPEP (24-hour urine sample) and urine immunofixation at screening (all subjects) and Day 22 to 28 of every cycle only if screening UPEP ≥200 mg/24 hours; 24-hour urine sample 
for UPEP/immunofixation is also required for any subject with unconfirmed or confirmed response of VGPR or better 
K 
Bone marrow aspirate and biopsy required at end of Cycle 2 and at time of suspected CR 
L 
Window Day 22 to 28 
M 
Height only required at baseline 
N 
Baseline and EOT scans are only needed in cases of suspected or known plasmacytoma. During treatment, plasmacytoma evaluations should be performed per institutional standard imaging modality 
every 4 cycles or to confirm a response of PR or better, or as clinically indicated to confirm PD. 
O 
Follow-up skeletal survey should be performed to look for evidence of disease progression, if clinically indicated 
P 
If hepatitis C serology is positive, HCV RNA test by PCR is required to confirm 
Q 
Microscopy required if urinalysis result is abnormal 
R 
UPCR via spot urine test 
S 
Multiple timepoints required for collection. See Section 6.2.3 for details. 
T 
Day –10 to 1.  
U 
Bone marrow aspirate and biopsy collected per standard of care at EOT and/or follow-up, should be submitted for central assessment  
V 
Obtain only for confirmation of CR for subjects who have not started another anticancer treatment 
W 
In the event of a ≥ Grade 3 infusion reaction or delayed hypersensitivity reaction 
X 
If subject is starting a new treatment post last SEA-BCMA dose, collect appropriate samples prior to start of new therapy. A phone call at 30 to 37 days is still required for AE check. 
Y 
If a subject has a clinically significant, unresolved AE on Day 15 that prevents dosing, the Day 15 visit may be delayed for <7 days. On the seventh day, if a subject cannot receive the dose, the Day 15 
visit is skipped and Day 22 performed. 
Z 
24-hour urine collection required if UPCR >2 mg/mg 
 
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Schedule of Events: Part B (SEA-BCMA Intensive Dosing)  
Assessment 
Type 
Day 
Screening/ 
Baseline 
Enrollment 
Treatment Cycles 
EOT 
Long-
Term F/U 
D -28 
to 1 
D -7 
to 1 
D -7 to 1 
D1 
D8 
D15 
D22 
30 to 37 days 
post last doseW 
Every 12 
weeks 
Visit window 
–1 
±1 
±1 
±1 
 
±2 weeks 
Baseline and 
Safety 
Assessments 
Informed consent 
X 
 
Eligibility documentation submitted to sponsor or 
designee prior to study start 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
X 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Physical examination 
 
X 
XC 
XD 
X 
XD 
X 
 
Vital signsS 
 
 
X 
XD 
X 
XD 
X 
 
Weight and height M 
 
X 
XC 
XD 
XD 
XD 
X 
 
ECG in triplicate 
 
X 
XA, B 
XA,D 
XA,D 
XA,D 
X 
 
ECOG performance status 
 
X 
XC 
XD 
X 
XD 
X 
 
Serum chemistryY 
 
X 
XC 
X 
X 
X 
X 
XF 
CBC with differentialY 
 
X 
XC 
X 
X 
X 
X 
XF 
Pregnancy testE 
 
X 
 
 
 
 
X 
 
Serology (hepatitis B, C)P 
X 
 
 
 
 
 
 
 
PT/PTT/INR 
 
X 
 
 
 
 
 
 
UrinalysisQ 
 
X 
XC 
XD 
X 
XD 
X 
 
UPCR calculationR 
 
XW 
XC,W 
XD 
X 
XD 
XG 
 
Concomitant medications and AEs 
Collect any related to study 
protocol procedures 
Collect from Day 1 (predose) through 30 days post last dose or through 
EOT visit, whichever is later 
Treatment 
PremedicationZ 
 
X 
X 
X 
X 
 
 
SEA-BCMA administration 
 
X 
XD, X 
XX 
XD, X 
 
 
PK/ATA 
Blood samples for PK 
 
See PK/ATA/Biomarkers table – Note visits at D2 and D4 in Cycle 1 
Blood samples for ATA 
 
Biomarkers 
BM for biomarkersI 
 
Blood sample for biomarkers 
 
Response 
Assessments 
BM aspirateI 
 
XT 
 
 
 
 
XK,L 
XU,V 
XF,U,V 
BM biopsyI 
 
XT 
 
 
 
 
XK,L 
XU,V 
XF,U,V 
Plasmacytoma evaluationN 
X 
 
 
 
 
 
XL 
X 
XF 
SPEP/Immunofixation 
 
X 
 
 
 
 
XL 
X 
XF 
UPEP/Immunofixation J 
 
X 
 
 
 
 
XL 
X 
XF 
Serum free light chain 
 
X 
 
 
 
 
XL 
X 
XF 
Quantitative immunoglobulins 
 
X 
 
 
 
 
XL 
X 
 
Beta-2 microglobulin 
 
X 
 
 
 
 
 
 
 
Skeletal surveyO 
 
X 
 
 
 
 
 
 
 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 109 of 158 
Assessment 
Type 
Day 
Screening/ 
Baseline 
Enrollment 
Treatment Cycles 
EOT 
Long-
Term F/U 
D -28 
to 1 
D -7 
to 1 
D -7 to 1 
D1 
D8 
D15 
D22 
30 to 37 days 
post last doseW 
Every 12 
weeks 
Visit window 
–1 
±1 
±1 
±1 
 
±2 weeks 
Survival status 
 
 
 
 
 
 
 
 
XH 
AE = adverse event; ATA = antitherapeutic antibody; BCMA = B-cell maturation antigen; BM = bone marrow; CBC = complete blood count; CR = complete response;  
D = day; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = end of treatment; F/U = follow-up; HCV = hepatitis C-virus;  
PCR = polymerase chain reaction; PD = progressive disease; PK = pharmacokinetic; PR = partial response; PT/PTT/INR = prothrombin time/ 
partial thromboplastin time/international normalized ratio; RNA = ribonucleic acid;  
SPEP = serum protein electrophoresis; UPCR = urine protein to creatinine ratio; UPEP = urine protein electrophoresis; VGPR = very good partial response 
 
A 
Multiple ECG timepoints. See requirements detailed in Section 6.3.3.1 (Day 1), Section 6.3.3.4 (Day 8), 6.3.3.5 (Day 15), 6.3.3.6 (Day 22) and 7.7.14 (global). 
B 
Cycle 1, 2, and 3 only 
C 
Not required in Cycle 1 if baseline is within 1 day of Day 1 
D 
Cycles 1 and 2 only 
E 
For subjects of childbearing potential 
F 
Obtain until disease progression or until initiation of subsequent anticancer therapy, whichever occurs first.  
G 
Only required if not conducted within 4 weeks prior to EOT 
H 
Contact subject for survival status and collection of first subsequent anticancer treatment information until death or study closure 
I 
Bone marrow aspirate and biopsy required at baseline, Cycle 2 Day 22 to 28, Cycle 6 and every 6 cycles thereafter, and to confirm CR in subjects with negative blood and urine M-protein. If a 
nonprotocol-mandated BM examination is conducted at any time, submit BM sample (aspirate and/or biopsy) for central assessment  
J 
Obtain urine for UPEP (24-hour urine sample) and urine immunofixation at screening (all subjects) and Day 22 to 28 of every cycle only if screening UPEP ≥200 mg/24 hours; 24-hour urine sample 
for UPEP/immunofixation is also required for any subject with unconfirmed or confirmed response of VGPR or better 
K 
Bone marrow aspirate and biopsy required at end of Cycle 2, Cycle 6, every 6 cycles thereafter, and at time of suspected CR 
L 
Window Day 22 to 28 
M 
Height only required at baseline 
N 
Baseline and EOT scans are only needed in cases of suspected or known plasmacytoma. During treatment, plasmacytoma evaluations should be performed per institutional standard imaging modality 
every 4 cycles or to confirm a response of PR or better, or as clinically indicated to confirm PD. 
O 
Follow-up skeletal survey should be performed to look for evidence of disease progression, if clinically indicated 
P 
If hepatitis C serology is positive, HCV RNA test by PCR is required to confirm 
Q 
Microscopy required if urinalysis result is abnormal 
R 
UPCR via spot urine test 
S 
Multiple timepoints required for collection. See Section 6.3.3 for details. 
T 
Day –10 to 1.  
U 
Bone marrow aspirate and biopsy collected per standard of care at EOT and/or follow-up, should be submitted for central assessment  
V 
Obtain only for confirmation of CR for subjects who have not started another anticancer treatment 
W 
If subject is starting a new treatment post last SEA-BCMA dose, collect appropriate samples prior to start of new therapy. A phone call at 30 to 37 days is still required for AE check. 
X 
In Cycles 1 and 2, if a subject has a clinically significant, unresolved AE that prevents dosing, the dose may be delayed for ≤3 days. On the third day, if a subject cannot receive the dose, the dose of 
SEA-BCMA will be eliminated and the corresponding visit will be skipped. In Cycle 3 and beyond, if a subject has a clinically significant, unresolved AE on Day 15 that prevents dosing, the Day 15 
visit may be delayed for <7 days. On the seventh day, if a subject cannot receive the dose, the Day 15 visit is skipped and Day 22 performed (see Section 5.2.3). 
Y 
Serum chemistry and CBC with differential must be performed at least weekly during dose delays 
Z 
Premedication for infusion reactions must be administered prior to SEA-BCMA infusion  
 
 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 110 of 158 
Schedule of Events: Part C (SEA-BCMA Plus Dexamethasone)  
Assessment 
Type 
Day 
Screening/ 
Baseline 
Enrollment 
Treatment Cycles 
EOT 
Long-Term 
F/U 
D -28 
to 1 
D -7 
to 1 
D -7 to 1 
D1 
D8 
D15 
D22 
30 to 37 days 
post last doseX 
Every 12 
weeks 
Visit window 
–1 
±1 
±1 
±1 
 
±2 weeks 
Baseline and 
Safety 
Assessments 
Informed consent 
X 
 
Eligibility documentation submitted to sponsor or 
designee prior to study start 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
X 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Physical examination 
 
X 
XC 
XD 
X 
XD 
X 
 
Vital signsS 
 
 
X 
XD 
X 
XD 
X 
 
Weight and heightM 
 
X 
XC 
 
X 
 
X 
 
ECG in triplicateA 
 
X 
 
 
 
 
X 
 
ECOG performance status 
 
X 
XC 
XD 
X 
XD 
X 
 
Serum chemistryZ 
 
X 
XC 
X 
X 
X 
X 
XF 
CBC with differentialZ 
 
X 
XC 
X 
X 
X 
X 
XF 
HbA1c 
 
XAA 
 
 
 
 
 
 
Pregnancy testE 
 
X 
 
 
 
 
X 
 
Serology (hepatitis B, C)P 
X 
 
 
 
 
 
 
 
PT/PTT/INR 
 
X 
 
 
 
 
 
 
UrinalysisQ 
 
X 
XC 
XD 
X 
XD 
X 
 
UPCR calculationR 
 
X 
XC 
XD 
X 
XD 
XG 
 
Concomitant medications and 
AEs 
Collect any related to study 
protocol procedures 
Collect from Day 1 (predose) through 30 days post last dose or 
through EOT visit, whichever is later 
Treatment 
Dexamethasone administrationCC 
 
 
 
X 
X 
X 
X 
 
 
PremedicationB 
 
 
 
X 
X 
X 
X 
 
 
SEA-BCMA administration 
 
 
 
X 
XD,W 
XY,W 
XD,W 
 
 
PK/ATA 
Blood samples for PK 
 
See PK/ATA/Biomarkers table – Note visits at D2 and D4 in Cycle 1 
Blood samples for ATA 
 
Biomarkers 
BM for biomarkersI 
 
Blood sample for biomarkers 
 
Response 
Assessments 
BM aspirateI 
 
XT 
 
 
 
 
XK,L 
XU,V 
XF,U,V 
BM biopsyI 
 
XT 
 
 
 
 
XK,L 
XU,V 
XF,U,V 
Plasmacytoma evaluationN 
X 
 
 
 
 
 
XL 
X 
XF 
SPEP/Immunofixation 
 
X 
 
 
 
 
XL 
X 
XF 
UPEP/ImmunofixationJ 
 
X 
 
 
 
 
XL 
X 
XF 
Serum free light chain 
 
X 
 
 
 
 
XL 
X 
XF 
Quantitative immunoglobulins 
 
X 
 
 
 
 
XL 
X 
 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 111 of 158 
Assessment 
Type 
Day 
Screening/ 
Baseline 
Enrollment 
Treatment Cycles 
EOT 
Long-Term 
F/U 
D -28 
to 1 
D -7 
to 1 
D -7 to 1 
D1 
D8 
D15 
D22 
30 to 37 days 
post last doseX 
Every 12 
weeks 
Visit window 
–1 
±1 
±1 
±1 
 
±2 weeks 
Beta-2 microglobulin 
 
X 
 
 
 
 
 
 
 
Skeletal surveyO 
 
X 
 
 
 
 
 
 
 
Qualitative InterviewBB 
 
 
 
 
 
 
 
 
 
Survival status 
 
 
 
 
 
 
 
 
XH 
AE = adverse event; ATA = antitherapeutic antibody; BCMA = B-cell maturation antigen; BM = bone marrow; CBC = complete blood count;  
CR = complete response; D = day; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = end of treatment; F/U = follow-up;  
HbA1c = Hemoglobin A1c; HCV = hepatitis C-virus; PCR = polymerase chain reaction; PD = progressive disease; PK = pharmacokinetic; PR = partial response;  
PT/PTT/INR = prothrombin time/partial thromboplastin time/international normalized ratio;  
RNA = ribonucleic acid; SD = stable disease; SPEP = serum protein electrophoresis; UPCR = urine protein to creatinine ratio; UPEP = urine protein electrophoresis;  
VGPR = very good partial response 
A 
See requirements detailed in Section 7.7.14. 
B 
Premedication for infusion reactions must be administered prior to SEA-BCMA infusion.  
C 
Not required in Cycle 1 if baseline is within 1 day of Day 1 
D 
Cohort 2 Cycles 1 and 2 only  
E 
For subjects of childbearing potential 
F 
Obtain until disease progression or until initiation of subsequent anticancer therapy, whichever occurs first.  
G 
Only required if not conducted within 4 weeks prior to EOT 
H 
Contact subject for survival status and collection of first subsequent anticancer treatment information until death or study closure 
I 
Bone marrow aspirate and biopsy required at baseline, Cycle 2 Day 22 to 28, Cycle 6, and every 6 cycles thereafter, and to confirm CR in subjects with negative blood and urine M-protein. If a 
nonprotocol-mandated BM examination is conducted at any time, submit BM sample (aspirate and/or biopsy) for central assessment  
J 
Obtain urine for UPEP (24-hour urine sample) and urine immunofixation at screening (all subjects) and Day 22 to 28 of every cycle only if screening UPEP ≥200 mg/24 hours; 24-hour urine sample 
for UPEP/immunofixation is also required for any subject with unconfirmed or confirmed response of VGPR or better 
K 
Bone marrow aspirate and biopsy only required at end of Cycle 2, Cycle 6, every 6 cycles thereafter, and at time of suspected CR 
L 
Window Day 22 to 28 
M 
Height only required at baseline 
N 
Baseline and EOT scans are only needed in cases of suspected or known plasmacytoma. During treatment, plasmacytoma evaluations should be performed per institutional standard imaging modality 
every 4 cycles or to confirm a response of PR or better, or as clinically indicated to confirm PD. 
O 
Follow-up skeletal survey should be performed to look for evidence of disease progression, if clinically indicated 
P 
If hepatitis C serology is positive, HCV RNA test by PCR is required to confirm 
Q 
Microscopy required if urinalysis result is abnormal 
R 
UPCR via spot urine test 
S 
Multiple timepoints required for collection. See Section 6.4.3 for details. 
T 
Day –10 to 1.  
U 
Bone marrow aspirate and biopsy collected per standard of care at EOT and/or follow-up, should be submitted for central assessment  
V 
Obtain only for confirmation of CR for subjects who have not started another anticancer treatment 
W 
In Cohort 2 Cycles 1 and 2, if a subject has a clinically significant, unresolved AE that prevents dosing, the dose may be delayed for ≤3 days. On the third day, if a subject cannot receive the dose, the 
dose of SEA-BCMA will be eliminated and the corresponding visit will be skipped (see Section 5.2.3) 
X 
If subject is starting a new treatment post last SEA-BCMA dose, collect appropriate samples prior to start of new therapy. A phone call at 30 to 37 days is still required for AE check. 
Y 
In Cohort 1, if a subject has a clinically significant, unresolved AE on Day 15 that prevents dosing, the Day 15 visit may be delayed for <7 days. On the seventh day, if a subject cannot receive the 
dose, the Day 15 visit is skipped and Day 22 performed (see Section 5.2.3) 
Z 
Serum chemistry and CBC with differential must be performed at least weekly during dose delays 
AA If HbA1c is elevated (≥6.5%), refer subject to appropriate provider prior to or within 1 week of starting study treatment in Cycle 1 for glucose management. 
BB Schedule qualitative interview at first PR or better or at the end of Cycle 4 for subjects with SD (see Section 6.4.4). 
CC Administer 1 to 3 hours prior to SEA-BCMA administration 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 112 of 158 
Schedule of Events: Part D (SEA-BCMA plus Pomalidomide and Dexamethasone)  
Assessment 
Type 
Day 
Screening/ 
Baseline 
Enrollment 
Treatment Cycles 
EOT 
Long-
Term F/U 
D -28 
to 1 
D -10 
to 1 
D -7 to 1 
D1 
D8 
D15 
D22 
30 to 37 
days post 
last doseW 
Every 12 
weeks 
Visit window 
 
 
 
–1 
±1 
±1 
±1 
 
±2 weeks 
Baseline and 
Safety 
Assessments 
Informed consent 
X 
 
Eligibility documentation submitted to sponsor or 
designee prior to study start 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
X 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Physical examination 
 
X 
XC 
 
X 
 
X 
 
Vital signsS 
 
 
X 
 
X 
 
X 
 
Weight and heightM 
 
X 
XC 
 
X 
 
X 
 
ECG in triplicateA 
 
X 
 
 
 
 
X 
 
ECOG performance status 
 
X 
XC 
 
X 
 
X 
 
Serum chemistryX 
 
X 
XC 
X 
X 
X 
X 
XF 
CBC with differentialX 
 
X 
XC 
X 
X 
X 
X 
XF 
HbA1c 
 
XY 
 
 
 
 
 
 
Pregnancy testE 
XCC 
XDD 
X 
 
X 
 
X 
 
Serology (hepatitis B, C)P 
X 
 
 
 
 
 
 
 
PT/PTT/INR 
 
X 
 
 
 
 
 
 
UrinalysisQ 
 
X 
XC 
 
X 
 
X 
 
UPCR calculationR 
 
X 
XC 
 
X 
 
XG 
 
Concomitant medications and 
AEs 
Collect any related to study 
protocol procedures 
Collect from Day 1 (predose) through 30 days post last dose or 
through EOT visit, whichever is later 
Treatment 
Dexamethasone administrationAA 
 
X 
X 
X 
X 
 
 
Pomalidomide administrationBB 
 
X 
Daily on Days 1 to 21 
 
 
PremedicationD 
 
X 
 
X 
 
 
 
SEA-BCMA administration 
 
X 
 
XB 
 
 
 
PK/ATA 
Blood samples for PK 
 
See PK/ATA/Biomarkers table – Note visits at D2 and D4 in Cycle 1 
Blood samples for ATA 
 
Biomarkers 
BM for biomarkersI 
 
Blood sample for biomarkers 
 
Response 
Assessments 
BM aspirateI 
 
XT 
 
 
 
 
XK,L 
XU,V 
XF,U,V 
BM biopsyI 
 
XT 
 
 
 
 
XK,L 
XU,V 
XF,U,V 
Plasmacytoma evaluationN 
X 
 
 
 
 
 
XL 
X 
XF 
SPEP/Immunofixation 
 
X 
 
 
 
 
XL 
X 
XF 
UPEP/ImmunofixationJ 
 
X 
 
 
 
 
XL 
X 
XF 
Serum free light chain 
 
X 
 
 
 
 
XL 
X 
XF 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 113 of 158 
Assessment 
Type 
Day 
Screening/ 
Baseline 
Enrollment 
Treatment Cycles 
EOT 
Long-
Term F/U 
D -28 
to 1 
D -10 
to 1 
D -7 to 1 
D1 
D8 
D15 
D22 
30 to 37 
days post 
last doseW 
Every 12 
weeks 
Visit window 
 
 
 
–1 
±1 
±1 
±1 
 
±2 weeks 
Quantitative immunoglobulins 
 
X 
 
 
 
 
XL 
X 
 
Beta-2 microglobulin 
 
X 
 
 
 
 
 
 
 
Skeletal surveyO 
 
X 
 
 
 
 
 
 
 
Qualitative InterviewZ 
 
 
 
 
 
 
 
 
 
Survival status 
 
 
 
 
 
 
 
 
XH 
AE = adverse event; ATA = antitherapeutic antibody; BCMA = B-cell maturation antigen; BM = bone marrow; CBC = complete blood count;  
CR = complete response; D = day; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = end of treatment; F/U = follow-up;  
HbA1c = Hemoglobin A1c; HCV = hepatitis C-virus; PCR = polymerase chain reaction; PD = progressive disease; PK = pharmacokinetic; PR = partial response;  
PT/PTT/INR = prothrombin time/partial thromboplastin time/international normalized ratio; RNA = ribonucleic acid; SPEP = serum protein electrophoresis; UPCR = urine protein to creatinine ratio; 
UPEP = urine protein electrophoresis; VGPR = very good partial response 
A 
See requirements detailed in Sections 7.7.14. 
B 
If a subject has a clinically significant, unresolved AE on Day 15 that prevents dosing, the Day 15 visit may be delayed for <7 days. On the seventh day, if a subject cannot receive the dose, the Day 15 
visit is skipped and Day 22 performed (see Section 5.2.3). 
C 
Not required in Cycle 1 if baseline is within 1 day of Day 1 
D 
Premedication for infusion reactions must be administered prior to SEA-BCMA infusion (see Section 5.5 for exceptions).  
E 
For subjects of childbearing potential 
F 
Obtain until disease progression or until initiation of subsequent anticancer therapy, whichever occurs first.  
G 
Only required if not conducted within 4 weeks prior to EOT 
H 
Contact subject for survival status and collection of first subsequent anticancer treatment information until death or study closure 
I 
Bone marrow aspirate and biopsy required at baseline, Cycle 2 Day 22 to 28, Cycle 6, and every 6 cycles thereafter, and to confirm CR in subjects with negative blood and urine M-protein. If a 
nonprotocol-mandated BM examination is conducted at any time, submit BM sample (aspirate and/or biopsy) for central assessment  
J 
Obtain urine for UPEP (24-hour urine sample) and urine immunofixation at screening (all subjects) and Day 22 to 28 of every cycle only if screening UPEP ≥200 mg/24 hours; 24-hour urine sample 
for UPEP/immunofixation is also required for any subject with unconfirmed or confirmed response of VGPR or better 
K 
Bone marrow aspirate and biopsy only required at end of Cycle 2, Cycle 6, every 6 cycles thereafter, and at time of suspected CR 
L 
Window Day 22 to 28 
M 
Height only required at baseline 
N 
Baseline and EOT scans are only needed in cases of suspected or known plasmacytoma. During treatment, plasmacytoma evaluations should be performed per institutional standard imaging modality 
every 4 cycles or to confirm a response of PR or better, or as clinically indicated to confirm PD. 
O 
Follow-up skeletal survey should be performed to look for evidence of disease progression, if clinically indicated 
P 
If hepatitis C serology is positive, HCV RNA test by PCR is required to confirm 
Q 
Microscopy required if urinalysis result is abnormal 
R 
UPCR via spot urine test 
S 
Multiple timepoints required for collection. See Section 6.5.3 for details. 
T 
Day –10 to 1.  
U 
Bone marrow aspirate and biopsy collected per standard of care at EOT and/or follow-up, should be submitted for central assessment  
V 
Obtain only for confirmation of CR for subjects who have not started another anticancer treatment 
W 
If subject is starting a new treatment post last SEA-BCMA dose, collect appropriate samples prior to start of new therapy. A phone call at 30 to 37 days is still required for AE check. 
X 
Serum chemistry and CBC with differential must be performed at least weekly during dose delays 
Y 
If HbA1c is elevated (≥6.5%), refer subject to appropriate provider prior to or within 1 week of starting study treatment in Cycle 1 for glucose management. 
Z 
Schedule qualitative interview at first PR or better (see Section 6.5.4). 
AA Administer 1 to 3 hours prior to SEA-BCMA administration 
BB Administer 1 to 3 hours prior to SEA-BCMA administration on Cycle 1, Day 1; daily self-administration thereafter 
CC 10 to 14 days prior to planned Cycle 1 Day 1 
DD Within 24 hours prior to Cycle 1 Day pomalidomide dose 
 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 114 of 158 
APPENDIX B. 
PK, ATA, AND BIOMARKER SAMPLING TIME POINTS  
Pharmacokinetic, immunogenicity, and biomarker sample collection time points – Part A  
Cycle 
Study day 
Time 
Window 
Relative 
Time 
Peripheral BloodA 
Bone MarrowA 
SEA-BCMA PK 
SEA-BCMA ATA 
Genotyping 
Immunophenotyping 
Plasma cytokines/ 
chemokines 
Soluble target and 
ligands 
Plasma Biomarkers 
PBMCs 
SFLC 
Modified SPEP L 
Immunophenotyping 
(including BCMA 
characterization) 
Gene 
expression/NGS/FISH 
MRD 
BM plasma 
NA 
Baseline/ 
screening 
Non-dosing 
D –10 to 1 
NA 
 
 
X 
XJ,P 
 
XJ 
XJ 
XJ 
X 
X 
XJ 
X 
X 
XJ 
Cycles 1, 2, 
and 3 
1 
Predose 
Within 4 h 
prior to dose 
START of 
infusion, 1st 
dose 
X 
XC 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
1 hr intradose 
±15 min 
START of 
infusion, 1st 
dose 
XN 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 hr intradose 
±15 min 
START of 
infusion, 1st 
dose 
XO 
 
 
 
 
 
 
 
 
 
 
 
 
 
End of study 
drug 
administration 
Within 
15 min post 
IV infusion 
END of 
infusion, 1st 
dose 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 hr 
±15 min 
END of 
infusion, 1st 
dose 
X 
 
 
XD,P 
XD 
 
 
 
 
 
 
 
 
 
6 hrM 
±15 min 
END of 
infusion, 1st 
dose 
X 
 
 
 
XD 
 
 
 
 
 
 
 
 
 
2H 
24 hr 
±4 hr 
START of 
infusion, 1st 
dose 
X 
 
 
XD,P 
XD 
 
 
 
 
 
 
 
 
 
4H 
72 hr 
±4 hr 
START of 
infusion, 1st 
dose 
X 
 
 
XD,J,P 
XD,J 
XD,J,P 
 
XD,J,P 
 
 
 
 
 
 
8 
168 hr 
±24 hr 
START of 
infusion, 1st 
dose 
X 
 
 
XD,P 
XD 
XD 
 
XD,P 
XD 
 
 
 
 
 
15 
336 hr 
±72 hr 
START of 
infusion, 1st 
dose 
XB 
 
 
 
 
 
 
 
 
 
 
 
 
 
Predose 
Within 4 hr 
prior to 
doseG 
START of 
infusion, 2nd 
dose 
X 
 
 
XE 
XE 
XE 
 
XE 
XE 
 
 
 
 
 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 115 of 158 
Cycle 
Study day 
Time 
Window 
Relative 
Time 
Peripheral BloodA 
Bone MarrowA 
SEA-BCMA PK 
SEA-BCMA ATA 
Genotyping 
Immunophenotyping 
Plasma cytokines/ 
chemokines 
Soluble target and 
ligands 
Plasma Biomarkers 
PBMCs 
SFLC 
Modified SPEP L 
Immunophenotyping 
(including BCMA 
characterization) 
Gene 
expression/NGS/FISH 
MRD 
BM plasma 
1 hr intradose 
±15 min 
START of 
infusion, 2nd 
dose 
XN,D 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 hr intradose 
±15 min 
START of 
infusion, 2nd 
dose 
XO,D 
 
 
 
 
 
 
 
 
 
 
 
 
 
End of study 
drug 
administration 
Within 
15 min post 
IV infusion 
END of 
infusion, 2nd 
dose 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 hr 
±15 min 
END of 
infusion, 2nd 
dose 
XD 
 
 
 
 
 
 
 
 
 
 
 
 
 
6 hrM 
±15 min 
END of 
infusion, 2nd 
dose 
XD 
 
 
 
 
 
 
 
 
 
 
 
 
 
16 
24 hr 
±4 hr 
START of 
infusion, 2nd 
dose 
XD,R 
 
 
 
 
 
 
 
 
 
 
 
 
 
18 
72 hr 
±4 hr 
START of 
infusion, 2nd 
dose 
XD,R 
 
 
 
 
 
 
 
 
 
 
 
 
 
22 
168 hr 
±24 hr 
START of 
infusion, 2nd 
dose 
XD 
 
 
XF,J,P 
XF,J 
XF,J 
 
XF,J 
XD 
X 
XF,J 
XF 
XF 
XF,J 
29 
336 hr 
±72 hr 
START of 
infusion, 2nd 
dose 
XB 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cycle 4 and 
subsequent 
cycles  
1 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 1st 
dose 
X 
XC 
 
 
X 
X 
XK 
X 
X 
 
 
 
 
 
End of study 
drug 
administration 
Within 15 
min post IV 
infusion 
END of 
infusion, 1st 
dose 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
15 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 2nd 
dose 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
End of study 
drug 
administration 
Within 15 
min post IV 
infusion 
END of 
infusion, 2nd 
dose 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 116 of 158 
Cycle 
Study day 
Time 
Window 
Relative 
Time 
Peripheral BloodA 
Bone MarrowA 
SEA-BCMA PK 
SEA-BCMA ATA 
Genotyping 
Immunophenotyping 
Plasma cytokines/ 
chemokines 
Soluble target and 
ligands 
Plasma Biomarkers 
PBMCs 
SFLC 
Modified SPEP L 
Immunophenotyping 
(including BCMA 
characterization) 
Gene 
expression/NGS/FISH 
MRD 
BM plasma 
22 
168 hr 
±24 hr 
START of 
infusion, 2nd 
dose 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
IHR visit 
NA 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
IHR follow-up visit 
NA 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
At time of CR assessment 
NA 
 
 
 
 
XJ 
XJ 
X 
XJ 
 
 
XJ 
X 
X 
XJ 
EOT 
NA 
X 
X 
 
XJ 
X 
X 
X 
X 
X 
X 
XI,J 
XI 
XI 
XI,J 
Follow-up 
NA 
 
 
 
 
 
 
 
 
 
XQ 
XI,Q 
XI,Q 
XI,Q 
XI,Q 
ATA = antitherapeutic antibody; BCMA = B-cell maturation antigen; BM = bone marrow; CR = complete response; EOT = end of treatment; FISH = fluorescent in situ hybridization;  
IHR = infusion/hypersensitivity reaction; IV = intravenous; MRD = minimal residual disease; NA = not applicable; NGS = next generation sequencing; PBMC = peripheral blood mononuclear cell; PK = pharmacokinetic;  
SFLC = serum free light chain; SPEP = serum protein electrophoresis 
 
A 
Blood and bone marrow aspirate and biopsy to be collected for central analysis. Analysis may include BCMA characterization (flow cytometry, gene expression, and immunohistochemistry), risk stratification (gene expression 
profiling, phenotypic profiling), and NGS analysis (including MRD determination). 
B 
Sample obtained only for subjects not starting the next dose on Day 15 or 29 [±72 h] and not in EOT visit 
C 
Required in first 5 cycles and every fifth cycle thereafter 
D 
Cycle 1 only  
E 
Cycle 1 and 2 only 
F 
End of Cycle 2 only (Day 22 to 28) 
G 
Cycle 1 Day 1 predose window is within 1 day of Day 1 
H 
Labs may be drawn at the site or, except for Cycle 1, may be drawn by a home healthcare provider 
I 
Bone marrow aspirate and bone marrow biopsy, if available, to be submitted for central assessment of response and resistance to SEA-BCMA. To be collected to confirm CR in subjects who have not started another anticancer 
treatment. 
J 
Blood and bone marrow samples must be collected on the same day, if applicable. A window of ±1 day in Cycle 1 is permitted to accommodate same-day sampling. 
K 
Every 3 cycles after Cycle 3: Cycle 6, 9, 12, etc. 
L 
For subjects with IgG myeloma only. Collect specimen at the same time as local disease assessment sample collection. 
M 
Collect only if SEA–BCMA infusion time is ≤2 hr 
N 
Collect only if infusion duration >1 hr, blood samples collected during SEA–BCMA infusion should be obtained from the contralateral arm, or different vascular access site relative to infusion site 
O 
Collect only if infusion duration >2 hr, blood samples collected during SEA–BCMA infusion should be obtained from the contralateral arm, or different vascular access site relative to infusion site 
P 
Collect only in expansion cohort. 
Q 
Collect until initiation of subsequent therapy 
R 
Specimens collections on Days 16 and 18 to be performed only for subjects who received SEA–BCMA administration at Day 15 
 
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Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 117 of 158 
Pharmacokinetic, immunogenicity, and biomarker sample collection time points – Part B  
Cycle 
Study 
day 
Time 
Window 
Relative 
Time 
Peripheral BloodA 
Bone MarrowA 
SEA-BCMA PK 
SEA-BCMA ATA 
Genotyping 
Plasma cytokines/ 
chemokines 
Soluble target and  
ligands 
Plasma Biomarkers 
PBMCs 
SFLC  
Modified SPEPK 
Immunophenotyping 
(including BCMA 
characterization) 
Gene expression/ 
NGS/FISH 
MRD 
BM plasma 
NA 
Baseline/ 
screening 
Non-dosing 
D –10 to 1 
NA 
 
 
X 
XI 
XI 
XI 
XI 
X 
X 
XI 
X 
X 
XI 
Cycles 1, 2 
and 3  
1 
Predose 
Within 4 h 
prior to doseF 
START of 
infusion, 1st 
dose 
X 
XB 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
1 hr intradose 
±15 min 
START of 
infusion, 1st 
dose 
XM,C 
 
 
 
 
 
 
 
 
 
 
 
 
2 hr intradose 
±15 min 
START of 
infusion, 1st 
dose 
XN,C 
 
 
 
 
 
 
 
 
 
 
 
 
End of study 
drug 
administration 
Within 15 
min post IV 
infusion 
END of 
infusion, 
1st dose 
XC 
 
 
 
XD 
 
 
 
 
 
 
 
 
2 hr 
±15 min 
END of 
infusion, 
1st dose 
XC 
 
 
XD 
 
 
 
 
 
 
 
 
 
6 hrL 
±15 min 
END of 
infusion, 
1st dose 
XC 
 
 
 
 
 
 
 
 
 
 
 
 
2G 
24 hr 
±4 hr 
START of 
infusion, 1st 
dose 
XC 
 
 
XC 
 
 
XC 
 
 
 
 
 
 
4G 
72 hr 
±4 hr 
START of 
infusion, 1st 
dose 
XC 
 
 
 
 
 
 
 
 
 
 
 
 
8 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 2nd 
dose 
XD 
 
 
XC 
XC 
 
 
XC 
 
 
 
 
 
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Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 118 of 158 
Cycle 
Study 
day 
Time 
Window 
Relative 
Time 
Peripheral BloodA 
Bone MarrowA 
SEA-BCMA PK 
SEA-BCMA ATA 
Genotyping 
Plasma cytokines/ 
chemokines 
Soluble target and  
ligands 
Plasma Biomarkers 
PBMCs 
SFLC  
Modified SPEPK 
Immunophenotyping 
(including BCMA 
characterization) 
Gene expression/ 
NGS/FISH 
MRD 
BM plasma 
15 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 3rd 
dose 
X 
 
 
XD 
XD 
 
XD 
XD 
 
 
 
 
 
22 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 4th 
dose 
XD 
 
 
XE,I 
XE,I 
 
XE,I 
XC 
X 
XE,I 
XE 
XE 
XE,I 
Cycle 4 
and 
subsequent 
cycles  
1 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 1st 
dose 
X 
XB 
 
 
 
 
 
X 
 
 
 
 
 
22 
168 hr 
±24 hr 
START of 
infusion, 2nd 
dose 
 
 
 
XO 
XO 
XO 
XO 
 
X 
XO 
XO 
XO 
XO 
At time of CR assessment 
NA 
 
 
 
XI 
XI 
XI 
XI 
 
 
XI 
XI 
XI 
XI 
EOT 
NA 
X 
X 
 
XI 
XI 
XI 
XI 
X 
X 
XH,I 
XH,I 
XH,I 
XH,I 
Follow-up 
NA 
 
 
 
 
 
 
 
 
XJ 
XH,J 
XH,J 
XH,J 
XH,J 
ATA = antitherapeutic antibody; BCMA = B-cell maturation antigen; BM = bone marrow; CR = complete response; EOT = end of treatment; FISH = fluorescent in situ hybridization;  
IHR = infusion/hypersensitivity reaction; IV = intravenous; MRD = minimal residual disease; NA = not applicable; NGS = next generation sequencing; PBMC = peripheral blood mononuclear cell; PK = pharmacokinetic;  
SFLC = serum free light chain; SPEP = serum protein electrophoresis 
 
A 
Blood and bone marrow aspirate and biopsy to be collected for central analysis. Analysis may include BCMA characterization (flow cytometry, gene expression, and immunohistochemistry), risk stratification (gene expression 
profiling, phenotypic profiling), and NGS analysis (including MRD determination). 
B 
Required in first 5 cycles and every fifth cycle thereafter 
C 
Cycle 1 only  
D 
Cycle 1 and 2 only 
E 
End of Cycle 2 (Day 22 to 28) and at time of suspected CR 
F 
Cycle 1 Day 1 predose window is within 1 day of Day 1 
G 
Labs may be drawn at the site or may be drawn by a home healthcare provider 
H 
Bone marrow aspirate and bone marrow biopsy, if available, to be submitted for central assessment of response and resistance to SEA–BCMA. To be collected to confirm CR in subjects who have not started another anticancer 
treatment. 
I 
Blood and bone marrow samples must be collected on the same day, if applicable. A window of ±1 day in Cycle 1 is permitted to accommodate same-day sampling. 
J 
Collect until initiation of subsequent therapy. 
K 
For subjects with IgG myeloma only. Collect specimen at the same time as local disease assessment sample collection. 
L 
Collect only if SEA–BCMA infusion time is ≤2 hr 
M 
Collect only if infusion duration >1 hr, blood samples collected during SEA–BCMA infusion should be obtained from the contralateral arm, or different vascular access site relative to infusion site 
N 
Collect only if infusion duration > 2 hr, blood samples collected during SEA–BCMA infusion should be obtained from the contralateral arm, or different vascular access site relative to infusion site 
O 
To be collected on Day 22 to 28 of Cycle 6 and every 6 cycles thereafter, and at time of suspected CR 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
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Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 119 of 158 
Pharmacokinetic, immunogenicity, and biomarker sample collection time points – Part C  
Cycle 
Study 
day 
Time 
Window 
Relative 
Time 
Peripheral BloodA 
Bone MarrowA 
SEA-BCMA PK 
Dexamethasone PK 
SEA-BCMA ATA 
Genotyping 
Plasma cytokines/ 
chemokines 
Soluble target and 
ligands 
Plasma Biomarkers 
PBMCs 
SFLC  
Modified SPEP L 
Immunophenotyping 
(including BCMA 
characterization) 
Gene expression/ 
NGS/FISH 
MRD 
BM plasma 
NA 
Baseline/ 
screening 
Non-dosing 
D –10 to 1 
NA 
 
 
 
X 
XJ 
XJ 
XJ 
XJ 
X 
X 
XJ 
X 
X 
XJ 
Cycles 1, 2 
and 3 
1 
Predose 
Within 4 h 
prior to doseG 
START of 
infusion, 
1st dose 
X 
XD 
XC 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
1 hr intradose 
±15 min 
START of 
infusion, 
1st dose 
XN,D 
XD 
 
 
 
 
 
 
 
 
 
 
 
 
2 hr intradose 
±15 min 
START of 
infusion, 
1st dose 
XO,D 
XD 
 
 
 
 
 
 
 
 
 
 
 
 
End of study 
drug 
administration 
Within 15 min 
post IV 
infusion 
END of 
infusion, 
1st dose 
XD 
XD 
 
 
 
XE 
 
 
 
 
 
 
 
 
2 hr 
±15 min 
END of 
infusion, 
1st dose 
XD 
XD 
 
 
XE 
 
 
 
 
 
 
 
 
 
6 hrM 
±15 min 
END of 
infusion, 
1st dose 
XD 
XD 
 
 
 
 
 
 
 
 
 
 
 
 
2H 
24 hr 
±4 hr 
START of 
infusion, 
1st dose 
XD 
XD 
 
 
XD 
 
 
XD 
 
 
 
 
 
 
4H 
72 hr 
±4 hr 
START of 
infusion, 
1st dose 
XD 
XD 
 
 
 
 
 
 
 
 
 
 
 
 
8 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 
2nd dose 
XP 
XD 
 
 
XD 
XD 
 
 
XD 
 
 
 
 
 
15 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 
3rd dose 
X 
XD 
 
 
XE 
XE 
 
XE 
XE 
 
 
 
 
 
22 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 
4th dose 
XB,E 
 
 
 
XF,J 
XE,J 
 
XF,J 
XD 
X 
XF,J 
XF 
XF 
XF,J 
Cycle 4 
and 
1 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 
1st dose 
X 
 
XC 
 
 
 
 
 
X 
 
 
 
 
 
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Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 120 of 158 
Cycle 
Study 
day 
Time 
Window 
Relative 
Time 
Peripheral BloodA 
Bone MarrowA 
SEA-BCMA PK 
Dexamethasone PK 
SEA-BCMA ATA 
Genotyping 
Plasma cytokines/ 
chemokines 
Soluble target and 
ligands 
Plasma Biomarkers 
PBMCs 
SFLC  
Modified SPEP L 
Immunophenotyping 
(including BCMA 
characterization) 
Gene expression/ 
NGS/FISH 
MRD 
BM plasma 
subsequent 
cycles 
22 
168 hr 
±24 hr 
START of 
infusion, 
2nd dose 
 
 
 
 
XK 
XK 
XK 
XK 
 
X 
XK 
XK 
XK 
XK 
At time of CR assessment 
NA 
 
 
 
XJ 
XJ 
XJ 
XJ 
 
 
XJ 
XJ 
XJ 
XJ 
EOT 
NA 
X 
X 
 
XJ 
XJ 
XJ 
XJ 
X 
X 
XI,J 
XI 
XI 
XI,J 
Follow-up 
NA 
 
 
 
 
 
 
 
 
XQ 
XI,Q 
XI,Q 
XI,Q 
XI,Q 
ATA = antitherapeutic antibody; BCMA = B-cell maturation antigen; BM = bone marrow; CR = complete response; EOT = end of treatment; FISH = fluorescent in situ hybridization;  
IHR = infusion/hypersensitivity reaction; IV = intravenous; MRD = minimal residual disease; NA = not applicable; NGS = next generation sequencing; PBMC = peripheral blood mononuclear cell; PK = pharmacokinetic;  
SFLC = serum free light chain; SPEP = serum protein electrophoresis 
 
A 
Blood and bone marrow aspirate and biopsy to be collected for central analysis. Analysis may include BCMA characterization (flow cytometry, gene expression, and immunohistochemistry), risk stratification (gene expression 
profiling, phenotypic profiling), and NGS analysis (including MRD determination). 
B 
Cohort 2 only 
C 
Required in first 5 cycles and every fifth cycle thereafter 
D 
Cycle 1 only  
E 
Cycle 1 and 2 only 
F 
End of Cycle 2 only (Day 22 to 28) and at time of suspected CR 
G 
Cycle 1 Day 1 predose window is within 1 day of Day 1; Collect predose samples before dexamethasone administration. 
H 
Labs may be drawn at the site or, may be drawn by a home healthcare provider 
I 
Bone marrow aspirate and bone marrow biopsy, if available, to be submitted for central assessment of response and resistance to SEA–BCMA. To be collected to confirm CR in subjects who have not started another anticancer 
treatment. 
J 
Blood and bone marrow samples must be collected on the same day, if applicable. A window of ±1 day in Cycle 1 is permitted to accommodate same-day sampling. 
K 
To be collected on Day 22 to 28 of Cycle 6, every 6 cycles thereafter, and at time of suspected CR. 
L 
For subjects with IgG myeloma only. Collect specimen at the same time as local disease assessment sample collection. 
M 
Collect only if SEA–BCMA infusion time is ≤2 hr 
N 
Collect only if infusion duration >1 hr, blood samples collected during SEA–BCMA infusion should be obtained from the contralateral arm, or different vascular access site relative to infusion site 
O 
Collect only if infusion duration >2 hr, blood samples collected during SEA–BCMA infusion should be obtained from the contralateral arm, or different vascular access site relative to infusion site 
P 
For cohort 1: Cycle 1 only; for cohort 2: Cycle 1 and 2 only  
Q 
Collect until initiation of subsequent therapy 
 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 121 of 158 
Pharmacokinetic, immunogenicity, and biomarker sample collection time points – Part D  
Cycle 
Study 
day 
Time 
Window 
Relative 
Time 
Peripheral BloodA 
Bone MarrowA 
SEA-BCMA PK 
Dexamethasone PK 
Pomalidomide PK 
SEA-BCMA ATA 
Genotyping 
Plasma cytokines/ 
chemokines 
Soluble target and 
ligands 
Plasma Biomarkers 
PBMCs 
SFLC  
Modified SPEP K 
Immunophenotyping 
(including BCMA 
characterization) 
Gene expression/ 
NGS/FISH 
MRD 
BM plasma 
NA 
Baseline/ 
screening 
Non-dosing 
D –10 to 1 
NA 
 
 
 
 
X 
XI 
XI 
XI 
XI 
X 
X 
XI 
X 
X 
XI 
Cycles 1, 2 
and 3  
1 
Predose 
Within 4 h 
prior to 
doseF 
START of 
infusion, 1st 
dose 
X 
XC 
XC 
XB 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
1 hr intradose 
±15 min 
START of 
infusion, 1st 
dose 
XM,C 
XC 
XC 
 
 
 
 
 
 
 
 
 
 
 
 
2 hr intradose 
±15 min 
START of 
infusion, 1st 
dose 
XN,C 
XC 
XC 
 
 
 
 
 
 
 
 
 
 
 
 
End of study 
drug 
administration 
Within 15 
min post IV 
infusion 
END of 
infusion, 
1st dose 
XC 
XC 
XC 
 
 
 
XD 
 
 
 
 
 
 
 
 
2 hr 
±15 min 
END of 
infusion, 
1st dose 
XC 
XC 
XC 
 
 
XD 
 
 
 
 
 
 
 
 
 
6 hrL 
±15 min 
END of 
infusion, 
1st dose 
XC 
XC 
XC 
 
 
 
 
 
 
 
 
 
 
 
 
2G 
24 hr 
±4 hr 
START of 
infusion, 1st 
dose 
XC 
XC 
 
 
 
XC 
 
 
XC 
 
 
 
 
 
 
4G 
72 hr 
±4 hr 
START of 
infusion, 1st 
dose 
XC 
XC 
 
 
 
 
 
 
 
 
 
 
 
 
 
8 
168 hr 
±24 hr 
START of 
infusion, 1st 
dose 
XC 
XC 
 
 
 
XC 
XC 
 
 
XC 
 
 
 
 
 
15 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 2nd 
dose 
X 
XC 
 
 
 
XD 
XD 
 
XD 
XD 
 
 
 
 
 
22 
168 hr 
±24 hr 
START of 
infusion, 2nd 
dose 
XD 
 
 
 
 
XE,I 
XD,I 
 
XEI 
XC 
X 
XE,I 
XE 
XE 
XE,I 
Cycle 4 
and 
1 
Predose 
Within 4 hr 
prior to dose 
START of 
infusion, 1st 
dose 
X 
 
 
XB 
 
 
 
 
 
X 
 
 
 
 
 
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Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 122 of 158 
Cycle 
Study 
day 
Time 
Window 
Relative 
Time 
Peripheral BloodA 
Bone MarrowA 
SEA-BCMA PK 
Dexamethasone PK 
Pomalidomide PK 
SEA-BCMA ATA 
Genotyping 
Plasma cytokines/ 
chemokines 
Soluble target and 
ligands 
Plasma Biomarkers 
PBMCs 
SFLC  
Modified SPEP K 
Immunophenotyping 
(including BCMA 
characterization) 
Gene expression/ 
NGS/FISH 
MRD 
BM plasma 
subsequent 
cycles  
22 
168 hr 
±24 hr 
START of 
infusion, 2nd 
dose 
 
 
 
 
 
XJ 
XJ 
XJ 
XJ 
 
X 
XJ 
XJ 
XJ 
XJ 
At time of CR assessment 
NA 
 
 
 
 
XI 
XI 
XI 
XI 
 
 
XI 
XI 
XI 
XI 
EOT 
NA 
X 
 
X 
 
XI 
XI 
XI 
XI 
X 
X 
XH,I 
XH 
XH 
XH,I 
Follow-up 
NA 
 
 
 
 
 
 
 
 
 
X
O 
XH,O 
XH,O 
XH,O 
XH,
O 
ATA = antitherapeutic antibody; BCMA = B-cell maturation antigen; BM = bone marrow; CR = complete response; EOT = end of treatment; FISH = fluorescent in situ hybridization;  
IHR = infusion/hypersensitivity reaction; IV = intravenous; MRD = minimal residual disease; NA = not applicable; NGS = next generation sequencing; PBMC = peripheral blood mononuclear cell; PK = pharmacokinetic;  
SFLC = serum free light chain; SPEP = serum protein electrophoresis 
 
A 
Blood and bone marrow aspirate and biopsy to be collected for central analysis. Analysis may include BCMA characterization (flow cytometry, gene expression, and immunohistochemistry), risk stratification (gene expression 
profiling, phenotypic profiling), and NGS analysis (including MRD determination). 
B 
Required in first 5 cycles and every fifth cycle thereafter 
C 
Cycle 1 only  
D 
Cycle 1 and 2 only 
E 
End of Cycle 2 only (Day 22 to 28) and at time of suspected CR 
F 
Cycle 1 Day 1 predose window is within 1 day of Day 1; Collect predose samples before dexamethasone and pomalidomide administration. 
G 
Labs may be drawn at the site or, may be drawn by a home healthcare provider 
H 
Bone marrow aspirate and bone marrow biopsy, if available, to be submitted for central assessment of response and resistance to SEA–BCMA. To be collected to confirm CR in subjects who have not started another anticancer 
treatment. 
I 
Blood and bone marrow samples must be collected on the same day, if applicable. A window of ±1 day in Cycle 1 is permitted to accommodate same-day sampling. 
J 
To be collected on Day 22 to 28 of Cycle 6, every 6 cycles thereafter, and at time of suspected CR. 
K 
For subjects with IgG myeloma only. Collect specimen at the same time as local disease assessment sample collection. 
L 
Collect only if SEA–BCMA infusion time is ≤2 hr 
M 
Collect only if infusion duration >1 hr, blood samples collected during SEA–BCMA infusion should be obtained from the contralateral arm, or different vascular access site relative to infusion site 
N 
Collect only if infusion duration >2 hr, blood samples collected during SEA–BCMA infusion should be obtained from the contralateral arm, or different vascular access site relative to infusion site 
O 
Collect until initiation of subsequent therapy 
 
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Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 123 of 158 
APPENDIX C. 
MODIFIED TOXICITY PROBABILITY INTERVAL DESIGN 
SIMULATION REPORT  
Introduction  
This is a phase 1 study with dose-escalation of SEA-BCMA in subjects with RRMM. The 
primary objective of this study is to evaluate the safety, tolerability, and identify the MTD and/or 
optimal dose of SEA-BCMA. Toxicity will be measured by DLTs observed within the first cycle 
of therapy. Dose-escalation will be conducted according to a modified toxicity probability 
interval (mTPI) method. 
Dose-escalation  
Overview  
The primary objective of the dose-escalation portion of the study is to estimate an MTD and/or 
optimal dose for SEA-BCMA. There will be 5 selected dose levels. Intermediate dose levels of 
SEA-BCMA may be included during the execution phase at the discretion of the sponsor upon 
recommendation by the SMC. 
The starting dose of SEA-BCMA will be dose level 1. Dose-escalation will be conducted 
according to the mTPI method and also according to a set of rules governing entry into the study 
and assignment of dose level. Decision rules are described in Section 3.1.1 of the study protocol 
and detailed in this appendix. Decision rules will be based on the posterior distribution of 
DLT-rate and derived independently for each dose level. The trial is continuously monitored for 
safety and for successfully identifying the MTD. In the event that the SMC recommends 
exploration of an intermediate level, (eg, a dose level between dose level 4 and dose level 5), an 
additional dose level may be added. In the event that SMC recommends a different schedule on 
the existing dose levels, the same dose-escalation algorithm will be applied separately. 
Modified Toxicity Probability Interval Method  
Dose-escalation is conducted using the mTPI method. The implementation programs are 
available at: http://health.bsd.uchicago.edu/yji/software2.htm.  
For each dose level i = 1, 2, …, 5, the probability of a DLT on dose i is denoted by pi. The target 
toxicity probability in this study is defined as 25%, with a 5% margin. The equivalence interval 
is [20%, 30%], which contains the doses close to the target DLT rate that physicians would deem 
acceptable for treating future subjects. The equivalence interval partitions the unit interval (0, 1) 
into 3 subintervals: (0%, 20%), (20%, 30%) and (30%, 100%). Doses in these 3 intervals 
correspond to: 
1. 
Under dosing: pi <20% 
2. 
Proper dosing: 20% ≤ pi ≤30% 
3. 
Over dosing: pi >30% 
In each dose level, we assume the prior distribution of DLT probability pi is noninformative 
Beta(1, 1). After each subject is treated and assessed for DLT, the posterior distribution of pi is 
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Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 124 of 158 
updated to Beta(1 + xi, 1 + ni - xi), where xi, ni denote the number of DLTs and number of DE 
subjects at dose level i respectively. The dose-escalation decision is based on the unit probability 
mass (UPM) on the posterior distribution of pi. For a given interval [a, b], the UPM is defined as 
the ratio of the probability of the interval to the length of the interval, where for any DLT 
probability pi and 0 ≤ a < b ≤1: 
UPM(a, b) = Pr(a < pi < b) / (b - a) 
After the toxicity outcomes are observed, the UPM on (0%, 20%), [20%, 30%] and (30%, 100%) 
at current dose will be calculated and the dosing decision rules would be: 
1. 
Escalate (E) if (0, 20%) has the largest UPM 
2. 
Stay at the current dose (S) if [20%, 30%] has the largest UPM  
3. 
De-escalate (D) if (30%, 100%) has the largest UPM  
Additionally, we define the toxicity of a dose being unacceptable if there is more than 95% 
probability that the DLT rate is higher than 25%: 
Toxicity at dose i is unacceptable: Pr(pi >25%) >95% 
If dose level i is determined to be unacceptable, the next cohort of subjects is treated at dose 
level i – 1 and dose i and higher are excluded from the trial. If i = 1, terminate the trial and, if no 
lower dose levels are of interest to explore, conclude that no dose level is safe. The decision rules 
for each dose level are provided in Table 9. 
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Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 125 of 158 
Table 9: 
Dose-finding spreadsheet for mTPI design 
 
Number of DLT-evaluable subjects treated at current dose 
Number of DLTs 
 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
0 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
1 
S 
S 
S 
S 
E 
E 
E 
E 
E 
E 
E 
E 
E 
E 
2 
DU 
D 
D 
S 
S 
S 
S 
S 
S 
S 
S 
S 
E 
E 
3 
DU 
DU 
DU 
D 
S 
S 
S 
S 
S 
S 
S 
S 
S 
4 
DU 
DU 
DU 
DU 
DU 
D 
S 
S 
S 
S 
S 
S 
5 
DU 
DU 
DU 
DU 
DU 
DU 
D 
S 
S 
S 
S 
6 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
D 
S 
7 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
8 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
9 
DU 
DU 
DU 
DU 
DU 
DU 
DU 
10 
DU 
DU 
DU 
DU 
DU 
DU 
11 
DU 
DU 
DU 
DU 
DU 
12 
DU 
DU 
DU 
DU 
13 
DU 
DU 
DU 
14 
DU 
DU 
15 
DU 
D = de-escalate to the next lower dose, DLT = dose-limiting toxicity, DU = current dose is unacceptably toxic, E = escalate to the 
next higher dose, mTPI = modified toxicity probability interval, S = stay at the current dose,  
 
At the end of the trial when the toxicity outcomes of all the enrolled subjects are observed, a 
dose will be selected as the estimated MTD. The estimation is separated from the design for dose 
finding. The MTD is selected by performing an isotonic regression that borrows strength cross 
doses. Let p̂ i be the posterior mean of DLT rate, the pooled adjacent violators algorithm is 
applied on p̂ i so that the resulting transformed values p̂ i* increase with the dose levels. That is p̂ i* 
≤ p̂ i+1* for all i. The recommended MTD is the dose with a toxicity probability p̂ i* closest to the 
target DLT rate 25%, ie: 
Estimated MTD = argmin |p̂ i* - 25%| 
Dose-escalation Rules  
Dose-escalation begins with enrollment subjects to dose level 1. In each cohort, up to 4 subjects 
are enrolled. Once all subjects in previous cohorts have completed DLT evaluation, the next 
cohort of subjects can be enrolled. Subsequent enrollment and dose selection occurs via the 
following rules: 
4. 
No untried dose levels may be skipped. At least 2 evaluable subjects per dose level is 
required to escalate until 1 DLT is observed at any dose level, then 3 evaluable subjects are 
required for further dose-escalation. 
5. 
If a dose level i is unacceptable, de-escalate to the lower dose level and never treat future 
subjects at level i. If i = 1, stop the trial and conclude no dose is safe. 
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Interim Monitoring  
The dose-escalation will be closely monitored for safety and for identifying the MTD. If no 
doses are safe, dose-escalation for that population will stop and no MTD will be declared. 
Safety Monitoring 
If no doses are safe, dose-escalation will stop and no MTD will be declared. Formally if: 
Pr(pi >25%) >95% for all i 
Identification of MTD  
After each dose level cohort, the estimation of MTD will be performed. If at least 6 DE subjects 
have been treated at the estimated MTD level and the model’s next recommended dose is the 
same or below the MTD, the dose-escalation may be stopped and MTD can be declared. 
Alternatively, if the model’s next recommended dose is above the estimated MTD level, and at 
least 6 DE subjects have already been treated at the higher dose level, and the observed DLT rate 
at the recommended higher dose level exceeds the target DLT rate of 25%, the dose-escalation 
may also be stopped and MTD can be declared. 
Simulation Studies  
To evaluate the operating characteristics of the dose-escalation design, simulation studies were 
performed considering the following different scenarios.  
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The plots illustrate the true DLT rate at each dose level.  
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In each scenario, the dose-escalation and MTD-estimation process is replicated with 
1000 replications. The probability of being selected as MTD, average number of DLT and the 
average number of subjects treated for each dose level is provided.  
 
Scenario 1: 
Dose 5 is MTD 
No dose is 
safe 
1 
2 
3 
4 
5 
True DLT rate 
 
0.02 
0.03 
0.05 
0.08 
0.12 
Mean # of subjects 
 
2.129 
2.350 
2.607 
2.963 
5.352 
Mean # of DLTs 
 
0.031 
0.087 
0.150 
0.264 
0.633 
Pr(Chosen MTD) 
0.003 
0.003 
0.015 
0.039 
0.082 
0.858 
DLT = dose-limiting toxicity; MTD = maximum tolerated dose; Pr = probability 
 
Under Scenario 1, the probability of selecting the true MTD is 0.858 according to simulation 
study. The observed average DLT rate is 0.075. 
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Scenario 2: 
Dose 4 is MTD 
No dose is 
safe 
1 
2 
3 
4 
5 
True DLT rate 
 
0.1 
0.13 
0.18 
0.25 
0.36 
Mean # of subjects 
 
2.957 
3.359 
3.499 
3.325 
2.126 
Mean # of DLTs 
 
0.290 
0.445 
0.641 
0.875 
0.804 
Pr(Chosen MTD) 
0.048 
0.070 
0.161 
0.239 
0.296 
0.186 
DLT = dose-limiting toxicity; MTD = maximum tolerated dose; Pr = probability 
 
Under Scenario 2, the probability of selecting the true MTD is 0.296 according to simulation 
study. The observed average DLT rate is 0.219 and the number of subjects treated above MTD is 
2.126. 
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Scenario 3: 
Dose 2 is MTD 
No dose is 
safe 
1 
2 
3 
4 
5 
True DLT rate 
 
0.2 
0.25 
0.3 
0.35 
0.45 
Mean # of subjects 
 
3.810 
3.471 
2.476 
1.615 
0.690 
Mean # of DLTs 
 
0.762 
0.836 
0.712 
0.521 
0.316 
Pr(Chosen MTD) 
0.170 
0.215 
0.247 
0.187 
0.138 
0.043 
DLT = dose-limiting toxicity; MTD = maximum tolerated dose; Pr = probability 
 
Under Scenario 3, the probability of selecting the true MTD is 0.247 according to simulation 
study. The observed average DLT rate is 0.318 and the number of subjects treated above MTD is 
4.781.  
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Scenario 4: 
Dose 1 is MTD 
No dose is 
safe 
1 
2 
3 
4 
5 
True DLT rate 
 
0.2 
0.35 
0.45 
0.5 
0.53 
Mean # of subjects 
 
4.579 
3.931 
1.777 
0.522 
0.163 
Mean # of DLTs 
 
0.949 
1.352 
0.793 
0.246 
0.077 
Pr(Chosen MTD) 
0.197 
0.358 
0.312 
0.096 
0.026 
0.011 
DLT = dose-limiting toxicity; MTD = maximum tolerated dose; Pr = probability 
 
Under Scenario 4, the probability of selecting the true MTD is 0.358 according to simulation 
study. The observed average DLT rate is 0.358 and the number of subjects treated above MTD is 
6.393. 
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Scenario 5: 
Dose 2 is MTD 
No dose is 
safe 
1 
2 
3 
4 
5 
True DLT rate 
 
0.12 
0.22 
0.37 
0.53 
0.7 
Mean # of subjects 
 
3.601 
4.630 
3.486 
1.337 
0.217 
Mean # of DLTs 
 
0.421 
1.069 
1.309 
0.703 
0.154 
Pr(Chosen MTD) 
0.065 
0.184 
0.414 
0.277 
0.057 
0.003 
DLT = dose-limiting toxicity; MTD = maximum tolerated dose; Pr = probability 
 
Under Scenario 5, the probability of selecting the true MTD is 0.414 according to simulation 
study. The observed average DLT rate is 0.291 and the number of subjects treated above MTD is 
5.04. 
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Scenario 6: 
Dose 1 is MTD 
No dose is 
safe 
1 
2 
3 
4 
5 
True DLT rate 
 
0.25 
0.4 
0.55 
0.7 
0.85 
Mean # of subjects 
 
4.976 
3.545 
1.174 
0.150 
0.002 
Mean # of DLTs 
 
1.267 
1.429 
0.675 
0.115 
0.002 
Pr(Chosen MTD) 
0.266 
0.432 
0.260 
0.040 
0.002 
0.000 
DLT = dose-limiting toxicity; MTD = maximum tolerated dose; Pr = probability 
 
Under Scenario 6, the probability of selecting the true MTD is 0.432 according to simulation 
study. The observed average DLT rate is 0.408 and the number of subjects treated above MTD is 
4.871.  
Overall, mTPI has high probability to identify the true MTD and avoid treating subjects at unsafe 
doses. Based on the simulation results, the mTPI method is both reliable and safe in 
dose-escalation. 
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APPENDIX D. 
PERFORMANCE STATUS SCALES CONVERSION  
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APPENDIX E. 
GUIDANCE ON CONTRACEPTION: PARTS A, B, AND C  
Acceptable methods for highly effective birth control  
Subjects who can father childrena and who are sexually active with a pregnant or breastfeeding 
person must use the contraceptives in Option 1 or 2:  
• Option 1: Male condom with spermicide and cervical cap  
• Option 2: Male condom with spermicide and diaphragm  
Subjects who are of childbearing potentialb or whose partners are of childbearing potential who 
are sexually active in a way that could lead to pregnancy may choose to use any TWO of the 
following methods:           
• Hormonal methods of contraception (excluding progestin-only pills). 
• Intrauterine device with failure rate <1% 
• Tubal ligation 
• Partner’s vasectomy (at least 90 days from the date of surgery with a semen analysis 
documenting azoospermia) 
• A barrier method (male or female condom with spermicide, cervical cap with 
spermicide, diaphragm with spermicide)c           
a A subject who can father children is anyone born male who has testes and who has not undergone surgical 
sterilization (eg, vasectomy followed by a clinical test proving that the procedure was effective). 
b A subject of childbearing potential is defined as anyone born female who has experienced menarche and who has 
not undergone surgical sterilization (eg, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or has not 
completed menopause. Menopause is defined clinically as 12 months of amenorrhea in a person born female over 
age 45 in the absence of other biological, physiological, or pharmacological causes. 
c A barrier method should only be used with a highly effective birth control method that is not a barrier method. 
Barrier methods alone, including a double-barrier method, are not considered highly effective contraceptive 
measures (see unacceptable methods of contraception) 
Unacceptable methods of contraception  
Tables adapted from “Recommendations related to contraception and pregnancy testing in clinical trials” advisory non-binding 
guidance represented at the Clinical Trials Facilitation Group meeting, Rome 2014. 
• Abstinence (including periodic 
abstinence) 
• Any barrier method without 
spermicide 
• No method 
• Spermicide only 
• Withdrawal 
• Progesterone-only pills 
• Rhythm 
• Barrier methods alone; including 
double-barrier methods 
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APPENDIX F. 
GUIDANCE ON CONTRACEPTION: PART D  
Acceptable methods for highly effective birth control  
Subjects who can father childrena and who are sexually active with a pregnant or breastfeeding 
person must use a condom even if the subject is vasectomized (must be confirmed by two 
negative semen analyses).           
Subjects who are of childbearing potentialb are sexually active in a way that could lead to 
pregnancy may choose to use any TWO of the following methods:           
• Intrauterine devices (IUD) excluding progesterone T 
• Hormonal methods of contraception (hormonal patches, injections, vaginal rings, 
implants, or birth control pills excluding progestin-only “mini pills”). 
• Tubal ligation 
• Partner’s vasectomy (must be confirmed by two negative semen analyses) 
• Barrier methods (male condoms and female diaphragm or cervical cap)c            
Subjects who can father childrena and are sexually active with a person of childbearing 
potentialb in a way that could lead to pregnancy must consistently use 2 methods of birth 
control, one of which must be a latex or synthetic condom even if the subject is vasectomized 
(must be confirmed by two negative semen analyses) along with any one of the following 
methods:            
• Intrauterine devices (IUD) excluding progesterone T 
• Hormonal methods of contraception (hormonal patches, injections, vaginal rings, 
implants, or birth control pills excluding progestin-only “mini pills) 
• Tubal ligation 
a A subject who can father children is anyone born male who has testes and who has not undergone surgical 
sterilization (eg, vasectomy followed by a clinical test proving that the procedure was effective). 
b A subject of childbearing potential is defined as anyone born female who has experienced menarche and who has 
not undergone surgical sterilization (eg, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or has not 
completed menopause. Menopause is defined per the pomalidomide REMS program as 24 months of amenorrhea 
in a person born female over age 50 in the absence of other biological, physiological, or pharmacological causes.  
c A barrier method should only be used with a highly effective birth control method that is not a barrier method. 
Barrier methods alone, including a double-barrier method, are not considered highly effective contraceptive 
measures (see unacceptable methods of contraception) 
Unacceptable methods of contraception  
Tables adapted from “Recommendations related to contraception and pregnancy testing in clinical trials” advisory non-binding 
guidance represented at the Clinical Trials Facilitation Group meeting, Rome 2014. 
• Abstinence (including periodic 
abstinence) 
• Female condom 
• No method 
• Cervical shield 
• Withdrawal 
• Spermicide only 
• Intrauterine device Progesterone T 
• Progesterone-only pills 
• Rhythm 
• Barrier methods alone; including 
double-barrier methods 
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APPENDIX G. 
NEW YORK HEART ASSOCIATION CLASSIFICATION  
Online source: http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/Classes-of-Heart-
Failure_UCM_306328_Article.jsp 
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APPENDIX H. 
PROHIBITED CONCOMINANT MEDICATIONS  
CYP3A4 
Strong Inhibitors1 
boceprevir, clarithromycin, cobicistat, 
danoprevir and ritonavir, elvitegravir and 
ritonavir, grapefruit juice, idelalisib, 
indinavir and ritonavir, itraconazole, 
ketoconazole, lopinavir and ritonavir, 
nefazodone, nelfinavir, paritaprevir and 
ritonavir and (ombitasvir and/or dasabuvir), 
posaconazole, ritonavir, saquinavir and 
ritonavir, telaprevir, tipranavir and ritonavir, 
telithromycin, troleandomycin, voriconazole 
Moderate Inhibitors2 
aprepitant, ciprofloxacin, 
conivaptan, crizotinib, cyclosporine, 
diltiazem, dronedarone, erythromycin, 
fluconazole, fluvoxamine, 
imatinib, tofisopam, verapamil  
Strong Inducers1 
apalutamide, carbamazepine, enzalutamide, 
mitotane, phenytoin, rifampin, St. John’s 
wort 
Moderate Inducers2 
bosentan, efavirenz, etravirine, 
phenobarbital, primidone  
P-gp 
Inhibitors1 
amiodarone, carvedilol, clarithromycin, 
dronedarone, itraconazole, lapatinib, 
lopinavir and ritonavir, propafenone, 
quinidine, ranolazine, ritonavir, saquinavir 
and ritonavir, telaprevir, tipranavir and 
ritonavir, verapamil 
Inducers2 
rifampin 
1 Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [online]. Available from: 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-
inhibitors-and-inducers. Accessed Jan 07, 2021. 
2 This information is based on or an extract from UW Drug Interaction Database (DIDB) Copyright University of 
Washington. Accessed: Jan 05, 2021. 
 
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APPENDIX I. 
MODIFICATION OF DIET IN RENAL DISEASE EQUATION  
• The estimated GFR should be calculated using the MDRD equation as applicable, with 
serum creatinine (Scr) reported in mg/dL (Levey 2006).  
• GFR (mL/min/1.73 m2) = 175 x (Scr)–1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if 
African American) 
 
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APPENDIX J. 
DEFINITION OF RESPONSE AND PROGRESSION CRITERIA 
(MODIFIED FROM IMWG)  
Response Subcategory 
Response Criteriaa 
Stringent Complete 
Response  
(sCR) 
CR, as defined below, plus the following: 
Normal FLC ratiob and absence of clonal cellsc in bone marrow by 
immunohistochemistry or immunofluorescence 
Complete Response 
(CR)b 
Negative immunofixation of serum and urine and disappearance of any soft tissue 
plasmacytomas, and <5% plasma cells in bone marrow. 
Very Good Partial 
Response  
(VGPR)b 
Serum and urine M-protein detectable by immunofixation but not on 
electrophoresis or ≥90% reduction in serum M-protein level plus urine 
M-protein level <100 mg per 24 hour. 
Partial Response  
(PR) 
≥50% reduction of serum M-protein and reduction in 24-hour urinary 
M-protein by ≥90% or to <200 mg per 24 hour. 
If serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference 
between involved and uninvolved FLC levels is required in place of the M-protein 
criteria. 
In addition to the above criteria, if present at baseline, ≥50% reduction in the size 
of soft tissue plasmacytomas is also required 
Minor (Minimal) 
Response  
(MR) 
25 to 49% reduction of serum M-protein and reduction in 24-hour urine M-protein 
by 50 to 89%, which still exceeds 200 mg per 24 hours. In addition, if present at 
baseline, 25 to 49% reduction in the size of soft tissue plasmacytomas is also 
required. No increase in the size or number of lytic bone lesions (development of 
compression fracture does not exclude response). 
Stable Disease 
 (SD) 
Not meeting criteria for CR, VGPR, PR, MR, or progression. 
Progressive disease 
Any of the following: 
• Increase of 25% from lowest response value in any one or more of the 
following: 
1. Serum M-component (absolute increase must be ≥0.5 g/dL)d and/or 
2. Urine M-component (absolute increase must be ≥200 mg per 24 hr) and/or 
3. Only in subjects without measurable serum and urine M-protein levels: the 
difference between involved and uninvolved FLC levels (absolute increase 
must be >10 mg/dL 
4. Bone marrow plasma cell percentage (absolute % must be ≥10%) 
• Definite development of new bone lesions or soft tissue plasmacytomas or 
definite increase in the size of existing bone lesions or soft tissue 
plasmacytomas 
• Development of hypercalcemia (corrected serum calcium >11.5 mg/100 mL) 
that can be attributed solely to the plasma cell proliferative disorder 
a 
All response categories require 2 consecutive assessments made at any time before the institution of any new therapy; all 
categories also require no known evidence of progressive or new bone lesions if radiographic studies were performed. 
Radiographic studies are not required to satisfy these response requirements. Bone marrow assessments need not be 
confirmed. 
b 
Note clarification to IMWG criteria for coding CR and VGPR in subjects in whom the only measurable disease is by serum 
FLC levels: CR in such subjects is defined as a normal FLC ratio of 0.26 to 1.65 in addition to CR criteria listed above. 
VGPR in such subjects is defined as a >90% decrease in the difference between involved and uninvolved FLC levels. 
c 
Presence or absence of clonal cells is based upon the / ratio. An abnormal / ratio by immunohistochemistry and/or 
immunofluorescence requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting presence of an 
abnormal clone is / of >4:1 or <1:2. 
d 
For progressive disease, serum M-component increase of  1 g/dL is sufficient to define progression if starting 
M-component is 5 g/dL 
Note: for IgA and IgD myelomas, quantitative immunoglobulin measurements are preferred for disease assessments; the 
same percentage change applies as for serum M-spike 
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APPENDIX K. 
INVESTIGATOR SIGNATURE PAGE  
Investigator Statement and Signature 
 
I have read the attached protocol entitled A phase 1 study of SEA-BCMA in subjects with 
relapsed or refractory multiple myeloma. 
I understand and agree to the provisions of the protocol, and I accept the responsibilities listed 
above in my role as principal investigator for the study. 
 
 
 
Investigator Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Investigator Name, Printed 
 
 
 
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APPENDIX L. 
DOCUMENT HISTORY  
Version 
Date 
Original 
26-Mar-2018 
Amendment 1 
17-May-2018 
Amendment 2 
14-Feb-2019 
Amendment 3 
27-Feb-2020 
Amendment 4 
13-May-2020 
Amendment 5 
04-Mar-2021 
Amendment 6 
22-Mar-2021 
Amendment 7 
06-Aug-2021 
Amendment 8 
31-Mar-2022 
Amendment 9 
03-Jun-2022 
 
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Summary of Changes in Amendment 1  
Section(s) 
Change 
Rationale 
3.1.1 
Table 2 
Revised the mTPI methodology to stipulate the following: 
Using a target DLT rate of 25% with a 5% margin, the 
3 intervals will be (0, 20%), (20%, 30%), and (30%, 100%), 
and the corresponding dosing decision rules would be:  
Escalate if current DLT rate is most likely <20%  
Continue if current DLT rate is most likely between 20% and 
30%  
De-escalate if current DLT rate is likely >30% 
The dose-finding spreadsheet was revised based to reflect the 
target DLT rate of 25% with a 5% margin 
To reflect that a target DLT 
rate 25% with a 5% margin 
will be used during dose-
escalation 
3.1.3 
5.2.3 
Revised the DLT criteria to clarify that any treatment-related 
deaths will be considered DLTs. 
In addition, AEs considered DLTs were revised to reflect the 
following: 
○ 
Grade 4 neutropenia lasting more than 5 days 
○ 
Thrombocytopenia ≥ Grade 4, or Grade 3 
thrombocytopenia with clinically significant bleeding 
○ 
Any ≥ Grade 4 infusion-related reactions (IRRs) or 
Grade 3 IRRs that do not resolve to ≤ Grade 2 within 24 hours 
with infusion interruption, infusion rate reduction, and/or 
standard supportive measures. In the event of a Grade 3 IRR 
in ≥20% of subjects (ie, 2 or more in the first 10 subjects), all 
subsequent subjects will require premedication and/or 
modification of infusion approach per the recommendation of 
the SMC. For subjects receiving premedication, any ≥ Grade 
3 IRR will be considered a DLT. 
○ 
Any Grade ≥3 electrolyte abnormality that does not 
resolve, with or without intervention, to ≤ Grade 1 or the 
baseline grade within 72 hours 
Section 5.2.3was revised to include additional follow-up for 
subjects with Grade 4 neutropenia or Grade 3 electrolyte 
abnormalities as follows: 
During dose-escalation, subjects with Grade 4 neutropenia 
must have a follow-up CBC with differential obtained 5 days 
from the time of assessment for evaluation of DLT. In 
addition, subjects with Grade 3 electrolyte abnormalities must 
have a follow-up chemistry panel obtained 72 hours from the 
time of assessment for evaluation of DLT. 
To provide more conservative 
DLT criteria during dose-
escalation 
3.1.4 
Revised the stopping criteria to indicate that the study will be 
halted if the rate of on-study toxic deaths unrelated to 
underlying disease occurring within 30 days of dose exceeds 
10% (initially, 2 or more of the first 20 subjects) 
To provide more conservative 
stopping criteria for on-study 
toxic deaths 
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Section(s) 
Change 
Rationale 
5.2.2 
6.4.1 
Revised the observation period for Cycle 1, Day 1 as follows: 
On Cycle 1, Day 1, subjects will be closely observed in the 
clinic for at least 6 hours after completion of study treatment 
administration during dose-escalation. Vital signs will be 
collected as described in Section 6.4. Additional monitoring 
for subsequent cycles will be considered upon review of 
safety data with the SMC. The observation period after 
completion of study treatment administration on Cycle 1, 
Day 1 may be reduced to 2 hours during dose expansion if the 
SMC determines that safety is adequate after review of data 
from the dose-escalation cohort. 
In addition, vital sign monitoring time points of 240 minutes 
and 360 minutes were added to Schedule of Events for the 
Cycle 1, Day 1 visit for subjects in dose-escalation 
Extended observation after the 
Cycle 1, Day 1 infusion will be 
utilized during dose-escalation, 
and may be discontinued 
during dose expansion if 
supported by safety data 
Table 4 
Revised the dose modifications for nonhematologic AEs and 
laboratory abnormalities as follows: 
Grade 3: Withhold dose until toxicity is ≤ Grade 1 or 
baselinea, and then resume treatment at a lower dose levelb 
Grade 4: Discontinue study treatment 
To revise the recommended 
dose modifications for 
SEA-BCMA-associated 
toxicity 
Appendix C 
Revised the mTPI simulation report to reflect a target DLT 
rate of 25% with a 5% margin 
Added Scenarios 5 and 6 to the simulation report 
To reflect the 25% target DLT 
rate and to expand the 
evaluation of the operating 
characteristics of the mTPI 
model  
AE = adverse event; DLT = dose-limiting toxicity; IRR = infusion-related reaction; mTPI = modified toxicity 
probability interval; SMC = Safety Monitoring Committee 
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Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 145 of 158 
Summary of Changes in Amendment 2  
Section(s) 
Change 
Rationale 
Multiple 
Revised to reflect that PK assessments are performed using 
serum samples only  
Correction 
3.1.1 
 
Revised the required observation period between dosing of 
the first 2 subjects above Dose Level 1 from 72 hours to 
24 hours 
To reduce the time to dosing of 
the second subject at each dose 
level above Dose Level 1 
7.6.1.2 
Revised the AE reporting requirements as follows: 
Progression of the Underlying Malignancy Cancer  
Since progression of underlying malignancy is being assessed 
as an efficacy variable, it should not be reported as an AE or 
SAE. The terms “Disease Progression”, “Progression of 
Disease” or “Malignant disease progression” and other similar 
terms should not be used to describe an AE or SAE. However, 
clinical symptoms of progression may be reported as AEs or 
SAEs if the symptom cannot be determined as exclusively 
due to progression of the underlying malignancy or does not 
fit the expected pattern of progression for the disease under 
study. In addition, complications from progression of the 
underlying malignancy should be reported as AEs or SAEs. 
Do not use the term “disease progression” alone when 
reporting AEs, including SAEs, because it is too nonspecific. 
Symptoms of disease progression that meet the criteria for an 
SAE must be reported. When possible, report the specific 
disease (clinical) manifestation of the progression (eg, 
“malignant pleural effusion”, “spinal bone metastases”, 
“lymphadenopathy”, “brain metastases”). Otherwise, it is 
acceptable to report the specific disease (eg, non-Hodgkin 
lymphoma) as an SAE. 
To clarify that disease 
progression should not be 
captured as an AE or SAE 
7.6.1.2 
Revised pregnancy monitoring requirements as follows: 
As part of the study, all pregnancies will be monitored for the 
full duration and all perinatal and neonatal outcomes should 
be reported. 
To clarify that pregnancy 
monitoring is to be performed 
as part of the study 
7.6.6 
Revised the requirement for electrocardiograms (ECGs) as 
follows: 
Subjects will be monitored for changes in cardiac 
repolarization through assessment of ECGs conducted in 
triplicate at times outlined in Appendix A and Section 6 There 
is a 30-minute window to perform ECGs. Waiting periods 
between replicate ECGs are not required. 
To clarify that all ECG 
measurements are to be 
collected in triplicate 
Appendix A 
Revised table to indicate that Day 15 ECG measurements are 
required during Cycle 1 only 
Revised footnote A to clarify ECG collection requirements 
Clarification 
Appendix B 
Revised the time point associated with the Baseline/Screening 
visit from “predose” to “non-dosing” 
Clarification  
AE = adverse event; ECG = electrocardiogram; PK = pharmacokinetic; SAE = serious adverse event 
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Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 146 of 158 
Summary of Changes in Amendment 3  
Section(s) 
Change 
Rationale 
Title page 
Updated phase of study from 1 to 1b 
To reflect the amended study design 
Synopsis, 
Sections 
1.6.1, 2, 
3.1.2, 3.1.8, 
3.1.8.2, 3.3, 
4.1, 6.3, 7.2, 
9.1, 9.3.10,  
Appendix A,  
Appendix B 
Added Part B: Monotherapy Intensive Dosing 
Affected sections include 
• 
Rationale for intensive dosing schedule 
• 
Objectives 
• 
Study design 
• 
Safety monitoring 
• 
Method of assigning subjects to treatment 
groups 
• 
Inclusion criteria  
o 
added criterion 4b. Part B and Part C: 
Subjects must have received at least 
3 prior lines of antimyeloma therapy and 
must be refractory to at least 1 agent in 
each of the following classes: PI, IMiD, 
and an anti-CD38 antibody 
• 
Study activities 
• 
Response/Efficacy assessments 
• 
Determination of sample size 
• 
Interim analyses 
• 
Schedule of events 
• 
PK, biomarker, and biomarker sampling time 
points 
To evaluate an alternative SEA-BCMA 
monotherapy dosing schedule 
Synopsis, 
Sections 
1.6.2, 2, 
3.1.3, 3.1.6, 
3.1.8, 3.1.8.2, 
3.3, 3.3.1.2, 
4.1, 4.2, 
4.4.1, 5.2.3, 
5.3, 5.4, 6.4, 
7.2, 7.3, 7.4, 
9.1, 9.3.7, 
9.3.10,  
Appendix A,  
Appendix B 
Added Part C: SEA-BCMA in combination with 
dexamethasone 
Affected sections include 
• 
Rationale for dexamethasone combination 
therapy 
• 
Objectives 
• 
Study design 
• 
Retreatment 
• 
Safety monitoring 
• 
Method of assigning subjects to treatment 
groups 
• 
Rationale for selection of combination 
therapy 
• 
Inclusion criteria  
o 
added criterion 4b. Part B and Part C: 
Subjects must have received at least 
3 prior lines of antimyeloma therapy and 
must be refractory to at least 1 agent in 
each of the following classes: PI, IMiD, 
and an anti-CD38 antibody 
• 
Exclusion criteria 
o 
Added exclusion criterion 17. Part C 
only: Known intolerance to 
corticosteroids 
To evaluate the safety, tolerability, and 
efficacy of SEA-BCMA in 
combination with dexamethasone 
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Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 147 of 158 
Section(s) 
Change 
Rationale 
o 
Added exclusion criterion 18. Part C 
only: Any uncontrolled psychoses 
• 
Discontinuation of study treatment 
• 
Dose modifications 
• 
Dexamethasone treatment 
o 
Description, method of procurement, 
dose and administration, dose 
modifications, storage and handling, 
packaging and labeling, and preparation 
• 
Required premedication and postmedication 
• 
Study activities 
• 
Response/Efficacy assessments 
• 
Qualitative interviews 
• 
Pharmacokinetic and immunogenicity 
assessments 
• 
Determination of sample size 
• 
Interim analyses 
• 
Schedule of events 
• 
PK, biomarker, and biomarker sampling time 
points 
 
Section 1.1 
Updated with newly approved regimens for subjects 
with MM.  
Removed the following sentence: SEA-BCMA in 
combination with an autologous T-cell product 
expressing an antibody-coupled T-cell receptor that 
recognizes antibodies, is currently being evaluated in 
a phase I study with MM subjects. 
Update with current information 
Section 2, 
9.2.6  
Added exploratory endpoint to assess MRD in 
subjects with VGPR or better 
To improve efficacy monitoring 
Section 3.1.4 
Edited the following DLT: 
• 
Any Grade ≥3 electrolyte asymptomatic 
laboratory abnormality that does not resolve, 
with or without intervention, to ≤ Grade 1 or 
the baseline grade within 72 hours 
To improve safety monitoring  
Section 3.1.7 
Added section to allow treatment beyond progression 
under specified conditions. 
To allow subjects receiving clinical 
benefit to be retreated 
Section 
3.3.1.1 
Added rationale for selection of monotherapy 
expansion dose 
Update with current information 
Sections 
5.2.3, 5.6.1 
Updated dose modifications recommendations for 
SEA-BCMA monotherapy 
To refine dose modification guidance; 
as IRRs have not yet been correlated 
with dose, and all IRRs that occurred 
during Cycle 1 Day 1 were successfully 
prevented by premedication at the next 
dose, dose reduction at the next dose 
can be considered but is not required 
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Clinical Protocol 
Amendment 9; 03-Jun-2022 
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Seagen Inc. - Confidential 
Page 148 of 158 
Section(s) 
Change 
Rationale 
Section 7.7.3 
Removed amylase and lipase from clinical laboratory 
tests 
Streamline safety monitoring; no signal 
of pancreatic toxicity has been detected 
thus far on the phase 1 trial 
Section 6.2, 
Appendix A, 
Appendix B 
Removed q4wk SEA-BCMA dosing schedule 
To remove unused dosing schedule 
Sections 6.2, 
6.3, 6.4, 6.9, 
7.1, 7.7.3,  
Appendix A 
Clarified that UPC calculation is urine protein to 
creatinine ratio and added units of mg/mg. For 
example, 
• 
Urine protein to creatinine ratio (UPCR) 
calculation; 24-hour urine collection required if 
UPCR >2 mg/mg 
Clarification 
Sections 6.6, 
6.7, 6.8 
Only subjects in Part A will have IHR and IHR 
follow-up visits 
To specify that IHR visits are 
conducted for subjects in Part A only 
Appendix H 
Added definition of response and progression criteria 
modified from IMWG guidance 
Clarification 
Throughout 
protocol  
Minor corrections and clarifications 
Corrections and clarifications 
BCMA = B-cell maturation antigen; CD38 = cluster of differentiation 38; DLT = dose-limiting toxicity; IHR = 
infusion/hypersensitivity reaction; IMiD = immunomodulatory drug; IMWG = International Myeloma Working 
Group; IRR = infusion-related reaction MM = multiple myeloma; MRD = minimal residual disease; PI = 
proteasome inhibitor; PK = pharmacokinetic; UPC = urine protein to creatinine; UPCR = urine protein to 
creatinine ratio; VGPR = very good partial response 
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Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 149 of 158 
Summary of Changes in Amendment 4  
Section(s) 
Change 
Rationale 
Section 
6.2.3.1, 
Appendix A 
Added text to specify that in Part A, ECGs will be 
conducted on Day 1 of Cycle 1, but not conducted on 
Day 1 of subsequent cycles. 
To specify that in Part A, ECGs should 
not be conducted on Day 1 of Cycle 2 
and subsequent cycles. 
ECG = electrocardiogram 
 
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Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 150 of 158 
Summary of Changes in Amendment 5  
Section(s) 
Change 
Rationale 
Throughout 
“Seattle Genetics” replaced with “Seagen” throughout 
To reflect change in the company name 
Synopsis, 
Sections 
3.1.1, 3.2, 
and 5.2.3 
Added criteria for intrasubject dose escalation. 
To provide objective criteria for 
decisions about intrasubject dose 
escalation 
Sections 
3.1.2 and 
3.1.3 
If 2 or more DLTs occur in the first 6 subjects in any 
Part B or C cohort, the MTD will be considered 
exceeded.  
To improve subject safety and enable a 
more accurate estimation of the MTD  
Sections 
3.1.3 and 
3.3.1.2 
Specified that in Part C Optional Cohort 2, 
SEA-BCMA will be administered at a dose of 800 mg 
during Cyles 1 and 2 
To clearly specify the starting dose of 
SEA-BCMA dose in Part C Optional 
Cohort 2 
Section 3.1.5 
Study stopping criteria apply throughout the entire 
study 
Clarification 
Section 3.1.7 
Removed section allowing treatment beyond 
progression 
To require treatment discontinuation at 
the time of IMWG confirmed 
progressive disease 
Section 5.2.3 
and 5.6.1 
Specified that recommended dose modifications are 
for toxicities regardless of relatedness to 
SEA-BCMA. 
Specified that after Grade 3 non-hematologic 
toxicities have recovered to baseline or ≤ Grade 1, 
SEA-BCMA may be resumed at 50% of the previous 
dose. 
To improve subject safety 
 
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Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 151 of 158 
Summary of Changes in Amendment 6  
Section(s) 
Change 
Rationale 
Protocol 
Synopsis 
Added criterion for Part D to Study Population. 
Added Number of Planned Subjects for Part D. 
Added Part D Study Design. 
Added pomalidomide to Combination Products. 
Changes Statistical Methods to include 30 to 70% 
ORR (previously 30 to 50%). 
To delineate the differences between 
Part D criterion, patient population, 
response benchmarks, and treatment 
from those for Parts A, B, and C. 
1.1 
Added information on the use of 
pomalidomide/dexamethasone in combination with 
monoclonal antibodies to treat multiple myeloma. 
Justification of this combination with 
SEA-BCMA. 
1.6  
Added information on the favorable safety profile and 
preliminary evidence of clinical activity based on data 
from Part A. 
Justification for the investigation of 
SEA-BCMA in combination with 
approved SOC agents. 
1.3.2.2  
Added rationale for pomalidomide and 
dexamethasone combination therapy. 
To describe the enhancement of natural 
killer cell expansion and its 
potentiation of ADCC. 
3.1  
Added Study Design Schema image. 
To visually clarify and summarize the 4 
parts of the study design. 
3.1.3  
Added Part D to Combination Therapy Cohorts. 
NA 
3.3.6  
Changed Retreatment criterion from a partial PR or 
better to clinical benefit (defined as stabilization or 
improvement of disease-related symptoms as assessed 
by the investigator). 
To allow for consideration of 
retreatment in subjects receiving 
clinical benefit. 
4.1  
Added Part D to Inclusion Criteria. 
Added more stringent guidance for subjects of 
childbearing potential. 
To delineate between criterion for Part 
D and those for Parts A, and B/C. 
4.2  
Added exclusion criterion specific to Part D. 
To capture risks specific to 
pomalidomide treatment.  
4.3  
Added washout period guidance for females treated 
with FSH. 
Improve subject safety  
4.3.1  
Added information specific to Part D for women of 
childbearing potential. 
To delineate between criterion for Part 
D and those for Parts A, and B/C. 
4.4.1  
Added Discontinuation of Study Treatment 
information specific to Part D. 
Information related to new Part D 
cohort. 
5.4  
Added pomalidomide section to Treatments. 
Information related to new part D 
cohort. 
5.6  
Added required premedication regimen 
Improve subject safety  
5.7.1  
Changes to Required Concomitant Therapy. 
Emerging safety data as well as the 
requirement of thromboembolic 
prophylaxis with pomalidomide.  
5.7.3  
Added Part D to Prohibited Concomitant Therapy. 
Information related to new Part D 
cohort. 
6.2.3, 6.4.3  
Added requirement that premedication be delivered 
approximately 45 to 90 minutes prior to the infusion 
of SEA-BCMA. 
Improve subject safety  
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Clinical Protocol 
Amendment 9; 03-Jun-2022 
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Seagen Inc. - Confidential 
Page 152 of 158 
Section(s) 
Change 
Rationale 
6.4.3.1  
Changed UPCR calculation to spot urine test. 
Clarification  
6.5  
Added Part D Study Activities. 
Information related to new Part D 
cohort. 
9.1  
Assumption for Determination of Sample Size 
changed from ORR between 30 and 50% to between 
30 and 70%.  
Upper range of response increased due 
to addition of Part D combination 
therapy in an earlier line. 
Appendix A  
Premedication added to Schedule of Event tables for 
Parts B and C. 
Schedule of events table added for Part D. 
Improve subject safety and information 
related to new Part D cohort. 
Appendix B 
PK, ATA, and Biomarker Sampling Timepoints 
added for Part D. 
Information related to new Part D 
cohort. 
Appendix F  
Contraceptive guidance specific to Part D added. 
Align with guidance required for 
pomalidomide.  
 
 
 
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Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 153 of 158 
Summary of Changes in Amendment 7  
Section(s) 
Change 
Rationale 
Global 
Changed the term “patient” to “subject” when 
referring to a person who is involved in a clinical 
study 
Modification to style guide 
 
 
Global 
Changed the phrase “approval of the SMC” to 
“recommendation of the SMC” 
Accuracy of terminology 
Synopsis 
Clarified patient run-in language for Part C Optional 
Cohort 2 
Clarification 
Synopsis, 
1.6.2.4, 3.1, 
3.3.1.2, 4, 
5.5, 5.7, 6.1, 
9.1, 9.3 1.2, 
1.6.2.3 
 
Added new cohort: SEA-BCMA in combination with 
nirogacestat and dexamethasone (Part E) 
New cohort 
Synopsis, 
 3.1.3, 
3.3.1.2, 6.5.3  
Added new cohort: intensive dosing of SEA-BCMA 
in combination with pomalidomide and 
dexamethasone (Part D) 
New cohort 
7.7 
Added adverse events of special interest to Reporting 
Periods 
Added investigator causality assessment to Serious 
Adverse Events Require Immediate Reporting 
New section on Adverse Events of Special Interest 
To improve subject safety 
Appendix A  
Appendix B  
Schedule of Events and PK/ATA/Biomarker 
Sampling Tables added for Part D Cohort 2 and 
Part E 
Information related to new cohorts 
Appendix E 
Appendix F  
Unacceptable methods of contraception language 
around barrier methods modified  
Clarification 
Appendix H  
New appendix with information on P-gp and 
CYP3A4 inducers/inhibitors 
Background on exclusion criteria 
surrounding the use strong inducers or 
moderate to strong inhibitors of 
CYP3A4 or strong inhibitors or 
inducers of P-glycoprotein for Parts D 
and E 
 
 
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Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 154 of 158 
Summary of Changes in Amendment 8  
Section(s) 
Change 
Rationale 
Synopsis, 
Section 2   
Modified the following primary objective: 
• 
Identify the maximum tolerated dose (MTD) and/or 
optimal dose and schedule of SEA-BCMA 
monotherapy, and in combination with 
dexamethasone, in subjects with RRMM 
 
Removed the following primary objective: 
• 
Evaluate the safety and tolerability of SEA-BCMA in 
combination with nirogacestat and dexamethasone in 
subjects with RRMM 
 
Removed the following exploratory objective: 
• 
Assess the PK of nirogacestat in combination with 
SEA-BCMA and dexamethasone. 
 
Modified the following exploratory objective: 
• 
Assess impact of SEA-BCMA in combination with 
standard of care therapies and SEA-BCMA in 
combination with nirogacestat and dexamethasone on 
health-related quality of life (HRQoL) from the 
subject’s perspective.  
Reflects modified study 
design 
Synopsis 
Study population for Parts B and C modified as follows: 
In Parts B, and C, and E, subjects must not have other 
therapeutic options known to provide clinical benefit in multiple 
myeloma available, must have received at least 3 prior lines of 
antimyeloma therapy, and must be refractory to aat least 1 agent 
in each of the following classes: PI, IMiD, and an anti-CD38 
antibody.  
Aligned with wording in 
Section 4 for clarity 
Synopsis, 
Sections 3, 9.1, 
9.3.10, Figure 1  
Study design and statistical methods updated to reflect the 
following changes to expected sample sizes: 
Up to approximately 305131 subjects are expected to be 
enrolled in this study. This number is based on the 
following assumptions: 
• 
Up to approximately 6545 subjects will be evaluated in 
Part A (monotherapy dose- escalation and expansion; 
every 2 weeks [q2wk] dosing). 
• 
Up to approximately 4020 subjects will be evaluated in 
Part B (monotherapy intensive dosing; once weekly 
[q1wk] for 8 weeks, followed by q2wk dosing). 
• 
Up to approximately 8060 subjects total will be 
evaluated in the Part C dexamethasone combination 
therapy cohorts (up to 4020 in each of 2 optional 
cohorts). Up to 20 subjects will be enrolled in cohort 1 
(standard dosing SEA-BCMA). Up to 40 subjects will 
be enrolled in cohort 2 (intensive dosing 
To reflect change in 
sample size for Parts A, B, 
C, and D; and removal of 
Part E.  
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Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 155 of 158 
Section(s) 
Change 
Rationale 
SEA-BCMA): 20 subjects in each of up to 2 parallel 
dose levels. 
• 
Up to approximately 806 DLT-evaluable subjects total 
will be evaluated in the Part D pomalidomide and 
dexamethasone combination cohorts (up to 40 in each 
of 2 optional cohortssafety run-in cohort. 
Synopsis, 
Section 4.1 
Part D inclusion criterion 2c and corresponding text in synopsis 
revised require that subjects have received 3 or more prior lines 
of therapy, and remove prohibition of prior pomalidomide 
therapy: 
 
In Part D, subjects must have not received prior pomalidomide, 
must have received at least 23 prior lines of antimyeloma 
therapy, including at least 2 consecutive cycles of both 
lenalidomide and a PI (given separately or in combination)a PI, 
IMiD, and an anti-CD38 antibody, and must have documented 
International Myeloma Working Group (IMWG) disease 
progression on or within 60 days of completion of their last 
treatment.  
Reflects modified study 
design 
Synopsis, 
Figure 1, 
Sections 3.1, 
3.3.1.2, 4, 6.5.3, 
9.1 
Removed Part D Cohort 2; modified Part D cohort 1 to a 6-
subject safety run-in.  
Reflects modified study 
design 
Synopsis, 
Figure 1, 
Sections 1.6.2, 
3.1, 3.3.1.2, 4, 
5.3.3, 5.5, 5.6.2, 
5.6.3, 5.7, 6, 
7.3, 7.7.9, 9.1, 
9.3.1.7.3, 
Appendix E 
Removed Part E (SEA-BCMA in combination with nirogacestat 
and dexamethasone) 
Reflects removal of Part E 
Section 3.1.2 
Removed the following text: 
Initially, up to 20 subjects may be enrolled in Part B; an interim 
futility analysis will be performed after 20 subjects are efficacy-
evaluable at optimal dose to determine whether the cohort may 
be expanded up to 40 subjects 
To reflect Part B sample 
size of 20 subjects 
Appendix A,  
B 
Removed schedule of events and sample collection schedule for 
Part E. 
Removed assessments specific to Part D Optional Cohort 2.  
Reflects modified study 
design 
Appendix H  
Removed list of p-gp and CYP3A inhibitors and inducers. List 
was applicable only to nirogacestat (Part E).  
Does not apply; 
Part E/nirogacestat 
removed from study 
design.  
 
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Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 156 of 158 
Summary of Changes in Amendment 9  
Section(s) 
Change 
Rationale 
Section 1.1  
Updated the description of current treatment landscape 
To reflect current 
treatment landscape in the 
US and Europe 
Section 1.6.1  
Discussion and Rationale for Study Design was moved from 
Section 3.2 to Section 1.6.1.  
Consolidate related 
information 
Section 1.6.3.3 
Added section for Patient Input Into Design 
Further details on study  
Section 1.7 
Added section for Benefit/Risk Assessment 
Improve subject safety 
Section 3.1.1 
Removed the following text from Section 3.1.1.1: 
Subjects may continue on treatment until progressive 
disease (PD) or unacceptable toxicity, whichever occurs 
first. 
Moved to Section 3.1.4 
Synopsis and 
Section 3.1.3.3 
Section 4.1 
Section 4.3.1  
Clarified that Part D will enroll subjects in the US only.  
Clarification 
Sections 3.1.4 
Added Section 3.1.4 to capture duration of treatment 
information for all cohorts in one location.  
Clarity of treatment 
duration 
Section 3.1.6.1 
Added Section 3.1.6.1 to detail when enrollment will be paused 
at the cohort level. 
Improve subject safety 
Section 3.1.6.2 
Added the following bolded text and removed text in 
strikethrough in Section 3.1.6.2 Enrollment Halt for the Entire 
Study: 
Enrollment in the entire study will be halted by the 
sponsor if the overall benefit-risk balance is considered 
unfavorable. 
Stopping criteria will be continuously monitored 
throughout the study by the sponsor in consultation with 
the SMC, considering enrollment halt if the incidence 
and/or the severity of toxicity leads to a risk-benefit 
assessment that is unacceptable to the study population. 
The sponsor will consult the SMC to consider whether to 
allow subjects already receiving treatment to continue, 
to consider modifying the protocol to continue the trial, or 
to terminate the study.  
If enrollment is halted due to safety concerns, 
enrollment can only be restarted after appropriate 
amendments and notifications to Regulatory 
Authorities, with approval to resume, if required by 
local regulationsIn the event there is a recommendation to 
amend the protocol to continue, regulatory authorities will 
be consulted. 
Improve subject safety 
Section 3.1.8 
Section added to describe study close 
Clarify study duration 
Section 4.1 
Inclusion Criterion 2b for Parts B and C was revised to add: 
Prior BCMA-directed myeloma therapy, excluding prior 
treatment with SEA-BCMA, is permitted (eg, ADC, 
CAR-T cell therapy, or bispecific antibody targeting 
BCMA) provided that at least 3 months will have elapsed 
from the last dose of prior BCMA targeting therapy and 
Change in treatment 
landscape of RRMM 
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Amendment 9; 03-Jun-2022 
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Page 157 of 158 
Section(s) 
Change 
Rationale 
Cycle 1 Day 1 of this study, and that the subject has 
recovered from any clinically significant toxicity of the 
prior BCMA-targeting therapy.  
Section 4.2 
Exclusion Criterion 1 modified, with deletions shown in 
strikethrough text: 
Parts A , B, C, and D: Prior exposure to any other 
BCMA-directed therapy 
Change in treatment 
landscape of RRMM 
Section 5.1 
Added the following bolded text to Treatments Administered: 
SEA-BCMA is a non-fucosylated monoclonal antibody 
directed against BCMA. Subjects will receive the 
investigational medicinal product SEA-BCMA as 
monotherapy or combination therapy (Section 3.1). 
Subjects in combination therapy cohorts will also 
receive dexamethasone or dexamethasone plus 
pomalidomide.  
Guidance for intrasubject dose-escalation for subjects who 
have the potential to achieve greater benefit at a dose 
higher than the dose level assigned during dose-escalation 
is described in Section 5.2.3. 
Clarify treatment regimens 
Section 5.2.7 
Section added regarding access to study drug after the end of 
the study.  
Clarify duration of access 
to study drug 
Section 5.3.2 
Dexamethasone method of procurement modified with new text 
in bold and deleted text in strikethrough: 
In the US, dexamethasone will be sourced by study sites 
from commercial supply. In other countries, oral 
dexamethasone will be provided to the study sites by the 
sponsor or dexamethasone (oral or IV) will be sourced 
by study sites from commercial supply. Dexamethasone 
is commercially available and approved by the US FDA. 
Dexamethasone will be supplied by the study site and 
billed to subjects and/or their third-party payer (insurance, 
a healthcare provider, or applicable government program). 
Reflect regional variability  
Section 5.4.2 
Pomalidomide method of procurement modified with new text 
in bold and deleted text in strikethrough: 
In the US, pomalidomide will be sourced by study sites 
from commercial supply. Pomalidomide is commercially 
available and approved by the US FDA. Pomalidomide will 
be supplied by the study site and billed to subjects and/or 
their third-party payer (insurance, a healthcare provider, or 
applicable government program). 
Reflect regional variability 
Section 6 
Skeletal survey defined as: via whole body plain film 
radiography, or via whole body computed tomography [CT] 
scan, to assess presence and size of lytic bony lesions 
To add definition of study 
assessment 
Sections 6, 7.1, 
7.2, 
Appendix A 
Added detail in bold to indicate plasmacytoma scans will be 
conducted: per institutional standard imaging modality 
To add definition of study 
assessment 
Synopsis, 
Sections 6.4.4, 
6.5.4, 7.3 
Indicated that qualitative interviews will be conducted in 
10 subjects total from Part C and Part D.  
Clarification 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)


 
Study SGNBCMA-001 
Clinical Protocol 
Amendment 9; 03-Jun-2022 
SEA-BCMA 
Seagen Inc. - Confidential 
Page 158 of 158 
Section(s) 
Change 
Rationale 
Appendix A 
Part C Schedule of Events: removed footnote DD “24-hour 
urine collection required if UPCR >2 mg/mg” 
Correction 
Appendix B 
Part D Schedule of Events footnotes C and P were redundant, so 
footnote P was replaced with footnote C. 
Correction 
Appendix B 
Pharmacokinetic, immunogenicity, and biomarkers sample 
collection tables for Parts B, C and D modified to remove 
peripheral blood immunophenotyping sample collection.  
To reflect updated sample 
collection requirement 
Throughout 
Minor corrections and clarifications 
Corrections and 
clarifications 
 
090177e1a1306a0b\Approved\Approved On: 03-Jun-2022 21:18 (GMT)

SAP_001.pdf: 
 
 
 
P art or all of t he i nf or mati o n i n t his statistical a nal ysis pla n ma y be u n p u blis he d mat erial. Acc or di n gl y, t his 
d oc u me nt is t o be treate d as c o nfi de ntial a n d restricte d t o its i nte n de d use. T his material is t he pr o pert y of 
Seattle Ge netics, I nc. a n d m ust n ot b e discl ose d or use d e xce pt as a ut h orize d i n writi n g b y Seattle Ge netics, I nc.  
S T A TI S TI C A L A N A L Y SI S  P L A N  
 
Pr ot oc ol N u m ber:  
S G N B C M A -0 0 1  
Pr ot oc ol Title:  
A p hase 1 st u d y of S E A -B C M A i n patie nts wit h r ela pse d or 
refract or y m ulti ple m yel o ma 
S p o ns or:  
Sea ge n I nc.  
2 1 8 2 3 3 0t h Dri ve S E  
B ot hell, W A 9 8 0 2 1, U S A  
 
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 2  of 2 2  
A P P R O V A L SI G N A T U R E S  
Pr o d uct:  
S E A -B C M A  
Pr ot oc ol N u m ber/ A me n d me nt:  
S G N B C M A -0 0 1  A me n d me nt 9  
S A P V ersi o n:  
Fi nal  
Versi o n D ate:  
1 5 -A u g -2 0 2 3  
 
T he i n di vi d uals si g ni n g b el o w ha ve re vie we d a n d a p pr o ve t his statistical  a n al ysis pla n.  
 
 
 
 
 
 
 
Date  
 
 
 
 
 
 
  
 
 
Date  
 
 
 
 
 
 
 
 
 
Date  
 
 
 
 
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)
P P D
P P D
P P D


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 3  of 2 2  
T A B L E O F C O N T E N T S  
LI S T O F A B B R E VI A TI O N S  ................................................................................................................................ 4  
1  
I N T R O D U C TI O N ........................................................................................................................................... 6  
2  
S T U D Y O BJ E C TI V E S A N D  C O R R E S P O N DI N G E N D P O I N T S ................................................................ 6  
3  
S T U D Y D E SI G N  ............................................................................................................................................ 7  
4  
A N A L Y SI S S E T S  ........................................................................................................................................... 8  
4. 1  
All Treate d P atie nts A nal ysis Set  .......................................................................................................... 8  
4. 2  
D L T E val ua ble ( D E) A nal ysis Set  ........................................................................................................ 8  
4. 3  
All Scree ne d P atie nts A nal ysis Set ........................................................................................................ 9  
4. 4  
All E nr olle d P atie nts A nal ysis Set  ........................................................................................................ 9  
5  
S T A TI S TI C A L C O N SI D E R A TI O N S  ............................................................................................................ 9  
5. 1  
Ge neral Pri nci ples  ................................................................................................................................. 9  
5. 2  
M o del -base d D ose Escalati o n R ules  ..................................................................................................... 9  
5. 3  
Deter mi nati o n of Sa m ple Size  ............................................................................................................. 1 1  
5. 4  
Ra n d o mizati o n a n d Bli n di n g  ............................................................................................................... 1 2  
5. 5  
Data Tra nsf or mati o ns a n d Deri vati o ns  ................................................................................................ 1 2  
5. 6  
Ha n dli n g of Dr o p o uts a n d Missi n g Data  ............................................................................................. 1 3  
5. 7  
M ultice nter St u dies  ............................................................................................................................. 1 3  
5. 8  
M ulti ple C o m paris o n/ M ulti pli cit y ....................................................................................................... 1 3  
5. 9  
E xa mi nati o n of S u b gr o u ps  .................................................................................................................. 1 3  
5. 1 0  C o variates  ............................................................................................................................................ 1 3  
5. 1 1  Ti mi n g of A nal ys es  ............................................................................................................................. 1 4  
6  
P L A N N E D A N A L Y S E S  .............................................................................................................................. 1 4  
6. 1  
Dis p ositi o n  .......................................................................................................................................... 1 4  
6. 2  
De m o gra p hic a n d B aseli ne C haracteristics  ......................................................................................... 1 4  
6. 3  
Pr ot oc ol De viati o ns  ............................................................................................................................. 1 4  
6. 4  
Treat me nt A d mi nistrati o n  ................................................................................................................... 1 4  
6. 5  
Efficac y A nal yses  ................................................................................................................................ 1 5  
6. 5. 1  
Efficac y E n d p oi nts  ................................................................................................................. 1 6  
6. 6  
Safet y A nal yses  ................................................................................................................................... 1 7  
6. 6. 1  
A d verse E ve nts  ....................................................................................................................... 1 8  
6. 6. 2  
D o se-Li miti n g T o xicit y  .......................................................................................................... 1 9  
6. 6. 3  
Cli nical La b orat or y P ara meters  .............................................................................................. 1 9  
6. 6. 4  
C o nc o mita nt Me dicati o ns  ....................................................................................................... 1 9  
6. 6. 5  
Deat hs  ..................................................................................................................................... 1 9  
6. 6. 6  
E C O G P erf or ma nce Stat us  ..................................................................................................... 1 9  
6. 7  
P har mac o ki netics a n d I m m u n o ge nicit y E n d p oi nts  ............................................................................. 1 9  
6. 7. 1  
P har mac o ki netics  .................................................................................................................... 1 9  
6. 7. 2  
A ntit hera p e utic A nti b o d y ( A T A) I nci de nce Rate  ................................................................... 2 0  
7  
I N T E RI M A N A L Y SI S.................................................................................................................................. 2 0  
8  
C H A N G E S F R O M P L A N N E D  A N A L Y S E S  .............................................................................................. 2 0  
8. 1  
C ha n ges fr o m t he Ori gi nal Pr ot oc ol  .................................................................................................... 2 0  
8. 2  
C ha n ges fr o m t he Ori gi nal S A P  .......................................................................................................... 2 0  
R E F E R E N C E S  ..................................................................................................................................................... 2 1  
A P P E N DI X A  
I M P U T A TI O N O F P A R TI AL L Y U N K N O W N A D V E R S E E V E N T D A T E S  ..................... 2 2  
 
 
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 4  of 2 2  
LI S T O F A B B R E VI A TI O N S  
ac M M A E  
a nti b o d y c o nj u gate d m o n o met h yl a uristati n E  
A D C  
a nti b o d y-dr u g c o nj u gate  
A DI  
A bs ol ute d ose i nte nsit y  
A E  
a d verse e ve nt  
A S T  
as partate a mi n otra nsferase  
A T A  
a ntit hera p e utic a nti b o dies  
B A P  
bi o mar ker a nal ysis pla n  
C B C  
c o m plete bl o o d c o u nt  
CI  
c o nfi de nce i nter val  
C R  
c o m plete res p o nse  
Cr Cl  
creati ni ne cleara nce  
C R F  
case re p ort  f or m 
C S R  
cli nical st u d y re p ort  
D E  
D L T -e val ua ble  
D L T  
d ose -li miti n g t o xicit y 
E C G  
electr ocar di o gra m  
E C O G  
Easter n C o o perati ve O nc ol o g y Gr o u p  
E E  
efficac y e val ua ble  
E O S  
e n d of st u d y  
E O T  
e n d of treat me nt  
I DI 
I nte n de d d ose i nte nsit y 
I Mi D 
i m m u n o m o d ulat or y dr u g 
I M W G 
I nter nati o nal M yel o ma W or ki n g Gr o u p 
I R R 
i nf usi o n-relate d reacti o n 
I V 
i ntra ve n o us 
L L O Q  
Me d D R A  
l o wer li mit of q ua ntificati o n 
Me dical Dicti o nar y f or Re g ul at or y Acti vities  
M M  
m ulti ple m yel o ma  
M M A E  
m o n o met h yl  a uristati n E  
M T D  
ma xi m u m t olerate d d ose  
m T PI  
m o difie d t o xicit y pr o ba bilit y i nter val  
N CI C T C A E  
Nati o nal Ca ncer I nstit ute C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts  
O R R  
o bj ecti ve res p o nse rate  
O S  
o verall s ur vi val  
P A V A  
P o ol -A dj ace nt -Vi olat ors Al g orit h m  
P D  
pr o gressi ve disease  
P F S  
pr o gressi o n -free s ur vi val 
PI  
pr oteas o me i n hi bit or  
P K  
p har mac o ki netic  
P R  
partial res p o nse  
R DI  
Relati ve d ose i nte nsit y  
R R M M  
rela pse d or refract or y m ulti ple m yel o ma 
q 3 w k  
o nce e ver y 3 wee ks  
s C R 
stri n ge nt c o m plete res p o nse 
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n 
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 5  of 2 2  
S D  
sta ble disease 
S M C  
Safet y M o nit ori n g C o m mittee  
U P C  
uri ne pr otei n t o creati ni ne  
U P M  
u nit pr o ba bilit y mass  
V G P R  
ver y g o o d partial res p o nse  
 
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 6  of 2 2  
1  
I N T R O D U C TI O N 
T his d oc u me nt o utli nes t he statistical met h o ds t o be i m ple me nte d wit hi n t he sc o pe of 
Pr ot oc ol S G N B C M A -0 0 1, e ntitle d ‘ A p hase 1 st u d y of S E A -B C M A i n patie nts wit h rela pse d 
or refract or y m ulti ple m yel o ma ’. Res ults of t he pr o p ose d a nal yses will bec o me t he basis of 
t he cli nical st u d y re p ort f or t his pr ot oc ol. 
T he p ur p ose of t his pla n is t o pr o vi de s pecific g ui deli nes fr o m w hic h t he a nal ysis will 
pr ocee d.  All pla n ne d a n al yses s pe cifie d i n t his d oc u me nt will be perf or me d.  A n y c ha n ges t o 
t his pla n, i n t he f or m of “ p ost h oc” or “ d ata dri ve n” a nal yses will be i de ntifi e d as s uc h i n the 
fi nal cli nical st u d y re p ort. A n y c ha n ges will eit her be refl ecte d i n a me n d m e nts t o t his pla n 
bef ore t h e data b ase l oc k or s pecificall y d o c u me nt e d i n t he cli nical st u d y re p ort.  
2  
S T U D Y O B J E C TI V E S  A N D C O R R E S P O N DI N G E N D P OI N T S  
T his  st u d y will e val uate t he safet y a n d a ntit u m or acti vit y of S E A-B C M A  i n patie nts wit h 
R R M M. S pecific o bjecti ves a n d c orres p o n di n g e n d p oi nts f or t he st u d y are s u m marize d 
bel o w  i n Err or! Refere n ce s o urce n ot f o u n d. . 
T a bl e  1 : 
O bj e cti v e s a n d c orr e s p o n di n g e n d p oi nt s  
Pri m ar y O bjecti ves  
C orres p o n di n g Pri m ar y E n d p oi nt  
E val uate t he safet y a n d t olera bilit y of S E A -B C M A 
m o n ot hera p y i n s u bj ects wit h rela pse d or refract or y 
m ulti ple m yel o ma ( R R M M)  
T y pe, i nci de nce, se verit y, seri o us ness, a n d relate d ness of 
a d verse e ve nts ( A Es)  
T y pe, i nci de nce, a n d se verit y of la b orat or y a b n or malities  
I nci de nce of d ose-li miti n g t o xicities ( D L Ts) 
I de ntif y t he ma xi m u m t olerate d d ose ( M T D) a n d/ or 
o pti mal d ose a n d sc he d ule of S E A -B C M A m o n ot hera p y, 
a n d i n c o m bi nati o n wit h de xa met has o ne,  i n s u bj ects 
wit h R R M M  
E val uate t he safet y a n d t olera bilit y of S E A -B C M A i n 
c o m bi nati o n wit h S O C t hera pi es i n s u bj ects wit h 
R R M M  
Sec o n d ar y O bjecti ves  
C orres p o n di n g Sec o n d ar y E n d p oi nts  
I de ntif y a rec o m me n de d si n gl e-a ge nt d ose a n d sc he d ule 
of S E A -B C M A  
Assess t he p har mac o ki netics ( P Ks) of S E A -B C M A  
Assess t he i m m u n o ge nicit y of S E A -B C M A  
Assess t he a ntit u m or acti vit y of S E A -B C M A  
I nci de nce of D L Ts, c u m ulati ve safet y a n d acti vit y b y 
d ose le vel a n d sc he d ule  
Ma xi m u m ser u m c o nce ntrati o n a n d area u n der t he ser u m 
c o nce ntrati o n -ti me c ur ve 
I nci de nce of S E A-B C M A a ntit hera pe utic a nti b o dies 
( A T A) 
Best res p o nse per t he I nter nati o nal M yel o ma W or ki n g 
Gr o u p ( I M W G) u nif or m res p o nse criteria (K u mar 2 0 1 6 ) 
O bj ecti ve res p o nse rate ( O R R)  
D urati o n of o bj ecti ve res p o nse ( O R) a n d c o m plete 
res p o nse ( C R) 
Pr o gressi o n -free s ur vi val ( P F S) 
O verall s ur vi val ( O S)  
E x pl or at or y O bjecti ves  
C orres p o n di n g E x pl or at or y E n d p oi nts  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 7  of 2 2  
Assess i nci de nce a n d le vel of B C M A e x pressi o n i n 
R R M M a n d relati o ns hi p t o cli nical res p o nse t o 
S E A -B C M A  
Assess t he p har mac o d y na mic effects a n d bi o mar kers of 
res p o nse, t o xicit y, a n d resista nce t o S E A-B C M A  
Assess mi ni mal resi d ual disease ( M R D) i n s u bj ects wit h 
ver y g o o d partial res p o nse ( V G P R) or better  
Assess i m pact of S E A -B C M A i n c o m bi nati o n wit h S O C 
t hera pies o n healt h-relate d q ualit y of life ( H R Q o L) fr o m 
t he s u bj ect’s pers pecti ve. 
C haracterizati o n of B C M A e x pressi o n o n  mali g na nt 
plas ma cells  
E x pl orat or y bi o mar kers of S E A -B C M A me diate d 
p har mac o d y na mic effects  
Rate of M R D cleara nce  
Descri pti ve o utc o mes of q ualitati ve i nter vie ws  
Ma xi m u m ser u m c o nce ntrati o n a n d area u n der t he ser u m 
c o nce ntrati o n -ti me c ur ve 
 
 
3  
S T U D Y D E SI G N   
T his is a p hase 1, o pe n -la bel, m ultice nter, d ose-escalati o n st u d y desi g ne d t o e val uate t he 
safet y, t olera bilit y, a n d a ntit u m or acti vit y of S E A-B C M A m o n ot hera p y a n d c o m bi nati o n i n 
a d ults wit h R R M M. T he st u d y will be c o n d uct e d i n 4 parts:  
Part A: M o n ot hera p y d os e -escalati o n a n d e x pa nsi o n  
D ose -es calati o n: U p t o a p pr o xi matel y 2 5 s u bjects will be treate d wit h S E A -B C M A 
m o n ot hera p y q 2 w k t o e v al uate t he safet y a n d t olera bilit y of S E A -B C M A, a n d t o i de ntif y t he 
M T D or o pti mal d ose.  
E x pa nsi o n: U p t o a p pr o xi matel y 2 0 s u bjects will be treate d wit h S E A-B C M A m o n ot hera p y 
at d ose le vels n ot e x cee di n g t he M T D or o pti mal d ose t o f urt her c haracterize t he safet y a n d 
a ntit u m or acti vit y of S E A -B C M A.  
Part B: M o n ot hera p y i nte nsi ve d osi n g. U p t o 2 0 s u bjects will be treate d at t he re c o m me n d e d 
d ose i n a n e x pa nsi o n c o h ort testi n g wee kl y i n d ucti o n d osi n g ( q 1 w k) of S E A -B C M A f or 8 
wee ks, f oll o we d b y q 2 w k mai nte na nce d osi n g. T his e x pa nsi o n c o h ort will be gi n wit h a 6 -
s u bject safet y r u n-i n wit h d ose de-es calati o n per mitte d.  
Part C: De x a met has o ne c o m bi nati o n t hera p y c o h orts. U p t o a p pr o xi matel y 6 0 s u bjects ma y 
be e nr olle d t o e v al uate t h e safet y a n d a ntit u m or acti vit y of S E A -B C M A i n c o m bi nati o n wit h 
de x a met has o ne.  
C o h ort 1: T he sta n dar d d osi n g c o m bi nati o n c o h ort will c o m bi ne de x a met has o ne wit h 
S E A -B C M A a d mi nistere d q 2 w k. T his e x pa nsi o n c o h ort will be gi n wit h a 6 -s u bject safet y 
r u n-i n wit h d ose de-escal ati o n per mitte d. C o h ort e x pa nsi o n u p t o 2 0 s u bjects ma y occ ur, if 
per mitte d after c o m pleti o n of t he safet y r u n -i n.   
C o h ort 2: T he i nte nsi ve d osi n g  c o m bi nati o n c o h ort will c o m bi ne de x a met has o ne wit h 
S E A -B C M A a d mi nistere d q 1 w k f or 8 wee ks, f oll o we d b y q 2 w k d osi n g. T his e x pa nsi o n 
c o h ort will c o m plete a 6 -s u bject safet y r u n-i n at 8 0 0 m g S E A -B C M A i nte nsi ve d osi n g ( d ose 
le vel – 1) a n d, if d ee me d t olera ble,  will be f oll o w e d b y a 6 -s u bject r u n i n at 1 6 0 0 m g 
S E A -B C M A i nte nsi ve d osi n g. C o h ort e x pa nsi o n u p t o a t otal of 2 0 s u bjects ma y occ ur i n 
eac h of u p t o 2 d os e le vel c o h orts, e g, 8 0 0 m g a n d 1 6 0 0 m g S E A -B C M A d ose le vels, if 
per mitte d after c o m pleti o n of eac h s afet y r u n-i n.   
Part D: P o mali d o mi de a n d de x a met has o ne c o m bi nati o n t hera p y c o h ort. U p t o 6 D L T 
e val ua ble s u bjects ma y b e e nr olle d i n t his safet y r u n -i n c o h ort t o e val uat e t he safet y of 
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 8  of 2 2  
S E A -B C M A a d mi nistere d q 2 w k i n c o m bi nati o n wit h p o mali d o mi de a n d de x a me t has o ne. 
Part D will be c o n d ucte d i n t he U S o nl y.  
C o h ort 1: T he sta n dar d d osi n g c o m bi nati o n c o h ort will c o m bi ne de x a met has o ne a n d 
p o mali d o mi de wit h S E A -B C M A a d mi nistere d q 2 w k. T his e x pa nsi o n c o h ort will be gi n wit h a 
6 -s u bject safet y r u n-i n wit h d ose de-escalati o n per mitte d.  
A Safet y M o nit ori n g C o m mittee ( S M C) c o nsisti n g of t he st u d y me di cal m o nit or, dr u g s afet y 
re pres e ntati ve, site i n vesti gat ors, a n d t he st u d y bi ostatisticia n will m o nit or t he safet y of 
s u bjects a n d ma ke d osi n g rec o m me n dati o ns t hr o u g h o ut dose -escalati o n, d ose -e x pa nsi o n, 
p ost -re missi o n treat me nt, a n d c o m bi nati o n t hera p y treat me nt. T he S M C ma y rec o m me n d 
i n vesti gati o n of a n i nter me diate d ose le vel or a n alter nati ve d osi n g sc he d ule if warra nte d b y 
c u m ulati ve safet y a n d P K/ p har mac o d y n a mic dat a.  
T he d ose -es calati o n part of S E A -B C M A m o n ot hera p y will be c o n d uct e d i n u p t o 
a p pr o xi matel y 2 5 s u bjects usi n g t he m o difie d t o xicit y pr o ba bilit y i nter val ( m T PI) met h o d (Ji 
2 0 1 0 ) t o e val uate s afet y a n d t olera bilit y, a n d t o i de ntif y t he M T D of S E A -B C M A. If t he 
M T D is n ot reac h e d, safet y, P K, p har m ac o d y na mi c, a n d bi o mar ker a n al ys es, as well as 
preli mi nar y a ntit u m or acti vit y, will be use d t o deter mi ne t he o pti mal d ose. De -es calati o n t o a 
l o wer d ose le v el ma y be perf or me d at a n y ti me b y t he s p o ns or i n c o ns ultati o n wit h t he S M C. 
I ntr as u bject d ose-escalati o n t o a d ose le vel s h o w n t o be safe ma y b e per mitt e d i n t he e ve nt 
t hat a s u bject has n ot e x perie nce d a Gra de ≥2 a d verse e ve nt ( A E) w hile o n st u d y treat me nt, 
has recei ve d at least 1 c ycle of S E A -B C M A at t he c urre nt d ose l e vel, a n d ac hie ves sta ble 
disease ( S D) or better.  
 
4  
A N A L Y SI S S E T S  
T his secti o n defi nes eac h of t he a nal y sis sets t hat will be utilize d. T he use of eac h a nal ysis set 
will be disc usse d i n Secti o n 6 . 
4. 1  All Tr e at e d P ati e nt s A n al y si s S et  
T he All Treat e d Patie nts set i ncl u des all patie nts w h o recei ve a n y a m o u nt of S E A -B C M A. 
T he All Treat e d Patie nts set will be use d f or prese ntati o n of safet y data a n d efficac y 
e n d p oi nts.  
4. 2  D L T E v al u a bl e ( D E) A n al y si s S et  
T he D L T -e val ua ble ( D E) a nal ysis s et will i ncl u de all treate d patie nts w h o eit her ( 1) 
e x perie nce a D L T , or  ( 2) recei v e at least 7 5 % of t h e i nte n de d S E A-B C M A d ose a n d are 
f oll o we d f or t he f ull D L T e val uati o n peri od . T h e D L T e val uati o n peri o d is defi ne d as c ycle 1 
of treat me nt . F or q 2 w k s c he d ule, c ycle 1 i ncl u des t he first 2 d oses of treat me nt.  Patie nts will 
be re pla ce d f or D L T e v al uati o n if t he y recei ve d pr o hi bite d me dicati o ns (as descri be d i n 
pr ot oc ol Secti o n s 5. 4. 2 a n d 5. 4. 3 ), or are dee me d i ne val ua ble f or cli nical r eas o ns b y t he 
S M C .  Patie nts o n t he q 2 w k d osi n g sc h e d ule w h o recei v e o nl y t h e 1 st d ose d uri n g c ycle 1 f or 
reas o ns ot her t h a n t o xicit y ma y n ot be D L T-e v al u a ble  a n d will be re place d.  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 9  of 2 2  
4. 3  All S cr e e n e d P ati e nt s A n al y si s S et  
T he all scree ne d p atie nts a nal ysis s et i ncl u des all p atie nts w h o si g n i nf or m e d c o nse nt.  
4. 4  All E nr oll e d P ati e nt s A n al y si s S et  
T he all e nr olle d p atie nts a nal ysis s et i ncl u des all p atie nts e nr olle d i n t he st u d y. A patie nt is 
c o nsi dere d e nr olle d if he/s he has met all criteria f or partici pati o n i n t he st u d y a n d h as Seattle 
Ge netics a p pr o val as d oc u me nte d i n t he e C R F.  
5  
S T A TI S TI C A L C O N SI D E R A TI O N S   
5. 1  G e n er al Pri n ci pl e s  
T his is a p hase 1  d ose -es calati o n  st u d y. All a nal ys es will be descri pti ve; h o we ver, c o nfi de n ce 
i nter vals ma y be prese nte d t o descri be precisi o n of esti mates. 
Descri pti ve statistics ( mea n, me dia n, sta n dar d de viati o n, mi ni m u m, a n d ma xi m u m) will be 
use d t o s u m marize c o nti n u o us varia bles. Fre q u e n cie s a n d perce nt a ges will be use d t o 
su m marize cate g orical varia bles.  T he t w o -si de d 9 5 % e x act c o nfi de nce i nter val usi n g 
Cl o p per -Pears o n met h o d ol o g y (C olle tt 1 9 9 1) will be calc ul ate d f or t he res p o nse rates w h ere 
a p plica ble (e. g., O R R).  
T he me dia n s ur vi val ti me will be esti mate d usi n g t he Ka pla n -M eier met h o d; t he ass ociate d 
9 5 % c o nfi de n ce i nter val ( CI) will be cal c ulate d base d o n t he c o m ple me ntar y l o g -l o g 
tra nsf or mati o n (C ollett 1 9 9 4 ). 
U nless ot her wise s pecifie d, data are t o be s u m mari ze d b y d ose le vel a n d o verall. D L T  
s u m marizati o n will o nl y i ncl u de patie nts i n t he d ose escal ati o n part  of t he st u d y , a n d will be 
d o ne b y d os e le vel. F or all ot her a nal ys es, patie nts treate d i n t he d ose escal ati o n part of t he 
st u d y ma y be p o ole d t o get her wit h patie nts  treate d at t he sa me d ose le vel i n t he e x pa nsi o n 
c o h orts. 
A n y a nal ysis n ot descri b e d i n t his pla n will be c o nsi dere d e x pl orat or y, a n d will be 
d oc u me nte d i n t he cli nic al  st u d y re p ort ( C S R) as a p ost h oc a nal ysis or a c ha n ge t o t he 
pla n ne d a nal ysis.  
T o c o m pl y wit h r e g ulat or y electr o ni c s u b missi o n g ui deli nes, listi n gs of all cli nical data will 
be s u b mitte d as electr o ni c data sets.  T o facilitate data re vie w f or t he st u d y re p ort, o nl y 
perti ne nt data listi n gs will be create d a n d attac he d t o t he a p pe n di x of t he C S R.  All statistical 
o ut p ut will be pr o d uce d usi n g S A S ® , versi o n 9. 3  or m ore rece nt.  Ot her statistical s oft ware, if 
use d, will be descri be d i n t he cli nical st u d y re p ort.  
5. 2  M o d el -b a s e d D o s e E s c al ati o n R ul e s  
T he i nitial d ose -escalati o n p orti o n of t he trial will be c o n d ucte d usi n g t he m o difie d t o xicit y 
pr o ba bilit y i nter val ( m T PI) met h o d (Ji 2 0 1 0). T his part of t he st u d y is desi g ne d  t o e val uate 
t he safet y a n d t olera bilit y,  a n d t o i de ntif y t he M T D of S E A -B C M A . T h e m T PI desi g n uses a 
Ba yesi a n statistical fra m e w or k a n d a beta/ bi n o mial hierarc hic m o del t o c o m p ute t he p osteri or 
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 1 0  of 2 2  
pr o ba bilities of 3 i nter vals t hat reflect t he relati ve dista nce bet wee n t he t o xicit y rate of eac h 
d ose le vel t o t he tar get D L T rate . U sin g a  t ar get D L T rate of 2 5% wit h a 5 % mar gi n, t he 3 
i nter vals will be ( 0, 2 0 %), [ 2 0 %, 3 0 %] a n d ( 3 0%, 1 0 0 % ), a n d t he c orres p o n di n g d osi n g 
decisi o n r ules w o ul d be:  
1.  Escalate if c urre nt D L T rate is m ost li kel y < 2 0 %  
2.  C o nti n ue if c urre nt D L T rate is m ost li kel y bet w ee n 2 0 % a n d 3 0 %  
3.  De -es calate if c urre nt D L T rate is m ost li kel y > 3 0 %  
D ose fi n di n g d ecisi o ns are s h o w n i n Ta ble 2 . E, S, a n d D re prese nt es calati n g t he d os e, 
sta yin g at t he s a me d ose, a n d de -es calati n g t he d os e, res pecti vel y. Decisi o n D U mea ns t hat 
t he c urre nt d ose le vel has a n  u nacce pta bl y   hi g h t o xicit y  rat e a n d s h o ul d be e x cl u de d fr o m 
t he trial.  
E nr oll me nt i n t his st u d y will occ ur o n a c o h ort -b y -c o h ort basis. M ulti ple c o h orts ma y b e 
treate d at eac h d os e le vel, wit h a ma xi m u m of 4 patie nts treate d per c o h ort. Decisi o ns o n 
d ose escal ati o n a n d s u bse q ue nt c o h ort size will be ma de b y t he s p o ns or i n c o ns ultati o n wit h 
t he safet y m o nit ori n g c o m mittee ( S M C) after c o m pleti o n of eac h c o h ort. Patie nts i n t he 
c urre nt c o h ort m ust be o bser ve d f or t he f ull d urati o n of t he D L T peri o d bef ore t he ne xt 
c o h ort of patie nts is e nr olle d. I n a d diti o n, as a preca uti o n, f or t he first 2 pati e nts i n t he st u d y 
t here will be a 7 2-h o ur o bser va ti o n peri o d bef ore t he ne xt patie nt ca n be d ose d. At d oses 
a b o ve D ose Le vel 1, a 7 2 -h o ur o bser vati o n peri o d is re q uire d after t he first patie nt i n eac h 
c o h ort recei ves t heir first d ose of S E A -B C M A pri or t o d osi n g s u bse q ue nt p atie nts i n t he 
c o h ort. At least  2 D L T -e val ua ble ( D E) patie nts will be treate d per d ose le vel u ntil t he first 
D L T is o bser ve d, t he n a mi ni m u m of 3 D E patie nts per d ose le vel will be re q uire d bef ore 
escalati o n t o all hi g h er d oses. Patie nts w h o are c o nsi dere d n ot e val u a ble f or D L T d uri n g 
C ycle 1 ma y b e re place d. A mi ni m u m of 6 D E patie nts will be o bser ve d at t he esti mate d 
M T D bef ore t he M T D or o pti mal d ose is deter mi ne d. T he M T D or o pti mal d ose will be 
esti mate d base d o n dat a fr o m all patie nts acr oss all e val uate d d oses.  
De -es calati o n t o a l o wer d ose le vel ma y be p erf or me d at a n y ti me b y t he s p o ns or i n 
c o ns ultati o n wit h t he S M C. I ntra p atie nt d ose es cal ati o n t o a d ose le vel s h o w n t o be safe m a y 
be per mitte d i n t he e ve nt t hat a patie nt t olerates S E A -B C M A a n d ac hie ves sta ble disease 
( S D) or better. 
Patie nts ma y c o nti n ue o n treat me nt u ntil pr o gressi ve disease or u nacce pta bl e t o xicit y, 
w hic he ver occ urs first.  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 1 1  of 2 2  
T a bl e 2 :  
D o s e -fi n di n g s pr e a d s h e et f or m T PI d e si g n 
 
N u m ber of D L T -e v al u a ble p atie nts tre ate d at c urre nt d ose  
N u m ber of D L Ts  
 
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
1 1  
1 2  
1 3  
1 4  
1 5  
0  
E  
E  
E  
E  
E  
E  
E  
E  
E  
E  
E  
E  
E  
E  
1  
S  
S  
S  
S  
E  
E  
E  
E  
E  
E  
E  
E  
E  
E  
2  
D U  
D  
D  
S  
S  
S  
S  
S  
S  
S  
S  
S  
E  
E  
3  
 
D U  
D U  
D U  
D  
S  
S  
S  
S  
S  
S  
S  
S  
S  
4  
 
 
D U  
D U  
D U  
D U  
D U  
D  
S  
S  
S  
S  
S  
S  
5  
 
 
 
D U  
D U  
D U  
D U  
D U  
D U  
D  
S  
S  
S  
S  
6  
 
 
 
 
D U  
D U  
D U  
D U  
D U  
D U  
D U  
D U  
D  
S  
7  
 
 
 
 
 
D U  
D U  
D U  
D U  
D U  
D U  
D U  
D U  
D U  
8  
 
 
 
 
 
 
D U  
D U  
D U  
D U  
D U  
D U  
D U  
D U  
9  
 
 
 
 
 
 
 
D U  
D U  
D U  
D U  
D U  
D U  
D U  
1 0  
 
 
 
 
 
 
 
 
D U  
D U  
D U  
D U  
D U  
D U  
1 1  
 
 
 
 
 
 
 
 
 
D U  
D U  
D U  
D U  
D U  
1 2  
 
 
 
 
 
 
 
 
 
 
D U  
D U  
D U  
D U  
1 3  
 
 
 
 
 
 
 
 
 
 
 
D U  
D U  
D U  
1 4  
 
 
 
 
 
 
 
 
 
 
 
 
D U  
D U  
1 5  
 
 
 
 
 
 
 
 
 
 
 
 
 
D U  
E = escalate t o t h e ne xt hi g her d ose, S = sta y at t h e c urre nt d ose, D = de -escalate t o t h e ne xt l o wer d ose, D U = c urre nt d ose 
is u nacce pta bl y t o xic 
 
At t he e n d of t he trial w h e n t he t o xicit y o utc o mes of all t he e nr olle d p atie nts  are o bser ve d, a  
d ose will be selecte d as t he esti mate d M T D. T he esti mati o n is se parate d fr o m t he desi g n f or 
d ose fi n di n g. T h e M T D is selecte d b y perf or mi n g a n is ot o nic re gressi o n t hat b orr o ws 
stre n gt h cr oss d oses. Let p̂i  be t he p osteri or mea n of D L T rat e, t he p o ole d a djace nt vi olat ors 
al g orit h m ( P A V A) is a p plie d o n p̂i* s o t hat t he res ulti n g tra nsf or m e d val ues p̂i* i ncrease wit h 
t he d ose le vels. T hat is p̂i* ≤ p̂i+ 1 *  f or all i. T he rec o m me n de d M T D is t he d ose wit h a 
t o xicit y pr o ba bilit y p̂i*  cl osest t o t he tar get D L T rate 2 5%, i.e. : 
Esti mate d M T D = ar g mi n | p̂i* - 2 5 %| . 
5. 3  D et er mi n ati o n of S a m pl e Si z e  
U p t o a p pr o xi matel y 1 3 1 s u bjects are e x pecte d t o be e nr olle d i n t his st u d y. T his n u m ber is 
base d o n t he f oll o wi n g ass u m pti o ns:  
•  U p t o a p pr o xi matel y 4 5 s u bjects  will be e val uate d i n Part A ( m o n ot hera p y d ose - 
escalati o n a n d e x pa nsi o n; q 2 w k d osi n g).  
Wit h t he m T PI st u d y desi g n, t he e x act n u m ber of s u bjects nee de d t o c o m plete t he 
d ose -escalati o n p orti o n of t he p hase 1 st u d y is u n k n o w n beca us e it de pe n ds o n t he 
n u m ber  of c o h orts re q uir e d t o reac h M T D a n d t he n u m ber of s u bjects e nr olle d i n eac h 
c o h ort. T his n u m ber is base d o n t he ass u m pti o n t hat a p pr o xi matel y 2 5 s u bjects will 
be e val uat e d i n d ose -es calati o n a n d t hat a p pr o xi matel y 2 0 s u bjects will be e val uate d 
i n a n e x pansi o n c o h ort at t he M T D or o pti mal d ose t o f urt her d efi ne t he s afet y a n d 
a ntit u m or acti vit y of S E A -B C M A.  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 1 2  of 2 2  
O perati n g c h aracteristics of t he d ose -es calati o n part of t he st u d y, i ncl u di n g t he 
a vera ge n u m ber of s u bjects all ocate d t o eac h d ose acr oss a v ariet y of  t o xicit y 
sce nari os are prese nte d i n t he si m ulati o n re p ort w hic h is i n a p pe n di x of pr ot oc ol.  
•  U p t o a p pr o xi matel y 2 0 s u bjects will be e val uate d i n Part B, u p t o 6 0 s u bjects will 
be e val uat e d i n Part C ( u p t o 2 0 s u bjects i n C o h ort 1; u p t o 2 0 s u bjects i n eac h 
d ose le vel i n C o h ort 2) a n d u p t o 6 s u bjects will be e val uat e d i n Part D.  
N o f or mal h y p ot hesis is pla n ne d. T he sa m ple siz e is selecte d b y pr o vi di n g a reas o n a ble 
esti mati o n precisi o n. Ass u mi n g t he o bser ve d O R R is bet wee n 3 0 t o 7 0 %, t h e 9 5 % bi n o mial 
e x act CIs are s u m mariz e d bel o w.  
O R R  
9 5 % CI ( N = 2 0)  
3 0 %  
1 2 %, 5 4 %  
4 0 %  
1 9 %, 6 4 %  
5 0 %  
2 7 %, 7 3 %  
6 0 %  
3 6 %, 8 1 %  
7 0 %  
4 6 %, 8 8 %  
 
5. 4  R a n d o mi z ati o n a n d Bli n di n g  
T his is a si n gle -ar m, o pe n -la bel st u d y. N o ra n d o mizati o n or bli n di n g will be utilize d. 
5. 5  D at a Tr a n sf or m ati o n s a n d D eri v ati o n s  
Re p orte d a ge i n years will be use d; if n ot a vaila ble, a ge i n years will be cal c ulate d wit h t he 
S A S I N T C K f u n cti o n ( wit h met h o d s pecifie d as “c o nti n u o us”) usi n g i nf or me d c o nse nt date 
a n d birt h date.  
St u d y D a y will be calc ul ate d as Dat e  –  First D os e Date  +  1 f or dates o n or after t he first d ose 
date.  F or dates pri or t o t h e first d ose date, St u d y D a y will be calc ulat e d as Date  –  First D ose 
Date.  F or all cal c ulati o ns of St u d y Da y, t h e First D ose Date will be t he earliest date o f 
treat me nt a d mi nistrati o n f or S E A -B C M A . 
Ot her ti me varia bl es base d o n t w o dates, e. g., Start Date a n d E n d Date, wi ll be calc ul ate d as 
( E n d Date –  Start D ate  +  1) (i n da ys) u nless ot her wise s pecifie d i n t he pla n ne d a nal ysis 
secti o n. 
T he f oll o wi n g u nit c o n v ersi o n will be i m ple me nte d u nless ot her wise s pecifie d:  
M o nt hs  =  Da ys  / 3 0. 4 3 7 5  
Years  =  Da ys  / 3 6 5. 2 5  
U nless ot her wise s pecifie d, baseli ne val ues use d i n all a nal ys es will be t he m ost rece nt n o n -
missi n g meas ure m e nt pri or t o t he first d ose of st u d y dr u g.  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 1 3  of 2 2  
T he e n d -of -treat me nt ( E O T) date will be t he d ate t he E O T visit is perf or me d; if a n E O T visit 
is n ot perf or me d t he n t he E O T date will be eit her t he (e n d-of -st u d y) E O S d ate or 3 0 da ys 
after t he l ast d ose of a n y st u d y dr u g, w hic h e ver is earlier.  
F or efficac y assess m e nts, t he date  of res p o nse will be t he latest of all diseas e e val uati o ns  f or 
t he gi ve n resta ge assess me nt. T he date of pr o gressi o n will be t he earliest of all disease 
e val uati o ns  f or t he gi ve n resta ge assess me nt, or t h e date of i n vesti gat or clai m of cli nical 
pr o gres si o n. Patie nts w h o ha ve a res p o nse of st a ble disease or better per I M W G u nif or m 
res p o nse criteria at t he s a me visit as i n vesti gat or cl ai m of cli nical pr o gressi o n will be c o u nte d 
as cli nical pr o gressi o n f or deter mi nati o n of best cli nical res p o nse.  A n i n vesti gat or cl ai m of 
cli nical pr o gressi o n is a d e q uate f or a n ass ess me nt of disease pr o gressi o n.  F or s u bjects w h o 
ha d C 1 D 2 2 c o nfir me d res p o nse of S D w hile u nc o nfir me d res p o ns e as P D a n d t he n 
disc o nti n ue d treat me nt wit h o ut recei vi n g a n y a d diti o nal treat me nt after c yc le 1, t he best 
c o nfir me d res p o nse will be c o u nte d as P D.   
 
5. 6  H a n dli n g of Dr o p o ut s a n d Mi s si n g D at a  
Wit h t he e x ce pti o n of t he sce nari os c o v ere d i n t his secti o n, missi n g data will n ot be i m p ute d . 
A E dates will be i m p ute d f or t he p ur p ose of calc ulati n g d urati o n  of e ve nts a n d treat me nt -
e mer ge nt stat us (see A p p e n di x A  f or i m p utati o n details).  Ce ns ori n g will be descri b e d i n 
Secti o n 6  wit h eac h pla n ne d a nal ysis, as a p plica ble.  
U nless ot her wise s pecifie d, la b val ues w hic h are rec or de d or pr o vi de d as b ei n g less t ha n t he 
l o wer li mit of q ua ntificati o n ( L L O Q), will be i ncl u de d  i n fi g ures a n d s u m maries as L L O Q.  
F or t he p ur p os e of gra di n g, la b v al ues re p orte d as l ess t ha n L L O Q will be i m p ute d as L L O Q . 
5. 7  M ulti c e nt er St u di e s  
T here are m ulti ple ce nt ers i n t his st u d y, h o we ver it is n ot a ntici pate d t hat a n y ce nter will 
accr ue e n o u g h p a tie nts t o warra nt a n a n al ysis b y ce nter. 
5. 8  M ulti pl e C o m p ari s o n/ M ulti pli cit y  
N o m ulti ple c o m paris o ns are pla n n e d a n d n o al p h a a dj ust me nt is nee de d i n t his p hase 1  
st u d y. 
5. 9  E x a mi n ati o n of S u b gr o u p s  
As e x pl orat or y a nal yses, s u b gr o u p a nal yses ma y b e c o n d ucte d f or selecte d e n d p oi nts.  
S u b gr o u ps ma y i ncl u de b ut are n ot li mite d t o t he f oll o wi n g:  
● A ge ( < 6 5 vs ≥6 5 years ol d)  
● B C M A e x pressi o n le vels  
5. 1 0  C o v ari at e s  
T his is a p hase 1 st u d y. C o variates are n ot c o nsi d ere d f or a dj ust me nt i n t he a nal yses.  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 1 4  of 2 2  
5. 1 1  Ti mi n g of A n al y s e s  
T he fi nal a n al ysis f or t his st u d y will occ ur after all s u bjects ha ve c o m plet e d t heir treat me nt 
a n d t he f oll o w -u p peri o d or f oll o wi n g st u d y ter mi nati o n b y t he s p o ns or.  
6  
P L A N N E D A N A L Y S E S   
6. 1  Di s p o siti o n  
A n acc o u nti n g of st u d y p atie nts b y dis p ositi o n will be ta b ulated b y d ose le vel  a n d t otal usi n g 
t he All Treate d  Patie nts a nal ysis set . Reas o ns f or disc o nti n uati o n of treat me nt a n d st u d y will 
be s u m mariz e d.  
6. 2  D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s  
De m o gra p hics a n d baseli ne c haracteristics, i ncl u di n g a ge, ge n d er, et h nicit y, race, b aseli ne 
hei g ht, w ei g ht, a n d E C O G sc ore will be liste d a n d s u m marize d; s u m maries will be prese n te d 
f or eac h d ose le v el a n d t otal usi n g t he All Tre ate d Patie nts a nal ysis set.  Dis ease s pecific 
c haracteristics, i ncl u di n g t he f oll o wi n g meas ur me nts at i nitial dia g n osis: M pr otei n, li g ht 
c hai n t y p e, I S S sta ge, c hr o m os o mal a b n or malities, L D H; refract or y or i nt olera nt t o selecte d 
classes of t hera p y ( PI, I Mi D, A nti -C D 3 8 a nti b o d y );  ti me fr o m dia g n osis; a n d pre vi o us 
ca ncer-relate d tr eat me nts will be liste d a n d s u m marize d f or eac h d ose l e vel  a n d t he t otal 
usi n g t he All Treate d Patie nts  a nal ysis set.  
6. 3  Pr ot o c ol D e vi ati o n s  
I m p ort a nt pr ot oc ol de viati o ns ( defi ne d as pr ot oc ol vi olati o ns b y Seattle Ge n etics) are t h ose 
t hat re pres e nt a di ver ge n ce fr o m t he pr ot oc ol t hat c o ul d ha ve a si g nifica nt effect o n t he 
i nte grit y of t he st u d y dat a, or o n t he s u bject’s ri g hts, safet y, or welfare. I m p orta nt pr ot oc ol 
de viati o ns als o i ncl u de e x e m pti o ns t o t he st u d y i n cl usi o n/e xcl usi o n criteria a n d will be 
s u m marize d b y cate g or y. A list of patie nts wit h i m p orta nt pr ot oc ol de viati o ns will be 
prese nte d.  
6. 4  Tr e at m e nt A d mi ni str ati o n  
Treat me nt a d mi nis trati o n will be s u m marize d b y d ose le vel usi n g t h e All Treate d Patie nts 
a nal ysis s et. S u m mar y st atistics f or d urati o n of t h era p y a n d t h e n u m ber of c ycles per patie nt 
will be prese nte d, as well as t he n u m ber a n d p erce nta ge of patie nts w h o w ere treate d at e ac h 
c ycle. C u m ulati ve d ose, a bs ol ute d ose i nte nsit y ( A DI) a n d relati ve d os e i nt e nsit y ( R DI) will 
be descri b e d.  T he n u m ber a n d perce nta ge of p atie nts w h ose d ose was e v er m o difie d will be 
s u m marize d i n ta bles b y m o dificati o n t y pe, c ycle, a n d o verall (i. e. o ver all dr u g 
a d mi nistrati o ns f or a pati e nt); listi n gs ma y b e prese nte d as well.    
D urati o n of treat me nt (e x ce pt w he n calc ulati n g e x p os ure) is defi n e d as t he ti me fr o m first 
d ose date t o t he earliest of :  
1.  L ast c ycle d a y 1 d ose  dat e  +  le n gt h of o ne d osi n g c ycle (i.e., 2 8) ,  
2.  date of deat h  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt.  1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 1 5  of 2 2  
3.  E n d of st u d y d ate  
4.  A nal ysis dat a c ut off d ate if t he s u bject is still o n treat me nt at t he ti me of dat a c ut off f or  
a n a nal ysis.  
F or t he p ur p os e of calc ul ati n g e x p os ure s u m maries, d urati o n of treat me nt is defi ne d as  
bel o w : 
F or q 2 w k sc h e d ule: [(last d ose date +  1 4 ) –  first d ose date]. 
F or t he sc h e d ule of q 1 w k i n d ucti o n f or 8 wee ks ( 2 c ycles), f oll o w e d b y q 2 w k d osi n g :  
•  If s u bjects recei ve d 2 or l ess c ycles, [(last d ose dat e + 7) –  first d ose date]. 
•  If s u bjects recei ve d 2 a n d m ore c ycles, [(last d ose date + 1 4) –  first d ose dat e]. 
I nte n d e d D ose I nte nsit y (I DI) is defi ne d as t he i nte n de d d ose of dr u g ( m g) per u nit of ti me.  
F or a n i nitial d ose of 1 0 0 m g, t his is 1 0 0 m g /2  wee ks  =  5 0  m g/ w k  wit h q 2 w k sc he d ule . 
F or t he sc h e d ule of q 1 w k i n d ucti o n f or 8 wee ks ( 2 c ycles), f oll o w e d b y q 2 w k d osi n g,  t he 
I DI is as bel o w. 
I nitial d osea 
T otal c ycles ( nc)  
I nte n de d t otal 
n u m ber of d oses( n d)  
I DI 
1 6 0 0 m g  
< = 2  
4 * nc  
1 6 0 0 m g / w k 
1 6 0 0 m g  
> 2  
4 * 2 + ( nc –  2) * 2  
= 2 * nc + 4  
(1 6 0 0 * n d ) /(4 * nc ) 
m g/ w k  
a: t he al g orit h m is si milar f or ot her i nitial d ose le vel. 
A bs ol ute D ose I nte nsit y ( A DI) is d efi ne d as t he act ual d ose ( m g ) per u nit of ti me t hat t he 
patie nt recei ve d o ver t h e e ntire treat me nt peri o d.  
Relati ve d ose i nte nsit y ( R DI) is defi ne d as t he a bs ol ute d ose i nte nsit y o ver t he i nte n de d d ose 
i nte nsit y. 
R DI  =  A DI  / I DI *  1 0 0 %  
6. 5  Effi c a c y A n al y s e s  
All efficac y a n al ys es will be prese nt e d usi n g t he All Trea te d patie nts a n al ysis set, u nless 
ot her wise s pecifie d , b y d ose le vel a n d t otal . A nal yses ma y als o be perf or me d usi n g t he 
s u b gr o u ps liste d i n Secti o n 5. 9 . C o variates  are n ot c o nsi dere d f or a dj ust me nt i n a nal yses.  
Res p o nse assess me nts, i ncl u di n g S P E P/i m m u n ofi x ati o n, U P E P/i m m u n ofi xati o n, S F L C, b o ne 
marr o w ass ess me nts  a n d plas mac yt o m a e val u ati o n b y i ma gi n g, as w ell as o verall disease 
assess me nt will be liste d.  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 1 6  of 2 2  
6. 5. 1  Effi c a c y E n d p oi nt s  
6. 5. 1. 1  O bj e cti v e R e s p o n s e R at e ( O R R)  
O bjecti ve res p o ns e  ( O R) rate ( O R R) is defi ne d as t he pr o p orti o n of patie nts wit h best 
res p o nse s C R, C R , V G P R or P R per i n vesti gat or . Patie nts w h ose disease res p o nse ca n n ot be 
e val uate d p er I M W G will be c o nsi dere d as n o n -res p o n der f or calc ulati n g t he O R R i n t he All 
Treate d Patie nts a n al ysis set.  Patie nts w h ose first O R  occ uers  after ne w a ntit u m or t hera p y 
ot her t ha n st u d y tr eat me nt will n ot be c o u nte d as a res p o n der.  
T he O R R per i n vesti gat or  a n d its e x act t w o -si de d 9 5 % co nfi de n ce i nter val usi n g t he 
Cl o p per -Pears o n met h o d (C ollett 1 9 9 1 ) will be calc ulate d.  T his e n d p oi nt ma y als o be 
ta b ulate d b y t he s u b gr o u ps defi ne d i n Secti o n 5. 9 . 
6. 5. 1. 2  C o m pl et e R e s p o n s e  R at e  
C o m plete res p o nse ( C R) rate is defi ne d as t he pr o p orti o n of patie nts wit h best res p o nse  s C R 
or C R per i n vesti gat or . Patie nts w h ose disease res p o nse ca n n ot be e val uate d  per  I M W G will 
be sc ore d as N ot E val ua ble f or calc ulati n g t h e C R rate i n t he All Treate d Patie nts a nal ysis 
set. Patie nts w h ose first C R occ uers aft er ne w a ntit u m or t hera p y ot her t ha n st u d y treat me nt 
will n ot be c o u nte d as a C R w he n calc ulati n g C R rate.  
T he  C R r ate a n d its e x act t w o -si de d 9 5 % c o nfi d e n ce i nter val usi n g t he Cl o p per-Pears o n 
met h o d (C ollett 1 9 9 1 ) will be calc ulate d.  T his e n d p oi nt ma y als o be ta b ul ate d b y t h e 
s u b gr o u ps d efi ne d i n Secti o n 5. 9 . 
6. 5. 1. 3  D ur ati o n of R e s p o n s e  
D urati o n of res p o ns e is defi ne d as t he ti me fr o m first d oc u me ntati o n of o bjecti ve res p o ns e 
(s C R, C R , V G P R, or P R ) t o t he first d oc u me ntati o n of disease pr o gressi o n ( P D) or t o deat h 
d ue t o a n y ca us e, w hic he ver c o mes first.  Disease pr o gressi o n i ncl u des ra di ol o gic e vi d e nce of 
t u m or pr o gressi o n a n d/ or cli nical pr o gressi o n per i n vesti gat or. D urati o n of res p o nse f or 
patie nts w h o d o n’t ha ve a d diti o nal res p o nse assess me nts after d oc u m e ntati o n of o bjecti ve 
res p o nse will be ce ns ore d as 1 da y.  
D urati o n of res p o ns e dat a will be ce ns ore d as des cri be d bel o w:  
● 
P atie nts w h o d o n ot ha ve disease pr o gressi o n a n d are still o n st u d y at t he ti me of a n 
a nal ysis will be ce ns or e d at t he date of t he l ast disease ass ess me nt d oc u me nti n g a bse n ce 
of pr o gressi ve dise ase . 
● 
P atie nts w h o ha ve  starte d a n a ntit u m or treat me nt ot her t ha n t he st u d y treat m e nt pri or t o 
d oc u me ntati o n of disease pr o gressi o n will be ce ns ore d at t he dat e of t he last disease 
assess me nt pri or t o start of ne w t hera p y . 
● 
P atie nts w h o are re m o ve d fr o m t he st u d y pri or t o d oc u me ntati o n of disease pr o gressi o n 
will be ce ns ore d at t he date of t he last di sease assess me nt d oc u me nti n g a bs e nce of 
pr o gressi ve dise ase.  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 1 7  of 2 2  
D urati o n of res p o ns e will o nl y be calc ulate d f or t h e s u b gr o u p of patie nts a c hie vi n g a  s C R, 
C R , V G P R or P R. D urati o n of res p o nse will be a n al yze d usi n g Ka pla n -Mei er met h o d ol o g y 
a n d Ka pla n-M eier pl ots will be pr o vi de d. T he me dia n d urati o n of res p o ns e a n d its t w o -si de d 
9 5 % CI usi n g t he c o m ple me ntar y l o g -l o g tra nsf or mati o n met h o d (C ollett 1 9 9 4 ) will be 
calc ulate d f or eac h e x pa nsi o n c o h ort a n d t otal.  
6. 5. 1. 4  Pr o gr e s si o n Fr e e S ur vi v al ( P F S)  
Pr o gressi o n -free s ur vi val ( P F S) is defi ne d as t h e ti me fr o m t he start of st u d y treat me nt t o t he 
first d oc u me ntati o n of disease pr o gressi o n ( P D) b ase d u p o n t he dis eas e ass ess me nt per 
I M W G 2 0 1 4 criteria or cli nical pr o gressi o n, or t o deat h d ue t o a n y ca use, w hic he ver c o mes 
first. S pecificall y, 
P F S  =  Date of  first d oc u me nte d P D or deat h –  Date of first st u d y tr eat me nt +  1.  
Patie nts w h o d o n’t ha ve p ost -treat me nt res p o ns e assess me nts or deat h will be c e nsore d o n 
t he treat me nt start dat e(i. e., P F S is ce ns ore d as 1 d a y). T he sa m e ce ns ori n g r ules o utli ne d i n 
Secti o n 6. 5. 1. 3  f or t he D O R will be a p plie d t o P F S. 
P F S will be a nal yze d usi n g t he K a pla n -M eier met h o ds a n d Ka pla n-M eier pl ots will be 
pr o vi de d. T he me dia n P F S a n d its  t w o-si de d 9 5 % c o nfi de nce i nter vals ( CI) will be calc ulate d 
usi n g t he c o m ple me nt ar y l o g -l o g tra nsf or mati o n met h o d (C ollett 1 9 9 4 ). 
T he  a nal ysis of P F S ma y be perf or me d f or eac h of t he s u b gr o u ps s p ecifie d i n Secti o n  5. 9 . 
6. 5. 1. 5  O v er all S ur vi v al ( O S)  
O verall s ur vi val is defi n e d as t he ti me fr o m t he start of st u d y tr eat me nt  t o d ate of deat h d ue 
t o a n y ca use. S pecificall y,  
O S  =  Date of d eat h  –  D ate of first st u d y treat me nt +  1 . 
I n t he a bse n ce of c o nfir m ati o n of deat h, O S will be ce ns ore d at t he last dat e t he patie nt is 
k n o w n t o be ali ve.  If t h e last rec or de d date w h ere a patie nt is k n o w n t o be ali ve is t he date of 
first d ose of st u d y treat m e nt, s ur vi val ti me will be ce ns ore d o n t h e treat me nt start date (i.e., 
O S d urati o n of 1 da y).  
O verall s ur vi val  will be  a nal yze d usi n g Ka pla n -M eier  met h o d ol o g y a n d Ka pla n -Meier pl ots 
will be pr o vi de d . T he  me dia n O S a n d its  t w o-si de d 9 5 % c o nfi de n ce i nter vals ( CI) will be 
calc ulate d usi n g t he c o m ple me ntar y l o g -l o g tra nsf or mati o n met h o d (C ollett 1 9 9 4 ). 
A T A i nci de nce will be s u m marize d b y d ose le vel  a n d t otal f or all treate d patie nts.  
6. 6  S af et y A n al y s e s  
T he All Treat e d Patie nts a nal ysis  s et will be use d t o s u m marize all safet y e n d p oi nts, b y d ose 
le vel a n d t otal. 
A d verse e ve nts will be c o de d usi n g Me di cal Dicti o nar y f or Re g ul at or y Acti vities ( Me d D R A, 
Versi o n  2 0 . 1 or hi g her).  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 1 8  of 2 2  
La b orat or y v al ues a n d a d verse e v e nts will be gra d e d acc or di n g t o t he Nati o nal Ca ncer 
I nstit ute C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts (N CI C T C A E versi o n 4. 0 3 ). 
C o nc o mita nt me dicati o ns will be c o de d usi n g W H O Dr u g ( versi o n: J u ne 2 0 1 7  or m ore 
rece nt). 
6. 6. 1  A d v er s e E v e nt s  
A d verse e ve nts will be s u m marize d b y Me d D R A preferre d t er m i n desce n di n g fre q ue n c y of 
occ urre nce u nless ot her wise s pecifie d.  F or i nci de nce re p orti n g, if a patie nt r e p orts m ore t ha n 
o ne A E t hat was c o de d t o t he sa me s yste m or ga n class or preferre d ter m, t he patie nt will be 
c o u nte d o nl y o n ce f or t hat s pecific s yste m or ga n class or preferre d ter m.  
A treat me nt -e mer ge nt A E is defi ne d as a n e wl y o cc urri n g or w orse ni n g A E after t he first 
d ose of S E A -B C M A . A n o verall s u m mar y of A Es will be pr o vi d e d b y d os e le vel  a n d t otal.  
S u m maries of A Es will als o be pr o vi de d b y d ose l e vel  a n d t otal  f or t h e f oll o wi n g, b y 
preferre d t er m, if n ot s pecifi e d ot her wise: 
● 
All treat me nt -e mer ge nt A Es  
● 
A Es relate d t o S E A -B C M A  
● 
Seri o us A d verse E v e nts ( S A Es)  
● 
S A Es relate d t o S E A -B C M A  
● 
A Es lea di n g t o d ose eli mi nati o n of S E A -B C M A  
● 
A Es lea di n g t o d ose dela y of S E A -B C M A  
● 
A E s lea di n g t o d ose i nterr u pti o n of S E A -B C M A  
● 
A E s lea di n g t o d ose re d u cti o n of S E A -B C M A  
● 
A Es lea di n g t o treat me nt disc o nti n uati o n  
● 
A Es lea di n g t o deat h  
● 
I nf usi o n relate d reacti o ns b y preferre d t er m 
● 
A d verse E v e nts c o nsi dere d as D L T  
● 
Treat me nt -e mer ge nt A Es b y s yste m or ga n class, preferre d t er m a n d ma xi m u m se v erit y 
● 
Gra de 3 – 5 tr eat me nt -e mer ge nt A Es  
● 
Treat me nt -e mer ge nt A Es b y s yste m or ga n class a n d preferre d t er m  
All a d verse e ve nts, a d verse e ve nts lea di n g t o treat me nt disc o nti n uati o n, a n d a d verse e ve nts 
lea di n g t o d eat h will be liste d. 
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n doc u me nt.  1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 1 9  of 2 2  
6. 6. 1. 1  A d v er s e E v e nt s of S p e ci al I m p ort a n c e  
A d verse e ve nts of inf usi o n relate d reacti o ns (I R Rs) a n d ass ociat e d s y m pt o ms ma y  be 
c o nsi dere d A Es of s peci al i m p orta nce.  
6. 6. 2  D o s e -Li miti n g T o xi cit y  
T he o bser ve d n u m ber a n d pr o p orti o n of patie nts e x perie nci n g a D L T will be re p ort e d  f or t he 
d ose escal ati o n part  of t h e st u d y . At eac h d os e le vel, m o del-base d esti mates of t he pr o ba bilit y 
of D L T  will be pres e nte d al o n g wit h t he c orres p o n di n g 9 5 % cre di ble i nter vals.  
6. 6. 3  Cli ni c al L a b or at or y P ar a m et er s  
Cli nical la b orat or y data will be s u m marize d  f or selecte d la b tests, b y d ose le vel  a n d 
sc he d ule d visit. S u m mar y statistics ma y be ta b ulate d w here a p pr o pri ate.  T he w orst p ost 
baseli ne gra d e will be prese nte d b y d ose le vel  a n d  t otal f or eac h la b test. 
La b orat or y res ults a n d N CI C T C A E gra des f or h e mat ol o g y, a n d ser u m c he mistr y will be 
prese nte d i n dat a listi n gs.  All la b orat or y data t hr o u g h t he e n d of treat me nt visit will be 
prese nte d i n sta n dar dize d u nits.  
6. 6. 4  C o n c o mit a nt M e di c ati o n s  
C o nc o mita nt me dicati o ns will be liste d b y patie nt.  
6. 6. 5  D e at h s  
T he n u m ber of t otal deat hs, deat hs t hat occ ur wit hi n 3 0 da ys of l ast st u d y tr eat me nt , a n d 
deat hs t hat occ ur m ore t h a n 3 0 da ys aft er last st u d y treat me nt as well as t he relati o ns hi p t o 
disease will be s u m mariz e d b y d os e le vel  a n d t otal.  I n a d diti o n, ca use of deat h will be 
i de ntifie d b y d esce n di n g Me d D R A preferre d ter m ( u nless ot her wise s pecifi e d) a n d 
su m marize d b y d ose le v el  a n d t otal. Deat h  i nf or m ati o n will be liste d b y patie nt. 
6. 6. 6  E C O G P erf or m a n c e St at u s  
S hifts fr o m baseli ne t o t he best a n d w orst p ost -b aseli ne sc ore will be ta b ulate d. 
6. 7  P h ar m a c o ki n eti c s a n d I m m u n o g e ni cit y E n d p oi nt s  
6. 7. 1  P h ar m a c o ki n eti c s  
P K c o nce ntrati o n will be s u m marize d wit h descri pti ve statistics or pl otte d at eac h P K 
sa m pli n g ti me p oi nt usi n g t he All Treate d Patie nts a nal ysis s et. T he f oll o wi n g P K para meters 
will be deter mi ne d w here data all o w  a n d will be s u m marize d usi n g All Treate d Patie nts 
a nal ysis s et.  
● Area u n d er t he c ur ve ( A U C)  
● C o nce ntrati o n at t he e n d of i nf usi o n ( C e oi) or ma xi m u m o bser ve d c o nce ntrati o n ( Cma x ) 
● Tr o u g h c o nce ntrati o n ( C tr o u g h) 
● Ter mi nal or a p p are nt ter mi nal half -life (t1/ 2) 
● S yste mic cle ara n ce a n d v ol u me of distri b uti o n at stea d y state  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 2 0  of 2 2  
● Acc u m ulati o n rati o  
 
6. 7. 2  A ntit h er a p e uti c A nti b o d y ( A T A) I n ci d e n c e R at e  
T he A T A i nci de n ce rate is defi ne d as t he pr o p orti o n of patie nts t hat de vel o p A T A  at a n y ti me 
d uri n g t he st u d y.  
7  
I N T E RI M A N A L Y SI S 
N o ot her f or m al statistical i nteri m a nal ys es are pla n ne d.  Data will be e val uate d after eac h 
d ose le vel t o deter mi ne D L Ts a n d i nf or m d ose-escalati o n decisi o ns. T he S M C will m o nit or 
t he trial f or safet y a n d D L Ts o n a n o n g oi n g b asis. T he pr ocess f or S M C decisi o ns a n d t he 
r oles a n d res p o nsi bilities of t he S M C will be detaile d i n a se parate d oc u me nt. 
8  
C H A N G E S F R O M P L A N N E D  A N A L Y S E S  
8. 1  C h a n g e s fr o m t h e Ori gi n al Pr ot o c ol  
Efficac y -E val u a ble A nal ysis Set was n ot use d i n t he fi nal C S R a nal ysis. 
8. 2  C h a n g e s fr o m t h e Ori gi n al S A P  
Efficac y -E val u a ble A nal ysis Set, P K  A nal ysis  set were n ot use d i n t he fi nal C S R a nal ysis.  
T he f oll o wi n g S u b gr o u ps will n ot be e x pl ore d.  
● C yt o ge netic ris k gr o u p ( hi g h, i nter me diat e, n or m al)  
● Refract or y t o  pri or t hera pies (refract or y t o I Mi D a n d PI vs n ot; r efract or y t o I Mi D 
a n d PI a n d a nti -C D 3 8 a nit b o d y vs n ot)  
● N u m ber of pri or t h era pies ( < 5 vs ≥5)  
● Baseli ne b eta -2 micr o gl o b uli n ( < 3. 5 vs ≥3. 5)  
● I S S sta ge at i nitial dia g n osis ( 1, 2, 3) 
● M R D -ne gati ve C R rate a n d  its e x act t w o-si de d 9 5 % c o nfi de n ce i nter val  will als o be 
prese nte d.  
M R D ne gati ve C R, a n d d urati o n of C R is n ot s u m marize d.  
E x p lorat or y a nal ys es  w hic h will be c o vere d b y Bi o mar ker A n al ysis Pla n are re m o ve d.  
I R R b y c ycl e a nal ysis is re m o ve d. 
E C G s u m mar y a n al ysis is re m o ve d.  
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 2 1  of 2 2  
R E F E R E N C E S   
Cl o p per CJ a n d P ears o n E S ( 1 9 3 4). T he use of c o nfi de nce or fi d ucial li mits ill ustrate d i n t he case of t he 
bi n o mial. Bi o metri ka 2 6: 4 0 4 -4 1 3.  
C ollett D ( 1 9 9 1). Statistical i nfere nce f or bi nar y data. M o delli n g Bi nar y Data. L o n d o n, C ha p ma n a n d Hall:  2 3 -
2 6.  
C ollett D ( 1 9 9 4). I nter val -ce ns ore d s ur vi val data. M o delli n g s ur vi val data i n me dical researc h. B oca Rat o n, 
Fla., C ha p ma n & Hall/ C R C:  2 3 7 -2 5 1.  
Ji Y, Li u P, Li Y a n d B e kele B N ( 2 0 1 0). A m o difie d t o xicit y pr o ba bilit y i nter val met h o d f or d ose -fi n di n g trials. 
Cli n Trials 7: 6 5 3 -6 3.  
Raj k u mar S V, Di m o p o ul os M A, P al u m b o A, Bla de J, Merli ni G, Mate os M V, K u mar S, Hille n gass J, Kastritis 
E, Ric har ds o n P, La n d gre n O, P ai va B, Dis pe nzieri A, Weiss B, Le Le u X, Z wee g m a n S, L o nial S, R osi n ol L, 
Za ma g ni E, J a ga n nat h S, Sezer O, Kristi nss o n S Y, Caers J, Us ma ni S Z, La h uerta JJ, J o h nse n H E, Be ksac M, 
Ca v o M, G ol dsc h mi dt H, T er p os E, K yle R A, A n ders o n K C, D urie B G, Mi g uel J F ( 2 0 1 4). I nter nati o nal 
M yel o ma W or ki n g Gr o u p u p date d criteria f or t he dia g n osis of m ulti ple m yel o ma. La ncet O nc ol 1 5( 1 2): e 5 3 8 -
4 8.  
 
 
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


St u d y S G N B C M A -0 0 1  
Statistical A nal ysis Pla n  Versi o n Err or! N o te xt of s pecifie d st yle 
i n d oc u me nt. 1 5 -A u g -2 0 2 3  
S E A -B C M A  
Seattle Ge netics, I nc. - C o nfi d e ntial  
P a ge 2 2  of 2 2  
A p p e n di x A  
I m p ut ati o n of P arti all y U n k n o w n A d v er s e E v e nt D at e s 
F or a n a d verse e ve nt ( A E) wit h a partial start or e n d date, if it ca n be deter mi ne d t hat t he e ve nt occ urre d pri or t o 
t he first d ose of a n y st u d y treat me nt, t he partial date will n ot be i m p ute d; ot her wise, t he A E partial date will be 
i m p ute d usi n g t he r ules descri be d bel o w.  
a  
A. A E occ urr e d  pri or t o t h e first d os e of a n y st u d y tr e at m e nt , i. e., s atisfi es eit h er i or ii b el o w:  
i. 
O ns et d at e is pri or t o t h e first d os e d at e  
ii. 
( O ns et d at e is c o m pl et el y missi n g or t h e s a m e as t h e first d os e d at e) a n d ( O ns et P eri o d is “st art e d 
b ef or e t h e si g ni n g of c o ns e nt” or “st art e d aft er c o ns e nt b ut b ef or e t h e first d os e of a n y st u d y 
tr e at m e nt”) 
5.  
B.  A E occ urr e d  aft er t h e first d os e of a n y st u d y tr e at m e nt , i. e., s atisfi es eit h er i or ii b el o w:  
i. 
O ns et d at e is aft er t h e first d os e d at e  
ii. 
(O ns et d at e is c o m pl et el y missi n g or t h e s a m e as t h e first d os e d at e ) a n d ( O ns et P eri o d is “st art e d 
aft er first d os e of a n y st u d y tr e at m e nt”  or missi n g)  
b  
N ot e: c o m p ar e A E o ns et d at e wit h t h e first d os e d at e o n t h e c o m m o n pr ecisi o n o nl y f or all t h e d at e 
c o m p aris o ns d escri b e d i n A a n d B a b o v e;  e. g., “ 2 0 1 9” is c o nsi d er e d gr e at er t h a n “ 2 0 1 8 -xx-xx”; “ 2 0 1 9-
0 3” is c o nsi d er e d e q u al t o “ 2 0 1 9-0 3 -xx”. Iss u e a W A R NI N G t o t h e l o g w h e n ( ons et d at e is c o m pl et el y 
missi n g or t h e s a m e as t h e first d os e d at e ) a n d O ns et P eri o d  is missi n g. 
F or A E occ urre d after t he first d ose of a n y st u d y tre at me nt  (see B. a b o ve) o nl y: 
•  
Im p ute i nc o m plete A E start date as t he f oll o wi n g s:  
❖ A E d a y o nl y is missi n g:   if t he m o nt h/ year is t he sa me as t he m o nt h/ year of first d ose of a n y 
st u d y treat me nt, A E start d ate will be i m p ute d as t he first d ose date of a n y st u d y treat me nt; if t he 
m o nt h/ year is after t he m o nt h/ year of first d ose of a n y st u d y treat me nt, A E start da te will be 
i m p ute d as t he first d a y of t he m o nt h 
❖ A E d a y a n d m o nt h are missi n g, or m o nt h o nl y is missi n g: if t he year is t he sa me as t he year of 
first d ose of a n y st u d y treat me nt, A E start date will be i m p ut e d as t he first d ose date of a n y st u d y 
treat me nt; if t he year is after t he year of first d ose of a n y st u d y treat me nt, A E start date will b e 
i m p ute d as J a n uar y 1st 
❖ A E d a y, m o nt h a n d ye a r are missi n g, or ye ar o nl y is missi n g:  A E start date will be i m p ute d as 
t he first d ose date of a n y st u d y treat me nt 
•  
I m p ute inc o m plete A E e n d date as t he f oll o wi n gs w he n A E o utc o me is “rec o veri n g/res ol vi n g”, 
“rec o vere d/res ol ve d ”, “rec o vere d/res ol ve d wit h se q uelae”, or “fatal”:  
❖ A E d a y o nl y is missi n g:  A E e n d date will be i m p ute d as t he mi ni m u m of (last da y of t he A E e n d 
date m o nt h/ year , deat h date, data e xtracti o n date, E O S date)  
❖ A E d a y a n d m o nt h are missi n g, or m o nt h o nl y is missi n g:  if t he year is e q ual t o t he year of t he 
last d ose date, A E e n d date will be i m p ute d as t he mi ni m u m of ( Dece m ber 3 1st of t he A E e n d date 
year, last d ose date + 3 0, deat h date, data e xtracti o n date, E O S date); if t he year is n ot e q ual t o t he 
year of t he las t d ose date, A E e n d date will be i m p ute d as t he mi ni m u m of ( Dece m ber 3 1st of t he 
A E e n d date year, deat h date, data e xtracti o n date, E O S date)  
❖ A E d a y, m o nt h a n d ye a r are missi n g, or ye ar o nl y is missi n g : A E c o n diti o n e n d date will n ot 
be i m p ute d  
N O T E:  if the s u bject di d n ot recei ve a n y d ose of t he st u d y tr eat me nt, d o n ot i m p ute 
a n y A E of t he s u bject  
 
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)


Si g nat ure Pa ge f or S G N- C LI N- 0 2 6 8 2 1 v 1. 0
Si g nat ure Pa ge f or S G N- C LI N- 0 2 6 8 2 1 v 1. 0
e Si g nat ure A p pr o val
Bi ostatistics
2 5- A u g- 2 0 2 3 1 9: 0 3: 5 5 G M T + 0 0 0 0
e Si g nat ure A p pr o val
Cli nical De vel o p me nt
2 5- A u g- 2 0 2 3 1 9: 4 1: 2 4 G M T + 0 0 0 0
e Si g nat ure A p pr o val
Bi ostatistics
3 0- A u g- 2 0 2 3 1 7: 3 7: 1 1 G M T + 0 0 0 0
0 9 0 1 7 7 e 1 a 1 3 0 8 d 3 5\ A p pr o v e d\ A p pr o v e d O n: 2 5- A u g- 2 0 2 3 2 2: 5 9 ( G M T)
P P D
P P D
P P D