A Multicenter Phase 2 Study of Belantamab Mafodotin in Relapsed or Refractory Plasmablastic Lymphoma and ALK+ Large B-cell Lymphoma
Phase: PHASE2
Conditions: Relapsed Plasmablastic Lymphoma, Refractory Plasmablastic Lymphoma, Anaplastic Lymphoma Kinase Positive Large B-Cell Lymphoma
Sponsor: Jacob Soumerai, MD

1
DF/HCC Protocol #: 20-404
TITLE:  A multicenter phase 2 study of belantamab mafodotin in relapsed or refractory 
plasmablastic lymphoma and ALK+ large B-cell lymphoma
Coordinating Center:
Massachusetts General Hospital
Cancer Center Protocol Office – PCORP
Program for Coordination and Oversight of Research Protocols 
Principal Investigator (PI):
Jacob D. Soumerai MD
Massachusetts General Hospital Cancer Center, Boston, MA
jsoumerai@mgh.harvard.edu 
 
Site Investigators:
Andrew D. Zelenetz MD, PhD
Memorial Sloan Kettering Cancer Center, New York, NY
zeleneta@mskcc.org 
 Ranjit Nair, MD
MD Anderson Cancer Center, Houston, TX
 RNair@mdanderson.org
Statistician:
Study Coordinator: 
Robert Redd, MS
Madeline Puccio
DF/HCC Biostatistics Core
MGH Cancer Center
rredd@jimmy.harvard.edu
mpuccio@mgh.harvard.edu
Responsible Research Nurse:
Responsible Data Manager: 
Rosalba Martignetti, RN
Connor Regan
MGH Cancer Center
MGH Cancer Center
rmartignetti@partners.org
CRegan7@mgh.harvard.edu
Other Agent(s):  Belantamab mafodotin (GlaxoSmithKline PSC)
IND #:  
152993
IND Sponsor:  
Jacob Soumerai, MD 
Protocol Version Date:
11/August/2023

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SCHEMA
 

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TABLE OF CONTENTS
SCHEMA
2
1.
OBJECTIVES7
1.1
Study Design............................................................................................................7
1.2
Primary Objectives...................................................................................................7
1.3
Secondary Objectives...............................................................................................7
2.
BACKGROUND .................................................................................................................7
2.1
Plasmablastic lymphoma and ALK+ large B-cell lymphoma .................................7
2.2
Current therapies for relapsed or refractory plasmablastic lymphoma and 
ALK+ large B-cell lymphoma .................................................................................8
2.3
Belantamab mafodotin.............................................................................................9
2.4
Rationale ................................................................................................................10
2.5
Correlative Studies Background ............................................................................11
3.
PARTICIPANT SELECTION...........................................................................................12
3.1
Eligibility Criteria..................................................................................................12
3.2
Exclusion Criteria ..................................................................................................14
3.3
Inclusion of Women and Minorities ......................................................................16
4.
REGISTRATION PROCEDURES ...................................................................................16
4.1
General Guidelines for DF/HCC Institutions ........................................................16
4.2
Registration Process for DF/HCC Institutions.......................................................16
4.3
General Guidelines for Other Investigative Sites ..................................................16
4.4.
Registration Process for Other Investigative Sites.................................................17
5.
TREATMENT PLAN........................................................................................................18
5.1
Treatment Regimen................................................................................................18
5.2
Pre-Treatment Criteria ...........................................................................................18
5.3
Agent Administration.............................................................................................18
5.4
Corneal Supportive Care Guidelines .....................................................................19
5.5
General Concomitant Medication and Supportive Care Guidelines......................19
5.6
Criteria for Taking a Participant Off Protocol Therapy.........................................20
5.7
Duration of Follow Up...........................................................................................21
5.8
Criteria for Taking a Participant Off Study ...........................................................21
6.
DOSING DELAYS/DOSE MODIFICATIONS ...............................................................21
6.1
Adjustments due to body weight........................................................................................21
6.2
Dose reductions for toxicity...............................................................................................21
7.
Stopping Criteria for Belantamab mafodotin.....................................................................27
7.1
Liver Stopping Criteria ......................................................................................................27

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7.2
QTc Stopping Criteria........................................................................................................28
7.3
Corneal Event Stopping Criteria........................................................................................29
7.4
Infusion Related Reaction Stopping Criteria.....................................................................29
7.5
Allergic Reaction and Anaphylactic Reaction Stopping Criteria ......................................29
8.
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ............................29
8.1
Adverse Event List for belantamab mafodotin..................................................................29
8.2
Expected Toxicities................................................................................................35
8.3
Adverse Event Characteristics...............................................................................36
8.4
Adverse Event Reporting.......................................................................................37
8.5
Reporting to the Food and Drug Administration (FDA) .......................................38
8.7
Expedited Reporting to GSK .................................................................................38
8.7
Reporting to Hospital Risk Management...............................................................40
8.8
Routine Adverse Event Reporting .........................................................................40
9.
PHARMACEUTICAL INFORMATION..........................................................................41
9.1
Belantamab mafodotin...........................................................................................41
10.
CORRELATIVE STUDIES ..............................................................................................44
11.
STUDY CALENDAR .......................................................................................................46
12. MEASUREMENT OF EFFECT .............................................................................................48
12.1
Antitumor Effect – 2014 Lugano Criteria..............................................................48
13. DATA REPORTING / REGULATORY REQUIREMENTS.................................................49
13.1
Data Reporting.......................................................................................................49
13.2
Data Safety Monitoring..........................................................................................49
13.3
Multi-Center Guidelines ........................................................................................50
13.4
Collaborative Agreements Language.....................................................................50
14
STATISTICAL CONSIDERATIONS...............................................................................50
14.1
Study Design/Endpoints ........................................................................................50
14.2
Sample Size, Accrual Rate and Study Duration ....................................................51
14.3
Stratification Factors..............................................................................................51
14.4
Interim Monitoring Plan ........................................................................................51
14.5
Analysis of Primary Endpoints..............................................................................52
14.6
Analysis of Secondary Endpoints..........................................................................52
14.7
Reporting and Exclusions ......................................................................................52
15
PUBLICATION PLAN .....................................................................................................52
16
REFERENCES ..................................................................................................................54

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APPENDIX A
Performance Status Criteria.......................................................................56
APPENDIX B
57
1.
INTRODUCTION .............................................................................................................59
1.1
Purpose...................................................................................................................59
2.
GENERAL ROLES AND RESPONSIBILITIES .............................................................59
2.1
Coordinating Center...............................................................................................59
2.2
External Site...........................................................................................................60
3.
DF/HCC REQUIREMENTS FOR MULTI-CENTER PROTOCOLS .............................61
3.1
Protocol Revisions and Closures ...........................................................................61
3.2
Informed Consent Requirements ...........................................................................61
3.3
IRB Re-Approval...................................................................................................62
3.4
DF/HCC Multi-Center Protocol Confidentiality ...................................................62
3.5
Participant Registration and Randomization .........................................................62
3.6
Data Management..................................................................................................62
3.7
Protocol Reporting Requirements..........................................................................63
4.
MONITORING: QUALITY CONTROL..........................................................................63
4.1
Ongoing Monitoring of Protocol Compliance.......................................................63
4.2
Monitoring Reports................................................................................................64
4.3
Accrual Monitoring................................................................................................65
5.
AUDITING: QUALITY ASSURANCE ...........................................................................65
5.1
DF/HCC Internal Audits........................................................................................65
5.2
Audit Notifications.................................................................................................65
5.3
Audit Reports.........................................................................................................65
5.4
External Site Performance .....................................................................................65
APPENDIX C
Ocular Monitoring and Mitigation Strategy ..............................................66
APPENDIX D
Liver Safety Required Actions and Follow Up Assessment......................68
ALT - absolute
68
ALT  5xULN
68
ALT Increase
68
Bilirubin1, 2
68
ALT  3xULN and total bilirubin  2xULN (>35% direct bilirubin) .......................................68
INR2
68
ALT  3xULN and INR>1.5 .......................................................................................................68

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Cannot Monitor
68
Symptomatic3
68
ALT  3xULN associated with symptoms (new or worsening) believed to 
be related to liver injury or hypersensitivity.................................................................68

Immediately discontinue study intervention...............................................................68

Report the event to GSK within 24 hours .................................................................68

Complete the liver event form and complete SAE data collection 
tool if the event also meets the criteria for an SAE2 ..................................................68

Perform liver event follow up assessments as described in the 
Follow Up Assessment column.....................................................................................68

Monitor the participant until liver chemistries resolve, stabilize, or 
return to within baseline (see MONITORING)............................................................68
MONITORING:
68

Repeat liver chemistries (include ALT, AST, alkaline phosphatase, 
total bilirubin and INR) and perform liver event follow up 
assessments within 24 hours.......................................................................................68
For All other criteria (bilirubin <2xULN and INR 1.5): ...................................................69

Repeat liver chemistries (include ALT, AST, alkaline phosphatase, 
total bilirubin and INR) and perform liver event follow up 
assessments within 24-72 hours .................................................................................69

Monitor participants weekly until liver chemistries resolve, stabilize 
or return to within baseline.............................................................................................69
APPENDIX E
Contraception.............................................................................................71
APPENDIX F
Lugano Response criteria (2014)...............................................................72
APPENDIX G
PROHIBITED MEDICATIONS ...............................................................75

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1.
OBJECTIVES
1.1
Study Design
This is a multicenter phase 2 study of belantamab mafodotin in patients with plasmablastic 
lymphoma and ALK+ large B-cell lymphoma. The primary objective will be to determine the 
overall response rate of belantamab mafodotin in patients with these histologies. Patients will 
receive belantamab mafodotin at 2.5 mg/kg IV on day 1 of a 21-day cycle until progression or 
intolerance.
1.2
Primary Objectives
1. To determine the overall response rate of belantamab mafodotin in previously treated 
patients with plasmablastic lymphoma and ALK+ large B-cell lymphoma 
1.3
Secondary Objectives
1. To assess safety and tolerability
2. To determine the complete response rate
3. To determine the durability of clinical benefit as measured by progression-free survival 
and overall survival
4. To determine the overall and complete response rates by subtype (i.e. plasmablastic 
lymphoma and ALK+ large B-cell lymphoma) 
2.
BACKGROUND
2.1
Plasmablastic lymphoma and ALK+ large B-cell lymphoma
Plasmablastic lymphoma (PBL) and ALK+ large B-cell lymphoma (ALK-LBL) are aggressive 
subtypes of diffuse large B-cell lymphoma with plasmablastic/immunoblastic morphology. They 
share three unique and important clinicopathologic characteristics: 
1. Immunoblastic or plasmablastic morphology 
2. Expression profile characteristic of plasma cells (with minimal expression of B cell 
markers)
3. Aggressive behavior with particularly poor prognosis and few long-term survivors. 
The poor outcomes observed in patients with PBL and ALK-LBL may reflect that they are 
biologically distinct from B-cell lymphomas, and that they lack the targets for the approved 
targeted therapies in large cell lymphoma (e.g. CD20, CD79b, CD19). As a result, these patients 
have generally been excluded from clinical trials and there is no standard treatment approach. In 
the relapsed/refractory setting, PBL and ALK-LBL are uniformly fatal. The pathogenesis and 
biology of each of these uncommon lymphomas is poorly understood and there is a critical need 
to identify tractable therapies for these lymphomas.

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2.2
Current therapies for relapsed or refractory plasmablastic lymphoma and ALK+ 
large B-cell lymphoma
2.2.1
Treatment of plasmablastic lymphoma
The prognosis of patients diagnosed with plasmablastic lymphoma are dismal, with a median OS 
of 3 months for HIV-positive plasmablastic lymphoma and 4 months for HIV-negative 
plasmablastic lymphoma.1 The prognosis following initial CHOP-like therapy is dismal leading 
to the current NCCN guidelines recommending more intensive regimens e.g. infusional 
etoposide, vincristine and doxorubicin with bolus cyclophosphamide and prednisone (EPOCH),2 
or cyclophosphamide, vincristine, doxorubicin, methotrexate alternating with ifosfamide, 
etoposide, and cytarabine (CODOX-M/IVAC).3–5 It is unclear treatment intensification has 
modified the natural history of this disease and the prognosis remains dismal.6–9 Two prospective 
studies are evaluating the safety and efficacy of infusional EPOCH in patients with high-risk 
DLBCL and include plasmablastic lymphomas (NCT01092182 and CTSU-9177). A small case 
series of patients receiving EPOCH and bortezomib was also reported with limited efficacy.10 
Given the dismal prognosis, we contend that no established standard therapy exists for patients 
with plasmablastic lymphoma, nor is there an established standard therapy for patients with 
relapsed or refractory disease. Most patients receive salvage chemotherapies regimens used in 
other aggressive lymphomas e.g. ICE, DHAP in the relapsed/refractory setting, and there is an 
urgent need to identify novel therapies for these patients. The role of consolidation with high 
dose chemotherapy and autologous stem cell rescue (HDT/ASCR) or allogeneic stem cell 
transplant (ASCT) is unknown. However, HDT/ASCR or ASCT is considered given the dismal 
prognosis of this disease.
2.2.2
Treatment of ALK+ large B-cell lymphoma
The prognosis of patients with ALK+ large B-cell lymphoma is dismal, with a median OS of 
20.3 months (95% CI, 12.2 to 42.6 months).11 Among patients with advanced stage disease, the 
median survival is only 12.2 months (95% CI, 9.1 to 32.5 months) with no long-term survivors 
reported in the literature.11 Given the rarity of this histology (100-200 patients reported 
throughout the literature), we have little-to-no data guiding management of these patients. For 
patients with limited stage disease, a combined modality approach with CHOP-like therapy and 
consolidative radiotherapy is often used and has been associated with durable remissions/cure in 
some patients. For patients with advanced stage disease, one series suggested a trend toward OS 
benefit with inclusion of etoposide (CHOP or da-EPOCH) over CHOP although this did not 
reach statistical significance in this small retrospective series (p=0.185).12 Given the dismal 
prognosis, we contend that no established standard therapy exists for patients with ALK+ large 
B-cell lymphoma, nor is there an established standard therapy for patients with relapsed or 
refractory disease. Most patients receive salvage chemotherapies regimens used in other 
aggressive lymphomas e.g. ICE, DHAP in the relapsed/refractory setting, and there is an urgent 
need to identify novel therapies for these patients. There are case reports of transient response to 
the ALK inhibitor crizotinib +/- chemotherapy.13,14 The role of consolidation with high dose 
chemotherapy and autologous stem cell rescue (HDT/ASCR) or allogeneic stem cell transplant 
(ASCT) is unknown. However, HDT/ASCR or ASCT is considered given the dismal prognosis 
of this disease.

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2.3
Belantamab mafodotin
Belantamab mafodotin (GSK2857916) is a dual acting Antibody-Drug Conjugate (ADC), 
comprised of an anti-B-Cell Maturation Antigen (BCMA) afucosylated humanized 
immunoglobulin G1 (IgG1) conjugated with the tubulin polymerization disrupting agent 
monomethyl auristatin F (MMAF). 
The normal function of BCMA is to promote cell survival by transduction of signals from two 
known ligands: B cell activating factor from the tumor necrosis factor (TNF) family 
(BAFF/BLys) and a proliferation inducing ligand (APRIL). BCMA expression is restricted to B 
cells at later stages of differentiation, with expression on germinal center B cells in tonsil, blood 
plasma blasts, and long-lived plasma cells. BCMA is expressed in various B cell malignancies, 
including multiple myeloma (MM), diffuse large B-cell lymphoma (DLBCL), large B-cell 
lymphoma (LBCL), chronic lymphocytic leukemia (CLL) and Waldenstrom’s 
macroglobulinemia (WM) at varying frequencies. 
Belantamab mafodotin binds to BCMA, is internalized, and releases free cys-mcMMAF, which 
disrupts the microtubule network, leading to cell cycle arrest and apoptosis. Belantamab 
mafodotin also mediates antibody-dependent cell-mediated cytotoxicity (ADCC) effector 
function directed towards BCMA-expressing cells. The mechanisms of action of belantamab 
mafodotin are designed to enable anti-tumor activity of cells by ADCC activity (non-dividing), 
as well as ADC activity (dividing cells). Moreover, ADC-induced apoptosis by belantamab 
mafodotin was recently shown to be potentially immunogenic as measured by cell surface 
externalization of calreticulin (CRT) and secretion of high mobility group box 1 (HMGB1) and 
adenosine triphosphate (ATP).
In the first-in-human study (BMA 117159) belantamab mafodotin was administered in a total of 
80 patients, 74 subjects with relapsed/refractory multiple myeloma and 6 patients with non-
Hodgkin lymphoma (NHL). In part 1, 38 patients were enrolled at dose levels ranging from 0.03 
mg/kg to 4.6 mg/kg. Belantamab demonstrated a manageable safety profile, and the 
recommended dose of 3.4 mg/kg was identified. In part 2 (MM), the confirmed overall response 
rate for all patients was 60% (95% CI 0.42 – 0.76), the median duration of response (mDOR) for 
responders was 14.3 months (95% CI 10.6 – NR) and the estimated progression free survival 
(PFS) was 12.0 months (95% CI 3.1 – NR). Grade 3 or 4 AEs were reported in 29 (83%) 
patients, the most common of which were thrombocytopenia (grade 3, 9/35 [26%]; grade 4, 3/35 
[9%]) and anemia (grade 3, 6/35 [17%]); no grade 5 AEs were reported. Serious AEs (SAEs) 
were reported in 17/35 (49%) patients, most commonly pneumonia (3/35; 9%), lung infection 
(2/35; 6%), and infusion-related reactions (2/35; 6%). Seven (20%) patients experienced SAEs 
related to study treatment, most commonly infusion-related reactions (2/35; 6%). Four patients 
died during the study, all due to progression of MM. 
A subsequent pivotal phase II study is evaluating the efficacy and safety of two doses of 
belantamab mafodotin as monotherapy in relapsed or refractory multiple myeloma refractory to 
proteasome inhibitors (PI) and immune-modulating drugs (IMiD). This study treated 196 
patients with belantamab mafodotin on day 1 of a 21-day cycle: 97 patients were treated with a 
dose of 2.5 mg/kg, 99 patients were treated with a dose of 3.4 mg/kg. As of June 21, 2019 

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(primary analysis data cut off date), 30 (31%, 97.5% CI 20.8 – 42.6) of the 97 patients in the 2.5 
mg/kg cohort and 34 (34%, 97.5% CI 23.9 – 46.0) of the 99 patients in the 3.4 mg/kg cohort 
achieved an overall response. This study demonstrates single-agent belantamab mafodotin anti-
myeloma activity with a manageable safety profile in patients with relapsed/refractory MM.  
2.4
Rationale
2.4.1
Plasmablastic lymphoma and ALK+ large B-cell lymphoma are biologically similar to 
plasma cell neoplasms and express BCMA
Plasmablastic lymphoma and ALK+ large B-cell lymphoma are biologically more similar to 
plasma cell neoplasms than B-cell lymphomas: 

ALK+ large B-cell lymphoma: ALK-LBL lacks expression of B-cell markers CD20, 
CD79, and PAX5, but plasma cell related antigens CD138, BLIMP1 are diffusely 
expressed in virtually all cases, and MUM1, kappa or lambda light chain and IgA is 
expressed in most cases. All cases of ALK-LBL are EBV and HHV8 negative. On the 
basis of the striking plasma cell phenotype of ALK-LBL, our group utilized hierarchical 
DNA methylation profiling to find that ALK-LBL clustered more with plasma cells and 
plasma cell myeloma than with diffuse large B-cell lymphoma, which clusters closely 
with normal B cells, and away from plasma cell myeloma.

Plasmablastic lymphoma: PBL expresses plasma cell markers, including CD38, CD138, 
MUM1, BLIMP1, and lacks expression of CD45 as well as markers of B-cell phenotype, 
including CD20, and PAX5. EBV is positive in 70% of cases, and HHV8 is always 
negative.
Given the striking plasma cell phenotype of both PBL and ALK-LBL, we hypothesized that 
BCMA would likely be expressed lymphomas, and may thus serve as viable therapeutic targets 
in these aggressive lymphomas that lack typical B cell markers. To this end, we stained a cohort 
of 11 cases of ALK-LBL with an antibody to BCMA and found that 9 of 11 cases of ALK-LBL 
were positive for BCMA. Similarly, BCMA has been shown to be uniformly and strongly 
expressed (3+) in PBL (7/7 cases; Khattar et al, ASH Proc 2017, Poster 622). Primary effusion 
lymphoma (PEL) is morphologically and immunophenotypically similar to plasmablastic and 
ALK+ B-cell lymphomas, with expression of the same plasma cell markers and without mature 
B cell markers. EBV and HHV8 are also often positive. Given its rarity, expression of BCMA 
has not been confirmed. However, given overlapping morphology and immunophenotype with 
plasmablastic and ALK+ B cell lymphomas, BCMA should be expressed in PEL. Therefore, we 
are conducting additional preclinical analysis of PEL cases to confirm BCMA expression, and 
would consider adding this histologic subtype if confirmed.
2.4.2
Belantamab mafodotin is active in ALK+ large B-cell lymphoma
We observed an objective response in a 44-year-old man with ALK-LBL refractory to 10 prior 
lines of therapy. Based on biopsy of an involved lymph node demonstrating refractory ALK+ 

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large B-cell lymphoma with expression of BCMA, we were granted access to belantamab 
mafodotin through the GSK Compassionate Use program (IND #209233). The patient had high 
burden disease at initiation of therapy, i.e. with prolonged ICU stay for management of 
spontaneous tumor lysis syndrome, and achieved rapid disease response with marked reduction 
in LDH (from 18,000 to normal), resolution of tumor lysis syndrome after initial surge related to 
treatment effect, and restaging PET-CT demonstrated PR. He had localized progression with 
gastric involvement during cycle 3 for which he received RT. He continued to derive benefit 
from belantamab mafodotin until he developed systemic progression after 3.5 months on 
treatment. Given our observed outstanding response, Dr. Andrew Zelenetz (Memorial Sloan 
Kettering Cancer Center) treated a patient with ALK-LBL with belantamab mafodotin through 
the GSK Compassionate Use program (IND #145928); this patient achieved an objective 
response followed by consolidation with allogeneic transplant. Given the natural history of ALK-
LBL characterized by a highly aggressive course and refractoriness to all available therapies, 
these observations warrant prospective study.
2.4.3
The current study
We hypothesize that the antibody drug conjugate belantamab mafodotin will be highly active in 
plasmablastic lymphoma and ALK+ large B-cell lymphoma. In the current study, we propose a 
multicenter phase 2 study of belantamab mafodotin in patients with plasmablastic lymphoma, 
and ALK+ large B-cell lymphoma. The primary objective will be to determine the overall 
response rate of belantamab mafodotin in patients with these histologies. Patients will receive 
belantamab mafodotin at 2.5 mg/kg IV on day 1 of a 21-day cycle until progression or 
intolerance.
2.5
Correlative Studies Background
Currently there are no available mouse models or reliable cell lines for most types of lymphoma, 
especially for uncommon types of lymphoma. As part of our research effort, our group has 
developed patient-derived xenograft (PDX) models of lymphoma for the study of lymphoma 
pathogenesis and to study mechanisms of drug response, refractoriness and resistance. Given our 
interest in belantamab mafodotin as potential therapy for ALK-LBL and PBL, we created a PDX 
model of ALK-LBL from a biopsy obtained from the index patient treated with belantamab 
mafodotin. The model was generated by surgical implantation of a 1mm x 1mm x 1mm portion 
of the patient’s biopsy sample into the space between the renal capsule and kidney surface in an 
immunodeficient mouse. The resultant mouse developed a massive tumor, ultimately filling the 
abdominal cavity. The histology of and immunophenotype of the lymphoma was identical to the 
patient’s original lymphoma. The lymphoma can be passaged over many generations, and the 
number of ALK+ LBCL PDX mice that can be created is scalable for need. As a point of 
reference, we are currently using this ALK+ LBCL PDX line to model therapeutic response to 
novel therapies in ALK+ LBCL. 

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3.
PARTICIPANT SELECTION
3.1
Eligibility Criteria 
3.1.1
Participants must have relapsed or refractory plasmablastic lymphoma or ALK+ large B-
cell lymphoma by WHO criteria.
3.1.2
Participants must have measurable disease, defined as at least one lesion that can be 
accurately measured in at least one dimension (longest diameter [LDi] to be recorded for 
non-nodal lesions and short axis for nodal lesions) as ≥15 mm in LDi for nodal disease 
or >10 mm in LDi for extranodal lesions.20
3.1.3
Participants must have received prior systemic lymphoma therapy.
3.1.4
Age ≥18 years. 
3.1.5
ECOG performance status ≤2 (Karnofsky ≥60%).
3.1.6
Participants must have adequate marrow function as defined below (unless abnormalities 
are considered related to marrow and/or splenic involvement by lymphoma). 
Transfusions are permitted for subjects to meet criteria for platelet and/or hemoglobin 
requirements:

absolute neutrophil count
≥1,000/mcL

platelets
≥50,000/mcL

hemoglobin
≥ 8.0 g/dL
3.1.7
Participants must have adequate organ function as defined below (unless abnormalities 
are considered related to involvement by lymphoma; upon initiation of treatment, refer to 
the corresponding stopping criteria as applicable):

total bilirubin
≤ 1.5 X institutional upper limit of normal (ULN); 
(Isolated bilirubin ≥1.5xULN is acceptable if 
bilirubin is fractionated and direct bilirubin <35%)

AST(SGOT)/ALT(SGPT)
≤2.5 × institutional ULN

Spot urine (albumin/creatinine)
<500 mg/g (56 mg/mmol)
OR
Urine Dipstick
Negative/trace (if ≥1+ only eligible if 
confirmed ≤ 500 mg/g (56 mg/mmol) by 
albumin/creatinine ratio (spot urine from first void)

Glomerular filtration rate (eGFR)≥30 mL/min/1.73 m2 (MDRD Formula).
3.1.8
Participants with known history or current symptoms of cardiac disease, or history of 
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac 
function using the New York Heart Association Functional Classification.  To be eligible 

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for this trial, participants should be class 2B or better.
3.1.9
Belantamab mafodotin is potentially teratogenic. A female participant is eligible to 
participate if she is not pregnant or breastfeeding. Women of child-bearing potential must 
agree to use adequate contraception (hormonal or barrier method of birth control; 
abstinence) prior to study entry, for the duration of study participation, and for at least 4 
months after the last dose of study intervention. Please see Appendix E for contraception 
guidance. Women must also agree not to donate eggs (ova, oocytes) for the purpose of 
reproduction during this period. Should a woman become pregnant or suspect she is 
pregnant while she or her partner is participating in this study, she should inform her 
treating physician immediately.  
Nonchildbearing potential is defined as follows (by other than medical reasons):

≥45 years of age and has not had menses for >1 year

Patients who have been amenorrhoeic for <2 years without history of a hysterectomy 
and oophorectomy must have a follicle stimulating hormone value in the 
postmenopausal range upon screening evaluation

Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented 
hysterectomy or oophorectomy must be confirmed with medical records of the actual 
procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with 
medical records of the actual procedure.
3.1.10 Women of childbearing potential must have a negative highly sensitive serum pregnancy 
test, and agree to repeat highly sensitive serum pregnancy testing within 72 hours before 
the first dose of study intervention (if screening pregnancy test was not within 72 hours 
of dosing).
3.1.11 Men treated or enrolled on this protocol must also agree to use adequate contraception 
prior to the study, for the duration of study participation, and 6 months after completion 
of administration. Men must also agree not to donate sperm during this period. Men may 
agree to remain abstinent from heterosexual intercourse as their preferred and usual 
lifestyle (abstinent on a long term and persistent basis) OR agree to use a male condom, 
even if they have undergone a successful vasectomy and female partner to use an 
additional highly effective contraceptive method with a failure rate of <1% per year when 
having sexual intercourse with a WOCBP (including pregnant females). Please see 
Appendix E for contraception guidance.
3.1.12 Participants with a prior or concurrent malignancy whose natural history or treatment 
does not have the potential to interfere with the safety or efficacy assessment of the 

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investigational regimen are eligible for this trial at the discretion of the overall PI.
3.1.13 Ability to understand and the willingness to sign a written informed consent document. 
3.2 Exclusion Criteria
3.2.1
Participants must not have current corneal epithelial disease except mild changes in 
corneal epithelium.
3.2.2
Participant must not have current unstable liver or biliary disease defined by the presence 
of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric 
varices, persistent jaundice, or cirrhosis.  Note: Stable non-cirrhotic chronic liver disease 
(including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement 
of malignancy is acceptable if otherwise meets entry criteria.
3.2.3
Participants who have not recovered from adverse events due to prior anti-cancer therapy 
(i.e., have residual toxicities > Grade 1) with the exception of alopecia. At the discretion 
of the overall PI, participants with residual toxicities > Grade 1 may be considered 
eligible if in the opinion of the overall PI the residual toxicity is not likely to interfere 
with the safety or efficacy assessment of the investigational regimen. 
3.2.4
Participants who are receiving any other investigational agents.
3.2.5
Participants must not have central nervous system involvement by lymphoma, as 
belantamab mafodotin is not known to penetrate the CNS.
3.2.6
Participant must not use contact lenses while participating in this study.
3.2.7
Participant must not be simultaneously enrolled in any interventional clinical trial.
3.2.8
Participant must not have used an investigational drug or approved systemic lymphoma 
therapy within 14 days or five half-lives, whichever is shorter, preceding the first dose of 
study drug. Steroids are permitted.
3.2.9
Participant must not have had major surgery within 4 weeks of initiating study treatment.
3.2.10 Participant must not have any evidence of active mucosal or internal bleeding.
3.2.11 Participants must not have known immediate or delayed hypersensitivity reaction or 
idiosyncratic reactions to belantamab mafodotin or drugs chemically related to 
belantamab mafodotin, or any of the components of the study treatment.
3.2.12 Participants must not have an uncontrolled intercurrent illness. 
3.2.13 Participant must not have an uncontrolled active infection. 
3.2.14 Participant must not have evidence of cardiovascular risk including any of the following:

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
Evidence of current clinically significant uncontrolled arrhythmias, including 
clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd 
degree atrioventricular (AV) block.

History of myocardial infarction, acute coronary syndromes (including unstable 
angina), coronary angioplasty, or stenting/bypass grafting within three (3) months of 
Screening.

Class III or IV heart failure as defined by the New York Heart Association functional 
classification system [NYHA, 1994].

Participant must not have uncontrolled hypertension defined as persistent systolic BP 
>160 mmHg or diastolic BP >100 mmHg.
3.2.15 Participant must not have psychiatric illness/social situations that would limit compliance 
with study requirements. Participants must not have any serious and/or pre-existing 
medical or other condition (including lab abnormalities) that could interfere with 
participant’s safety in the opinion of the investigator. 
3.2.16 Women who are pregnant or lactating are excluded from this study because belantamab 
mafodotin can cause embryo-fetal harm when administered to a pregnant woman.  
Because there is an unknown but potential risk for adverse events in nursing infants 
secondary to treatment of the mother with belantamab mafodotin, breastfeeding should be 
discontinued if the mother is treated with belantamab mafodotin.
3.2.17 Participant must not have presence of hepatitis B surface antigen (HBsAg), or hepatitis B 
core antibody (HBcAb) at screening or within 3 months prior to first dose of study 
treatment. Patients with presence of HBsAg, but demonstrate both HBSag and HBV PCR 
negativity will be eligible for the study.  
3.2.18 Participant must not have positive hepatitis C antibody test result or positive hepatitis C 
RNA test result at screening or within 3 months prior to first dose of study treatment.  
Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be 
enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.
Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C 
antibody test are not required to also undergo Hepatitis C RNA testing.
3.2.19 Participant must not have uncontrolled HIV infection. HIV-infected patients on effective 
anti-retroviral therapy are eligible if they (1) have an undetectable viral load within the 
prior 6 months, or (2) have a detectable viral load with an absolute CD4 count of 200 
cells per microliter or higher.

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3.2.20 Participant must not have invasive malignancies other than disease under study, unless 
the second malignancy has been medically stable for at least 2 years and, in the opinion 
of the principal investigators, will not affect the evaluation of the effects of clinical trial 
treatments on the currently targeted malignancy. Participants with adequately treated 
basal, squamous cell carcinoma or non-melanomatous skin cancer, carcinoma in situ of 
the cervix, superficial bladder cancer not treated with intravesical chemotherapy or BCG 
within 6 months, localized prostate cancer and PSA <1.0 mg/dL on 2 consecutive 
measurements at least 3 months apart with the most recent one being within 4 weeks of 
study entry, may be enrolled without a 2-year restriction.
3.3
Inclusion of Women and Minorities
Both men and women of all races and ethnic groups are eligible for this trial.
4.
REGISTRATION PROCEDURES
4.1
General Guidelines for DF/HCC Institutions
Institutions will register eligible participants in the Clinical Trials Management System (CTMS) 
OnCore. Registrations must occur prior to the initiation of any protocol-specific therapy or 
intervention. Any participant not registered to the protocol before protocol-specific therapy or 
intervention begins will be considered ineligible and registration will be denied.
An investigator will confirm eligibility criteria and a member of the study team will complete the 
protocol-specific eligibility checklist.
Following registration, participants may begin protocol-specific therapy and/or intervention. 
Issues that would cause treatment delays should be discussed with the Principal Investigator (PI) 
of the registering site. If the subject does not receive protocol therapy following registration, the 
subject must be taken off study in the CTMS (OnCore) with an appropriate date and reason 
entered.  
4.2
Registration Process for DF/HCC Institutions
Applicable DF/HCC policy (REGIST-101) must be followed.  
4.3
General Guidelines for Other Investigative Sites
Eligible participants will be entered on study centrally at Massachusetts General Hospital by the 
Coordinating Center.  All sites should call the Coordinating Center to verify slot availabilities.  
Following registration, participants should begin protocol therapy within 5 days. Issues that 
would cause treatment delays should be discussed with the Sponsor-Investigator.  If the subject 

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does not receive protocol therapy following registration, the subject must be taken off study in 
the CTMS (OnCore) with an appropriate date and reason entered.  The Coordinating Center 
should be notified of cancellations as soon as possible.
4.4. Registration Process for Other Investigative Sites
To register a participant, the following documents should be completed by the participating site 
and sent to the Coordinating Center:

Copy of source documentation verifying all eligibility criteria and screening procedures, 
including but not limited to:

Pathology report

Radiology results/report

Medical history with details of prior treatments and therapies

Physical Exam

Laboratory report

Concomitant medication list

Study entry note confirming any eligibility criteria not directly addressed in 
source

Demographic information

Signed participant consent form

HIPAA authorization form

Eligibility Checklist
The Coordinating Center will review the above documentation to confirm eligibility and consent. 
To complete the registration process, the Coordinating Center will follow DF/HCC Standard 
Operating Procedure for Human Subject Research Titled Subject Protocol Registration (Policy#: 
REGIST-101) and register the participant on the protocol.  Once registered a confirmation email 
with the participant study number, and if applicable the dose treatment level, will be sent to the 
participating site.  
NOTE:  Registrations can only be conducted by the Coordinating Center during the business 
hours of 8:30 AM and 5:00 PM Eastern Standard Time (or Eastern Daylight Time when 
applicable), Monday through Friday.  A complete registration packet, including all documents 
listed above, must be received at least 24 hours prior to the anticipated registration to ensure 
adequate review.  Same day treatment registrations will only be accepted with prior notice and 
discussion with the Coordinating Center. 
Treatment may not begin without confirmation from the Coordinating Center that the 
participant has been registered.
5.
TREATMENT PLAN

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5.1
Treatment Regimen
 
A treatment cycle is defined as 21 consecutive days.
Belantamab mafodotin will be administered intravenously as a 2.5 mg/kg calculated dose on day 
1 of each cycle. Treatment is intended to be administered on an outpatient basis. Reported 
adverse events and potential risks are described in Section 8. Appropriate dose modifications are 
described in Section 6.  No investigational or commercial agents or therapies other than those 
described below may be administered with the intent to treat the participant's malignancy. 
5.2
Pre-Treatment Criteria
5.1.1. Cycle 1, Day 1
Cycle 1 Day 1 (C1D1) laboratories need to be reviewed before treatment. Participants must have 
adequate organ and marrow function without clinically significant change to proceed with 
treatment. 
5.1.2. Subsequent Cycles 
Patients should be assessed clinically for toxicity at each visit using the NCI CTCAE v5.0 
(http://evs.nci.nih.gov/ftp1/CTCAE) grading scale.  Dosing should occur only if a patient’s 
clinical assessment and laboratory test values are acceptable (See Section 5.1.1). The CBC with 
differential and chemistries must be reviewed prior to treatment administration.
5.3
Agent Administration
Belantamab mafodotin will be administered as a monotherapy intravenously as a 2.5 mg/kg 
calculated dose (see Section 9.1.8).  Premedication is not required prior to infusion unless 
deemed medically necessary by the investigator. The dose of belantamab mafodotin must not 
exceed 2.5 mg/kg over a 21-day period. 
For any participant experiencing an infusion-related reaction (IRR), immediately interrupt 
belantamab mafodotin infusion and manage symptoms. Once reaction symptoms resolve, resume 
infusion at a reduced rate as described in Section 6 Table 2. Premedication may be required with 
subsequent infusions as described in Section 6 Table 2. Participants that experience a Grade 4 
IRR associated with belantamab mafodotin should be permanently withdrawn from the study. 

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Guidance on management of IRRs in provided in Section 6 Table 2.
5.4
Corneal Supportive Care Guidelines
Changes in visual acuity, which commonly manifest as changes in corneal epithelium, have been 
observed on ocular exams with antibody drug conjugates, including those conjugated to MMAF. 
Sites are required to establish a close collaboration with an ophthalmologist or optometrist (if an 
ophthalmologist is not available) who will be responsible for assessing patients and managing 
those who develop changes in corneal epithelium on ocular examination:
-
On-study ocular exams to be performed by an ophthalmologist or optometrist (if an 
ophthalmologist is not available) at baseline, prior to each dose of belantamab 
mafodotin in all cycles (should be within 5 days prior to dosing [supersedes window 
below in calendar] and all efforts should be made to schedule as close to belantamab 
mafodotin dosing as possible), and promptly for worsening symptoms. 
i. Additional exams may be performed by ophthalmologist as clinically 
indicated.
ii. If vision changes or ocular symptoms develop, patient should be evaluated 
by an ophthalmologist.
iii. In case of persistent or newly developed ocular symptoms or vision 
changes, the participants will have further ophthalmologic exams, at least 
every 3 months until resolution (to grade 1 or baseline) or more frequently 
as clinically indicated by the eye care specialist.
Patients will receive the following supportive care to reduce the risk of corneal epithelium 
changes:
-
Prophylactic preservative-free artificial tears must be administered in each eye at least 4-
8 times daily beginning on C1D1 until end of treatment. In the event of ocular symptoms 
(i.e. dry eyes), the use of artificial tears may be increased up to every 2 hours as needed.
-
Corticosteroid eye drops are not required but can be used if clinically indicated per 
discretion of an eye-care specialist. Allow at least 5-10 minutes between administration 
of artificial tears and steroid eye drops (if administered).
-
At the start of each infusion, participants may apply cooling eye masks to their eyes for 
approximately 1 hour or as long as tolerated.
Further information regarding changes in the corneal epithelium associated with belantamab 
mafodotin, including a grading scale and prophylactic measures are in Appendix C.
5.5
General Concomitant Medication and Supportive Care Guidelines
Participants should receive prophylactic allopurinol (or febuxostat if intolerant/allergy to 
allopurinol) and be encouraged to hydrate well on days 1-7 of cycle 1 for prevention of tumor 
lysis syndrome (may be started earlier or continued later at investigator discretion). For patients 
with elevated uric acid on C1D1, prophylactic rasburicase should be administered.
Participants should receive full supportive care during the study, including transfusions of blood 

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products, growth factors, and treatment with antibiotics, anti-emetics, antidiarrheal, and 
analgesics, as appropriate.  
Elimination pathways for belantamab mafodotin and cys-mcMMAF have not been characterised 
in humans, however, cys-mcMMAF was shown to be a substrate of P-gp and OATP transporters 
in vitro.  Caution should be exercised when belantamab mafodotin is combined with strong 
inhibitors of P-gp, and strong inhibitors of OATP should be avoided unless considered medically 
necessary.
The following medications and devices are prohibited while receiving study treatment:

Concomitant administration of strong P-glycoprotein (P-gp) inhibitors and strong 
inhibitors of OATP with belantamab mafodotin should be avoided unless considered 
medically necessary.

Any other anti-cancer therapy not specified in this protocol, and any investigational 
agents other than belantamab mafodotin.

Contact lenses.
o
NOTE: Contact lens use may be restarted after the ophthalmologist (or an 
optometrist if an ophthalmologist is not available) confirms there are no other 
contraindications.
5.6
Criteria for Taking a Participant Off Protocol Therapy
Duration of therapy will depend on individual response, evidence of disease progression and 
tolerance. In the absence of treatment delays due to adverse event(s), treatment may continue for 
until one of the following criteria applies:

Disease progression

Intercurrent illness that prevents further administration of treatment

Unacceptable adverse event(s)

Participant demonstrates an inability or unwillingness to comply with the intravenous 
medication regimen and/or documentation requirements

Participant decides to withdraw from the protocol therapy

Participant has met any of the protocol defined safety stopping criteria

Pregnancy

General or specific changes in the participant's condition render the participant 
unacceptable for further treatment in the judgment of the treating investigator
Participants will be removed from the protocol therapy when any of these criteria apply.  The 
reason for removal from protocol therapy, and the date the participant was removed, must be 
documented in the case report form (CRF). Alternative care options will be discussed with the 
participant.
When a participant is removed from protocol therapy and/or is off of the study, the participant’s 
status must be updated in OnCore in accordance with REGIST-OP-1.

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5.7
Duration of Follow Up
Participants will be followed for 2 years after removal from protocol therapy or until death, 
whichever occurs first.  Participants removed from protocol therapy for unacceptable adverse 
event(s) will be followed until resolution or stabilization of the adverse event. Participants with 
corneal signs or symptoms at the End of Treatment Visit will be followed once a month (± 7 
days) until deemed clinically stable by an ophthalmologist (or an optometrist if an 
ophthalmologist is not available), or up to 1 year (whichever comes first).  
5.8
Criteria for Taking a Participant Off Study
Participants will be removed from study when any of the following criteria apply:

Lost to follow-up

Withdrawal of consent for data submission

Death
The reason for taking a participant off study, and the date the participant was removed, must be 
documented in the case report form (CRF). In addition, the study team will ensure the 
participant’s status is updated in OnCore in accordance with REGIST-OP-1.
6. DOSING DELAYS/DOSE MODIFICATIONS
6.1 Adjustments due to body weight
The actual body weight in kg at baseline (assessed on C1D1 prior to dosing) will be used for 
dose calculation of belantamab mafodotin in all participants during the treatment period. 
However, if the change of body weight is greater than 5%, the dose must be recalculated based 
on the actual body weight at the time of dosing.
Dose delays and modifications will be made as indicated in the following table(s). The 
descriptions and grading scales found in the revised NCI Common Terminology Criteria for 
Adverse Events (CTCAE) version 5.0 will be utilized for dose delays and dose modifications. A 
copy of the CTCAE version 5.0 can be downloaded from the CTEP website
 http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
6.2  Dose reductions for toxicity
After Cycle 1, dose modifications may be made for individual participants, based on safety 
findings. Dose interruptions and reductions are permitted throughout the study per guidance in 
Table 1.

Guidance for belantamab mafodotin dose reductions and delays - Table 2.

Dose modification and management guidelines for drug-related adverse events not 
otherwise specified - Table 3.

Dose Modification guidelines for belantamab mafodotin related corneal events – Table 4. 

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Table 1. Permitted Dose Reductions
Starting 
belantamab 
mafodotin dose
1st reduction
2nd reduction
3rd reduction
2.5 mg/kg
1.9 mg/kg
1.4 mg/kg
Discontinue
The dose allowed for belantamab mafodotin may be reduced. If the participant is unable 
to tolerate at least belantamab mafodotin at 1.4 mg/kg, they will be withdrawn from the 
study due to unacceptable toxicity.
In case of full resolution of symptoms which lead to dose reduction, further treatment at 
the previous dose may be considered by the investigator. 
Dosing delays are permitted in the case of medical/surgical events or for logistical reasons not 
related to study therapy (e.g., elective surgery, unrelated medical events, participant vacation 
and/or holidays) but not for participants’ decision to delay treatment.  If a dose is delayed, the 
participant should wait for the next scheduled dose to resume treatment.  In individual cases, 
where in the judgement of an investigator waiting a full cycle to resume treatment after delay 
(skipping dose) related to toxicity which has resolved would be detrimental to patient’s health, 
an earlier re-start may be considered at the discretion of the Sponsor-Investigator. The dosing 
with belantamab mafodotin cannot occur more frequently than every 21 days ( 3-day window). 
Table 2. Dose Modification Guidelines for belantamab mafodotin-related 
Adverse Events
Toxicity
Grade/description 
of toxicity
Recommendations for belantamab 
mafodotin
Elevated serum 
creatinine which cannot 
be explained by 
concomitant sepsis, 
TLS, other severe 
condition with fever, or 
dehydration
If absolute serum 
creatinine 
increases from 
baseline by >0.5 
mg/dL

Repeat serum creatinine within 48 hours

If confirmed: withhold therapy, institute 
treatment and monitoring as clinically 
indicated, and follow for resolution
Serum creatinine 
>Grade 3
>3.0 mg/dL from 
baseline
or
3.0-6.0x 
institutional ULN

Provide appropriate medical treatment.

Permanently discontinue treatment with 
belantamab mafodotin 

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Toxicity
Grade/description 
of toxicity
Recommendations for belantamab 
mafodotin
Spot urine (albumin / 
creatinine ratios)
>2000 mg/g
(or 224 mg/mmol)

Re-test (at least 7 days apart).

If not confirmed, continue belantamab 
mafodotin at 100% dose

If confirmed on re-test and no clear 
evidence of disease progression
o
Interrupt treatment with belantamab 
mafodotin
o
Repeat testing within 4 weeks
i.
If spot urine ≤2000 mg/g (224 
mg/mmol), may restart 
belantamab mafodotin with 1 
dose level reduction
ii.
If spot urine remains >2000 mg/g 
(224 mg/mmol) after 4weeks, 
permanently discontinue 
belantamab mafodotin and 
withdraw participant from study; 
provide treatment as clinically 
indicated and follow for 
resolution
Grade 2

May continue belantamab mafodotin 
dosing.

Confirm by quantitative assessment using 
albumin/creatinine (spot urine from first 
void)

If albumin/creatinine 2000mg/g, at the 
next cycle follow guidance above for spot 
urine
Urine Dipstick
Grade ≥ 3

Interrupt treatment and follow up for 
recovery. Implement quantification of 
albumin/creatinine ratio
Thrombocytopenia 
(on days of dosing) 
Grade 3

No bleeding: continue treatment with 1 
dose level reduction. Consider reverting to 
previous dose once thrombocytopenia 
recovered to G2 or less.

With bleeding: withhold the dose, 
continue treatment after recovery to G2 or 
less with 1 dose level reduction

Consider additional supportive treatment 
(e.g. transfusion), as clinically indicated 
and per local guidance.

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Toxicity
Grade/description 
of toxicity
Recommendations for belantamab 
mafodotin

Withhold the dose.  Consider restarting 
with 1 dose level reduction if recovered to 
G3 only if there is no active bleeding at 
time of treatment re-start
Thrombocytopenia
(On days of dosing)
Grade 4

If thrombocytopenia is considered disease 
related, is not accompanied by bleeding, 
and recovers with transfusion to 
>25x109/L continuing treatment with 1 
dose level reduction may be considered
Afebrile neutropenia
(graded according to 
NCI-CTCAE criteria)
Grade 3-4 (defined 
as ANC 
<1000/mm3)

If noted on Day 1 of any cycle, withhold 
belantamab mafodotin dose.

Resume belantamab mafodotin at pre-held 
dose once neutropenia recovers to Grade ≤ 
2 (ANC ≥ 1000/mm3) on Day 1 of a 
subsequent cycle.

Prophylactic antibiotics, per physician 
discretion and local institutional guidance. 

Consider growth factors.

Local guidance must be followed for 
hematological monitoring, if more 
conservative than the protocol schedule of 
activities specifications.

In cases of frequent recurrent neutropenia 
(ANC <1000/mm3), consider dose 
reduction of belantamab mafodotin by 1 
dose level.
Febrile neutropenia
(graded according to 
NCI-CTCAE criteria)
Grade 3-4
(defined as: single 
temp of 38.3oC, or 
sustained 38oC for 
>1 hr. AND ANC 
<1000/mm3)

Withhold the dose

Hospitalize participant and implement 
appropriate management, per institutional 
guidance

Consider additional supportive treatment 
per local practice (e.g. growth factors)

Continue treatment after resolution.  
Consider a dose reduction of belantamab 
mafodotin, if neutropenia was drug related
Grade 2

Stop the infusion, provide medical 
treatment and continue at half the original 
infusion rate after resolution to Grade 0-1
Infusion Reactiona
Grade 3

Continuation only allowed after recovery 
to G1 and with pre-medication, and 
extension of infusion time to 2-4 hours.  
Any future infusion needs to be pre-
medicated

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Toxicity
Grade/description 
of toxicity
Recommendations for belantamab 
mafodotin
Grade 4

Permanently discontinue
Grade 2

Withhold the dose

When resolved, restart treatment with a 1 
dose level reduction

If patient is already at the lowest dose 
level, then rechallenge with the same dose 
must be discussed with Medical Monitor
Pneumonitis
Grade 3-4

Permanently discontinue
a.
If symptoms resolve within one hour of stopping infusion, the infusion may be restarted at 
50% of the original infusion rate (e.g., from 100 mL/hr. to 50 mL/hr.).  Otherwise dosing will 
be held until symptoms resolve and the participant must be pre-medicated for the next 
scheduled dose.
Table 3. 
General Dose Modification and Management Guidelines for Drug-
related Adverse Events Not Otherwise Specifieda
Severity
Management
Follow-up
Grade 1

Administer symptomatic 
treatment as appropriate

Continue study drug(s)a
Provide close follow-up to evaluate for increased 
severity, no dose modification necessary
Grade 2

Administer symptomatic 
treatment

Investigate etiology

Consider consulting 
subspecialist, and/or 
diagnostic procedure
Symptoms resolved in ≤7 days:
Continue after resolution at the current dose
Symptoms ongoing >7 days or worsening:

Delay study drug, or consider 1 dose level 
reduction. If recovery takes >3 weeks, consult 
with study medical monitor

If symptoms continue or worsen to G3-4, see 
below
Grade 3

Provide appropriate 
medical treatment 

Consider Consulting 
subspecialist

Delay treatment till recovery to G1 or less.  

Consider dose reduction. 

Exceptions: Participants who develop G3 
toxicities which respond to standard treatment 
and resolve to ≤G1 within 48 hours may 
continue treatment at scheduled or reduced 
dose 
Grade 4

Provide appropriate 
medical treatment 

Consider Consulting 
subspecialist

Interrupt treatment.  

Further treatment with belantamab mafodotin 
only allowed on individual basis it is agreed 
that benefits outweigh the risks for a given 
participant
a.
Treatment-related decisions can be made based on local laboratory results if central results 
are not available or delayed.

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Table 4. 
Dose Modification Guidelines for Corneal-Related Adverse Events 
Associated with belantamab mafodotin
Grade/description of toxicity (as 
described in belantamab mafodotin 
Prescribing Information)
Recommendations
Grade 1: Based on worst finding in the 
worst affected eye, and should be based on 
either a corneal examination finding or a 
change in visual acuity per the Keratopathy 
and Visual Acuity Scale: 
Corneal examination finding(s):
-
Mild superficial keratopathy 
(documented worsening from 
baseline), with or without 
symptoms
Change in best-corrected visual acuity:
-
Decline from baseline of 1 line on 
Snellen Visual Acuity due to 
treatment-related corneal findings
Continue treatment at current dose.
Grade 2: Based on worst finding in the 
worst affected eye, and should be based on 
either a corneal examination finding or a 
change in visual acuity per the Keratopathy 
and Visual Acuity Scale:
Corneal examination finding(s):
-
Moderate superficial keratopathy 
with or without patchy microcyst-
like deposits, subepithelial haze 
(peripheral), or a new peripheral 
stromal opacity.
Change in best-corrected visual acuity:
-
Decline from baseline of 2 or 3 
lines on Snellen Visual Acuity and 
not worse than 20/200
Hold treatment and allow to recover to 
≤G1 (both corneal examination findings 
and change in best corrected visual 
acuity). 
Once recovered, resume therapy with 1 
dose level reduction. 

If already on 1.4 mg/kg, participant 
continues treatment at same dose. 
Upon resolution (e.g., G1), re-escalation 
to previous dose level may be considered 
with overall PI approval.
Grade 3: Based on worst finding in the 
worst affected eye, and should be based on 
either a corneal examination finding or a 
Hold treatment and allow to recover to 
≤G1 (both corneal examination findings 

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Grade/description of toxicity (as 
described in belantamab mafodotin 
Prescribing Information)
Recommendations
change in visual acuity per the Keratopathy 
and Visual Acuity Scale:
Corneal examination finding(s):
-
Severe superficial keratopathy with 
or without diffuse microcyst-like 
deposits, subepithelial haze 
(central), or a new central stromal 
opacity.
Change in best-corrected visual acuity:
-
Decline from baseline by more than 
3 lines on Snellen Visual Acuity 
and not worse than 20/200
and change in best corrected visual 
acuity). 
Once recovered, resume therapy with 1 
dose level reduction. 

If already on 1.4 mg/kg, participant 
resumes at same dose.
If after event resolution eye symptoms 
are considered stable for at least 3 cycles 
and if vision is ≤G1, consider re-
escalation to dose prior to dose level 
reduction.
Grade 4: Based on worst finding in the 
worst affected eye, and should be based on 
either a corneal examination finding or a 
change in visual acuity per the Keratopathy 
and Visual Acuity Scale:
Corneal examination finding(s):
-
Corneal epithelial defect such as 
corneal ulcers.
Change in best-corrected visual acuity:
-
Snellen Visual Acuity worse than 
20/200
Hold treatment, restart only after 
discussion with sponsor for patients 
whose vision improves to ≤G1 (both 
corneal examination findings and change 
in best corrected visual acuity).
Resume treatment with 1 dose level 
reduction.  If participant was already on 
1.4 mg/kg, continue at the same dose.
7. STOPPING CRITERIA FOR BELANTAMAB MAFODOTIN
7.1 Liver Stopping Criteria
Liver chemistry stopping/increased monitoring criteria have been designed to assure participant 
safety and evaluate liver event etiology. Discontinuation of study treatment for abnormal liver 
tests related to belantamab mafodotin is required when the participant satisfies any of the 
stopping rules as shown below.

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If a participant meets liver chemistry stopping criteria, do not restart/re-challenge participant 
with study treatment without overall approval by overall PI and Sponsor Medical Monitor.
7.2 QTc Stopping Criteria
ECGs are obtained at screening then only as clinically indicated (i.e. recommended if new QTc 
prolonging medications are initiated after treatment initiation). If a participant has corrected QT 
(QTc) interval duration criteria >530 msec, 2 additional ECGs will be obtained over a brief 
period (e.g., within approximately 10 minutes of the abnormal ECG and approximately 2 
minutes apart from each other, if possible). 
-
QTc is calculated by Fridericia’s formula (QTcF) 
-
In the setting of a bundle branch block (BBB): 
QTc = calculated QTcF - (BBB duration – 120 msec)
If the averaged QTc values of the 3 ECGs is >530 msec, treatment will be withheld. Attempts 
should be made to correct the QTc (e.g. by reducing or stopping other QTc-prolonging 
medications and/or correcting electrolyte abnormalities), and study treatment may subsequently 
be resumed if the averaged QTc values of 3 ECGs is <500 msec.

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7.3 Corneal Event Stopping Criteria
All belantamab mafodotin dose modifications and stopping criteria are to be based on the 
CTCAE v5. Corneal events will be graded according to Keratopathy and Visual Acuity (KVA) 
criteria for eye disorders. 
Participants who develop Grade 4 corneal events must be discussed in detail with the treating 
ophthalmologist (or an optometrist if an ophthalmologist is not available), in order to determine 
whether the participant can be allowed to continue treatment with belantamab mafodotin, or 
permanently discontinue treatment. If a participant is allowed to continue treatment, the dose of 
belantamab mafodotin will be reduced by 1 dose level (Section 6). The decision will be 
documented in study files, together with individual assessment of risk-benefit.
7.4 Infusion Related Reaction Stopping Criteria
Premedication is not required prior to infusion unless deemed medically appropriate by the 
investigator following evaluation of infusion-related reactions (IRRs). Premedication should be 
considered in any participant who experienced an IRR at first or any subsequent infusion with 
belantamab mafodotin, and are administered per institutional policy. For infusion reactions of 
any grade/severity, immediately interrupt the belantamab mafodotin infusion and manage 
symptoms. Once reaction symptoms resolve, resume the infusion at a reduced rate. 
Premedication may be required with subsequent infusions.
A participant that experiences a Grade 4 IRR associated with belantamab mafodotin should be 
permanently withdrawn from the study without overall approval by overall PI and Sponsor 
Medical Monitor.
7.5 Allergic Reaction and Anaphylactic Reaction Stopping Criteria
All participants will be monitored carefully for evidence of allergic response to treatment. A 
participant who exhibits severe hypersensitivity or anaphylaxis will receive appropriate medical 
treatment and will permanently discontinue study treatment.
8. ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The 
following list of reported and/or potential AEs (Section 8.1) and the characteristics of an 
observed AE (Section 8.3) will determine whether the event requires expedited reporting in 
addition to routine reporting.
8.1 Adverse Event List for belantamab mafodotin
Please refer to section 6 of the current investigator brochure for the comprehensive and updated 
list of adverse events. 

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Potential Risk of 
Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
Study Treatment belantamab mafodotin 
Changes on Ocular 
Examination 
Changes to the corneal 
epithelium on ocular examination 
have been frequently observed 
with belantamab mafodotin. This 
was most commonly associated 
with: blurred vision, dry eyes, 
photophobia, and changes in 
vision.  
Active monitoring for superficial 
corneal changes according to the 
study calendar (Section 8). 
Recommendations for dose 
delays/reductions are provided in 
Section 5.
Infusion-Related 
Reaction (IRR)
IRRs were reported in 
participants treated with 
belantamab mafodotin. Most 
IRRs observed to date were 
Grade 1 to 2 and manageable 
with medical treatment.
Participants will be closely 
monitored for signs of IRR. 
Premedication prior to first 
infusion of belantamab mafodotin 
is not mandatory but may be 
considered based on investigator 
judgment, and may be given per 
institution policy.
If an IRR occurs during 
belantamab mafodotin 
administration, management will 
follow guidance in Section 5.  
Thrombocytopenia
Thrombocytopenic events 
(Grades 1 to 4) are among the 
most common AEs associated 
with belantamab mafodotin.
Routine monitoring of 
haematologic panels as outlined in 
Section 8.  
Supportive therapy (including 
transfusions) per local medical 
practice
Recommended dose reductions or 
treatment discontinuations are 
outlined in Section 5.
Neutropenia
Neutropenic events, including 
febrile neutropenia have been 
observed with treatment with 
belantamab mafodotin, 
In a study of belantamab 
mafodotin in combination with 
lenalidomide/ dexamethasone, 
two fatal cases of severe 
infections associated with 
neutropenia have been observed.   
Routine monitoring of 
haematologic panels as outlined in 
Section 7.   
Prophylactic antibiotics, per 
institutional guidance, in 
participants with Grade 3-4 
neutropenia (absolute neutrophil 
count [ANC] <1.0x109/L)
Immediately hospitalize 
participants with febrile 
neutropenia 
Consider additional supportive 

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Potential Risk of 
Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
treatment(s) per local practice 
(e.g., transfusion, growth factors). 
Dose reductions or treatment 
discontinuations are outlined in 
Section 6.
Potential for 
Cardiotoxicity 
Related to an 
Inflammatory 
Response
Nonclinical studies, 
predominantly in monkey, 
increased activation of 
macrophages was noted in a 
number of organs at ≥3 
mg/kg/week, reflective of a 
systemic inflammatory response.  
Minimal inflammatory changes 
(inflammatory cell infiltrate 
and/or haemorrhage) were also 
noted in hearts (atrial 
epicardium, ventricle 
endocardium) of single monkeys, 
which were nonadverse and 
reversible.
Incidence of cardiac events 
reported to date with belantamab 
mafodotin was relatively low and 
mostly Grade 1-2.
Participants with significant 
cardiac risk factors will be 
excluded from study participation.
Electrocardiogram and LVEF will 
be measured as clinically 
indicated.
Hepatotoxicity
In nonclinical studies liver is a 
target organ for toxicity, with 
increased liver weights and/or 
raised hepatobiliary enzymes and 
transaminases observed in both 
rat and monkey. These changes 
in the liver were without clinical 
consequence in the shorter 
duration studies and in the rat 13-
week study. In the monkey 13-
week study, progression of liver 
toxicity to include minimal 
multifocal hepatocellular 
necrosis was observed at all 
doses administered (≥3 
mg/kg/week). 
Mild elevations of liver enzymes 
have been reported in some 
Only participants with well-
preserved liver function per the 
inclusion/exclusion criteria will be 
allowed on study. 
Participants with chronic HBV and 
HCV will be excluded. 
Liver function tests will be 
regularly monitored (Section 7)
Liver stopping criteria outlined in 
Section 7.

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Potential Risk of 
Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
participants treated with 
belantamab mafodotin.
Nephrotoxicity
Non-clinical safety studies have 
demonstrated dose dependent 
and reversible primary 
glomerular injury and tubular 
degeneration (in rat and 
monkey), accompanied by large 
molecular proteinuria 
(albuminuria) and enzymuria. 
Single cell necrosis of the kidney 
and bladder urothelium was also 
noted in the 13-week monkey 
study. Severe tubular 
degeneration/regeneration and 
marked glomerulonephritis 
exacerbated by immune complex 
disease, likely associated with 
ADA, led to the early euthanasia 
of one monkey following 5 
weekly doses of 10 mg/kg. 
No significant renal findings 
were reported to date in clinical 
trials
Participants will be monitored for 
kidney function by assessing 
creatinine, eGFR, electrolytes, and 
albumin / creatinine ratios (spot 
urine).  
Participants will be educated about 
the need of maintaining adequate 
urinary output.  
Dose reductions and treatment 
stopping criteria will be applied 
according to Section 5 and Section 
6.
Pulmonary toxicity 
(pneumonitis)
Nonclinical safety experiments 
have demonstrated the presence 
of progressive microscopic 
changes in the lungs (prominent 
alveolar macrophages associated 
with eosinophilic material; mixed 
perivascular/neutrophilic 
inflammation) in rats at all doses 
tested.  
To date no significant pulmonary 
toxicity has been reported in 
clinical trials.
Monitoring for clinical signs and 
symptoms potentially related to 
pulmonary toxicity. 
Further diagnostic tests and 
management will be implemented 
immediately according to 
recommendations provided in 
Section 6.
Immunosuppression
In nonclinical studies belantamab 
mafodotin has been associated 
with decreases in 
immunoglobulins in monkeys at 
all doses.  An increase in 
immunoglobulins was seen in 
rats (rats are not an antigen 
Participants who have active 
infection will be excluded. 
Patients with an active infection 
excluded.
Monitoring for infections and 
immediate treatment according to 
standard practice.

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Potential Risk of 
Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
specific species for belantamab 
mafodotin).
MM participants frequently are 
immunodeficient due to the 
underlying condition. 
Assessment of changes in 
immunoglobulin levels is 
challenging in participants with 
MM
Potential for Other 
Laboratory 
Abnormalities
An increased magnitude of 
aspartate aminotransferase (AST) 
relative to alanine 
aminotransferase (ALT) 
consistent with increased skeletal 
troponin I was observed in the 
single dose monkey study. 
Increased skeletal troponin I 
and/or creatine kinase and 
aldolase were observed in the rat 
3-week study. 
Cases of elevated AST, lactic 
dehydrogenase (LDH) and 
creatine kinase (CK), and gamma 
glutamyl transferase (GGT) 
alone or concomitant with no 
clear clinical correlate have been 
observed in clinical studies.
Laboratory parameters will be 
monitored as outlined in the study 
calendar (Section 11). 
Participants with significant 
laboratory elevations (≥3x 
institutional upper limit of normal 
[ULN]) should, where possible, 
have a sample sent for central 
testing of CK and LDH isoenzyme 
levels. 
Embryo-Fetal 
Toxicity
Nonclinical reproductive studies 
with belantamab mafodotin have 
not been conducted. Embryo-
fetal toxicity is expected due to 
the cytotoxic component, cys-
mcMMAF via nonspecific 
uptake and/or BCMA-mediated 
toxicity (due to reports of BCMA 
expression in human placental 
cells).
Use of belantamab mafodotin in 
pregnant women may cause fetal 
harm.
Pregnancy testing outlined in the 
study calendar (Section 11).
See Contraception requirements in 
Appendix E.
Impaired Male and 
Female Fertility
In animal studies, belantamab 
mafodotin treatment has resulted 
in testicular toxicity and adverse 
Men who may wish to father 
children in the future will be 
advised to have sperm samples 

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Potential Risk of 
Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
effects on spermatogenesis. 
Reversibility of testicular toxicity 
is unknown at this time. 
In addition, luteinized non-
ovulatory follicles were observed 
in the ovaries of rats after 3 
weekly doses. Ovarian toxicity 
not observed following 12 weeks 
off dose and only after weekly 
dosing.
frozen and stored prior to 
belantamab mafodotin treatment.
Women of childbearing potential 
who may desire offspring in the 
future will be counselled about the 
option of having eggs frozen 
before treatment.
See Contraception requirements in 
Appendix E.
Risks from Study Procedures
Bone Marrow 
Aspiration/Biopsy
Pain, infection, bleeding may 
occur after the procedure.
Participants will be treated 
according to institution’s practice
Incidental Findings 
During Imaging 
Data Acquisition
During the acquisition of 
imaging data (e.g., MRI, CT, 
PET, ECHO), non-MM disease 
or drug-related clinical 
abnormalities could be found by 
the radiographer or 
echocardiographer performing 
the exams.
All imaging scans will be reported 
to the site by an appropriate 
imaging clinician (non-
anonymized) for non-MM disease- 
or drug-related and non-specific 
findings on clinical abnormalities.

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8.2
Expected Toxicities
8.2.1. Adverse Events List
8.2.1.1.
Adverse Event List for belantamab mafodotin
Single-agent belantamab mafodotin was demonstrated to have a manageable safety profile in 
heavily pre-treated participants with RRMM. Safety data for single-agent belantamab mafodotin 
was pooled (data as of 20Sep2019) for study 205678 (DREAMM-2) and supportive FTIH study 
BMA117159 (DREAMM-1) by treatment cohorts of 2.5 mg/kg and 3.4 mg/kg.
The most common AEs in both treatment cohorts were keratopathy (corneal epithelium changes 
observed on ophthalmic examination), thrombocytopenia and anaemia. The incidence of AEs, 
including Grade 3/4 AEs was comparable between belantamab mafodotin 2.5 mg/kg and 3.4 
mg/kg cohorts. Adverse events leading to dose delays, and reductions were less frequent in 2.5 
mg/kg cohort, 51% and 32% compared with the 3.4 mg/kg cohort, 67% and 52%, respectively. 
AEs leading to permanent treatment discontinuation occurred in 10% and 11% of participants in 
the 2.5 and 3.4 mg/kg cohorts, respectively. More participants in the 3.4 mg/kg cohort 
experienced SAEs (50%) and fatal SAEs (6%) compared with the 2.5 mg/kg cohort (41% and 
3%, respectively).
Single agent belantamab mafodotin 2.5 mg/kg was selected as the recommended dose based on 
comparable efficacy with a more favourable safety profile (i.e. lower incidence of 
thrombocytopenia and neutropenia and less frequent dose delays or reductions) compared with 
the 3.4 mg/kg dose.
8.2.1.2.
Description of key adverse event for belantamab mafodotin
Tumor lysis syndrome
On the basis of grade 4 tumor lysis syndrome (TLS) observed in the first patient enrolled on 
study, who exhibited very high pre-treatment disease burden, TLS was added to the informed 
consent form and investigators were advised to consider inpatient hospitalization / observation 
for close TLS monitoring during cycle 1 in patients with very high disease burden. This is at the 
discretion of the treating investigator per standard practice/care for patients with high-burden 
lymphoma initiating anti-lymphoma therapy.
Corneal Events
Corneal events, reported in most cases as keratopathy, blurred vision and dry eye events are the 
most frequently reported AEs with belantamab mafodotin.
In DREAMM-2 (data as of 31Jan2020), events in the Eye disorders SOC occurred in 78% of 
participants treated with belantamab mafodotin 2.5 mg/kg. The most common ocular AEs were 
keratopathy (71%, changes in corneal epithelium identified on eye exam, with or without 
symptoms), blurred vision (22%), and dry eye (13%). Decreased vision defined as Snellen score 
worse than 20/50 in the better seeing eye was reported in 18% of participants receiving 
belantamab mafodotin 2.5mg/kg. Severe vision loss defined as 20/200 or worse in the better 

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seeing eye was reported in 1% of participants receiving belantamab mafodotin 2.5 mg/kg.
The median time to onset of Grade 2 or above corneal findings (best corrected visual acuity or 
corneal examination) was 36 days (range: 19 to 143 days) in participants receiving belantamab 
mafodotin 2.5 mg/kg. The median time to resolution of these corneal findings was 91 days 
(range: 21 to 201 days).
Participants with history of dry eye were more prone to develop corneal examination findings. 
Therefore, active management of dry eye symptoms prior to and during treatment is 
recommended (i.e. administration of preservative-free artificial tears).
The ocular sub-study of DREAMM-2 provided no evidence that corticosteroid eye drops are 
beneficial in preventing or mitigating corneal events.
Infusion-Related Reactions
Infusion-related reactions (IRRs) are expected for biologic agents. In DREAMM-2 (data as of 
31Jan2020), IRRs occurred in 21% of participants in the belantamab mafodotin 2.5 mg/kg, 
which were Grade 1 - 3 in severity. Most IRRs occurred with the first infusion and few 
participants experienced IRRs with subsequent infusions.
Although not protocol-mandated, pre-medications for IRR prophylaxis (including paracetamol, 
antihistamines, and steroids) were administered to 26%–27% of participants. One participant (2.5 
mg/kg cohort) discontinued treatment due to IRRs (Grade 3 IRRs at first and second infusion).
Thrombocytopenia
In DREAMM-2 (data as of 31Jan2020), thrombocytopenic events (thrombocytopenia and 
platelet count decreased) occurred in 38% participants treated with belantamab mafodotin 2.5 
mg/kg; severity ranging between Grade 1 and 4. The incidence of Grade 3 bleeding events was 
low (2%), with no Grade 4 or 5 events reported in participants treated with belantamab 
mafodotin 2.5 mg/kg.
Most participants had a decrease from baseline in their platelet counts during the study. In 
general, participants who initiated treatment with lower platelet numbers tended to continue to 
have thrombocytopenia while on treatment with belantamab mafodotin.
8.3 Adverse Event Characteristics

CTCAE term (AE description) and grade:  The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 will be utilized for AE reporting.  All appropriate treatment areas should have access 
to a copy of the CTCAE version 5.0.  A copy of the CTCAE version  5.0 can be 
downloaded from the CTEP web site 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.
-
Other AEs for the protocol that do not require expedited reporting are outlined in the 
next section (Expedited Adverse Event Reporting) under the sub-heading of Protocol-

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Specific Expedited Adverse Event Reporting Exclusions.

Attribution of the AE:

- Definite – The AE is clearly related to the study treatment.

- Probable – The AE is likely related to the study treatment.

- Possible – The AE may be related to the study treatment.

- Unlikely – The AE is doubtfully related to the study treatment.

- Unrelated – The AE is clearly NOT related to the study treatment.
8.4 Expedited Adverse Event Reporting 
In the event of an unanticipated problem or life-threatening complications treating investigators 
must immediately notify the PI and the Coordinating Center.
Investigators must report to the PI/Coordinating Center any serious adverse event (SAE) that 
occurs after the initial dose of study treatment, during treatment, or within 70 days of the last 
dose of treatment regardless of causality or expectedness.  SAEs that occur after that must be 
reported if suspected as related to the study treatment. Reports should be submitted within 1 
business day of event awareness using the FDA MedWatch 3500 form.
An adverse event is considered serious if it results in ANY of the following outcomes:  
1. Death
2. A life-threatening adverse event 
3. An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization for ≥ 24 hours 
4. A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
5. A congenital anomaly/birth defect. 
6. Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition.
8.4.1. DF/HCC Expedited Reporting Guidelines
For Multi-Center Trials, each participating institution must abide by the reporting requirements set 
by the DF/HCC and DFCI IRB.  The following events require expedited reporting:

All life threatening and fatal Serious Adverse Events (grade 4 and 5) considered serious, 
unexpected, and related, must be submitted via a written adverse event report to the DFCI 
Office for Human Research Studies (OHRS) within 5 working days from notification of 
the event. 

For all other Serious Adverse Events considered serious, unexpected, and related, a full 
written adverse event report must be submitted to OHRS within 10 working days from 
notification of the event. 

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
Any unrelated adverse event does not require reporting to OHRS except grade 5 events 
which must be reported at the time of continuing review.
‘Reasonable possibility’ means there is evidence to suggest a causal relationship between the 
study intervention and the adverse event.
Unexpected means the adverse event is not listed in the investigator brochure or is not listed at 
the specificity or severity that has been observed, or, if an investigator brochure is not required or 
available, is not consistent with the risk information described in the general investigational plan 
(e.g., protocol or consent form).
Investigative sites within DF/HCC will report AEs directly to the DFCI Office for Human 
Research Studies (OHRS) per the DFCI IRB reporting policy.
Other investigative sites will report SAEs to the Coordinating Center and to their respective IRB 
according to the local IRB’s policies and procedures in reporting adverse events. The 
Coordinating Center will report external site events to OHRS per the requirements above.  
)
8.4.2. Protocol-Specific Adverse Event Reporting Exclusions
For this protocol only, the AEs/grades listed below do not require expedited reporting to 
the DF/HCC Sponsor-Investigator.  However, they still must be recorded through the 
routine reporting mechanism (i.e. case report forms).
CTCAE 
SOC
Adverse 
Event
Grade
Hospitalization/ 
Prolongation of 
Hospitalization
Attribution
Comments
N/A
8.5 Reporting to the Food and Drug Administration (FDA)
The Sponsor-Investigator will be responsible for all communications with the FDA. The 
Coordinating Center, on behalf of the Sponsor-Investigator, will report to the FDA, regardless of 
the site of occurrence, any serious adverse event that meets the FDA’s criteria for expedited 
reporting following the reporting requirements and timelines set by the FDA. Initial and follow-
up reports should be submitted to the Coordinating Center using the FDA MedWatch 3500 form.
8.7
Expedited Reporting to GSK
All SAEs and pregnancies, and follow up information must be reported to GSK on an SAE 

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Report Form or Pregnancy report form within 24 hours of Coordinating Center investigator 
becoming aware of the initial event or follow-up information. The Coordinating Center will 
submit all adverse events reports to GSK regardless of the site of occurrence. The Sponsor 
Institution must provide a causality assessment and must sign, and date all SAE Report Forms.
If supporting documentation is included in the submission to GSK (e.g., hospital reports, 
consultant reports, death certificates, autopsy reports, etc.), please redact any patient identifiers 
(including Medical Record number).
GSK SAE and Pregnancy Reporting Information
Email: OAX37649@gsk.com
On at least an annual basis, the Sponsor Institution will provide a copy of the safety reports 
submitted to applicable Regulatory Authorities or IECs.  Annual reports should be provided to 
GSK within 3 business days of submission to the applicable regulatory body.
On a quarterly basis the Sponsor Institution will provide GSK with a line listing of all adverse 
events (serious and non-serious) received during a defined quarter. The line listing will include a 
subject ID, the AE term, onset date, outcome, causality assessment, severity, and study drug 
dosing information.   
8.6.1. Relationship to Study Drug
The Investigator must provide a causality assessment regarding the relationship of the event with 
the study drug for all AEs.  One of the following categories should be selected based on medical 
judgment, considering all contributing factors:

Related: There is a reasonable possibility of a causal relationship between the medicinal 
product and AE, i.e. there are facts, evidence, and/or arguments to suggest a causal 
relationship, rather than a relationship cannot be ruled out. Alternative causes, such as 
underlying disease(s), concomitant therapy, and other risk factors, as well as the temporal 
relationship of the event to study treatment administration will be considered and 
investigated.

Not Related: A causal relationship between the medicinal product and the AE cannot be 
established, based on consideration of factors described above. 
The investigator may change their opinion of causality in light of follow-up information, and 
provide an updated causality assessment, in the originally completed SAE form, as applicable.
8.6.2. Adverse Events of Special Interest (AESI) for Belantamab mafodotin
An Adverse Event of Special Interest (AESI) is defined as any AE (serious or non-serious) that is 
of scientific and medical concern specific to the study treatment. 
AESI’s for belantamab mafodotin include the following: 

Thrombocytopenia

Infusion related reactions

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
Corneal events 
Severity of corneal events will be graded according to the CTCAE v5.
8.6.3. Collection of Pregnancy Information
Male participants with partners who become pregnant:

Investigator will attempt to collect pregnancy information on any male participant’s 
female partner of a male study participant who becomes pregnant while participating in 
this study and for 6 months following the last dose of belantamab mafodotin. This 
applies only to male participants who receive study intervention.

After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
send it to the Coordinating Center for submission to GSK within 24 hours of learning of 
the partner’s pregnancy. 

The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to GSK

Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure. 
Female participants who become pregnant:

Investigator will collect pregnancy information on any female participant, who becomes 
pregnant while participating in this study and for 9 months following the last dose of 
belantamab mafodotin. 

Information will be recorded on the appropriate form and submitted to GSK by the 
Coordinating Center within 24 hours of learning of a participant's pregnancy. 

Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on participant and neonate, which will be 
forwarded to GSK Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.  

Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure. 

While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be reported 
as an AE or SAE. 

A spontaneous abortion is always considered to be an SAE and will be reported as such.  

Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study intervention by the investigator, will be reported to GSK.  
While the investigator is not obligated to actively seek this information in former study 
participants, he or she may learn of an SAE through spontaneous reporting. 
Any female participant who becomes pregnant while participating will discontinue study 

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treatment. 
8.7 Reporting to Hospital Risk Management
Participating investigators will report to their local Risk Management office any participant 
safety reports, sentinel events or unanticipated problems that require reporting per institutional 
policy. 
8.8 Routine Adverse Event Reporting
All Adverse Events must be reported in routine study data submissions to the PI on the toxicity 
case report forms.  AEs reported through expedited processes (e.g., reported to the IRB, 
FDA, etc.) must also be reported in routine study data submissions.
9. PHARMACEUTICAL INFORMATION
A list of the adverse events and potential risks associated with the investigational agent 
administered in this study can be found in Section 8.1.
9.1 Belantamab mafodotin
9.1.1. Description
Please refer to the current investigator brochure.
Belantamab mafodotin (GSK2857916) is a dual acting Antibody-Drug Conjugate (ADC), 
comprised of an anti-B-Cell Maturation Antigen (BCMA) afucosylated humanized 
immunoglobulin G1 (IgG1) conjugated with the tubulin polymerization disrupting agent 
monomethyl auristatin F (MMAF). 
The normal function of BCMA is to promote cell survival by transduction of signals from 
two known ligands: B cell activating factor from the tumor necrosis factor (TNF) family 
(BAFF/BLys) and a proliferation inducing ligand (APRIL). BCMA expression is 
restricted to B cells at later stages of differentiation, with expression on germinal center B 
cells in tonsil, blood plasma blasts, and long-lived plasma cells. BCMA is expressed in 
various B cell malignancies, including multiple myeloma (MM), diffuse large B-cell 
lymphoma (DLBCL), large B-cell lymphoma (LBCL), chronic lymphocytic leukemia 
(CLL) and Waldenstrom’s macroglobulinemia (WM) at varying frequencies. 
Belantamab mafodotin binds to BCMA, is internalized, and releases free cys-mcMMAF, 
which disrupts the microtubule network, leading to cell cycle arrest and apoptosis. 
Belantamab mafodotin also mediates antibody-dependent cell-mediated cytotoxicity 
(ADCC) effector function directed towards BCMA-expressing cells. The mechanisms of 
action of belantamab mafodotin are designed to enable anti-tumor activity of cells by 
ADCC activity (non-dividing), as well as ADC activity (dividing cells). Moreover, ADC-
induced apoptosis by belantamab mafodotin was recently shown to be potentially 

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immunogenic as measured by cell surface externalization of calreticulin (CRT) and 
secretion of high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP).
Belantamab mafodotin (GSK2857916) is an afucosylated humanized IgG1κ monoclonal 
antibody conjugated with an average of four maleimidocaproyl monomethyl auristatin F 
(mcMMAF [SGD-1269]) that binds to BCMA.
The theoretical mass of protein containing carbohydrate conjugated with four drug linker 
molecules is 152.1 kDa (intact mass).
Plasma half-life is 12 days after the first dose and increases over time to be 14 days. 
Following a single IV administration of 10 mg/kg 3H-cys-mcMMAF to rats, the majority 
of the radioactive dose was excreted in the faeces (approximately 83%). Urinary 
excretion (approximately 13%) was a minor route. Radioactivity was excreted rapidly, 
with 94% of the administered dose recovered in the first 48 hours after dosing. The total
recovery of radioactivity over the 7-day collection period was 96%. Cys-mcMMAF was 
detected in human urine following IV administration. However it was not possible to 
make a quantitative assessment of renal excretion from the data.
No pharmacodynamic studies have been performed to evaluate possible interactions of 
belantamab mafodotin (GSK2857916) with other drugs that may be co-administered.
9.1.2. Form
Belantamab mafodotin (GSK2857916) is clear to opalescent; colorless to yellow to
brown liquid and is administered intravenously (IV) via infusion.
Belantamab mafodotin 
Dosage form:
Lyophilized powder, 100 mg/vial in single-use vial for 
reconstitution 
Unit dose strengths:
100 mg/vial (Lyophilized powder)
Route of Administration:
Delivered as IV solution over at least 30 minutes*.  
Dosing instructions:
Reconstitute belantamab mafodotin lyophilized powder 
100 mg/vial 2.0mL of water for injection (WFI); dilute 
with saline before use.  
Manufacturer/ Source of 
Procurement:
 GSK/Baxter
9.1.3. Storage and Stability
Belantamab mafodotin (GSK2857916) for Injection, 100 mg drug product is supplied as 
a lyophilized powder for solution for infusion. Prepared doses should be used as soon as 
possible because the product does not contain an antimicrobial preservative.

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The recommended storage condition is 2-8 degrees C, protected from light. The expiry 
date, where required, is stated on the product label.
9.1.4. Compatibility
Belantamab mafodotin (GSK2857916) for Injection, 100 mg should not be administered 
concomitantly with other drugs in the same administration assembly.
9.1.5. Handling
Qualified personnel, familiar with procedures that minimize undue exposure to 
themselves and the environment, should undertake the preparation, handling, and safe 
disposal of the chemotherapeutic agent in a self-contained and protective environment. 
9.1.6. Availability
Belantamab mafodotin (GSK2857916) is available from GlaxoSmithKline/Baxter. 
9.1.7. Preparation
For IV administration, the drug product is reconstituted with 2.0 mL of WFI before use.
Please visually inspect the product solution to confirm it appears clear to opalescent; 
colorless to yellow to brown; free from visible particles. If the inspected solution does not 
match this description, do not use and alert GSK for further instructions. Once 
reconstituted, the solution should be used to prepare the dose as soon as possible. The 
dose is stable after dilution with 0.9% Sodium Chloride for Injection to 2 mg/mL – 0.2 
mg/mL for up to 6 hours from initial vial reconstitution when stored at 15-25 degrees C 
and is compatible with the following contact materials: polyvinylchloride, polyolefin, 
polyurethane catheter and 0.2 μm polyethersulfone (PES) filters. It is recommended to 
prepare and administer the dosing solution in a 250 mL IV bag. If a closed system 
transfer device (CSTD) is used, instructions provided by the manufacturer must be 
followed to ensure intended dose is delivered. 
9.1.8. Administration
Belantamab mafodotin (GSK2857916) is delivered as IV solution over at least 30 
minutes. 
9.1.9. Ordering
Belantamab mafodotin (GSK2857916) will be provided by GlaxoSmithKline/Baxter. 
9.1.10. Accountability

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The investigator, or a responsible party designated by the investigator, should maintain a 
careful record of the inventory and disposition of the agent using the NCI Drug 
Accountability Record Form (DARF) or another comparable drug accountability form.  
(See the NCI Investigator’s Handbook for Procedures for Drug Accountability and 
Storage.)
9.1.11. Destruction and Return
Any expired supplies of the belantamab mafodotin will be destroyed. Belantamab 
mafodotin should be destroyed at the investigational site if permitted by local regulations. 
10. CORRELATIVE STUDIES 
Based on our preclinical data in ALK+ LBCL, we hypothesize that large cell lymphoma 
subtypes characterized by a plasma cell phenotype are more likely to respond to belantamab 
mafodotin. It will important to obtain a detailed understanding of both the biology underlying 
this response, as well as mechanisms that may lead to refractoriness in particular cases. In 
addition, there may be a need to understand mechanisms of possible resistance in particular cases 
after certain intervals of therapy. The generation of PDX lymphoma models can serve as a 
critical resource to achieve these goals. Note that we will collect research specimens for 
correlative studies with aim to perform these correlative studies for all subjects on study, 
although we recognize that in practice these correlative studies may not be completed in all 
enrolled patients.
To this end, we propose to establish a PDX line for each patient at the time of enrollment, 
in order to achieve the following specific aims: 
1. Generation of a PDX lymphoma line from a biopsy obtained from each patient 
enrolled: 
We will obtain a biopsy sample from each patient at the time of biopsy both to confirm 
disease and to generate PDX mouse models. These models will be generated by direct 
implantation of biopsy samples into the renal subcapsular space of recipient NOD scid 
gamma (NSG) mice. The mouse lines can then be easily propagated indefinitely by the 
serial transfer of dissociated tumor cells into subsequent generations of mice by tail vein 
injection. Each PDX lymphoma line will be characterized by histology, 
immunohistochemical markers, and targeted sequencing and fusion analysis for disease 
confirmation. 
2. Model therapeutic response of ALK-LBL and PBL in PDX lymphoma models: 
For each PDX line, we will generate a cohort of PDX lymphoma mice for treatment with 
belantamab mafodotin (n=6) or vehicle (n=6). We will examine the impact of therapy on 
tumor growth (in-vivo by ultrasound monitoring) and survival. We will deploy genetic, 
epigenetic, and transcriptomic profiling on PDX tumors treated with belatamab 
mafodotin and vehicle to (a) identify potential predictive biomarkers of response to 
belatamab mafodotin and (b) examine molecular changes that occur secondary to therapy. 
As part of this we will carefully examine the effects of therapy on BCMA expression on 
lymphoma cells, and the kinetics of this effect. We will be able to study the persistence of 

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remissions over time in mice to evaluate for relapse and then investigate mechanisms of 
resistance using the same molecular assays. Ultimately, we will correlate these potential 
predictive biomarkers as well as the histologic subtype to treatment outcomes in all 
enrolled patients and their respective PDX lines. The PDX mice may later be useful in 
studying any questions that may later be of interest, including the impact of drug 
combinations.
3. Other investigations: 
Tumor biopsies and PDX mouse models may be used be used for other correlative 
investigations aimed at better understanding the underlying biology of these rare 
histologies. Additionally, the PDX mice may later be useful in studying any questions 
that may later be of interest, including the impact of drug combinations.
Refer to the lab manual for details on sample collection and processing.

46
11.
STUDY CALENDAR
Cycle = 21 days
Screening
Cycle 1
Subsequent 
Treatment Cycles
Survival/Follow-
Up6
Window
+/- 4 days
+/- 4 days
+/- 14 days
Study Day(s)
-30 to 0
1
2
1
EOT Visit 30d 
+/- 7d after 
discontinuation10
Every 3 Months
EDC Timepoints
Belantamab mafodotin
X
X
D1 of Every Cycle
Cooling eye masks, 
preservative-free artificial tears7
X
X
D1 of Every Cycle
Informed consent
X
Screening
Medical history
X
X6
Concurrent medications
X
X
X
X
Every study visit
Adverse Event Evaluation9
X
X
X
X
X5
C1D8 and every subsequent 
study visit
Vital signs
X
X
X
X
X
Every study visit
Physical exam
X
X
X
X
X
Every study visit
Ocular exam7
X7
X7
X7
X7
D1 of Every Cycle
Height
X
Screening
Weight
X
X
X
D1 of Every Cycle
ECOG performance status
X
X
X
X
D1 of Every Cycle
CBC with differential
X
X
X
X
X
Every study visit
Comprehensive metabolic panel, 
uric acid, phosphorus, CPK
X
X
X
X
X
Every study visit
Urinalysis (dipstick) or Spot 
Urine for albumin/creatinine 
ratio
X
X8
LDH
X
X
X
Every study visit
B2-microglobulin
X
X
Screening
G6PD
X
EKG
X
Screening
Serum pregnancy test (B-HCG)1
X1
X1
X
X
X
Screening and D1 of every 
cycle
HIV, Hepatitis B and C testing2
X2
Screening
PET-CT imaging3
X3
X3
X3
Screening, C3D1, C5D1, C7D1, 
every 6 months thereafter 
(C13D1, C19D1, etc.)
Fresh tumor biopsy for 
correlative studies4
X4
X4
X4
Screening
Saliva sample for correlative 
studies4
X4
1- Not necessary if male or woman who is not of childbearing potential. If screening pregnancy test not within 72 hours prior to first dose, then 
this must be repeated to ensure negative highly sensitive serum pregnancy test within 72 hours prior to first dose of belantamab mafodotin. 

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For questionable cases, follicle-stimulating hormone (FSH) and estradiol (as needed in WOCBP) should be performed at local lab to 
determine childbearing potential. WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1. 
Subsequent pregnancy tests on dosing days may be either serum or urine. Final pregnancy test (serum or urine) must be performed in 
WOCBP at the EOT Visit. Follow up pregnancy assessment by telephone (for WOCBP only) should be performed 9 months after the last 
dose of belantamab mafodotin.
2- HIV, Hepatitis B and C testing may be performed within 30 days prior to date of protocol therapy start.  See Exclusion Criteria for additional 
information.
3- CT neck/chest/abdomen/pelvis and FDG-PET scan are required during Screening; after 2 months (C3D1); after 4 months (C5D1); after 6 
months (C7D1); then every 6 months on therapy (C13D1, C19D1, C25D1, et cetera), and at EOT.
4- Fresh tumor biopsy is required at Screening and per PI’s discretion at subsequent progression. Saliva sample is required at Screening. See Lab 
Manual for details regarding collection, processing, and shipping of fresh tumor biopsy for correlative studies. In patients who do not have a 
site of disease amenable to biopsy, biopsy may be deferred with approval from the overall PI.
5- If clinically significant adverse event or abnormal result is observed that is not resolved by the end-of study visit, continue to monitor and 
record through 70 days after belantamab mafodotin discontinuation.
6- Survival/Follow-Up may be conducted in clinic or by telephone and is intended to document long term outcomes in patients who respond to protocol therapy and are no 
longer receiving active protocol therapy e.g. after undergoing consolidation with HDT/ASCR or ASCT.
7- For details on ophthalmic assessments, please see Section 5.4 and Appendix C. 
a.
If screening ocular exam occurs > 5 days prior to Belantamab mafodotin initiation, then this exam should be conducted again prior to first dose.
b.
On-study ocular exams to be performed by an ophthalmologist or optometrist (if an ophthalmologist is not available) at baseline, prior to each dose of 
belantamab mafodotin in all cycles (should be within 5 days prior to dosing [supersedes window below in calendar] and all efforts should be made to schedule 
as close to belantamab mafodotin dosing as possible), and promptly for worsening symptoms. 
i.
Additional exams may be performed by ophthalmologist as clinically indicated.
ii.
If vision changes or ocular symptoms develop, patient should be evaluated by an ophthalmologist.
iii.
In case of persistent or newly developed ocular symptoms or vision changes, the participants will have further ophthalmologic exams, at least every 3 
months until resolution (to grade 1 or baseline) or more frequently as clinically indicated by the eye care specialist. 
c.
Corneal management information: 
i.
Prophylactic preservative-free artificial tears must be administered in each eye at least 4-8 times daily beginning on Cycle 1 Day 1 until end of 
treatment. In the event of ocular symptoms (i.e. dry eyes), the use of artificial tears may be increased up to every 2 hours as needed.
ii.
Corticosteroid eye drops are not required but can be used if clinically indicated per discretion of an eye-care specialist. Allow at least 5-10 minutes 
between administration of artificial tears and steroid eye drops (if administered).
iii.
At the start of each infusion, participants may apply cooling eye masks to their eyes for approximately 1 hour or as long as tolerated.
8- Albumin/creatinine ratio (spot urine, preferably from first void) to be performed every 6 weeks from C1D1 OR Urine dipstick for protein may be used to assess for 
presence of urine protein. Albumin/creatinine ratio needs to be done in any participant with urine dipstick result of ≥2+, or with positive protein if urine dipstick protein 
quantification is not available.
9- AE/SAEs will be collected from the start of study treatment until at least 70 days following EOT, regardless of initiation of new cancer therapy. SAEs related to study 
participation or a GSK product are collected from time of consent up to and including any follow up.  
10- EOT visits may be conducted by telephone and assessments may be omitted at the discretion of the investigator if determined infeasible for subject to come into clinic.

48
12. MEASUREMENT OF EFFECT
12.1
Antitumor Effect – 2014 Lugano Criteria
12.1.1 Selection of Target Lesions
Up to six of the largest dominant nodes or tumor masses selected according to all of the 
following:
1. Clearly measurable in two diameters (longest diameter [LDi] and shortest diameter) 
at baseline
a.
All nodal lesions must measure  1.5 cm in longest diameter regardless of 
short axis measurement
b. All measurable extranodal lesions should have a longest tumor diameter  1.0 
cm
2. All other lesions (including nodal, extranodal, and assessable disease) should be 
followed as non-target lesions
3. If possible, the lesions should be from disparate regions of the body
4. Should include mediastinal and retroperitoneal areas of disease whenever these sites 
are involved
12.1.2 Selection of Non-Target Lesions
Non-target lesions will be qualitatively assessed at each subsequent time point. All sites of 
disease present at baseline and not classified as target lesions will be classified as non-target 
lesions, including any measurable lesions that were not chosen as target lesions.
Examples of non-target lesions include:
1. All bone lesions, irrespective of the modality used to assess them
2. Lymphangitis of the skin or lung
3. Cystic lesions
4. Splenomegaly and hepatomegaly (all lymphomas)
a.
Cutoff for splenomegaly of more than 13 cm
b. Diffusely increased or focal uptake, with or without focal or disseminated 
nodules, supports spleen or liver involvement
5. Irradiated lesions
6. Measurable lesions beyond the maximum number of six
7. Groups of lesions that are small and numerous
8. Pleural/pericardial effusions and/or ascites
a.
Effusions, ascites, or other fluid collections will be followed as non-target lesions

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b. At each assessment point, radiologists will check for the presence or absence of 
effusions/ascites. If there is a significant volume increase in the absence of a 
benign etiology, progression can be assessed.
c.
Significant new effusions, ascites or other fluid collections, which are 
radiographically suggestive of malignancy should be recorded as new lesions and 
should be assessed
Response should be determined on the basis of radiographic and clinical evidence of disease. 
Assessment by PET should follow the Lugano criteria described by Cheson et al20 which is 
summarized in Appendix F. 
13. DATA REPORTING / REGULATORY REQUIREMENTS
Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 8.0 
(Adverse Events: List and Reporting Requirements).
13.1
Data Reporting
13.1.1 Method
The DF/HCC Office of Data Quality (ODQ) will collect, manage, and perform quality 
checks on the data for this study.
13.1.2 Responsibility for Data Submission
Investigative sites are responsible for submitting data and/or data forms to the Office of 
Data Quality (ODQ) in accordance with DF/HCC policies.
13.2
Data Safety Monitoring
The DF/HCC Data and Safety Monitoring Committee (DSMC) will review and monitor toxicity 
and accrual data from this study. The committee is composed of medical oncologists, research 
nurses, pharmacists and biostatisticians with direct experience in cancer clinical research.  
Information that raises any questions about participant safety will be addressed with the Sponsor-
Investigator and study team.
The DSMC generally reviews each protocol up to four times a year with the frequency 
determined by the outcome of previous reviews. Information to be provided to the committee 
may include: up-to-date participant accrual; current dose level information; DLT information; all 
grade 2 or higher unexpected adverse events that have been reported across all sites; summary of 
all deaths occurring within 30 days of intervention for Phase I or II protocols; for gene therapy 
protocols, summary of all deaths while being treated and during active follow-up; any response 
information; audit results, and a summary provided by the study team. Other information (e.g. 
scans, laboratory values) will be provided upon request. 

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13.2.1 Triggers for Safety review
The phase I study of belantamab mafodotin (BMA 117159) included patients with non-Hodgkin 
lymphoma. Belantamab mafodotin was deemed well tolerated in this population. Additionally, 
we have not observed unexpected rates/severity of toxicity in the first five patients enrolled, and 
all-cause AEs of interest included corneal toxicity (one patient, grade 3 keratitis), infusion 
related reaction (one patient, grade 3), platelet count decreased (one patient, grade 4), AST 
increase (one patient, grade 2), and no Safety Events (defined below). Therefore, formal stopping 
rules are not warranted in this phase II study of belantamab mafodotin in these NHL subtypes. 
However, we designed predefined rules that trigger Safety Review led by by overall PI and site 
investigators. When ≤9 patients have been enrolled: If a Safety Event occurs in 3 or more of the 
first 9 patients enrolled in this protocol, overall PI and site investigators from all participating 
sites will convene to review safety data to monitor overall toxicity. When >9 patients have been 
enrolled: If a Safety Event occurs in one-third or more of the number patients enrolled in the 
study at any timepoint after >9 patients have been enrolled, overall PI and site investigators from 
all participating sites will convene to review safety data to monitor overall toxicity. Additionally, 
safety events must be reported to DSMC and indicated on the DSMC form at the next review. 
A Safety Event is defined as an SAE meeting protocol-defined criteria for reporting to the 
DF/HCC IRB, which also meets at least one of the two following criteria (based on grading from 
CTCAE v5.0):
1. Grade 4 hematologic toxicity, deemed possibly, probably, or definitely related to protocol 
therapy, which does not improve to Grade 2 or better within 7 days despite adequate 
supportive care; OR
2. Grade 3 or higher non-hematologic toxicity deemed possibly, probably, or definitely 
related to protocol therapy, which does not improve to Grade 2 or better within 7 days 
despite adequate supportive care
If any death occurs on study and is considered possible, probably, or definitely related to study 
drug, we will pause enrollment to review and monitor toxicity from this study to provide 
guidance regarding whether to continue enrollment or terminate the study. 
13.3
Multi-Center Guidelines
This protocol will adhere to DF/HCC Policy MULTI-100 and the requirements of the DF/HCC 
Multi-Center Data and Safety Monitoring Plan. The specific responsibilities of the Sponsor-
Investigator, Coordinating Center, and Participating Institutions and the procedures for auditing 
are presented in the Data and Safety Monitoring Plan (Appendix B).
13.4
Collaborative Agreements Language
N/A

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14 STATISTICAL CONSIDERATIONS
This is a multicenter phase II study of belantamab mafodotin in patients with relapsed/refractory 
plasmablastic lymphoma and ALK+ large B-cell lymphoma. As described in Section 2, PBL and 
ALK LBCL is associated with a dismal prognosis which is typically measured in months from 
diagnosis. This is especially pronounced in the relapsed or refractory setting where these diseases 
are almost universally fatal. The primary objective will be to determine the overall response rate 
of belantamab mafodotin in patients with these histologies. Patients will receive belantamab 
mafodotin at 2.5 mg/kg IV on day 1 of a 21-day cycle until progression or intolerance.
14.1
Study Design/Endpoints
14.1.1 Primary efficacy endpoints
1. To describe the overall response rate
14.1.2 Secondary efficacy endpoints
1. To describe the complete response rate
2. To estimate the progression-free survival and overall survival
3. To determine the overall and complete response rates by subtype (i.e. plasmablastic 
lymphoma and ALK+ large B-cell lymphoma) 
14.1.3 Primary safety endpoints
1. To describe the nature, frequency, severity, and timing of adverse events
14.2
Sample Size, Accrual Rate and Study Duration
The study will use a single-stage, exact binomial design. An objective response rate (ORR, PR or 
better) of at least 30% will be considered promising whereas an ORR of 10% or less will be 
considered non-promising. Twenty-five eligible patients will be enrolled. If at least 5 responses 
are observed in 25 patients, the study will be considered successful and the regimen worthy of 
further study. If the total number of responses observed is 4 or fewer, the regimen will be 
considered non-promising. This design has an overall power of 91% and a type I error of 0.098 
and will use an exact binomial test. With a total sample size of 25 patients, the 90% exact 
binomial confidence interval for ORR will be no wider than 35%.
The study duration will be 4 years; 2 years of accrual and 2 years of follow-up on the last 
participant enrolled. 
Accrual Targets
Sex/Gender
Ethnic Category
Females
Males
Total
Hispanic or Latino
5
+
5
=
10
Not Hispanic or Latino
8
+
7
=
15
Ethnic Category: Total of all subjects
13
(A1)
+
12
(B1) =
25
(C1)

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Racial Category
American Indian or Alaskan Native
0
+
0
=
0
Asian
1
+
1
=
2
Black or African American
5
+
5
=
10
Native Hawaiian or other Pacific 
Islander
0
+
0
=
0
White
7
+
6
=
13
Racial Category: Total of all subjects
13
(A2)
+
12
(B2) =
25
(C2)
(A1 = A2)
(B1 = B2)
(C1 = C2)
14.3
Stratification Factors
N/A
14.4
Interim Monitoring Plan
The DF/HCC DSMC will monitor safety and data quality across all participating institutions. 
Regular study teleconferences with all participating institutions will be held to discuss SAEs or 
other toxicities and study progress.
14.5
Analysis of Primary Endpoints
See Section 14.2 for description of the statistical methodology used to address the study’s 
primary aim. 
Patients will have their response classified per the 2014 Lugano criteria. The frequency of 
complete response will be tabulated and summarized descriptively. 
14.6
Analysis of Secondary Endpoints
14.6.1 Complete response rate
Patients will have their response classified per the 2014 Lugano criteria (see Section 12). The 
frequency of complete response will be tabulated and summarized descriptively.
14.6.2 Progression-free and overall survival
Median Progression-free survival and overall survival will be summarized using Kaplan-Meier 
method with time of registration as time origin. Participants will be followed for 2 years after 
removal from protocol therapy or until death, whichever occurs first. Participants will be 
censored at the date of their last evaluation.
14.6.3 Nature, frequency, severity, and timing of adverse events
Patients will have their toxicities graded and reported at every visit according to criteria listed in 

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CTAE ver. 5.0. The nature, frequency, severity, and timing of adverse events will be tabulated 
and summarized descriptively.
14.7
Reporting and Exclusions
14.7.1 Evaluation of Toxicity
All participants will be evaluable for toxicity from the time of their first treatment.
14.7.2 Evaluation of the Primary Efficacy Endpoint
All eligible participants included in the study must be assessed for response/outcome to therapy, 
unless they withdraw consent prior to first response evaluation. Participants who withdraw 
consent prior to first response evaluation will be replaced.
15 PUBLICATION PLAN
The results should be made public within 24 months of reaching the end of the study. The end of 
the study is the time point at which the last data items are to be reported, or after the outcome 
data are sufficiently mature for analysis, as defined in the section on Sample Size, Accrual Rate 
and Study Duration. If a report is planned to be published in a peer-reviewed journal, then that 
initial release may be an abstract that meets the requirements of the International Committee of 
Medical Journal Editors. A full report of the outcomes should be made public no later than three 
(3) years after the end of the study. 

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16 REFERENCES
1.
Castillo, J. J. et al. Clinical and pathological differences between human 
immunodeficiency virus-positive and human immunodeficiency virus-negative 
patients with plasmablastic lymphoma. Leuk. Lymphoma (2010). 
doi:10.3109/10428194.2010.516040
2.
Wilson, W. H. et al. Phase II study of dose-adjusted EPOCH and rituximab in 
untreated diffuse large B-cell lymphoma with analysis of germinal center and post-
germinal center biomarkers. J. Clin. Oncol. (2008). doi:10.1200/JCO.2007.13.1391
3.
Magrath, I. et al. Adults and children with small non-cleaved-cell lymphoma have a 
similar excellent outcome when treated with the same chemotherapy regimen. J. Clin. 
Oncol. (1996). doi:10.1200/JCO.1996.14.3.925
4.
Lacasce, A. et al. Modified Magrath regimens for adults with Burkitt and Burkitt-like 
lymphomas: Preserved efficacy with decreased toxicity. Leuk. Lymphoma (2004). 
doi:10.1080/1042819031000141301
5.
Zelenetz, A. D. et al. NCCN Guidelines Insights: B-Cell Lymphomas, Version 
3.2019. J. Natl. Compr. Cancer Netw. 17, 650–661 (2019).
6.
Barta, S. K. et al. Treatment factors affecting outcomes in HIV-associated non-
Hodgkin lymphomas: A pooled analysis of 1546 patients. Blood (2013). 
doi:10.1182/blood-2013-04-498964
7.
Castillo, J. J. et al. Human immunodeficiency virus-associated plasmablastic 
lymphoma: Poor prognosis in the era of highly active antiretroviral therapy. Cancer 
(2012). doi:10.1002/cncr.27551
8.
Barta, S. K., Lee, J. Y., Kaplan, L. D., Noy, A. & Sparano, J. A. Pooled analysis of 
AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional 
EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. Cancer (2012). 
doi:10.1002/cncr.26723
9.
Castillo, J. J. et al. Prognostic Factors in Chemotherapy‐Treated Patients with 
HIV‐Associated Plasmablastic Lymphoma. Oncologist (2010). 
doi:10.1634/theoncologist.2009-0304
10.
Castillo, J. J., Reagan, J. L., Sikov, W. M. & Winer, E. S. Bortezomib in combination 
with infusional dose-adjusted EPOCH for the treatment of plasmablastic lymphoma. 
Br. J. Haematol. (2015). doi:10.1111/bjh.13300
11.
Laurent, C. et al. Anaplastic lymphoma kinase-positive diffuse large B-cell 
lymphoma: A rare clinicopathologic entity with poor prognosis. J. Clin. Oncol. 
(2009). doi:10.1200/JCO.2008.21.5020
12.
Jiang, X. N., Yu, B. H., Wang, W. G., Zhou, X. Y. & Li, X. Q. Anaplastic lymphoma 
kinase-positive large B-cell lymphoma: Clinico-pathological study of 17 cases with 
review of literature. PLoS One (2017). doi:10.1371/journal.pone.0178416
13.
Li, J., Ouyang, J., Zhou, R., Chen, B. & Xu, Y. Promising response of anaplastic 
lymphoma kinase-positive large B-cell lymphoma to crizotinib salvage treatment: 
Case report and review of literature. Int. J. Clin. Exp. Med. (2015).
14.
Kothari, S., Ud-Din, N., Lisi, M. & Coyle, T. Crizotinib in anaplastic lymphoma 
kinase-positive anaplastic large cell lymphoma in the setting of renal insufficiency: A 
case report. J. Med. Case Rep. (2016). doi:10.1186/s13256-016-0963-y
15.
Shimada, K., Hayakawa, F. & Kiyoi, H. Biology and management of primary effusion 

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lymphoma. Blood 132, 1879–1888 (2018).
16.
Boulanger, E. et al. Prognostic factors and outcome of human herpesvirus 8-
associated primary effusion lymphoma in patients with AIDS. J. Clin. Oncol. (2005). 
doi:10.1200/JCO.2005.07.084
17.
Bryant, A. & Milliken, S. Successful Reduced-Intensity Conditioning Allogeneic 
HSCT For HIV-Related Primary Effusion Lymphoma. Biology of Blood and Marrow 
Transplantation (2008). doi:10.1016/j.bbmt.2008.01.010
18.
Won, J. H. et al. Successful eradication of relapsed primary effusion lymphoma with 
high-dose chemotherapy and autologous stem cell transplantation in a patient 
seronegative for human immunodeficiency virus. Int. J. Hematol. (2006). 
doi:10.1532/IJH97.A30510
19.
Waddington, T. W. & Aboulafia, D. M. Failure to Eradicate AIDS-Associated 
Primary Effusion Lymphoma with High-Dose Chemotherapy and Autologous Stem 
Cell Reinfusion: Case Report and Literature Review. AIDS Patient Care STDS 
(2004). doi:10.1089/108729104322802498
20.
Cheson, B. D. et al. Recommendations for Initial Evaluation, Staging, and Response 
Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. J. 
Clin. Oncol. 32, 3059–3067 (2014).

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APPENDIX A
PERFORMANCE STATUS CRITERIA
ECOG Performance Status Scale
Karnofsky Performance Scale
Grade
Descriptions
Percent
Description
100
Normal, no complaints, no evidence 
of disease.
0
Normal activity.  Fully active, able 
to carry on all pre-disease 
performance without restriction.
90
Able to carry on normal activity; 
minor signs or symptoms of disease.
80
Normal activity with effort; some 
signs or symptoms of disease.
1
Symptoms, but ambulatory.  
Restricted in physically strenuous 
activity, but ambulatory and able 
to carry out work of a light or 
sedentary nature (e.g., light 
housework, office work).
70
Cares for self, unable to carry on 
normal activity or to do active work.
60
Requires occasional assistance but is 
able to care for most of his/her 
needs.
2
In bed <50% of the time.  
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities.  Up and about 
more than 50% of waking hours.
50
Requires considerable assistance and 
frequent medical care.
40
Disabled, requires special care and 
assistance.
3
In bed >50% of the time.  Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours.
30
Severely disabled, hospitalization 
indicated.  Death not imminent.
20
Very sick, hospitalization indicated. 
Death not imminent.
4
100% bedridden.  Completely 
disabled.  Cannot carry on any 
self-care.  Totally confined to bed 
or chair.
10
Moribund, fatal processes 
progressing rapidly.
5
Dead.
0
Dead.

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APPENDIX B
  
Dana-Farber/Harvard Cancer Center
Multi-Center Data and Safety Monitoring Plan

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TABLE OF CONTENTS
1.
INTRODUCTION .............................................................................................................57
1.1
Purpose...................................................................................................................57
2.
GENERAL ROLES AND RESPONSIBILITIES .............................................................57
2.1
Coordinating Center...............................................................................................57
2.2
External Site...........................................................................................................58
3.
DF/HCC REQUIREMENTS FOR MULTI-CENTER PROTOCOLS .............................59
3.1
Protocol Revisions and Closures ...........................................................................59
3.2
Informed Consent Requirements ...........................................................................59
3.3
IRB Re-Approval...................................................................................................60
3.4
DF/HCC Multi-Center Protocol Confidentiality ...................................................60
3.5
Participant Registration and Randomization .........................................................60
3.5.1
Initiation of Therapy ..............................................................................................60
3.5.2
Eligibility Exceptions.............................................................................................60
3.6
Data Management..................................................................................................60
3.7
Data Forms Review................................................................................................60
3.8
Protocol Reporting Requirements..........................................................................61
3.9
Protocol Deviations, Exceptions and Violations ...................................................61
3.10
Reporting Procedures.............................................................................................61
3.11
Guidelines for Processing IND Safety Reports .....................................................61
4.
MONITORING: QUALITY CONTROL..........................................................................61
4.1
Monitoring Reports................................................................................................62
4.2
Accrual Monitoring................................................................................................63
5.
AUDITING: QUALITY ASSURANCE ...........................................................................63
5.1
DF/HCC Internal Audits........................................................................................63
5.2
Audit Notifications.................................................................................................63
5.3 Audit Reports...............................................................................................................63
5.4
External Site Performance .....................................................................................63

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1.
INTRODUCTION
The Dana-Farber/Harvard Cancer Center Multi-Center Data and Safety Monitoring Plan 
(DF/HCC DSMP) outlines the procedures for conducting a DF/HCC Multi-Center research 
protocol. The DF/HCC DSMP serves as a reference for any sites external to DF/HCC that 
are participating in a DF/HCC clinical trial. 
1.1
Purpose
To establish standards that will ensure that a Dana-Farber/Harvard Cancer Center Multi-
Center protocol will comply with Federal Regulations, Health Insurance Portability and 
Accountability Act (HIPAA) requirements and applicable DF/HCC Policies and 
Operations.  
     
2.
GENERAL ROLES AND RESPONSIBILITIES
For DF/HCC Multi-Center Protocols, the following general responsibilities apply, in 
addition to those outlined in DF/HCC Policies for Sponsor-Investigators: 
2.1
Coordinating Center 
The Coordinating Center is the entity that provides administrative support to the DF/HCC 
Sponsor in order that he/she may fulfill the responsibilities outlined in the protocol 
document and DSMP, and as specified in applicable regulatory guidelines (i.e. CTEP Multi-
Center Guidelines). 
The general responsibilities of the Coordinating Center may include but are not limited to:

Assist in protocol development. 

Maintain CTEP, FDA or OBA correspondence, as applicable.

Review registration materials for eligibility and register participants from External 
Sites in the DF/HCC clinical trial management system (CTMS).

Distribute protocol and informed consent document updates to External Sites as 
needed.

Review and approve External Site informed consent forms

Oversee the data collection process from DF/HCC and External Sites.

Maintain documentation of Serious Adverse Event (SAE) reports and 
deviations/violation submitted by External Sites and provide to the DF/HCC 
Sponsor for timely review and submission to the IRB of record, as necessary. 

Distribute serious adverse events reported to the DF/HCC Sponsor that fall under 
the reporting requirements for the IRB of record to all DF/HCC and External Sites.

Provide External Sites with information regarding DF/HCC requirements that they 
will be expected to comply with.

Carry out approved plan to monitor DF/HCC and External Sites either by on-site or 
remote monitoring. 

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
Maintain Regulatory documents of External Sites which includes but is not limited 
to the following: local IRB approvals/notifications from all External Sites, 
confirmation of Federalwide Assurances (FWAs) for all sites, all SAE 
submissions, Screening Logs for all sites, IRB approved consents for all sites

Conduct regular communications with all Sites (conference calls, emails, etc) and 
maintain documentation all relevant communications.
2.2
External Site
An External Site is an institution that is outside the DF/HCC and DF/PCC consortium that 
is collaborating with DF/HCC on a protocol where the sponsor is a DF/HCC investigator.  
The External Site acknowledges the DF/HCC Sponsor as having the ultimate authority and 
responsibility for the overall conduct of the study. 
Each External Site is expected to comply with all applicable DF/HCC requirements stated 
within this Data and Safety Monitoring Plan and/or the protocol document. 
The general responsibilities for each External Site may include but are not limited to:

Document the delegation of research specific activities to study personnel.

Commit to the accrual of participants to the protocol.

Submit protocol and/or amendments to their IRB of record. For studies under a 
single IRB, the Coordinating Center will facilitate any study-wide submissions.

Maintain regulatory files as per ICH GCP and federal requirements.

Provide the Coordinating Center with regulatory document, study logs (i.e. 
enrollment log, biospecimen log and violation log) or source documents as 
requested.

Participate in protocol training prior to enrolling participants and throughout the trial 
as required.

Update Coordinating Center with research staff changes on a timely basis.

Register participants through the Coordinating Center prior to beginning research 
related activities. 

Submit Serious Adverse Event (SAE) reports to sponsor, Coordinating Center, and 
IRB of record as applicable, in accordance with DF/HCC requirements. 

Submit protocol deviations and violations to the Sponsor, Coordinating Center, and 
IRB of record as applicable, in accordance with DF/HCC requirements.

Order, store and dispense investigational agents and/or other protocol mandated 
drugs per federal guidelines and protocol requirements.

Participate in any quality assurance activities and meet with monitors or auditors at 
the conclusion of a visit to review findings.

Promptly provide follow-up and/or corrective action plans for any monitoring 
queries or audit findings.

Notify the sponsor immediately of any regulatory authority inspection of this 
protocol at the External Site.

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3.
DF/HCC REQUIREMENTS FOR MULTI-CENTER PROTOCOLS
Certain DF/HCC Policy requirements apply to External Sites participating in DF/HCC 
research. The following section will clarify DF/HCC requirements and further detail the 
expectations for participating in a DF/HCC Multi-Center protocol. 
3.1
Protocol Revisions and Closures
The External Sites will receive notification of protocol revisions and closures from the 
Coordinating Center.  When under a separate IRB, it is the individual External Site’s 
responsibility to notify its IRB of these revisions.

Protocol revisions: External Sites will receive written notification of protocol 
revisions from the Coordinating Center. All protocol revisions should be IRB 
approved and implemented within a timely manner from receipt of the notification.

Protocol closures and temporary holds: External Sites will receive notification of 
protocol closures and temporary holds from the Coordinating Center. Closures and 
holds will be effective immediately.  In addition, the Coordinating Center, will 
update the External Sites on an ongoing basis about protocol accrual data so that 
they will be aware of imminent protocol closures.
3.2
Informed Consent Requirements
The DF/HCC approved informed consent document will serve as a template for the 
informed consent for External Sites. The External Site consent form must follow the consent 
template as closely as possible and should adhere to specifications outlined in the DF/HCC 
Guidance Document on Model Consent Language for Investigator-Sponsored Multi-Center 
Trials.  This document will be provided separately to each External Site upon request.
External Sites must send their version of the informed consent document to the Coordinating 
Center for sponsor review and approval prior to local submission. If the HIPAA 
authorization is a separate document, please submit to the sponsor for the study record. Once 
sponsor approval is obtained, the External site may submit to their IRB of record, as 
applicable. In these cases, the approved consent form must also be submitted to the 
Coordinating Center after approval by the local IRB for all consent versions.
The Principal Investigator (PI) at each External Site will identify the appropriate members 
of the study team who will be obtaining consent and signing the consent form for protocols. 
External Sites must follow the DF/HCC requirement that for all interventional drug, 
biologic, or device research, only attending physicians may obtain initial informed consent 
and any re-consent that requires a full revised consent form.  

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3.3
IRB Re-Approval
Verification of IRB re-approval for the External Sites is required in order to continue 
research activities.  There is no grace period for continuing approvals.
The Coordinating Center will not register participants if a re-approval letter is not received 
for the External Site on or before the anniversary of the previous approval date.  
3.4
DF/HCC Multi-Center Protocol Confidentiality
All documents, investigative reports, or information relating to the participant are strictly 
confidential. Whenever reasonably feasible, any participant specific reports (i.e. Pathology 
Reports, MRI Reports, Operative Reports, etc.) submitted to the Coordinating Center should 
be de-identified. It is recommended that the assigned participant registration number be used 
for all participant specific documents. Participant initials may be included or retained for 
cross verification of identification. 
3.5
Participant Registration and Randomization 
Please refer to protocol [Section 4.0: Registration Procedures] 
3.5.1
Initiation of Therapy
Participants must be registered with the DF/HCC CTMS before the initiation of treatment 
or other protocol-specific interventions. Treatment and other protocol-specific interventions 
may not be initiated until confirmation of the participant’s registration has been received. 
The DF/HCC Sponsor and IRB of record must be notified of any violations to this policy.
3.5.2
 Eligibility Exceptions
No exceptions to the eligibility requirements for a protocol without IRB approval will be 
permitted. All External Sites are required to fully comply with this requirement. The process 
for requesting an eligibility exception is defined below.
  
3.6
Data Management
DF/HCC develops case report forms (CRF/eCRFs), for use with the protocol.  These forms 
are designed to collect data for each study. DF/HCC provides a web based training for all 
eCRF users.
Data should be entered promptly and completely after each assessment, but no later than 2 
weeks after the completion of a study visit/timepoint.
3.6.1
Data Forms Review
Data submissions are monitored for timeliness and completeness of submission. If study 
forms are received with missing or questionable data, the submitting institution will receive 

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a written or electronic query from the DF/HCC Office of Data Quality, Coordinating Center, 
or designee. 
Responses to all queries should be completed and submitted within 14 calendar days.  
If study forms are not submitted on schedule, the External Sites will periodically receive a 
Missing Form Report from the Coordinating Center noting the missing forms. 
3.7
Protocol Reporting Requirements
3.7.1
Protocol Deviations, Exceptions and Violations
Federal Regulations require an IRB to review proposed changes in a research activity to 
ensure that researchers do not initiate changes in approved research without IRB review 
and approval, except when necessary to eliminate apparent immediate hazards to the 
participant. DF/HCC requires all departures from the defined procedures set forth in the 
IRB approved protocol to be reported to the DF/HCC Sponsor and to the IRB of record.
3.7.2
Reporting Procedures
Requests to deviate from the protocol require approval from the IRB of record and the 
sponsor. 
All protocol violations must be sent to the Coordinating Center in a timely manner.  Major 
violations should be reported within 1 business day of identification; minor violations are 
reported cumulative on a monthly basis. The Coordinating Center will provide training for 
the requirements for the reporting of violations. 
3.7.3
Guidelines for Processing IND Safety Reports 
The DF/HCC Sponsor will review all IND Safety Reports per DF/HCC requirements, and 
ensure that all IND Safety Reports are distributed to the External Sites as required by 
DF/HCC Policy. External Sites will review/submit to the IRB according to their 
institutional policies and procedures.
4. MONITORING: QUALITY CONTROL
The Coordinating Center, with the aid of the DF/HCC Office of Data Quality, provides 
quality control oversight for the protocol.
4.1
Ongoing Monitoring of Protocol Compliance
DF/HCC and External Sites will be subject to on-site and remote monitoring conducted by 
the Coordinating Center and may be required to submit participant source documents to the 
Coordinating Center for monitoring. 
The Coordinating Center will implement ongoing monitoring activities to ensure that all 
Sites are complying with regulatory and protocol requirements, data quality, and participant 
safety. Monitoring will occur before the clinical phase of the protocol begins, continue 

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during protocol performance and through study completion. Monitoring practices include 
but are not limited to; source data verification and review and analysis of the following: 
eligibility requirements of all participants, informed consent procedures, adverse events and 
all associated documentation, study drug administration/treatment, regulatory files, protocol 
departures, pharmacy records, tissue and biospecimen sample logs, response assessments, 
and data management.
All DF/HCC and External Sites will undergo on-site monitoring by the Coordinating Center 
within 3 months of completion of the first patient accrual; Combination on-site and remote 
monitoring will occur every 4-6 months thereafter with at least 1 on-site visit every 12 
months.  Remote monitoring may be done in lieu of on-site monitoring if no active patients 
are on trial.  Once all site participants are off treatment and have completed the post-
treatment assessment, remote monitoring will be conducted annually for confirmation of 
long term follow-up data and regulatory documentation.  
For remote monitoring visits, External Sites will be asked to provide remote electronic 
medical record access to the monitor or will be required to forward redacted copies of 
participants’ medical record and source documents to the Coordinating Center to aid in 
source data verification.  The participants and CRFs to be reviewed at the visit will be 
communicated at least 2 weeks in advance of the scheduled monitoring visit.  Source 
documentation can be provided to the Coordinating Center via an encrypted memory stick 
or via a secure file transfer system.  During remote monitoring visits, the Site Specific File 
will be reviewed in lieu of the site regulatory binder.
On-Site Monitoring will be scheduled several weeks in advance and will be conducted over 
a 2-3 day period.  During an on-site monitoring visit 2-4 participants will be monitored. 
Source documentation verification (SDV) will be conducted by having access to 
participants’ complete medical record and source documents.  DF/HCC and External Sites 
will be expected to coordinate the necessary resources for the monitor, including a desk, 
access to all participant medical and research records (electronic and hard copy), the 
regulatory binders and access to a photocopier.  The Site research team will also be asked 
to assist in scheduling a pharmacy visit and a brief exit interview on the final day of the visit 
with the Study Coordinator and the Site investigator.
All Sites will be required to participate in monthly Coordinating Center initiated 
teleconferences.  Once all participants have completed treatment, teleconferences will be 
scheduled as needed.  
4.2
Monitoring Reports
The DF/HCC Sponsor will review all monitoring reports to ensure protocol compliance. 
The DF/HCC Sponsor may increase the monitoring activities at External Sites that are 
unable to comply with the protocol, DF/HCC Sponsor requirements or federal and local 
regulations. 

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4.3
Accrual Monitoring
Prior to extending a protocol to an external site, the DF/HCC Sponsor will establish accrual 
requirements for each External Site. Accrual will be monitored for each External Site by the 
DF/HCC Sponsor or designee. Sites that are not meeting their accrual expectations may be 
subject to termination.  For this study, the minimum accrual requirement is 3 participants 
per site/annually.  However, given the additional regulatory burden and cost of overseeing 
each site, a consideration of 5 per site/annually should be a minimum target for each site.
5. AUDITING: QUALITY ASSURANCE
5.1
DF/HCC Internal Audits
All External Sites are subject to audit by the DF/HCC Office of Data Quality (ODQ). 
Typically, approximately 3-4 participants would be audited at the site over a 2-day period. 
If violations which impact participant safety or the integrity of the study are found, more 
participant records may be audited. 
5.2
Audit Notifications
It is the External Site’s responsibility to notify the Coordinating Center of all external audits 
or inspections (e.g., FDA, EMA, NCI) that involve this protocol. All institutions will 
forward a copy of final audit and/or re-audit reports and corrective action plans (if 
applicable) to the Coordinating Center, within 12 weeks after the audit date. 
5.3
Audit Reports 
The DF/HCC Sponsor will review all final audit reports and corrective action plans, if 
applicable. The Coordinating Center, must forward any reports to the DF/HCC ODQ per 
DF/HCC policy for review by the DF/HCC Audit Committee. For unacceptable audits, the 
DF/HCC Audit Committee would forward the final audit report and corrective action plan 
to the IRB as applicable.
5.4
External Site Performance
The DF/HCC Sponsor and the IRB of record are charged with considering the totality of an 
institution’s performance in considering institutional participation in the protocol.
External Sites that fail to meet the performance goals of accrual, submission of timely and 
accurate data, adherence to protocol requirements, and compliance with state and federal 
regulations, may be put on hold or closed

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APPENDIX C
OCULAR MONITORING AND MITIGATION STRATEGY 
Ocular Examinations:
Patients will be assessed by ophthalmologist or optometrist (if an ophthalmologist is not 
available). A full screening/baseline ophthalmic examination for all participants must include for 
both eyes (OU), but is not limited to:
1- Best corrected visual acuity 
2- Documentation of manifest refraction and the method used to obtain best corrected visual 
acuity
3- Current glasses prescription (if applicable)
4- Intraocular pressure measurement & time checked.
5- Selected anterior segment (slit lamp) examination with focus on the cornea and lens, 
including fluorescein staining of the cornea. 
6- Dilated fundoscopic exam.
The on treatment ophthalmic exam should match the baseline (screening) exam should be 
performed for both eyes (OU) as described below:
1- Best corrected visual acuity. 
2- Documentation of manifest refraction and the method used to obtain best corrected visual 
acuity. 
The end of study treatment and last follow-up ophthalmic exam should match the 
screening/baseline exam.
Additional examinations should be performed at the discretion of the treating eye specialist.
Changes in Corneal Epithelium: Severity Grading and Mitigation Strategy 
AEs including corneal, will be graded by the investigator according to the NCI-CTCAE v5.
In order to minimize the changes in corneal epithelium associated with belantamab mafodotin, 
patients must receive prophylactic preservative-free artificial tears.  The recommended 
administration is to use one drop in each eye at least 4 to 8 times daily, beginning on Cycle 1 
Day 1 until the subject discontinues treatment.  In the event of ocular symptoms (e.g., dry eyes), 
the use of artificial tears may be increased up to every 2 hours as needed.
Corticosteroid eye drops are not required but can be used if clinically indicated per discretion of 
an eye-care specialist. Allow at least 5-10 minutes between administration of artificial tears and 
steroid eye drops (if administered together). If steroid eye drops are deemed medically necessary 
and prescribed, intraocular pressure must be monitored if used for >7 days.
While not yet clinically demonstrated, it is theoretically possible that the application of a cooling 
eye mask during belantamab mafodotin administration, and in the first few hours after infusion 
may subsequently decrease ocular side effects.  

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On the day of infusion at the discretion of the patient and the physician, the following may be 
considered: Beginning with the start of each belantamab mafodotin infusion, patients may apply 
cooling eye masks to their eyes for approximately 1 hour or as much as tolerated. Patients may 
continue using the cooling eye mask beyond the first hour for up to 4 hours.  Further use beyond 
4 hours is at the patient’s discretion.
Contact lenses are prohibited while the participant is on study treatment. Contact lens use may be 
restarted after a qualified eye care specialist confirms there are no other contraindications.
Use of bandage contact lenses is permitted during study treatment as directed by the treating 
qualified eye care specialist.
An ophthalmology or optometry (if ophthalmology is not available) consult is required for all 
patients who develop signs or symptoms of changes in corneal epithelium.
A summary of prophylactic interventions for changes in corneal epithelium associated with 
belantamab mafodotin is provided in 
Table .  Changes in corneal epithelium must be graded according to the NCI-CTCAE scale. 
Table 5
Prophylactic measures for changes in corneal epithelium associated with 
belantamab mafodotin 
Prophylactic 
Measure
Dose and Administration
Timing
Preservative-free 
artificial tears
Administer in each eye at 
least 4 to 8 times daily
Administer daily beginning on Cycle 
1 Day 1 until EOT.  
Cooling eye mask
May apply cooling eye mask 
to both eyes for 
approximately 1 hour or as 
much as tolerated 
During belantamab mafodotin 
infusion administration in the first 
hour for up to 4 hours, as tolerated

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APPENDIX D
LIVER SAFETY REQUIRED ACTIONS AND FOLLOW UP 
ASSESSMENT
Liver chemistry stopping and increased monitoring criteria have been designed to assure 
subject safety and evaluate liver event etiology (in alignment with the FDA premarketing clinical 
liver safety guidance).
Liver Chemistry Stopping Criteria – Liver Stopping Event
ALT - absolute
ALT  5xULN
ALT Increase
ALT  3xULN persists for 4 weeks
Bilirubin1, 2
ALT  3xULN and total bilirubin  2xULN (>35% direct 
bilirubin) 
INR2 
ALT  3xULN and INR>1.5
Cannot 
Monitor
ALT  3xULN and cannot be monitored weekly for 4 weeks
Symptomatic3
ALT  3xULN associated with symptoms (new or worsening) 
believed to be related to liver injury or hypersensitivity
Required Actions, Monitoring and Follow up Assessments 
Actions
Follow Up Assessments
Immediately discontinue study 
intervention 
Report the event to GSK within 24 
hours
Complete the liver event form and 
complete SAE data collection tool if 
the event also meets the criteria for 
an SAE2
Perform liver event follow up 
assessments as described in the 
Follow Up Assessment column
Monitor the participant until liver 
chemistries resolve, stabilize, or 
return to within baseline (see 
MONITORING)
For the purpose of these guidelines 
“baseline” refers to laboratory 
assessments performed closest and prior 
to first dose of study intervention
MONITORING:
Viral hepatitis serology4
Obtain INR and recheck with each 
liver chemistry assessment until the 
aminotransferases values show 
downward trend
Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH), 
gamma glutamyl transferase [GGT], 
and serum albumin.
Fractionate bilirubin, if total 
bilirubin2xULN
Obtain complete blood count with 
differential to assess eosinophilia
Record the appearance or worsening 
of clinical symptoms of liver injury, or 
hypersensitivity
Record use of concomitant 
medications including acetaminophen, 
herbal remedies, recreational drugs 
and other over the counter 
medications

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If ALT≥3xULN AND total bilirubin  
2xULN or INR >1.5: 
Repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, total 
bilirubin and INR) and perform liver 
event follow up assessments within 
24 hours
Monitor participants twice weekly until 
liver chemistries resolve, stabilize or 
return to within baseline
A specialist or hepatology consultation is 
recommended
For All other criteria (bilirubin 
<2xULN and INR 1.5): 
Repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, total 
bilirubin and INR) and perform liver 
event follow up assessments within 
24-72 hours 
Monitor participants weekly until liver 
chemistries resolve, stabilize or return 
to within baseline
RESTART/RECHALLENGE

Restart/rechallenge is allowed 
per protocol but do not resume 
study intervention unless 
Sponsor approval is granted;  If 
restart/rechallenge is not granted, 
permanently discontinue study 
intervention and continue 
participant in the study for any 
protocol specified follow up 
assessments. 
Record alcohol use
If ALT 3xULN AND total bilirubin 
2xULN or INR >1.5 obtain the 
following in addition to the 
assessments listed above:
Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total immunoglobulin G 
(IgG or gamma globulins)
Serum acetaminophen adduct 
assay should be conducted 
(where available) to assess 
potential acetaminophen 
contribution to liver injury unless 
acetaminophen use is very 
unlikely in the preceding week. 
(e.g., where the participant has 
been resident in the clinical unit 
throughout) 
Liver imaging (ultrasound, magnetic 
resonance, or computerised 
tomography) to evaluate liver disease;
Liver biopsy may be considered and 
discussed with local specialist if 
available, for instance:
o In patients when serology raises 
the possibility of autoimmune 
hepatitis (AIH)
o In patients when suspected DILI 
progresses or fails to resolve on 
withdrawal of study intervention
o In patients with acute or chronic 
atypical presentation: 
1.
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin 
fractionation is not immediately available, discontinue study intervention for that participant if ALT 
 3xULN and total bilirubin  2xULN. Additionally, if serum bilirubin fractionation testing is 
unavailable, record presence of detectable urinary bilirubin on dipstick, indicating direct 
bilirubin elevations and suggesting liver injury. 
2.
All events of ALT  3xULN and total bilirubin  2xULN (>35% direct bilirubin) or ALT  3xULN 
and INR>1.5, which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as 
an SAE (excluding studies of hepatic impairment or cirrhosis); the INR threshold value 
stated will not apply to participants receiving anticoagulants

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3.
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, or jaundice) or believed to be related to 
hypersensitivity (such as fever, rash or eosinophilia)
4.
Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); 
Hepatitis C RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody 
(or if unavailable, obtain heterophile antibody or monospot testing); Hepatitis E IgM antibody. In 
those with underlying chronic hepatitis B at study entry (identified by positive hepatitis B surface 
antigen) quantitative hepatitis B DNA and hepatitis delta antibody.  Only include for studies with 
clearly non-immunosuppressive agents. For studies with potent immunosuppressive agents these 
participants are to be excluded; see additional guidance regarding eligibility criteria.  If hepatitis 
delta antibody assay cannot be performed, it can be replaced with a PCR of hepatitis D RNA 
virus (where needed) [Le Gal, 2005].
5.4.1.1.1
Phase I/II liver chemistry increased monitoring criteria with continued study 
intervention
Liver Chemistry Increased Monitoring Criteria and Actions with Continued 
Study Intervention Liver Monitoring Event
Criteria
Actions
ALT 3xULN but <5xULN and total 
bilirubin <2xULN or INR ≤1.5, 
without symptoms believed to be 
related to liver injury or 
hypersensitivity and who can be 
monitored weekly for 4 weeks
Notify the Sponsor medical monitor within 
24 hours of learning of the abnormality to 
discuss participant safety. 
Participant must return weekly for repeat 
liver chemistries (ALT, AST, alkaline 
phosphatase, total bilirubin and INR) until 
they resolve, stabilise or return to within 
baseline 
For the purpose of these guidelines 
“baseline” refers to laboratory assessments 
performed closest and prior to first dose of 
study intervention
If at any time participant meets the liver 
chemistry stopping criteria, proceed as 
described above
If, after 4 weeks of monitoring, ALT 
<3xULN and total bilirubin <2xULN and 
INR ≤1.5, monitor participants twice 

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monthly until liver chemistries resolve 
or return to within baseline.
References
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee WM. 
Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen Overdose and 
Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784.
Le Gal F, Gordien E, Affolabi D, Hanslik T, Alloui C, Dény P, Gault E.  Quantification of 
Hepatitis Delta Virus RNA in Serum by Consensus Real-Time PCR Indicates Different Patterns 
of Virological Response to Interferon Therapy in Chronically Infected Patients.  J Clin 
Microbiol. 2005;43(5):2363–2369.

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APPENDIX E
CONTRACEPTION
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
Highly Effective Methodsb That Have Low User Dependency 

Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)c

Bilateral tubal occlusion

Vasectomized partner

Note: Vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days.
Highly Effective Methodsb That Are User Dependent

Combined (estrogen-/progestogen-containing) hormonal contraception associated with 
inhibition of ovulation

oral

intravaginal

transdermal

injectable

Progestogen-only hormone contraception associated with inhibition of ovulation

oral

injectable

Sexual abstinence. Note: Sexual abstinence is considered a highly effective method only if 
defined as refraining from heterosexual intercourse during the entire period of risk 
associated with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual lifestyle of 
the participant
a.
Contraceptive use by men or women should be consistent with local regulations regarding 
the use of contraceptive methods for those participating in clinical studies.
b. Failure rate of <1% per year when used consistently and correctly. Typical use failure rates 
differ from those when used consistently and correctly.
c.
Male condoms must be used in addition to hormonal contraception. If locally required, in 
accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable 
contraceptive methods are limited to those which inhibit ovulation as the primary mode of 
action.
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal 
(coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not 
acceptable methods of contraception for this study. Male condom and female condom should 
not be used together (due to risk of failure with friction).

73
APPENDIX F
LUGANO RESPONSE CRITERIA (2014)
Response and 
Site
PET-CTBased Response
CT-Based Response
Complete 
Response
Complete metabolic response
Complete radiologic response (all of the following)
Lymph nodes 
and 
extralymphatic 
sites
Score 1, 2, or 3 a with or without a residual mass on 5PS b
It is recognized that in Waldeyer’s ring or extranodal sites with high physiologic 
uptake or with activation within spleen or marrow (e.g., with chemotherapy or 
myeloid colony-stimulating factors), uptake may be greater than normal 
mediastinum and/or liver. In this circumstance, complete metabolic response 
may be inferred if uptake at sites of initial involvement is no greater than 
surrounding normal tissue even if the tissue has high physiologic uptake.
Target nodes/nodal masses must regress to  1.5 cm in 
LDi
No extralymphatic sites of disease
Nonmeasured 
lesion
Not applicable
Absent
Organ 
enlargement
Not applicable
Regress to normal
New lesions
None
None
Bone marrow
No evidence of FDG-avid disease in marrow
Normal by morphology; if indeterminate, IHC-negative
Partial 
Response
Partial metabolic response
Partial remission (all of the following): 
Lymph nodes 
and 
extralymphatic 
sites
Score 4 or 5b with reduced uptake compared with baseline and residual mass(es) 
of any size.
At interim, these findings suggest responding disease
At end of treatment, these findings indicate residual disease.
 50% decrease in SPD of up to 6 target measurable 
nodes and extranodal sites
When a lesion is too small to measure on CT, assign 5 
mm  5 mm as the default value
When no longer visible, 0  0 mm
For a node  5 mm  5 mm, but smaller than normal; 
use actual measurement for calculation
Nonmeasured 
lesions
Not applicable
Absent/normal, regressed, but no increase
Organ 
enlargement
Not applicable
Spleen must have regressed by  50% in length beyond 
normal
New lesions
None
None
Bone marrow
Residual uptake higher than uptake in normal marrow but reduced compared with 
baseline (diffuse uptake compatible with reactive changes from chemotherapy 
allowed). If there are persistent focal changes in the marrow in the context of 
a nodal response, consideration should be given to further evaluation with 
MRI or biopsy or an interval scan.
Not applicable

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Response and 
Site
PET-CTBased Response
CT-Based Response
No Response or 
Stable 
Disease
No metabolic response
Stable disease
Target 
nodes/nodal 
masses, 
extranodal 
lesions
Score 4 or 5 with no significant change in FDG uptake from baseline at interim or 
end of treatment
 50% decrease from baseline in SPD of up to 
6 dominant, measurable nodes and extranodal sites; 
no criteria for progressive disease are met
Nonmeasured 
lesions
Not applicable
No increase consistent with progression
Organ 
enlargement
Not applicable
No increase consistent with progression
New lesions
None
None
Bone marrow
No change from baseline
Not applicable
Progressive 
Disease
Progressive metabolic disease
Progressive disease requires at least one of the 
following 
Individual 
target 
nodes/nodal 
masses
Score 4 or 5 with an increase in intensity of uptake from baseline and/or
PPD progression:
Extranodal 
lesions
New FDG-avid foci consistent with lymphoma at interim or end-of-treatment 
assessment
An individual node/lesion must be abnormal with
LDi  1.5 cm and
Increase by  50% from PPD nadir and
An increase in LDi or SDi from nadir
0.5 cm for lesions  2 cm
1.0 cm for lesions  2 cm
In the setting of splenomegaly, the splenic length must 
increase by  50% of the extent of its prior increase 
beyond baseline (e.g., a 15 cm spleen must increase 
to  16 cm). If no prior splenomegaly, must 
increase by at least 2 cm from baseline. New or 
recurrent splenomegaly
Nonmeasured 
lesions
None
New or clear progression of preexisting nonmeasured 
lesions

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Response and 
Site
PET-CTBased Response
CT-Based Response
New Lesions
New FDG-avid foci consistent with lymphoma rather than another etiology (e.g., 
infection, inflammation). If uncertain regarding etiology of new lesions, 
biopsy or interval scan may be considered.
Regrowth of previously resolved lesions
A new node  1.5 cm in any axis
A new extranodal site  1.0 cm in any axis; if  1.0 cm 
in any axis, its presence must be unequivocal and 
must be attributable to lymphoma
Assessable disease of any size unequivocally 
attributable to lymphoma
Bone Marrow
New or recurrent FDG-avid foci
New or recurrent involvement
Abbreviations: 5PS  5-point scale; CT  computed tomography; FDG  fluorodeoxyglucose; GI  gastrointestinal; IHC  immunohistochemistry; LDi, 
longest transverse diameter of a lesion; MRI  magnetic resonance imaging; PET  positron emission tomography; PPD  cross product of the LDi and 
perpendicular diameter; SDi  shortest axis perpendicular to the LDi; SPD  sum of the product of the perpendicular diameters for multiple lesions.
a Measured dominant lesions: up to six of the largest dominant nodes, nodal masses, and extranodal lesions selected to be clearly measurable in two 
diameters. Nodes should preferably be from disparate regions of the body and should include, where applicable, mediastinal and retroperitoneal areas. Non-
nodal lesions include those in solid organs (e.g., liver, spleen, kidneys, lungs), GI involvement, cutaneous lesions, or those noted on palpation. Nonmeasured 
lesions: any disease not selected as measured, dominant disease and truly assessable disease should be considered not measured. These sites include any 
nodes, nodal masses, and extranodal sites not selected as dominant or measurable or that do not meet the requirements for measurability but are still 
considered abnormal, as well as truly assessable disease, which is any site of suspected disease that would be difficult to follow quantitatively with 
measurement, including pleural effusions, ascites, bone lesions, leptomeningeal disease, abdominal masses, and other lesions that cannot be confirmed and 
followed by imaging. In Waldeyer’s ring or in extranodal sites (e.g., GI tract, liver, bone marrow), FDG uptake may be greater than in the mediastinum with 
complete metabolic response, but should be no higher than surrounding normal physiologic uptake (e.g., with marrow activation as a result of chemotherapy 
or myeloid growth factors).
b PET 5PS: 1, no uptake above background; 2, uptake   mediastinum; 3, uptake   mediastinum but   liver; 4, uptake moderately   liver; 5, uptake markedly 
higher than liver and/or new lesions; X, new areas of uptake unlikely to be related to lymphoma.

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APPENDIX G
PROHIBITED MEDICATIONS
The following table provides a list of clinically relevant inhibitors and inducers of P-gp. Drugs that are listed as P-gp inhibitors have 
been shown in a clinical study to increase the AUC of a sensitive substrate more than 25% or decrease the clearance of a sensitive 
substrate more than 20%. Drugs listed as P-gp inducers have been shown in a clinical study to decrease the AUC of a sensitive 
substrate more than 20% or increase the clearance of a sensitive substrate more than 25%.
 
It is important to note that information related to P-gp inhibitors and inducers abd OATP interactions changes rapidly and thus the 
contents of this table should only be considered to represent a snapshot of the information available at the time that this document was 
generated.
P-glycoprotein Inhibitors
P-glycoprotein Inducers
Amiodarone
Apalutamide
Azithromycin (Systemic)
CarBAMazepine
Capmatinib
Fosphenytoin
Carvedilol
Lorlatinib
Clarithromycin
Phenytoin
Cobicistat
RifAMPin
CycloSPORINE (Systemic)
St John's Wort
Daclatasvir
Dronedarone
Elagolix
Elagolix, Estradiol, Norethindrone
Elexacaftor, Tezacaftor, and Ivacaftor
Eliglustat
Erythromycin (Systemic)
Flibanserin
Fostamatinib
Glecaprevir and Pibrentasvir
Itraconazole
Ivacaftor
Ketoconazole (Systemic)

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P-glycoprotein Inhibitors
P-glycoprotein Inducers
Lapatinib
Ledipasvir
Neratinib
Ombitasvir, Paritaprevir, and Ritonavir
Osimertinib
Propafenone
QuiNIDine
QuiNINE
Ranolazine
Ritonavir
Rolapitant
Simeprevir
Tezacaftor and Ivacaftor
Tucatinib
Velpatasvir
Vemurafenib
Verapamil
Voclosporin
Examples of clinical inhibitors for transporters (for use in clinical DDI studies and drug labeling) (9/26/2016)
Transporter
Gene
Inhibitor
 
P-gp(a)
ABCB1
amiodarone, carvedilol, clarithromycin, dronedarone, itraconazole, lapatinib, lopinavir 
and ritonavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir and ritonavir, 
telaprevir, tipranavir and ritonavir, verapamil
 
BCRP
ABCG2
curcumin, cyclosporine A, eltrombopag
 
OATP1B1, OATP1B3
SLCO1B1, 
SLCO1B3
atazanavir and ritonavir, clarithromycin, cyclosporine, erythromycin, gemfibrozil, 
lopinavir and ritonavir, rifampin (single dose), simeprevir
 

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OAT1, OAT3
SLC22A6, 
SLC22A8
p-aminohippuric acid (PAH)(b), probenecid, teriflunomide
MATE1, MATE2-K
SLC47A1, 
SLC47A2
cimetidine, dolutegravir, isavuconazole, ranolazine, trimethoprim, vandetanib
 
Note:
Criteria for selecting in vivo inhibitors are as follows:

P-gp: (1) AUC fold-increase of digoxin ≥2 with co-administration and (2) in vitro inhibitor.

BCRP: (1) AUC fold-increase of sulfasalazine ≥1.5 with co-administration and (2) in vitro inhibitor. Cyclosporine A and 
eltrombopag were also included, although the available DDI information was with rosuvastatin, where inhibition of both 
BCRP and OATPs may have contributed to the observed interaction.

OATP1B1/OATP1B3: (1) AUC fold-increase ≥2 for at least one of clinical substrates in Table 2-3 with co-administration and 
(2) in vitro inhibitor.

OAT1/OAT3: (1) AUC fold-increase ≥1.5 for at least one of clinical substrates in Table 2-3 with co-administration and (2) in 
vitro inhibitor.<. i="">

OCT2/MATE: (1) AUC fold-increase of metformin ≥ 1.5 with co-administration and (2) in vitro inhibitor.
This table is prepared to provide examples of clinical inhibitors for various transporters and not intended to be an exhaustive list. 
DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database 
[Hachad et al. (2010), Hum Genomics, 5(1):61].
(a)Most of P-gp inhibitors also inhibit CYP3A. (b)In vivo data suggested specific inhibition of OAT1.
Abbreviations:
AUC: area under the plasma concentration-time curve.