A Phase 1/2 Dose-Finding Study to Evaluate the Safety, Feasibility, and Activity of BPX-701, a Controllable PRAME T-Cell Receptor Therapy, in HLA-A2+ Subjects With AML, Previously Treated MDS, or Metastatic Uveal Melanoma
Phase: PHASE1
Conditions: Acute Myeloid Leukemia, Myelodysplastic Syndrome, Uveal Melanoma
Sponsor: Bellicum Pharmaceuticals

Bellicum Pharmaceuticals                                                                               
Protocol Number BP-011 
 
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A PHASE 1/2 DOSE-FINDING STUDY TO EVALUATE THE SAFETY, FEASIBILITY, 
AND ACTIVITY OF BPX-701, A CONTROLLABLE PRAME T-CELL RECEPTOR 
THERAPY, IN HLA-A2+ SUBJECTS WITH RELAPSED ACUTE MYELOID 
LEUKEMIA, PREVIOUSLY TREATED MYELODYSPLASTIC SYNDROME, OR 
METASTATIC UVEAL MELANOMA  
Protocol Number: 
BP-011 
Investigational Products: 
BPX-701 – Autologous T cells genetically modified to express 
the αβ T cell receptor reacting with PRAME peptide/HLA-A2.01 
(PRAME TCR) and an inducible caspase-9 (iCasp9) safety 
switch  
Rimiducid – dimerizer infusion to activate iCasp9 and induce 
apoptosis of the BPX-701 T cells in the event of toxicity 
Study Sponsor: 
Bellicum Pharmaceuticals, Inc. 
2130 W. Holcombe Blvd, Suite 800 
Houston, TX 77030 
Medical Monitor Contact 
Information: 
Primary Medical Monitor:
 
 
 
 
Backup Medical Monitor: 
 
 
 
ClinicalTrials.Gov Number: 
NCT02743611 
Version Number: 
3.0 
Version Date: 
07 September 2018 
Confidentiality Statement 
This document contains confidential information confidential owned by Bellicum Pharmaceuticals, Inc. 
(Study Sponsor). Any viewing or disclosure of such information that is not authorized in writing by the 
Sponsor is strictly prohibited unless such disclosure is required by applicable law or regulations. Such 
information may be used solely for the purpose of reviewing or performing this study. In any event, persons 
to whom the information is disclosed must be informed that the information is privileged or confidential and 
may not be further disclosed by them. These restrictions on disclosure will apply equally to all future 
information supplied that is indicated as privileged or confidential. 
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Bellicum Pharmaceuticals                                                                               
Protocol Number BP-011 
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INVESTIGATOR AGREEMENT SIGNATURE PAGE 
I have read this protocol and agree to comply with all provisions set forth in this protocol, 
including all statements regarding confidentiality, and to complete the study within the time 
designated. 
 
I assume responsibility for the conduct of this study at my study site. I will ensure that I have 
sufficient resources allocated to this project such that the safety of my subjects is protected at 
all times and that I complete my obligations to the sponsor according to the agreed timelines. I 
will delegate responsibilities only to those who are qualified by training and experience. I will 
ensure the integrity of the data generated by my team and that all team members are familiar 
with the study protocol and the study medication. 
 
I agree that I will grant access to the applicable records, my staff allocated to the conduct of this 
protocol and my facilities for the purposes of monitoring, auditing and any required inspections 
associated with the conduct of this clinical trial. 
 
I agree to comply with the ICH Guideline on Good Clinical Practice, applicable EMA 
regulations and applicable FDA guidelines set forth in 21 CFR Parts 11, 50, 54, 56, and 312. 
 
Confidential information contained in the protocol document will not be used for any other 
purpose other than the evaluation or conduct of the clinical investigation without the prior 
written consent of the sponsor. 
 
 
 
 
 
 
Signature 
Date 
 
 
 
Printed 
Name 
Investigator 
 
 
Bellicum Pharmaceuticals, Inc., BPX-701
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Bellicum Pharmaceuticals, Inc., BPX-701
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Bellicum Pharmaceuticals                                                                               
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Table of Contents 
 
Table of Contents 
4 
1.1 Preferentially Expressed Antigen in Melanoma (PRAME) 
23 
1.2 Study Rationale 
23 
2.1 PRAME-Expressing Malignancies with Significant Unmet Medical Need 
24 
3.1 BPX-701:  PRAME TCR Immunotherapy 
27 
3.2 Summary of Clinical Experience: BPX-701 
33 
3.3 Rimiducid: Dimerizer Drug 
33 
5.1 Overview of Rationale and Design 
36 
5.2 BPX-701 T Cell Starting Dose Rationale 
38 
5.3 Dose-Limiting Toxicity 
38 
5.4 Clinical Design 
39 
5.5 Safety Review Committee 
41 
5.6 Study Duration 
42 
5.7 Subject Enrollment, Registration, and Assignment to Treatment 
43 
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Bellicum Pharmaceuticals                                                                               
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5.8 Subject Evaluability and Replacement 
43 
5.9 Study Completion 
44 
5.10 Study Discontinuation/Withdrawal 
44 
6.1 Inclusion Criteria 
45 
6.2 Exclusion Criteria 
47 
7.1 Investigational Products 
49 
7.2 Apheresis 
50 
7.3 Lymphodepletion Prior to BPX-701 T Cell Infusion 
51 
7.4 BPX-701 T Cell Infusion 
51 
7.5 Rimiducid Infusion 
52 
7.6 Toxicity Management and Supportive Care Guidelines 
53 
7.7 Concomitant Therapies 
61 
7.8 Prohibited Therapies 
61 
8.1 General Assessments 
63 
8.2 Safety Assessments 
64 
8.3 Rimiducid Concentration Measurements (Pharmacokinetics) 
68 
8.4 Research Laboratory Assessments 
68 
8.5 Efficacy Assessments for Subjects with AML or MDS 
71 
8.6 Efficacy Assessments for Subjects with Uveal Melanoma 
71 
9.1 Safety Parameters and Definitions 
72 
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Bellicum Pharmaceuticals                                                                               
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9.2 Adverse Events 
72 
9.3 Serious Adverse Events (SAE) 
73 
9.4 Assessment of Adverse Events by the Investigator 
73 
9.5 Disease-Related Events Not Qualifying as AEs 
74 
9.6 Adverse Event Reporting Period 
74 
9.7 Reporting Requirements for SAEs 
75 
9.8 Adverse Events of Special Interest 
76 
9.9 Adverse Event Follow-Up Reporting 
76 
9.10 Pregnancy Reporting 
76 
9.11 Safety Reporting Contact Information 
77 
10.1 Sample Size Determination 
77 
10.2 Analysis Sets 
79 
10.3 Subject Disposition 
79 
10.4 Safety Analyses 
79 
10.5 Pharmacokinetic Analyses 
80 
10.6 Efficacy Variables and Analyses 
80 
10.7 Research Laboratory Analyses 
81 
10.8 Interim Analysis 
81 
11.1 Institutional and Ethical Review 
82 
11.2 Investigator Responsibilities 
82 
11.3 Subject Informed Consent and Human Subject Protection 
82 
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Bellicum Pharmaceuticals                                                                               
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11.4 Confidentiality and Privacy 
83 
11.5 Clinical Monitoring 
83 
11.6 Data Handling and Record Keeping 
83 
11.7 Protocol Deviations 
84 
13.1 Appendix 1:  Schedule of Assessments 
91 
13.2 Appendix 2:  Biomarker Sampling Schedule during Treatment Month 1 (Day 0 
thru Day 28) 
95 
13.3 Appendix 3:  Pharmacokinetics, ECG, and Safety Biomarker Sampling Schedule 
for Subjects that receive Rimiducid 
95 
13.4 Appendix 4:  Eastern Cooperative Oncology Group Performance Status 
96 
13.5 Appendix 5:  New York Heart Association Criteria 
97 
13.6 Appendix 6:  Common Corticosteroids and Conversion Half-Lives 
98 
13.7 Appendix 7:  Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Quick 
Reference 
99 
13.8 Appendix 8:  Immune-Related Response Criteria (irRC)                                             
102 
13.9 Appendix 9:  ELN Response Criteria for AML                                                            
104 
13.10 Appendix 10:  IWG Response and Hematological Improvement Criteria for 
Myelodysplasia                                                                                                             
105 
 
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Bellicum Pharmaceuticals                                                                               
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List of Figures 
Figure 1:  BPX-701 Retroviral iCasp9 Vector Construct ..................................................27 
Figure 2:  iCaspase-9 Safety Switch ..................................................................................28 
Figure 3:  In vivo imaging of myeloma tumors following treatment with BPX-701 .........30 
Figure 4:  BPX-701 modified T cells persist in vivo at least 7 weeks ...............................31 
Figure 5: Active, persisting BPX-701 T cells remain sensitive to rimiducid after 7 weeks32 
Figure 6:  Rimiducid-mediated elimination of BPX-701 T cells in vivo ............................ 33 
Figure 7:  Study Design Schematic ..................................................................................... 37 
 
List of Tables 
Table 1:  Dose Escalation/De-Escalation Enrollment Algorithm ......................................40 
Table 2:  Planned BPX-701 T Cell Dose Levels ...............................................................40 
Table 3:  Grading Criteria for Cytokine Release Syndrome ..............................................54 
Table 4:  Recommendations for the Management of Cytokine Release Syndrome ..........54 
Table 5:  Recommendations for the Management of Neurotoxicity..................................57 
Table 6:  Clinical Laboratory Tests ...................................................................................67 
Table 7:  Gene Therapy Monitoring Schedule ...................................................................71 
Table 8:  Safety Reporting Periods ....................................................................................75 
 
 
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Bellicum Pharmaceuticals                                                                               
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PROTOCOL SYNOPSIS 
Protocol No. : 
BP-011 
Protocol Title: 
A Phase 1/2 Dose-Finding Study to evaluate the Safety, Feasibility, and 
Activity of BPX-701, a Controllable PRAME T-cell Receptor Therapy, in 
HLA-A2+ Subjects with Relapsed Acute Myeloid Leukemia, Previously 
Treated Myelodysplastic Syndrome, or Metastatic Uveal Melanoma 
Study Phase:  
Phase 1/2 
Duration of 
Study: 
Subject Accrual: Approximately 18-24 Months 
Screening Period: Up to 42 Days prior to BPX-701 T cell infusion 
Treatment Period: Up to 12 Months following BPX-701 T cell infusion 
Posttreatment Follow Up Period: Up to 15 Years following BPX-701 
T cell infusion 
Number of 
Subjects: 
Up to 116 subjects 
Number of 
Sites: 
Up to 12 
Study Design: 
This is a Phase 1/2, multicenter, open-label, non-randomized study to 
characterize the feasibility, safety, and clinical activity of BPX-701, a 
genetically modified autologous T cell product incorporating an 
HLA-A2.01-restricted PRAME-directed T cell receptor (TCR) and an 
inducible caspase-9 (iCasp9) safety switch, when administered to subjects 
with relapsed acute myeloid leukemia (AML; Arm 1), previously treated 
myelodysplastic syndrome (MDS; Arm 1) or metastatic uveal melanoma 
(Arm 2).  Arms 1 and 2 will be conducted in parallel.  For each Arm, the 
study will be comprised of multiple parts, beginning initially with Part 1 
(Phase 1).  Treatment will be administered in an inpatient setting.  Subject 
safety will be monitored throughout all parts of the study by a safety review 
team established by the sponsor. 
Part 1 (or Phase 1) is a Cell Dose Escalation phase to identify the 
recommended BPX-701 cell dose for expansion (RDE) using a 3+3 dose 
escalation design (escalating doses from 1.25 x 106 cells/kg up to 
5.0 x 106 cells/kg administered by intravenous infusion).  Dose escalation 
will proceed in sequential cohorts of at least 3 and up to 6 subjects until an 
RDE is defined.  RDE is represented by the dose of BPX-701 that provides 
adequate T cell persistence and biological activity while not exceeding the 
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Bellicum Pharmaceuticals                                                                               
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maximum tolerated dose (MTD) or maximum administered dose.  For the 
initial cell dose escalation cohort in each of Arms 1 and 2, the first 3 subjects 
will be enrolled sequentially with subjects 2 and 3 enrolled no sooner than 
1 month (28 days) after the prior subject has been infused with BPX-701.  
All subsequent subjects will be enrolled in the usual manner for a 3+3 
design. 
The evaluation period for defining dose limiting toxicity (DLT) and 
informing dose escalation decisions is from the start of the BPX-701 infusion 
on Day 0 through Day 28.  DLT is defined as any of the following unless 
clearly due to disease progression or extraneous causes: 
• Any treatment-emergent CTCAE Grade 4 or 5 cytokine release 
syndrome (CRS) 
• Any treatment-emergent CTCAE Grade 3 CRS that does not resolve 
to Grade ≤2 within 7 days 
• Any treatment-emergent autoimmune toxicity Grade ≥3 
• CTCAE Grade ≥3 infusion reaction 
• Any other treatment-emergent CTCAE Grade ≥3 organ toxicity 
(cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, 
renal/genitourinary, or neurologic) not pre-existing or due to the 
underlying malignancy that does not resolve to Grade ≤2 within 
7 days 
Parts 2 and 3 (Phase 2) comprise a Dose Expansion phase to further assess 
safety, pharmacodynamics (including BPX-701 T cell persistence and 
response to rimiducid as applicable), and clinical activity of BPX-701 T cells 
administered at the RDE.  Part 2 will begin once an RDE is determined in 
Part 1 (i.e., RDE-1 triggers Part 2 for Arm 1; RDE-2 triggers Part 2 for Arm 
2).  The opening of Part 3 is dependent upon antitumor activity observed in 
Part 2.  Within each Arm, subjects will be monitored for clinical activity to 
enable early stopping for futility if sufficient antitumor activity is not 
demonstrated.  For each Arm, the maximum planned enrollment in dose 
expansion is 40 subjects (Parts 2 and 3 combined). 
• Arm 1: Up to 10 eligible subjects with relapsed AML or previously 
treated MDS will initially be enrolled (Part 2).  If ≥2 subjects achieve 
complete or partial remission per the European Leukemia Network 
(ELN) criteria or International Working Group (IWG) criteria for 
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Bellicum Pharmaceuticals                                                                               
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AML or MDS, respectively, Part 3 may be opened to enroll up to an 
additional 30 subjects.   
• Arm 2: Up to 10 eligible subjects with metastatic uveal melanoma 
will initially be enrolled (Part 2).  If one of the following are observed 
in Part 2, then Part 3 may be opened to enroll up to an additional 
30 subjects: 
o ≥1 complete or partial response as defined by the Response 
Evaluation Criteria in Solid Tumors (RECIST) v1.1; or, 
o ≥4 months median time to next treatment defined as the time 
from BPX-701 T cell infusion to initiation of next systemic 
therapy for the disease under study 
During Parts 1, 2, or 3, rimiducid (1 or more doses at 0.4 mg/kg) may be 
administered following BPX-701 T cell infusion in response to 
treatment-related toxicity (i.e., both on-target/off-tumor as well as 
on-target/on-tumor side effects).  
No formal hypothesis testing will be conducted. Rather, the statistical 
analysis will be descriptive and will summarize data by dose level/Part and 
tumor type (i.e., Arm 1 reported separately from Arm 2). Continuous 
variables will be summarized using the number of observations, mean, 
standard deviation, coefficient of variation, median, and range as appropriate. 
Categorical values will be summarized using the number of observations and 
percentages as appropriate.  Descriptive summaries of time to event data 
from Kaplan Meier estimates will include the number of events, number 
censored, medians, quartiles and 95% CIs. Graphical summaries of the data 
may be presented. All data will be listed for all subjects. 
The sponsor will establish a clinical data cutoff date for clinical study report 
analysis reporting 12 months after the last subject has received BPX-701 or 
after all subjects have discontinued the study, whichever comes first.  
Study 
Objectives: 
Primary Objectives: 
• Phase 1 / Arm 1: To characterize the safety and tolerability and to 
identify the MTD and/or the RDE of BPX-701 T cells administered 
to subjects with relapsed AML or previously treated MDS 
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Bellicum Pharmaceuticals                                                                               
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• Phase 1 / Arm 2: To characterize the safety and tolerability and to 
identify the MTD and/or RDE of BPX-701 T cells administered 
subjects with metastatic uveal melanoma 
• Phase 2 / Arm 1: To evaluate the remission rate following BPX-701 
T cell infusion to subjects with relapsed AML or previously treated 
MDS 
• Phase 2 / Arm 2: To evaluate the antitumor activity of BPX-701 
T cells administered to subjects with metastatic uveal melanoma 
Secondary Objectives: 
• To characterize the pharmacodynamics (PD) of BPX 701 T cells 
• To assess the response to rimiducid in those subjects with 
treatment-emergent BPX-701 toxicity 
• To characterize the pharmacokinetics (PK) of rimiducid after a single 
or repeat doses 
• To evaluate the clinical efficacy of BPX-701 T cells administered to 
subjects with relapsed AML or previously treated MDS 
• To evaluate the clinical efficacy of BPX-701 T cells administered to 
subjects with metastatic uveal melanoma 
• To assess the long-term safety of BPX-701 T cells 
Exploratory Objectives: 
• To assess the immunogenicity of BPX-701 T cells 
• To evaluate the frequency and level of PRAME expression in AML 
or MDS and uveal melanoma 
• To explore the relationship between BPX-701 PD biomarkers (e.g., 
BPX-701 T cell persistence, phenotyping, functional activity, tumor 
infiltration) and genetic and/or protein profiles in tumor tissue/bone 
marrow and peripheral blood 
• To explore the relationship between tumor tissue/blood-based 
immune biomarkers (including but not limited to PRAME) and 
clinical response or resistance to BPX-701 T cells 
Inclusion 
Criteria: 
 
1. Each subject (or their legally acceptable representative) must sign and 
date an informed consent form approved by the institutional review 
board/ethics committee, as appropriate, indicating that he/she 
understands the purpose of and procedures required for the study and are 
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Bellicum Pharmaceuticals                                                                               
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willing to comply.  Consent is to be obtained prior to the performance of 
any study-specific procedures or tests that are not part of the standard of 
care for the subject’s disease. 
2. Arm 1:  
• MDS not responding to hypomethylation therapy or recurrence after 
initial response; or, 
• AML with disease relapse following first complete remission with 
intermediate or adverse genetics according to the ELN criteria  
– Subjects with a prior treatment history of stem cell transplant 
must be >100 days post-transplant with no evidence of active 
graft-versus-host disease and not requiring systemic 
immunomodulatory or immunosuppressive therapy defined as 
>10mg prednisone or equivalent per day and active use of a 
calcineurin inhibitor 
Arm 2: 
• Histologically or cytologically confirmed diagnosis of metastatic 
uveal melanoma 
• Measurable disease (at least one target lesion) per RECIST v1.1  
• Adequate bone marrow function defined as: 
– Absolute neutrophil count ≥1,000/µL 
– Platelets ≥75,000/µL 
3. Human leukocyte antigen (HLA)-A2.01 positive by local assessment 
4. Documented positive myeloid blast or tumor expression of PRAME as 
determined by central testing of an available, representative bone 
marrow aspirate (fresh sample) or tissue specimen (formalin-fixed 
paraffin-embedded tissue, either from an archived sample or fresh 
biopsy) for Arm 1 and Arm 2, respectively 
5. Absolute lymphocyte count ≥200/µL 
6. Age ≥18 years  
7. Life expectancy >12 weeks  
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1  
9. Subjects must have adequate venous access for apheresis or agree to use 
of a central line for apheresis collection 
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Bellicum Pharmaceuticals                                                                               
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10. Subject has adequate organ function: 
Cardiac: Left ventricular ejection fraction at rest must be ≥lower limit 
of institutional normal 
Coagulation: International normalized ratio ≤1.5 
Hepatic: 
• Direct bilirubin ≤2x upper limit of normal (ULN), or ≤3x if due to 
Gilbert’s disease 
• Aspartate aminotransferase and alanine aminotransferase ≤3 x ULN, 
or ≤5 x ULN if liver metastases are present 
Renal: Creatinine ≤1.5 x ULN  
11. Before planned BPX-701 T cell infusion, as well as during the study, a 
female subject must be either: 
• Not of childbearing potential defined as:  
– Premenarchal,  
– Postmenopausal (>45 years of age with amenorrhea ≥12 months),  
– Permanently sterilized,  
– Otherwise incapable of pregnancy; or, 
• Of childbearing potential and agrees to use 2 highly effective 
methods of birth control for at least 12 months after lymphodepletion 
Exclusion 
Criteria: 
1. Arm 1: 
• Diagnosis of Acute Promyelocytic Leukemia  
• Primary refractory AML 
• Uncontrolled disseminated intravascular coagulation 
• Symptomatic or untreated central nervous system involvement by 
malignant cells 
• Peripheral blast count ≥20,000/µL 
2. Arm 2: 
• Symptomatic, untreated or actively progressing central nervous 
system metastases.  Subjects with prior brain metastases treated at 
least 2 weeks prior to the planned BPX-701 T cell infusion who are 
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Bellicum Pharmaceuticals                                                                               
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clinically stable and do not require chronic corticosteroid treatment 
are allowed 
• History of leptomeningeal disease 
3. Ongoing toxicities related to prior anticancer therapy that have not 
resolved to Grade ≤1.  Current unresolved Grade ≥2 non-hematologic 
toxicity may be allowed following discussion with and approval by the 
sponsor 
4. Participation in any investigational drug study within 4 weeks prior to the 
planned BPX 701 T cell infusion 
5. Chemotherapy (excluding hydroxyurea), targeted therapy, or 
radiotherapy (excluding palliative radiation) within 2 weeks, hydroxyurea 
within 1 week, or immunotherapy within 4 weeks prior to BPX-701 
T cell infusion, other than salvage/lymphodepletion chemotherapy 
6. Active autoimmune disease requiring immunosuppressive therapy.  
Subjects with vitiligo; type I diabetes; hypothyroidism, adrenal 
insufficiency, or hypophysitis only requiring hormone replacement; 
psoriasis not requiring systemic treatment or conditions not expected to 
recur; or history of Hashimoto’s Thyroiditis on stable dose of thyroid 
hormone replacement therapy should not be excluded 
7. Impaired cardiac function or clinically significant cardiac disease, 
including any of the following: 
• Symptomatic congestive heart failure requiring treatment; 
• Clinically significant cardiac arrhythmia; 
• Uncontrolled hypertension; 
• Acute myocardial infarction or unstable angina pectoris within 
3 months prior to BPX-701 T cell infusion; or, 
• Marked limitation of physical activity due to symptoms, or unable to 
carry on any physical activity without discomfort (i.e., New York 
Heart Association Functional Class III-IV) 
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Bellicum Pharmaceuticals                                                                               
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8. Major surgical procedure, other than for diagnosis, within 4 weeks prior 
to BPX-701 T cell infusion, or anticipation of the need for a major 
surgical procedure during the study 
9. Received a vaccine containing live virus within 4 weeks prior to the 
planned BPX 701 T cell infusion. Seasonal flu vaccines that do not 
contain live virus are permitted 
10. Treatment with systemic chronic steroid therapy (prednisone >10mg 
daily or equivalent) within 7 days or 7 half-lives, whichever is shorter, 
prior to the planned apheresis date.  Local steroid therapies (e.g., otic, 
ophthalmic, intra-articular or inhaled medications) are acceptable  
11. Uncontrolled intercurrent illness including but not limited to poorly 
controlled hypertension or diabetes, or any medical condition determined 
by the investigator to be a risk for enrolling on the protocol 
12. Uncontrolled infection requiring systemic therapy.  Prior oral or IV 
antibiotics antifungals or antiviral medications must be discontinued at 
least 2 weeks prior to BPX-701 T cell infusion except for use of 
prophylactic antimicrobial agents 
13. Active hepatitis B virus (HBV) infection (chronic or acute), defined as 
having a positive hepatitis B surface antigen (HBsAg) test during 
Screening.  Subjects with a past or resolved HBV infection, defined as 
having a negative HBsAg test and a positive total hepatitis B core 
antibody (HBcAb) test at screening are eligible for the study if HBV 
DNA test is negative.  If a patient has a negative HBsAg test and a 
positive total HBcAb test at screening, an HBV DNA test should be 
performed 
14. Active hepatitis C virus (HCV) infection, defined as having a positive 
HCV antibody test followed by a positive HCV RNA test during 
Screening.  The HCV RNA test will be performed only for patients who 
have a positive HCV test 
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Bellicum Pharmaceuticals                                                                               
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15. History of human immunodeficiency virus (HIV), or positive HIV test 
during Screening (unless not permitted by local regulations) 
16. Subject is a woman of child-bearing potential is pregnant (positive serum 
β-human chorionic gonadotropin test at Baseline), planning to become 
pregnant within 12 months after lymphodepletion or is breastfeeding 
17. Subject is a man who plans to father a child within 12 months after 
lymphodepletion 
18. Known bovine product allergy 
19. Malignant disease other than that being treated in this study.  Exceptions 
to this exclusion are: 
• Malignancies that were treated curatively and have not recurred 
within 2 years prior to Screening 
• Completely resected basal cell and squamous cell skin cancers 
• Any malignancy considered to be indolent and that has never required 
therapy 
 
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Bellicum Pharmaceuticals                                                                               
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LIST OF ABBREVIATIONS AND TERMS 
Abbreviation 
Definition 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
AML 
Acute myeloid leukemia 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
BLI 
Bioluminescent imaging 
CAR 
Chimeric antigen receptor 
CFR 
Code of Federal Regulations 
CID 
Chemical inducer of dimerization 
Cmax 
Maximum concentration 
CNS 
Central nervous system 
CR 
Complete remission 
CRi 
Complete remission with incomplete hematologic 
recovery
CRMRD- 
Complete remission without minimal residual disease 
CR 
Complete response 
CRF 
Case report form 
CRP 
C-reactive protein 
CRS 
Cytokine release syndrome 
CSF 
Cerebral spinal fluid 
CT 
Computed tomography 
CTA 
Cancer testis antigen 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCR 
Disease control rate 
DLT 
Dose limiting toxicity 
DOR 
Duration of response 
EC 
Ethics committee 
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Abbreviation 
Definition 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EEG 
Electroencephalogram 
EFS 
Event free survival 
ELN 
European Leukemia Network 
EMA 
European Medicines Agency 
EOT 
End of treatment 
FDA 
Food and Drug Administration 
FFPE 
Formalin fixed paraffin embedded 
FKBP 
FK binding protein 
GCP 
Good Clinical Practice 
GMCSF 
Granulocyte-macrophage colony-stimulating factor 
GMP 
Good Manufacturing Practice 
GvHD 
Graft-versus-host disease 
HBV 
Hepatitis B virus 
HBcAb 
Hepatitis B core antibody 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
HLA 
Human leukocyte antigen 
HSCT 
Hematopoietic stem cell transplant 
HTLV 
Human T-lymphotropic virus 
HUS 
Hemolytic-uremic syndrome 
iCasp9 
Inducible caspase-9 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
ICU 
Intensive care unit 
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Abbreviation 
Definition 
IFN 
Interferon 
IL 
Interleukin 
INR 
International normalized ratio 
IWG 
International Working Group 
IRB 
Institutional review board 
irRC 
Immune-related Response Criteria 
ITT 
Intent-to-treat 
IV 
Intravenous 
kg 
Kilogram 
LDH 
Lactate dehydrogenase 
LLN 
Lower limit of normal 
LN2 
Liquid nitrogen 
LVEF 
Left ventricular ejection fraction 
MAD 
Maximum administered dose 
MDS 
Myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
min 
Minute 
mg 
Milligram 
µL 
Microliter 
MLFS 
Morphologic leukemia-free state 
mm 
Millimeter 
MMSE 
Mini mental status exam 
MRD 
Minimal residual disease 
MRI 
Magnetic resonance imaging 
msec 
Millisecond 
MTD 
Maximum tolerated dose 
MUGA 
Multi-gated acquisition 
NCI 
National Cancer Institute 
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Abbreviation 
Definition 
ng 
Nanogram 
NT 
Non-transduced 
ORR 
Objective response rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cell 
PD 
Pharmacodynamics 
PD 
Progressive disease 
PFS 
Progression free survival 
PID 
Primary immunodeficiency 
PK 
Pharmacokinetics 
PR 
Partial remission 
PR 
Partial response 
PRAME 
Preferentially expressed antigen in melanoma 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
qPCR 
Quantitative polymerase chain reaction 
RCR 
Replication competent retrovirus 
RDE 
Recommended dose for expansion 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RFS 
Relapse free survival 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic blood pressure 
SD 
Stable disease 
SDV 
Source data verification 
SRC 
Safety review committee 
SUSAR 
Suspected unexpected serious adverse reaction 
TCR 
T-cell receptor 
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Abbreviation 
Definition 
TNF 
Tumor necrosis factor 
TTP 
Thrombotic thrombocytopenic purpura 
ULN 
Upper limit of normal 
VASST 
Vasopressin and Septic Shock Trial 
 
 
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INTRODUCTION  
1.1 
Preferentially Expressed Antigen in Melanoma (PRAME) 
Cancer-testis antigens (CTAs) comprise a category of non-mutated genes expressed at high levels 
in germinal tissues and certain cancers including both hematologic and solid tumor malignancies, 
but which are absent from or detected at low levels in other tissues (Haqq 2005).  CTA genes 
encode antigenic peptides that are naturally recognized by T lymphocytes.  This, along with their 
limited expression pattern, makes CTA family members both an ideal target for anticancer 
immunotherapy as well as biomarkers for disease diagnosis and/or prognosis.     
PRAME, or preferentially expressed antigen in melanoma, is one of the best characterized CTA 
family members.  PRAME has a biological role in the regulation of retinoic acid signaling and acts 
to repress the retinoic acid receptor.  Through this mechanism, PRAME likely confers a growth 
advantage to cancer cells although whether it is a driver or passenger gene remains to be 
established.  In normal tissues, PRAME is expressed in the testis, adrenal gland, ovary, 
endometrium, and kidney epithelium and its expression levels are lower by more than 
3 logarithmic series compared with that in tumor tissues (Ikeda 1997).  Initially identified in 1997 
by Ikeda and colleagues in melanoma tissue of cutaneous origin, PRAME was subsequently 
detected in both acute and chronic lymphoid and myeloid malignancies (van Baren 1998; 
Radich 2006) as well as uveal melanoma in addition to other solid tumor types including breast 
(Epping 2008), lung (Ikeda 1997), head and neck (Figueiredo 2006), and neurological cancers 
(Oberthuer 2004; Orlando 2018).  High expression of PRAME has been associated with poor 
survival and shortened disease-free survival.  
As is characteristic for CTAs, PRAME is naturally immunogenic.  Through the T cell receptor 
(TCR) complex, ex vivo expanded T cells were shown to target PRAME peptide in context of 
human leukocyte antigen (HLA)-restricting elements (Amir 2011).  Furthermore, PRAME has 
been shown to be a candidate for immunotherapy, inducing strong immune responses in healthy 
volunteers as well as patients with leukemia and cutaneous melanoma (Wadelin 2010).  Together, 
these data provide clinical evidence that PRAME is a relevant target of interest for therapeutic 
intervention.  
1.2 
Study Rationale 
BPX-701 is an investigational, controllable TCR immunotherapy candidate in early clinical 
development intended for the treatment of PRAME-expressing hematologic and solid tumor 
malignancies, specifically acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and 
uveal melanoma.  The high-affinity TCR expressed within BPX-701 recognizes and binds to 
PRAME antigen presented by HLA-A2 on the surface of a cancer cell, initiating downstream 
signaling that leads to tumor cell apoptosis.  Inclusion of an inducible safety switch within 
BPX-701 provides a mechanism to remove gene-modified T cells in response to uncontrollable 
treatment-emergent toxicity.  Preclinical data with this first-in-clinic, inducible caspase-9 
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(iCasp9)-enabled TCR product candidate not only demonstrate antitumor activity against myeloma 
cells expressing PRAME/HLA-A2 but also illustrate the effectiveness and specificity of the safety 
switch in rapidly eliminating the genetically modified T cells.   
It is hypothesized that the addition of an inducible “off” switch to BPX-701 provides a selective 
and controllable suicide signal, thereby mitigating the potential risk for treatment-related toxicity 
(i.e., both on-target/off-tumor as well as on-target/on-tumor side effects).  Considering historical 
data that validate PRAME as a therapeutic target, this study aims to evaluate the safety, feasibility, 
and clinical activity of a PRAME-directed cellular therapy in selected oncology indications with 
high unmet medical need and without other disease-directed treatment options. 
 
BACKGROUND AND SCIENTIFIC RATIONALE 
2.1 
PRAME-Expressing Malignancies with Significant Unmet Medical Need 
2.1.1 
Leukemia 
Leukemia is a cancer of the blood and bone marrow cells, affecting a group of white blood cells 
known as myeloid progenitors. MDS and AML exist along a pathology spectrum starting with 
early-stage MDS, which may progress to advanced disease.  Across this spectrum, leukemia is 
characterized by an overproduction of immature blood cells.  Disease onset has been associated 
with smoking, exposure to certain chemicals especially benzene, radiation exposure, inherited 
blood disorders, and certain genetic syndromes.  Additionally, around 5-10% of patients with solid 
tumors that receive chemotherapy, radiation, or autologous stem cell transplantation as part of their 
anticancer treatment regimen eventually go on to subsequently develop chemotherapy-related 
MDS or AML even in circumstances where the original malignancy has resolved or stabilized.  
Acute Myeloid Leukemia 
It is estimated that 19,520 patients will be diagnosed with AML in 2018 (SEER 2018).  While this 
represents only 1.1% of all new cancer cases, the 5-year mortality rate following initial diagnosis 
is 72.6% which highlights not only the aggressive pathology of this disease but also the need to 
develop effective therapies with the potential to impact long-term survival. 
Rather than a single disease type, AML is a group of related diseases with a complex classification 
system based on leukemia cell morphology, chromosomal abnormalities, and molecular genetics 
and mutation profiling (Dohner 2017).  Depending on the latter, patients are grouped into 
prognostic risk categories which help to inform treatment decisions.  Generally, AML is difficult 
to treat, and current interventions come with significant toxicity.  Initially, intensive chemotherapy 
combinations with or without targeted agent, if applicable, are administered to eliminate as many 
leukemia cells as possible.  In addition, normal bone marrow cells are also depleted.  This results 
in side effects that include increased risk of anemia, bleeding, infections, weight loss, bone pain, 
and an enlarged liver and spleen and require intensive supportive care management with antibiotics 
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and recurring blood product transfusions.  If initial therapy is effective in reducing tumor burden 
and remission is achieved, a hematopoietic stem cell transplant (either autologous or allogeneic) 
with or without high-dose chemotherapy is often pursued not only to destroy any leftover leukemia 
cells but also prevent disease relapse.   
For patients initially treated with aggressive induction chemotherapy, between 20-40% will not 
obtain a remission and are considered to have primary refractory disease (Cheson 2004).  The 
prognosis for these patients as well as those with disease recurrence post-transplant are poor.  
Indeed, a retrospective analysis study of 594 patients with AML undergoing second salvage 
therapy after standard treatment, which includes stem cell transplantation, reported a median 
survival of 1.5 months with a 1-year survival of 8%.  Subgroup analysis of those attaining 
remission (13%) showed only a 7-month median remission duration.  Multivariate analysis 
revealed several poor prognostic features including age >60, initial remission duration 
<12 months, and second remission duration <6 months (Giles 2005). Importantly, standard 
therapies do not appear to favorably impact patients who relapse in <12 months (Kumar 2002).   
Elderly patients not eligible for intensive chemotherapy or transplant generally have poor 
outcomes and remain a significant therapeutic challenge.  Beyond best supportive care or off-label, 
low-dose use of certain chemotherapy drugs, no standard treatment is currently available. Out of 
those with sufficient performance status to receive chemotherapy, 30-40% will achieve a remission 
with standard induction yet the median survival approximates only 10 months (Oran 2012).  
PRAME overexpression has been assessed in AML and was shown to be present in approximately 
32-55% of patients depending on the study (Ding 2012; Goswami 2014; Qin 2009; van Baren 
1998).  In acute leukemia cells, inhibition of PRAME resulted in apoptosis suggesting it plays a 
key role in tumorigenesis and disease progression (Tanaka 2011).  The clinical relevance is less 
clear as some studies have reported an association between high PRAME expression and favorable 
cytogenetics (van Baren 1998) as well as survival outcomes (Greiner 2006; Tajeddine 2008), 
whereas other studies have not (Paydas 2005; Guinn 2009).   
Myelodysplastic Syndrome 
The American Cancer Society estimates approximately 10,000 patients are diagnosed annually 
with MDS (American Cancer Society 2018), although incidence rates reported by others is much 
higher.  Age and gender are key risk factors for MDS, with onset most commonly observed in 
females at least 70 years old.  Other risk factors are similar to those reported for AML.  Like AML, 
patients with MDS are classified into different risk groups using a formal prognostic scoring 
system based on bone marrow morphology, chromosomal abnormalities, and peripheral blood cell 
counts.  The resulting score determines overall risk category thereby informing treatment strategy. 
The standard of care for intermediate- or high-risk MDS is azacitadine or decitabine either with 
(for candidates with good performance status and an eligible matched donor) or without an 
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allogeneic hematopoietic stem cell transplant.  For patients with relapse or failure in response to 
initial hypomethylation-based therapy, overall prognosis is poor with no evidence of benefit of 
any available treatment relative to best supportive care.  Moreover, standard algorithms 
recommend clinical trials for disease management in this setting (Sekeres 2014). 
PRAME expression in MDS has been studied as a marker for higher risk disease with worse 
outcomes although this observation has not been validated in larger cohorts of patients.  Data from 
Qian et al showed that 11 of 56 patients (19.6%) with MDS had PRAME gene promoter 
hypomethylation, a frequency that was higher in the context of abnormal cytogenetics and higher 
blast counts (Qian 2011).  In this study, PRAME methylation status was predictive for overall 
survival with a 50% survival time of 11 versus 26 months for those with hypomethylated versus 
methylated PRAME, respectively.  Other groups have reported similar findings in a study of 
73 MDS patients that identify a correlation between high PRAME expression and poor survival 
(Liberante 2013). 
Collectively these observations (i.e., PRAME hypomethylation is associated with worse outcomes 
along with the standard use of hypomethylating agents in early treatment lines) together suggest 
that a PRAME-directed agent may be uniquely poised to provide potential clinical benefit to 
intermediate-to-high risk MDS patients with relapse or progression after initial therapy. 
2.1.2 
Uveal Melanoma 
Melanoma of the uveal tract (iris, ciliary body, and choroid), though rare, is the most common 
primary intraocular malignancy in adults. Uveal melanoma is biologically different from 
cutaneous melanoma.  The American Cancer Society estimates approximately 3500 people will be 
diagnosed with ocular cancer in 2018 (American Cancer Society 2018) with risks for disease onset 
being higher for those of Caucasian ethnicity with lighter eye color.  While treatment of primary 
uveal melanoma, usually with surgery or radiotherapy, is almost invariably successful, cumulative 
rates of metastases at 5, 10, and 15 years after treatment were 25%, 34%, and 50% respectively 
(Diener-West 2005; Kujala 2003).  The 5-year survival rate for metastatic uveal melanoma is about 
15% (American Cancer Society 2018).  No therapy has demonstrated a survival advantage for 
patients with metastatic uveal melanoma making this disease one of the few remaining 
malignancies for which there are no effective treatments in the metastatic setting.  Thus, there is 
an urgent need to develop novel, proven treatments for this disease. 
PRAME is a known prognostic biomarker of metastatic risk in patients with uveal melanoma 
(Field 2016).  As for AML or MDS, PRAME has been proposed as a potential therapeutic target 
in uveal melanoma given its lack of expression in normal versus malignant tissues.  Indeed, a 
retrospective study showed 69% of patients with metastatic uveal melanoma expressed PRAME 
(Gaugin 2017).  This same trial demonstrated that HLA-A2-restricted PRAME-specific T cells 
recognized and were active against PRAME-positive uveal melanoma cell lines.  Experimental 
vaccines targeting PRAME have been investigated for the treatment of cutaneous melanoma 
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(NCT01149343) and other PRAME-expressing solid tumors (NCT01853878).  Together these 
data provide scientific rationale for evaluating the potential clinical benefit of PRAME-directed 
immunotherapy in metastatic uveal melanoma where no approved standard treatment currently 
exists. 
 
INVESTIGATIONAL PRODUCTS: BPX-701 AND RIMIDUCID 
For the most comprehensive nonclinical and clinical information regarding BPX-701 and 
rimiducid, refer to the latest version of the Investigator Brochure for each product (BPX-701 
Investigator Brochure, Rimiducid Investigator Brochure). 
3.1 
BPX-701:  PRAME TCR Immunotherapy 
BPX-701 is a PRAME-directed, genetically modified, autologous T cell product candidate that 
binds to PRAME-expressing cells.  In an HLA-A2.01-restricted manner, BPX-701 targets PRAME 
with an αβ TCR containing a traditional CD3ζ cytoplasmic signaling domain (Figure 1).  The 
PRAME TCR selected for inclusion into BPX-701 has a natural high affinity, but this has not been 
further enhanced during product development.  Further analysis of this T cell clone isolated from 
a patient with AML showed high reactivity against a panel of PRAME-positive tumor cells 
including cutaneous melanoma, sarcoma, and AML.  No reactivity to normal cell types was 
observed except for low reactivity against kidney epithelial cells and intermediate reactivity 
against mature dendritic cells, a finding that is consistent PRAME expression in normal tissues 
(Ikeda 1997). 
In addition to the PRAME TCR, BPX-701 T cell therapy is engineered to express an inducible 
caspase-9 (iCasp9) safety switch comprised of two FK binding proteins (FKBP) in-frame with 
signaling domain from caspase-9.  The rationale for the molecular design as well as the in vitro 
and in vivo characterization of this inducible safety switch are described elsewhere 
(Straathof 2005). 
Figure 1:  BPX-701 Retroviral iCasp9 Vector Construct 
iCasp9 functions as a molecular switch to induce apoptosis of T cells in the presence of the small 
molecule dimerizer rimiducid (Figure 2).  The tandem FKBP domains provide a ligand 
dimerization scaffold, which induces iCasp9 in a rimiducid-dependent manner (Straathof 2005).  
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Figure 2:  iCaspase-9 Safety Switch 
 
Several historical reports have demonstrated the clinical benefit of an adoptive cell therapy 
approach using ex vivo expanded T cells that are restricted against both an HLA antigen and a 
selected tumor peptide depending on the disease under study.  While BPX-701 employs a similar 
mechanistic approach based off HLA-A2.01 and the PRAME TCR, this is the first example of a 
PRAME-directed autologous cell product candidate that is also designed to leverage the clinical 
utility of an inducible safety switch in response to treatment-emergent, uncontrollable toxicity.  
The latter is hypothesized to be a potential differentiating factor for BPX-701 relative to other cell 
therapy alternatives (e.g., chimeric antigen receptor-T [CAR-T] cells).  Given the high frequency 
of PRAME overexpression in metastatic uveal melanoma and the current lack of any approved 
therapy, the rational design of BPX-701 suggests that it may have an opportunity to provide clinical 
benefit while also mitigating the risk of associated treatment side effects not only in this solid 
tumor disease setting but also for hematologic malignancies. 
3.1.1 
Summary of Preclinical Experience: BPX-701 
3.1.1.1 
In Vitro Studies 
In preclinical studies, PRAME-specific clones showed high reactivity against a panel of PRAME 
positive tumor cell lines, metastatic melanoma, sarcomas and neuroblastoma tissues, and no 
reactivity against normal cell types, with the exception of low reactivity against kidney epithelial 
cells and intermediate reactivity against mature dendritic cells.  
In vitro studies showed that T cells expressing the PRAME-specific BPX-701 TCR recognized a 
variety of tumor cell lines and primary AML blasts, positive for both PRAME and HLA-A2, as 
indicated by cytokine (i.e., interferon-γ) production (Amir 2011).  Additional preclinical results 
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demonstrate complete elimination of BPX-701 cells in response to rimiducid (BPX-701 
Investigator Brochure). 
3.1.1.2 
In Vivo Studies 
Although immunodeficient mouse models have historically not been helpful in predicting 
clinically relevant toxicity, such in vivo models have been utilized to demonstrate the antitumor 
activity of BPX-701 T cells as well as the functional elimination of BPX-701 T cells by rimiducid.  
Collectively, these data demonstrate that BPX-701 cells are effective against PRAME-expressing 
tumor cells and that iCasp9 effectively eliminates transduced T cells following rimiducid 
treatment.  Results of these experiments are briefly described below.   
Antitumor activity of normal human T cells modified with PRAME TCR and iCasp9  
PRAME-expressing myeloma tumors were established in immunodeficient (NOD/SCID/γcnull) 
NSG mice by tail vein injection of 2 x 106 U266-EGFP-luciferase (U266-EGFPluc) tumor cells 
per animal. On Day 24 following successful tumor engraftment, mice received either 1 x 107 
nontransduced (NT) T cells (n=5) or an equivalent dose of BPX-701 T cells (n=5) (Bellicum 
Report BEL-R&D-RP-0014).  Tumor size was evaluated weekly using an in vivo imaging system.  
Treatment with a single dose of BPX-701 T cells resulted in complete myeloma tumor elimination 
in less than two weeks after administration and controlled tumor growth for over 50 days, whereas 
injection of NT cells failed to affect tumor growth (Figure 3). Using average radiance as a surrogate 
marker of tumor burden, mice that received NT cells had ~800-fold more U266-EGFPluc cells 
than those that were treated with BPX-701; this difference in tumor burden reached statistical 
significance within 8 days (p=0.002). These data indicate that a single injection of 1 x 107 BPX-701 
T cells but not NT cells results in antitumor activity against PRAME-positive myeloma tumors in 
vivo.  
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Figure 3:  In vivo imaging of myeloma tumors following treatment with BPX-701 
 
 
In vivo persistence of T cells modified with PRAME TCR and iCasp9 
Spleen and bone marrow cells were harvested on Day 51 post-injection from mice treated with 
NT or BPX-701 T cells as described above (Bellicum Report BEL-R&D-RP-0014).  Cells were 
counted and analyzed by flow cytometry for Vβ1 expression (BPX-701 transduction marker) on 
CD4 and CD8 T cells.  Despite the lack of detectable tumor by in vivo imaging, BPX-701 T cells 
persisted in the spleen and bone marrow (Figure 4).  Approximately 600-fold more total CD8+ 
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T cells and ~130-fold more Vβ1+CD8+ T cells were observed in the spleens of mice that received 
BPX-701 T cells than those treated with NT cells.  Thus, following a single injection, BPX-701 
T cells exhibit measurable in vivo persistence >7 weeks. 
Figure 4:  BPX-701 modified T cells persist in vivo at least 7 weeks 
 
 
 
Persisting T cells modified with PRAME TCR and iCasp9 are sensitive to rimiducid 
 
To evaluate the functionality of iCasp9 in persisting BPX-701 T cells, a fraction of spleen and 
bone marrow cells from BPX-701-treated mice as described above were isolated on Day 51 
post-injection and cultured overnight with or without rimiducid (Bellicum Report BEL-R&D-RP-
0014).  Rimiducid significantly reduced the fraction of Vβ1+ T cells recovered from both spleen 
and bone marrow (p<0.05).  These data show that iCasp9 gene function is both maintained over 
time and is not affected by antitumor activity (Figure 5).   
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Figure 5: Active, persisting BPX-701 T cells remain sensitive to rimiducid after 7 weeks 
 
AP1903 = rimiducid 
 
 
iCasp9 is a functioning safety switch in BPX-701 T cells in vivo 
 
Following tail-vein injection into immunodeficient (NOD/SCID/γcnull) NSG mice, BPX-701 
T cells (1 x 107) were detected in the spleen as early as 24 hours and further increased in number 
at 48 hours post-injection (Bellicum Report BEL-R&D-RP-0015).  Therefore, the latter time point 
was chosen to assess the effect of rimiducid on BPX-701 cell viability in vivo. 
Rimiducid (5 mg/kg) was administered to NSG mice (n=8) by intraperitoneal injection following 
treatment with BPX-701 T cells while an equivalent number of mice (n=8) were untreated (i.e., 
mice received BPX-701 T cells alone).  Spleens harvested 24 hours following intraperitoneal 
injection were analyzed by flow cytometry.  Although NT cells were detected in 5 out of 8 mice 
per treatment group, the frequency of BPX-701 T cells in rimiducid-treated mice was significantly 
reduced compared to untreated mice (7.3 ± 0.2% versus 42 ± 1.1%, p<0.0001; Figure 6). 
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Figure 6:  Rimiducid-mediated elimination of BPX-701 T cells in vivo 
 
Top row: untreated mice; Bottom row: rimiducid-treated mice 
 
3.2 
Summary of Clinical Experience: BPX-701 
BPX-701 is a first-in-class, suicide-inducible T cell therapy for subjects with PRAME-expressing 
hematologic or solid tumor malignancies with high unmet medical need.  This study is the first 
experience with BPX-701 T cells in human subjects; therefore, no prior clinical data are available. 
3.3 
Rimiducid: Dimerizer Drug 
Rimiducid is a member of a new class of synthetic lipid-permeable compounds termed chemical 
inducers of dimerization or CIDs.  Rimiducid is a small molecule, high affinity ligand (~0.1 nM) 
that functions to promote cross-linking and activation of engineered proteins inside cells.  By 
chemical design, rimiducid has no known natural biologic target; ligand binding is restricted to a 
mutated signaling domain of the human protein FKBP (Rimiducid Investigator Brochure). 
3.3.1 
Summary of Clinical Experience: Rimiducid 
Refer to the Investigator Brochure for a summary of preclinical studies as well as additional 
information regarding clinical experience with rimiducid (Rimiducid Investigator Brochure).  An 
abbreviated summary of clinical results is provided below. 
Phase I Study in Healthy Volunteers 
The safety and pharmacokinetics of rimiducid were previously evaluated in a single-blind, 
placebo-controlled phase I clinical trial in 28 healthy adult volunteers (Iuliucci 2001). Eligible 
subjects received either a single dose of rimiducid, placebo, or normal saline administered by 
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intravenous infusion over 2 hours.  Ascending dose levels of rimiducid (0.01, 0.05, 0.1, 0.5, and 
1.0 mg/kg) were investigated.  
Rimiducid was shown to be safe and well tolerated at all dose levels and demonstrated a favorable 
pharmacokinetic profile (Iuliucci 2001). No drug-related adverse events were observed except for 
facial flushing at the 1.0 mg/kg dose level.  No adverse events met the protocol definition of 
dose-limiting toxicity (DLT).  Rimiducid plasma levels were directly proportional to the 
administered dose, with mean Cmax values ranging from approximately 10 to 1275 ng/mL over the 
0.01 to 1.0 mg/kg dose range. Following the infusion period, blood concentrations revealed a rapid 
distribution phase, with plasma levels being reduced to approximately 18%, 7%, and 1% of the 
maximal concentration at 0.5, 2, and 10 hours post-infusion, respectively. The mean terminal 
half-life varied somewhat with dose, ranging from 3.92 hours at 0.05 mg/kg to 12.0 hours at 
1.0 mg/kg, and was determined to likely be a function of assay sensitivity. 
Phase I and II Studies in Patients 
The safety and pharmacokinetics of rimiducid have been similarly evaluated in early clinical trials 
in pediatric and adult patients with primary immunodeficiencies (PID) or hematologic 
malignancies.  In a combined analysis from two phase 1/2 studies (NCT02065869; 
NCT03301168), 59 children with PID received an investigational T cell product containing the 
iCasp9 safety switch following a polyclonal α/β T-cell and B-cell-depleted HLA-haploidentical 
hematopoietic stem cell transplant (HSCT) as a means not only of facilitating transplant 
engraftment and preventing infections but also with the unique ability to promptly and durably 
resolve graft-versus-host disease (GvHD) symptoms (Pagliara 2018).  Nineteen patients developed 
acute GvHD; of these, 7 received at least 1 dose of rimiducid for treatment-related side effects not 
responsive to standard of care intervention or for visceral involvement.  Overall, response to 
rimiducid was >80% in evaluable PID patients.  Rimiducid induced rapid (within 7-10 days) and 
significant (>50%) decreases in the frequency of peripheral iCasp9 cells.  No adverse events 
related to rimiducid were reported.  
In a parallel phase 1/2 study (NCT02065869), 38 children with first complete remission (CR1) 
high risk and CR2 AML were treated with the same investigational T cell product containing the 
iCasp9 safety switch described previously. At the time of HSCT, eligible patients were infused 
with adjuvant polyclonal iCasp9 T cells derived from an HLA-partially matched family donor after 
negative selection of α/β T-cells.  The cumulative incidence of Grade II-IV and Grade III-IV acute 
GvHD within 100 days of HSCT was 2.6% and 0%, respectively (Kapoor 2018). Eleven patients 
developed GvHD (acute or chronic); of these, 5 received at least 1 dose of rimiducid for GvHD 
not responsive to corticosteroids.  Four out of 5 patients achieved complete resolution of GvHD 
after administration of rimiducid (80% response rate); time to complete response ranged from 7 to 
55 days.  T-cell kinetics in response to rimiducid were similar to what was observed in patients 
with PID.  No patient experienced a relapse after administration of rimiducid.  No adverse events 
related to rimiducid were reported.
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OBJECTIVES AND ENDPOINTS 
OBJECTIVES 
ENDPOINTS 
Primary 
• Phase 1 / Arm 1: To characterize the safety and 
tolerability and to identify the maximum tolerated 
dose (MTD) and/or the recommended dose for 
expansion (RDE) of BPX-701 T cells 
administered to subjects with relapsed AML or 
previously treated MDS 
• Incidence of dose-limiting toxicity, frequency and 
severity of adverse events (AEs) and serious AEs 
(SAEs), changes from baseline in safety parameters 
• Phase 1 / Arm 2: To characterize the safety and 
tolerability and to identify the MTD and/or RDE 
of BPX-701 T cells administered subjects with 
metastatic uveal melanoma 
• Incidence of dose-limiting toxicity, frequency and 
severity of treatment emergent AEs and SAEs, 
changes from baseline in safety parameters 
• Phase 2 / Arm 1: To evaluate the remission rate 
following BPX-701 T cell infusion to subjects 
with relapsed AML or previously treated MDS 
• AML: Percentage of subjects with complete remission 
(CR; including CRMRD-, CR, CRi) or partial remission 
(PR) as determined by the investigator according to 
the European LeukemiaNet (ELN) criteria for AML 
• MDS: Percentage of subjects with CR (including 
marrow CR) or PR as determined by the investigator 
according to the International Working Group (IWG) 
criteria for MDS  
• Phase 2 / Arm 2: To evaluate the antitumor 
activity of BPX-701 T cells administered to 
subjects with metastatic uveal melanoma 
• Percentage of subjects with complete response (CR) or 
partial response (PR) determined by the investigator 
according to the Response Evaluation Criteria in Solid 
Tumors (RECIST) v1.1 
Secondary 
• To characterize the pharmacodynamics (PD) of 
BPX-701 T cells 
• Expansion and persistence of peripheral BPX-701 
T  cells over time, change from baseline in serum 
cytokines 
• To assess the response to rimiducid in those 
subjects with treatment-emergent BPX-701 
toxicity 
• Time to event resolution and persistence of peripheral 
BPX-701 T cells after rimiducid administration 
• To characterize the pharmacokinetics (PK) of 
rimiducid after a single or repeat doses 
• Serum concentration-time profiles and PK parameters 
(including Cmax and AUC) 
• To evaluate the clinical efficacy of BPX-701 
T cells administered to subjects with relapsed 
AML or previously treated MDS 
• AML: Percentage of subjects with stable disease 
(SD), and morphologic leukemic-free state (MLFS); 
time to next treatment, relapse-free survival, event-
free survival, and overall survival per the ELN criteria 
for AML 
• MDS: Percentage of subjects with SD, cytogenetic 
response, and hematologic improvement;  time to next 
treatment, relapse-free survival, event-free survival, 
and overall survival per the IWG criteria for MDS  
• To evaluate the clinical efficacy of BPX-701 
T cells administered to subjects with metastatic 
uveal melanoma 
• Percentage of subjects with disease control; 
progression-free survival, time to next treatment, and 
duration of response; and, overall survival per 
RECIST v1.1 
• To assess the long-term safety of BPX-701 T cells 
• Proportion of subjects with detectable replication 
competent retrovirus in peripheral blood up to 
15 years following BPX-701 T cell infusion 
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OBJECTIVES 
ENDPOINTS 
Exploratory 
• To assess the immunogenicity of BPX-701 T cells 
• To evaluate the frequency and level of PRAME expression in AML or MDS and uveal melanoma 
• To explore the relationship between BPX-701 PD biomarkers (e.g., BPX-701 T cell persistence, phenotyping, 
functional activity, tumor infiltration) and genetic and/or protein profiles in tumor tissue/bone marrow and 
peripheral blood 
• To explore the relationship between tumor tissue/blood-based immune biomarkers (including but not limited 
to PRAME) and clinical response or resistance to BPX-701 T cells 
 
 
STUDY RATIONALE AND CLINICAL DESIGN 
5.1 
Overview of Rationale and Design 
While adoptive T cell therapies have yielded high objective response rates in blood cancers, serious 
and sometimes fatal side effects have arisen as a result of treatment.  For example, the 
commercially available CD19-directed CAR-T cell treatments KYMRIAH™ and YESCARTA™ 
both carry black box warnings associated with the risk of life-threatening cytokine release 
syndrome (CRS) and neurological toxicities (Kymriah Package Insert 2018; Yescarta Package 
Insert 2017).  Among clinical trial patients who died due to any cause after receiving these cell 
therapies in an investigational setting, the majority had ongoing CRS at time of death (Kymriah 
Package Insert 2018; Neelapu 2018).  Furthermore, the frequency of Grade ≥3 CRS and 
neurological toxicities in subjects with B-cell lymphoma treated in pivotal studies for 
KYMRIAH™ and YESCARTA™ ranged from 13-23% and 18-28%, respectively.  A strategy to 
selectively modulate donor T cell function in vivo could potentially overcome these potential 
limitations thereby significantly improving the safety profile.   
Preclinical data illustrate both the in vivo antitumor activity of BPX-701 against PRAME 
expressing-myeloma cells as well as the functionality of the iCasp9 safety switch in response to 
the dimerizer rimiducid.  The latter rapidly eliminated PRAME-TCR-specific T cells in vivo within 
24 hours and therefore may serve as a mechanism to help alleviate the risk of BPX-701-related 
side effects.  Prior clinical evaluation of rimiducid in healthy volunteers (Iuliucci 2001) as well as 
in transplantation studies for mitigation of GvHD showed this dimerizer to be safe and effective 
and supports its use in combination with BPX-701 T cells (Kapoor 2018; Pagliara 2018), as 
needed, for the treatment of relapsed AML or previously treated MDS, as well as advanced uveal 
melanoma.   
The goal of this study is to characterize the safety, feasibility, and clinical activity of BPX-701, a 
genetically modified autologous T cell product incorporating an HLA-A2.01-restricted 
PRAME-directed TCR and an inducible iCasp9 safety switch, when administered to subjects with 
relapsed AML (Arm 1), previously treated MDS (Arm 1), or metastatic uveal melanoma (Arm 2).  
Arms 1 and 2 are intended to be conducted in parallel; however, the overall assessment of BPX-701 
safety, feasibility, and clinical activity observed in Arm 1 will be evaluated independently from 
Arm 2.  For each Arm, the study will be comprised of multiple parts: 
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• Part 1 (Phase 1): Cell dose escalation to identify the maximum dose of BPX-701 T cells 
(escalating doses from 1.25 x 106 cells/kg up to 5.0 x 106 cells/kg to be explored)  
• Parts 2 and 3 (Phase 2): Dose expansion to assess the safety, pharmacodynamics 
(including BPX-701 T cell persistence and response to rimiducid as applicable), and 
clinical activity at the recommended dose identified in Part 1 
• During Parts 1, 2, or 3, rimiducid (1 or more doses at 0.4 mg/kg) may be administered 
following BPX-701 T cell infusion in response to treatment-emergent toxicity (i.e., both 
on-target/off-tumor as well as on-target/on-tumor side effects) 
A diagram of the study design is provided in Figure 7.  Study eligibility will be determined based 
on sequenced Prescreening/Screening assessments.  Accrual of eligible subjects will begin in 
Part 1.  Dose escalation decisions for each Arm will be made independently.  Therefore, more than 
one RDE may be defined (i.e., RDE-1 for Arm 1 and RDE-2 for Arm 2).  Once an RDE is 
determined in Part 1, enrollment in Part 2 will be initiated.  Part 3 will commence provided 
sufficient clinical activity is observed in Part 2.  Alternately, if treatment-emergent BPX-701 
toxicity is not responsive to rimiducid, there is an unfavorable change to risk/benefit, 
pharmacodynamic responses are deemed insufficient, or BPX-701 clinical activity is considered 
inadequate, Parts 2 and 3 (i.e., Arm 1, Arm 2, or both) may not be initiated and/or the study may 
be prematurely terminated prior to completing the planned enrollment. 
Figure 7:  Study Design Schematic 
 
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5.2 
BPX-701 T Cell Starting Dose Rationale 
For Arm 1 and Arm 2, the recommended initial starting dose for BPX-701 T cells is 
1.25 x 106 cells/kg.  This starting dose was chosen based on preclinical studies and for consistency 
with other experimental TCR immunotherapies directed against alternate antigens expressed by 
solid tumors and/or hematologic malignancies.  While some of these trials reported safe infusion 
of cell doses as high as 1 x 1010 (Rapoport 2015), others have observed dose-limiting toxicity at 
2 x 108 cells (Parkhurst 2011) as well as patient fatalities upon infusion of larger cell numbers (i.e., 
>1 x 109) (Linette 2013; Morgan 2013; van den Berg 2015).  Although no acute toxicities following 
BPX-701 infusion were observed in preclinical animal studies at a dose of 1 x 107 T cells, a lower 
dose was selected for initial safety evaluation in humans and allows for escalation to higher cell 
dose levels provided a favorable safety profile is maintained.  In addition, and unique from 
previously evaluated TCR immunotherapies, BPX-701 contains an inducible safety switch that 
provides for rapid elimination of T cells in the event of treatment-emergent toxicity. 
5.2.1 
Rimiducid 
Rimiducid will be administered at a fixed dose of 0.4 mg/kg in this study.  Prior clinical experience 
with IV administration of doses up to 1.0 mg/kg with no evidence of clinical intolerability is 
described elsewhere (Iuliucci 2001) and provides rationale this recommended dose in accordance 
with the Investigator Brochure (Rimiducid Investigator Brochure). 
5.3 
Dose-Limiting Toxicity 
Toxicities will be graded for severity according to the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE).  The evaluation period for defining DLT 
and informing dose escalation decisions is from the start of the BPX-701 infusion on Day 0 through 
Day 28.  However, toxicities that occur outside of this window may be considered in decisions 
regarding the RDE.   
Dose-limiting toxicity is defined as any of the following unless clearly due to disease progression 
or extraneous causes: 
• Any treatment-emergent CTCAE Grade 4 or 5 CRS 
• Any treatment-emergent CTCAE Grade 3 CRS that does not resolve to Grade ≤2 within 
7 days 
• Any treatment-emergent autoimmune toxicity Grade ≥3 
• CTCAE Grade ≥3 infusion reaction 
• Any other treatment-emergent CTCAE Grade ≥3 organ toxicity (cardiac, dermatologic, 
gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing 
or due to the underlying malignancy that does not resolve to Grade ≤2 within 7 days 
(except treatment-emergent CTCAE Grade ≥3 hematologic toxicity observed in subjects 
with AML/MDS) 
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Events that meet the definition of DLT are considered adverse events of special interest for this 
study.  Refer to Section 9.8 for reporting procedures. 
5.4 
Clinical Design 
5.4.1 
Part 1 (Phase 1): Cell Dose Escalation 
Part 1 is a Cell Dose Escalation phase designed to determine the appropriate BPX-701 T cell dose 
for expansion using a 3+3 dose escalation design.  Enrollment in sequential dose escalation cohorts 
will proceed as described in Table 1.   
For each of Arms 1 (AML and MDS) and 2 (uveal melanoma), Cohort 3 (1.25 x 106 cells/kg) is 
the initial starting cohort for cell dose escalation decisions in Part 1.  Cohorts of at least 3 and up 
to 6 evaluable subjects will be treated with escalating doses of BPX-701 T cells on Day 0 until the 
MTD or RDE is achieved.  Planned doses of BPX-701 T cells are detailed in Table 2.  The 
initial 3 subjects in each of Arms 1 and 2 (Cohort 3) will be enrolled sequentially, with the second 
and third subjects enrolled no sooner than 1 month (28 days) after the prior subject has been infused 
with BPX-701.  The first patient of the next cohort will be infused no sooner than 1 month 
(28 days) after the last patient in Cohort 3 has been infused. All subsequent patients will be enrolled 
in the usual manner for a 3+3 design. 
Subjects will be considered evaluable for dose escalation assessment if the scheduled dose of 
BPX-701 T cells was administered, the subject received a sufficient number of BPX-701 T cells 
to satisfy dose level requirements, and the DLT evaluation period (Day 0 through Day 28) was 
completed, or the subject experienced a DLT-defining event (Section 5.3).  If the subject was 
infused with an inadequate number of BPX-701 T cells or could not complete scheduled 
evaluations (due to reasons other than toxicity) in the DLT evaluation period (e.g., disease 
progression, missed visits, non-compliance, subject withdrawal), the subject will be considered 
non-evaluable for DLT and will be replaced with a new subject.  Evaluation of a cell dose level 
with at least 3 subjects completing the DLT evaluation period is required prior to determining the 
BPX-701 T cell dose for the next cohort.  Dose escalation decisions for each Arm will be made 
independently.  Therefore, more than one RDE may be defined (i.e., RDE-1 for Arm 1 and RDE-2 
for Arm 2).   
As of the date of this protocol amendment, Cohort 1 (Arm 1) is ongoing.  Two subjects have been 
enrolled and received the BPX-701 infusion as planned (Table 2).  No DLTs, SAEs, or 
treatment-related AEs have been reported.  Neither subject has experienced a treatment-emergent 
adverse event necessitating rimiducid infusion.  The inclusion of Arm 2 in the study design will 
proceed with approval of this amendment.  Initiation of Arm 2 accrual expected thereafter; 
sequenced enrollment of an initial 3 uveal melanoma subjects into Cohort 1 (1.25 x 106 cells/kg) 
will be as described above. 
  
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Table 1:  Dose Escalation/De-Escalation Enrollment Algorithm 
Cohorta, b 
If 0/3 subjects have 
DLTc 
If 1/3 subjects 
have DLT 
<1/6 subjects have 
DLT 
>2 subjects have  
DLT 
1 
Expand to 6  
evaluable subjects 
Expand to 6  
evaluable subjects 
Declare RDE or 
expand by ≤6 subjects 
to confirm RDE 
MTD exceeded;  
consider stopping rules 
(Section 5.6.2) 
2 
Expand to 6  
evaluable subjects 
Expand to 6 
 evaluable subjects 
Declare RDE or 
expand by ≤6 subjects 
to confirm RDE 
MTD exceeded;  
de-escalate to Cohort 1 
3d 
Escalate to  
Cohort 4 
Expand to 6 
 evaluable subjects 
Escalate to Cohort 4 
MTD exceeded;  
de-escalate to Cohort 2 
4 
Escalate to  
Cohort 5 
Expand to 6 
 evaluable subjects 
Escalate to Cohort 5 
MTD exceeded;  
no further enrollment at 
dose level 
5 
Expand to 6  
evaluable subjects 
Expand to 6  
evaluable subjects 
Declare RDE or 
expand by ≤6 subjects 
to confirm RDE 
MTD exceeded;  
no further enrollment at 
dose level 
DLT = dose limiting toxicity; MTD = maximum tolerated dose; RDE = recommended dose for expansion 
a. Applicable to Arm 1 and Arm 2.  Dose escalation decisions for each Arm will be made independently. 
b. Refer to Table 2 for planned BPX-701 T cell dose levels assigned to each Cohort. 
c. DLT evaluation period is Day 0 (BPX-701 T cell infusion) through Day 28. 
d. Initial cohort for BPX-701 T cell dose escalations.  For the first 3 subjects enrolled in Cohort 3, BPX-701 
T cell infusions must be staggered by ≥28 days. 
 
Table 2:  Planned BPX-701 T Cell Dose Levels 
Cohort 
BPX-701 (PRAME TCR+) T cells 
1 
0.3 x 106 (±20%) cells/kg 
2 
0.625 x 106 (±20%) cells/kg 
3 (Starting Dose) 
1.25 x 106 (±20%) cells/kg 
4 
2.5 x 106 (±20%) cells/kg 
5 
5 x 106 (±20%) cells/kg 
 
Maximum Tolerated Dose (MTD) is defined as the highest BPX-701 T cell dose level at which 
≤33% subjects experience a DLT during the DLT evaluation period. 
Maximum Administered Dose (MAD) is defined as the highest BPX-701 T cell dose 
administered in the event an MTD cannot be defined. 
Recommended Dose for Expansion (RDE) is either identical to the MTD or MAD or a lower 
dose level of BPX-701 T cells selected on the basis of cumulative review of all available 
treatment-emergent data observed in Part 1 for Arms 1 and 2 independently.  RDE will be 
represented by the dose of BPX-701 T cells administered that provides adequate BPX-701 T cell 
persistence and biological activity while not exceeding the MTD or MAD. 
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Additional subjects (up to 3) may be enrolled to a completed dose level that has previously been 
declared safe to better characterize safety and pharmacodynamic relationships.  Intermediate dose 
levels between a non-tolerated dose level and a previous dose level determined to be safe may also 
be explored. 
The total number of subjects enrolled in Part 1 will depend on the frequency of DLT and when 
RDE is determined for each Arm; however, it is estimated that approximately 12 to 18 subjects 
per Arm will be treated. Dose escalation in each Arm will proceed until the MTD is determined, 
or in the absence of an MTD, escalation will stop at the MAD (5.0 x 106 cells/kg). 
5.4.2 
Parts 2 and 3 (Phase 2): Dose Expansion 
Parts 2 and 3 comprise a dose expansion phase designed to further safety, pharmacodynamics 
(including BPX-701 T cell persistence and response to rimiducid as applicable), and clinical 
activity of BPX-701 T cells administered at the RDE.  Part 2 will begin once an RDE is determined 
in Part 1 (i.e., RDE-1 triggers Part 2 for Arm 1; RDE-2 triggers Part 2 for Arm 2).  The opening 
of Part 3 is dependent upon antitumor activity observed in Part 2.  Within each Arm, subjects will 
be monitored for clinical activity to enable early stopping for futility if sufficient antitumor activity 
is not demonstrated.  For each Arm, the maximum planned enrollment in dose expansion is 
40 subjects (Parts 2 and 3 combined). 
• Arm 1: Up to 10 eligible subjects with relapsed AML and/or previously treated MDS will 
initially be enrolled (Part 2).  If ≥2 subjects achieve complete or partial remission per ELN 
criteria or IWG criteria for AML and/or MDS, respectively, Part 3 may be opened to enroll 
up to an additional 30 subjects (Section 10.1). 
• Arm 2: Up to 10 eligible subjects with metastatic uveal melanoma will initially be enrolled 
(Part 2).  If one of the following are observed in Part 2, then Part 3 may be opened to enroll 
up to an additional 30 subjects (Section 10.1): 
o ≥1 complete or partial response as defined by RECIST v1.1; or, 
o ≥4 months median time to next treatment defined as the time from BPX-701 T cell 
infusion to initiation of next systemic therapy for the disease under study 
5.5 
Safety Review Committee 
Subject safety will be monitored throughout all parts of the study by a Safety Review Committee 
(SRC) established by the sponsor, and will include representatives from Clinical Science, Safety 
Science/Pharmacovigilance, and Biostatistics.  The SRC will meet at a regular frequency 
throughout execution of the clinical study to review all necessary cumulative data.  In addition to 
safety and clinical assessments, a review of the incidence, nature, and severity of adverse events, 
serious adverse events, deaths, and laboratory abnormalities will be performed by the principal 
investigators and the study medical monitor.  At each SRC review, appropriate recommendations 
will be made to the study team (e.g., continuation of the study as planned, study pause to 
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enrollment pending new safety evaluations, study discontinuation, specific indication or treatment 
arm/part closure, protocol modification/amendment).  Decisions by the SRC will be made based 
on the totality of the available data.  Ad-hoc SRC meetings may be called in addition to regularly 
scheduled meetings, as necessary, to provide recommendations on management of new or 
emerging safety concerns.  Specific operational details of the SRC composition, frequency/timing 
of meetings, and member roles and responsibilities are detailed in the SRC charter. 
5.6 
Study Duration 
Subjects will undergo routine safety monitoring and disease evaluations according to the schedule 
of assessments (Appendix 1) until disease progression is confirmed.  At the time of confirmed 
progression or 12 months after the BPX-701 infusion, whichever comes first, subjects will 
complete an end of treatment (EOT) safety assessment.  Thereafter, subjects will continue to be 
followed for long-term safety and vital status monitoring at least once annually for 15 years after 
the BPX-701 T cell infusion, death, the subject is lost to follow up, or consent is withdrawn, 
whichever occurs first. 
5.6.1 
End of Study 
The end of the study is defined as the date when all subjects have completed the final 
protocol-specified safety assessment and/or discontinued study participation (withdrawal of 
consent or lost to follow-up), whichever occurs first. 
The sponsor may terminate the study at any time for any reason. Should the study be terminated, 
subjects will be required to complete protocol-defined safety follow-up procedures. 
5.6.2 
Stopping Rules 
The sponsor has the right to terminate the study at any time.  Reasons for study termination may 
include but are not limited to incidence or severity of adverse events in this or other related studies 
which may indicate a potential hazard to subjects or unsatisfactory subject enrollment.  The 
sponsor will notify the investigator if the sponsor decides to terminate the study. 
Subjects will be monitored throughout the study for treatment emergent safety, DLTs and 
unacceptable toxicities (Section 5.3) by the SRC.  The following safety stopping rules will be 
applied to mitigate potential risk to subjects: 
• Grade 5 toxicity (death) due to any cause other than assessed as progressive disease by the 
investigator in ≥20% of all treated subjects (as defined in Section 10.2) within 28 days after 
the BPX-701 T cell infusion (i.e., Day 0 through Day 28) 
• Grade ≥3 CRS, neurotoxicity, autoimmune, or other specific organ toxicity in ≥20% of all 
treated subjects (as defined in Section 10.2) unless clearly related to an alternative cause 
other than study treatment 
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5.7 
Subject Enrollment, Registration, and Assignment to Treatment 
 
Informed consent will be obtained from each subject after the nature of the study is explained and 
prior to the performance of any study-specific procedures.  This study will utilize more than one 
informed consent form (ICF): 
• Prescreening ICF: applies only to study assessments during the Prescreening period 
(Section 8 and Appendix 1).  Consent for Prescreening assessments should be obtained 
from all potential subjects. 
• Screening/Study Treatment ICF: applies to study assessments during the Screening, 
Treatment, and Posttreatment Follow Up periods (Section 8 and Appendix 1).  The 
Screening/Study Treatment ICF is applicable only for subjects who satisfy all Prescreening 
requirements. 
After signing the Screening/Study Treatment ICF, an eligibility determination based on the study 
inclusion/exclusion criteria (Section 6) will be conducted for each subject at a Screening Visit 
(Appendix 1).  The investigator or designee shall complete a Subject Registration Form for eligible 
subjects and submit to the sponsor.  The sponsor will provide the site with the planned treatment 
assignment (i.e., Arm, study Part, planned BPX-701 T cell dose level) and identification number 
for the subject.  Subjects with assigned treatment will undergo apheresis according to the Schedule 
of Assessments (Appendix 1) and subsequently return to the site for a baseline evaluation and 
lymphodepletion within 1 week of the planned BPX-701 T cell infusion. 
For this study, subjects who receive the BPX-701 T cell infusion are considered to be enrolled.  
Subjects that sign the Screening/Study Treatment ICF but do not receive BPX-701 T cells for any 
reason are considered to be screen failures.  Furthermore, subjects that are determined to be 
PRAME-negative or have a positive result per infectious disease monitoring (Section 8.2.8 and 
Appendix 1) during the Prescreening period are also considered to be screen failures. 
5.8 
Subject Evaluability and Replacement  
The criteria for subject evaluability and replacement for Part 1 is described in Section 5.4.1. 
In Parts 2 and 3, subjects may be replaced when one of the following occurs: 
• The subject is infused with a sub-optimal or an inadequate number of BPX-701 T cells that 
does not satisfy the RDE for the disease under study. 
• The subject discontinues prior to the first planned on-study disease evaluation for reasons 
other than disease progression. 
Any subject that meets the above replacement criteria must still be followed for 
treatment-emergent safety (Section 9.6) as well as long-term gene therapy monitoring 
(Section 8.4.6). 
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5.9 
Study Completion 
A subject will be considered to have completed the study if he or she has completed assessments 
up to and including the last protocol-specified visit or has experienced a clinical endpoint that 
precludes further continuation in the study (e.g., death). 
5.10 
Study Discontinuation/Withdrawal 
Subjects are free to discontinue participation or withdraw consent from the study at any time, for 
any reason, and without prejudice to further treatment.  Subjects who discontinue/withdraw from 
the study will receive treatment as deemed appropriate by the investigator and local standards of 
care.  A subject will be withdrawn for the study for any of the following reasons: 
• Lost to follow-up defined as documented, repeated failure after at least 3 attempts to 
contact the subject 
• Withdrawal of consent 
• Study termination by the sponsor or regulatory authority 
When a subject is withdrawn prior to completing the study, the investigator will provide a reason 
for withdrawal. 
A subject's participation in the study also may be discontinued at any time at the discretion of the 
investigator.  The following may be justifiable reasons for the investigator to remove a subject 
from the study: 
• The subject was erroneously included in the study 
• The subject receives other investigational product(s) during the study 
• The subject experiences an adverse event that is considered intolerable by the subject or 
the investigator 
Data from discontinued/withdrawn subjects will be collected, stored and, whenever indicated, 
analyzed.  These subjects will continue to be monitored for long-term safety (Section 8.4.6 and 
Section 9.6) and efficacy outcomes (Section 8.5 and Section 8.6) provided that the subject has not 
withdrawn consent for further follow-up. 
 
SUBJECT ELIGIBILITY 
Subject eligibility will be evaluated during the Prescreening and Screening periods of the study 
(Appendix 1).  To undergo lymphodepletion and subsequent BPX-701 T cell infusion, subjects 
must satisfy inclusion/exclusion requirements at the Baseline visit (Appendix 1). 
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No waivers for study participation will be issued by the sponsor; subjects must meet all eligibility 
criteria as defined below. 
6.1 
Inclusion Criteria 
1. 
Each subject (or their legally acceptable representative) must sign and date an informed 
consent form approved by the institutional review board/ethics committee, as 
appropriate, indicating that he/she understands the purpose of and procedures required 
for the study and are willing to comply.  Consent is to be obtained prior to the 
performance of any study-specific procedures or tests that are not part of the standard 
of care for the subject’s disease. 
2. 
Arm 1:  
• MDS not responding to hypomethylation therapy or recurrence after initial 
response; or,  
• AML with disease relapse following first complete remission with intermediate 
or adverse genetics according to the ELN criteria (Dohner 2017) 
– Subjects with a prior treatment history of stem cell transplant must be 
>100 days post-transplant with no evidence of active GvHD and not 
requiring systemic immunomodulatory or immunosuppressive therapy 
defined as >10mg prednisone or equivalent per day and active use of a 
calcineurin inhibitor 
Arm 2: 
• Histologically or cytologically confirmed diagnosis of metastatic uveal 
melanoma 
• Measurable disease (at least one target lesion) per RECIST v1.1 
(Eisenhauer 2009) 
• Adequate bone marrow function defined as: 
– Absolute neutrophil count ≥1,000/µL 
– Platelets ≥75,000/µL 
3. 
HLA-A2.01 positive by local assessment 
4. 
Documented positive myeloid blast or tumor expression of PRAME as determined by 
central testing of an available, representative bone marrow aspirate (fresh sample) or 
tissue specimen (formalin-fixed paraffin-embedded tissue, either from an archived 
sample or fresh biopsy) for Arm 1 and Arm 2, respectively 
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5.  
Absolute lymphocyte count ≥200/µL  
6. 
Age ≥18 years 
7. 
Life expectancy >12 weeks  
8. 
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix 4) 
9. 
Subjects must have adequate venous access for apheresis or agree to use of a central 
line for apheresis collection 
10. 
Subject has adequate organ function: 
Cardiac: Left ventricular ejection fraction at rest must be ≥lower limit of institutional 
normal 
Coagulation: International normalized ratio ≤1.5 
Hepatic: 
• Direct bilirubin ≤2x upper limit of normal (ULN), or ≤3x if due to Gilbert’s 
disease 
• Aspartate aminotransferase and alanine aminotransferase ≤3 x ULN, or 
≤5 x ULN if liver metastases are present 
Renal: Creatinine ≤1.5 x ULN 
11. 
Before planned BPX-701 T cell infusion, as well as during the study, a female subject 
must be either: 
• Not of childbearing potential defined as:  
(1) Premenarchal,  
(2) Postmenopausal (>45 years of age with amenorrhea ≥12 months),  
(3) Permanently sterilized,  
(4) Otherwise incapable of pregnancy; or, 
• Of childbearing potential and agrees to use 2 highly effective methods of birth 
control for at least 12 months after lymphodepletion 
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6.2 
Exclusion Criteria 
Subjects who meet any of the following criteria are NOT eligible for the study.  Waivers are NOT 
permitted. 
1. 
Arm 1: 
• Diagnosis of Acute Promyelocytic Leukemia  
• Primary refractory AML 
• Uncontrolled disseminated intravascular coagulation 
• Symptomatic or untreated central nervous system involvement by malignant cells 
• Peripheral blast count ≥20,000/µL 
2. 
Arm 2: 
• Symptomatic, untreated or actively progressing central nervous system 
metastases.  Subjects with prior brain metastases treated at least 2 weeks prior 
to the planned BPX-701 T cell infusion who are clinically stable and do not 
require chronic corticosteroid treatment are allowed 
• History of leptomeningeal disease 
3. 
Ongoing toxicities related to prior anticancer therapy that have not resolved to Grade ≤1.  
Current unresolved Grade ≥2 non-hematologic toxicity may be allowed following 
discussion with and approval by the sponsor 
4. 
Participation in any investigational drug study within 4 weeks prior to the planned 
BPX-701 T cell infusion 
5. 
Chemotherapy (excluding hydroxyurea), targeted therapy, or radiotherapy (excluding 
palliative radiation) within 2 weeks, hydroxyurea within 1 week, or immunotherapy 
within 4 weeks prior to BPX-701 T cell infusion, other than salvage/lymphodepletion 
chemotherapy (Section 7.3 and Section 7.8) 
6. 
Active autoimmune disease requiring immunosuppressive therapy.  Subjects with 
vitiligo; type I diabetes; hypothyroidism, adrenal insufficiency, or hypophysitis only 
requiring hormone replacement; psoriasis not requiring systemic treatment or 
conditions not expected to recur; or history of Hashimoto’s Thyroiditis on stable dose 
of thyroid hormone replacement therapy should not be excluded 
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7. 
Impaired cardiac function or clinically significant cardiac disease, including any of the 
following: 
• Symptomatic congestive heart failure requiring treatment; 
• Clinically significant cardiac arrhythmia; 
• Uncontrolled hypertension; 
• Acute myocardial infarction or unstable angina pectoris within 3 months prior 
to BPX-701 T cell infusion; or, 
• Marked limitation of physical activity due to symptoms, or unable to carry on 
any physical activity without discomfort (i.e., New York Heart Association 
Functional Class III-IV; Appendix 5) 
8. 
Major surgical procedure, other than for diagnosis, within 4 weeks prior to BPX-701 
T cell infusion, or anticipation of the need for a major surgical procedure during the 
study 
9. 
Received a vaccine containing live virus within 4 weeks prior to the planned BPX-701 
T cell infusion. Seasonal flu vaccines that do not contain live virus are permitted 
10. 
Treatment with systemic chronic steroid therapy (prednisone >10mg daily or 
equivalent) within 7 days or 7 half-lives, whichever is shorter, prior to the planned 
apheresis date (See Appendix 6 on half-lives of common corticosteroids).  Local 
steroid therapies (e.g., otic, ophthalmic, intra-articular or inhaled medications) are 
acceptable  
11. 
Uncontrolled intercurrent illness including but not limited to poorly controlled 
hypertension or diabetes, or any medical condition determined by the investigator to be 
a risk for enrolling on the protocol 
12. 
Uncontrolled infection requiring systemic therapy.  Prior oral or IV antibiotics 
antifungals or antiviral medications must be discontinued at least 2 weeks prior to 
BPX-701 T cell infusion except for use of prophylactic antimicrobial agents 
13. 
Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a 
positive hepatitis B surface antigen (HBsAg) test during Screening.  Subjects with a 
past or resolved HBV infection, defined as having a negative HBsAg test and a positive 
total hepatitis B core antibody (HBcAb) test at screening are eligible for the study if 
HBV DNA test is negative.  If a patient has a negative HBsAg test and a positive total 
HBcAb test at screening, an HBV DNA test should be performed 
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14. 
Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody 
test followed by a positive HCV RNA test during Screening.   The HCV RNA test will 
be performed only for patients who have a positive HCV test 
15. 
History of human immunodeficiency virus (HIV), or positive HIV test during 
Screening (unless not permitted by local regulations) 
16. 
Subject is a woman of child-bearing potential is pregnant (positive serum β-human 
chorionic gonadotropin test at Baseline), planning to become pregnant within 
12 months after lymphodepletion or is breastfeeding 
17. 
Subject is a man who plans to father a child within 12 months after lymphodepletion 
18. 
Known bovine product allergy 
19. 
Malignant disease other than that being treated in this study.  Exceptions to this 
exclusion are: 
• Malignancies that were treated curatively and have not recurred within 2 years 
prior to Screening 
• Completely resected basal cell and squamous cell skin cancers 
• Any malignancy considered to be indolent and that has never required therapy 
 
STUDY TREATMENTS AND ADDITIONAL MEDICATIONS 
7.1 
Investigational Products 
Refer to the Pharmacy Manual for details on the storage, preparation, and administration of 
BPX-701 T cells and rimiducid. 
7.1.1 
BPX-701 T Cells 
BPX-701 is a genetically modified, autologous T cell product that incorporates a high affinity, 
HLA-A2.01-restricted PRAME-directed TCR and an inducible iCasp9 safety switch. 
Manufacturing Process Description: BPX-701 is prepared from a patient’s peripheral blood 
mononuclear cells (PBMCs), which are obtained via a standard apheresis procedure (Section 7.2). 
PBMCs are enriched for T cells which are then washed and expanded in cell culture. Once a target 
number of cells are available, the expanded T cells are transduced with a replication incompetent 
retroviral vector containing the PRAME TCR and rimiducid-inducible iCasp9 safety switch. The 
transduced T cells are formulated into a suspension, and cryopreserved. The final BPX-701 
product must pass release testing, including a sterility test, before shipping as a frozen suspension 
in a patient-specific infusion bag(s).  The estimated time from BPX-701 manufacture to release is 
approximately 2 to 4 weeks. 
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Packaging and Formulation: BPX-701 T cells are cryopreserved in 10-15 mL freezing medium 
(CryoStor, BioLife) and are stored frozen in cryostorage bags in the vapor phase of liquid nitrogen. 
Labeling: The product label and insert for BPX-701 T cells contain the following information: lot 
number (which includes the subject ID number), BPX-701 T cell dose level, date of manufacture, 
storage conditions, sponsor, and product name.  All products manufactured are also labeled with: 
“For Autologous Use Only” and “Caution: Limited by Federal Law to Investigational Use”.  The 
product will be labeled according to the requirement of each competent authority. 
Shipping and Storage: Cryopreserved BPX-701 T cells will be shipped in the vapor phase of 
liquid nitrogen to clinical sites in a validated shipping container.  BPX-701 T cells must be stored 
frozen in the vapor phase of liquid nitrogen (less than or equal to minus 150ºC) until the time of 
infusion. 
7.1.2 
Rimiducid for Injection 
Rimiducid for Injection is a lipid-permeable analog of tacrolimus that functions as a dimerizing 
agent to induce clustering of engineered proteins containing the cognate dimerizer-binding 
domain.  
Packaging and Formulation: Rimiducid for Injection is packaged in a 3 mL Type 1 clear glass 
serum vial. The contents of each vial are composed of the labeled content (10 mg in 2 mL) of 
rimiducid drug substance dissolved in a sterile, endotoxin free, 25% Solutol HS 15/Water for 
Injection solution at a rimiducid concentration of 5 mg/mL and at pH 5.0-7.5. Each vial is 
stoppered with a Teflon© coated serum stopper and a flip-off seal. 
Labeling: The primary product label (applied directly to the vial) for the Rimiducid for Injection 
will contain the following information: product name, AP1903 (Rimiducid) Concentrate for 
Injection; the manufacturer’s lot number; product concentration, 5 mg/mL; volume of solution 
available in the vial, 2 mL; total Rimiducid contents of the vial (10 mg); a statement, “For IV 
Infusion after Dilution” and the IND notation, “Caution: New Drug-Limited by Federal Law to 
Investigational Use”.  The product will be labeled according to the requirement of each competent 
authority. 
Storage: Rimiducid for Injection vials must be stored at 5°C ± 3°C (41°F ± 5°F) in a limited 
access, qualified refrigerator, preferably without light. 
 
7.2 
Apheresis 
After signing the Screening/Study Treatment ICF, subjects will undergo PBMC collection 
according to local institutional standards.  To help mitigate the risk of insufficient sample 
collection due to treatment-related myelosuppression, the scheduled apheresis date should be at 
least 14 days or 5 half-lives, whichever is shorter, after the last dose of any prior or ongoing 
anticancer therapy. Prior to apheresis, hematologic parameters will be measured and recorded.  
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Results must demonstrate that the subject has adequate bone marrow function as follows.  Use of 
transfusion and growth factor support is permitted in order to meet these criteria:   
• Hemoglobin ≥8 g/dL 
• Hematocrit ≥24% 
• Platelets ≥20/µL 
• Absolute lymphocyte count ≥200/µL 
Using standardized continuous flow centrifugation, collect and process up to approximately 
12-15 liters (goal range of 5 to 10 x 106 mononuclear cells) per institutional standard procedures.  
Record the volume processed and the duration of apheresis.  A second day of collection is 
permitted.  If the collection goal is not met after 2 collection days, the sponsor must be consulted 
immediately.  During and after the apheresis procedure, subjects should undergo infectious disease 
monitoring per established regulatory guidelines.  Evaluation prior to apheresis, venous access, 
monitoring and treatment of apheresis complications will be conducted according to institutional 
guidelines and must comply with federal, state, and the Foundation for the Accreditation of Cell 
Therapy regulations. 
7.3 
Lymphodepletion Prior to BPX-701 T Cell Infusion 
Confirm availability of BPX-701 T cells prior to initiating the lymphodepletion regimen at the 
study site. 
Refer to the Schedule of Assessments (Appendix 1) for safety assessments to be completed and 
recorded prior to initiation of lymphodepletion.  Results must demonstrate that the subject meets 
institutional standards for lymphodepletion; conditioning chemotherapy should be withheld until 
resolution of clinically significant symptoms.  If lymphodepletion is delayed in order to allow 
symptom management and recovery, the sponsor should be notified as soon as possible. 
Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m2 
intravenously and fludarabine 30 mg/m2 intravenously on the fifth, fourth, and third day before 
infusion of BPX-701 T cells. 
If the combination of cyclophosphamide and fludarabine is not tolerated, or if the investigator 
determines that combination-based lymphodepletion presents an unfavorable safety risk to a 
subject, then lymphodepletion should proceed with cyclophosphamide alone as per the 
aforementioned regimen following discussion with the sponsor. 
7.4 
 BPX-701 T Cell Infusion 
BPX-701 T cells are for autologous use only. 
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The Subject ID number must match the subject identifiers on the BPX-701 T cell infusion 
bag(s).  Do not infuse BPX-701 T cells if the information on the subject-specific label does not 
match the intended patient. 
BPX-701 T cells should be thawed and diluted as instructed in the Pharmacy Manual.  BPX-701 
T cells should be administered by IV infusion over 15-30 minutes using either central or peripheral 
venous access devices.  The start and stop time of the infusion will be recorded. 
BPX-701 T cells must be administered in an inpatient setting.  Prior to administering BPX-701 
T cells, subjects should receive premedication with acetaminophen and diphenhydramine per 
institutional standards for T cell products.  Subjects will be observed for at least 4 hours after 
infusion and discharged once considered clinically stable.  The expected inpatient stay is 1 night 
(i.e., admission on Day 0 with discharge on Day 1) unless unexpected toxicity occurs.   
7.5 
Rimiducid Infusion 
Rimiducid drug substance is dissolved in a Solutol HS15 and therefore has the potential to induce 
an infusion or hypersensitivity reaction.  To minimize or mitigate infusion-related toxicity, 
subjects should receive premedication with acetaminophen, diphenhydramine, ranitidine, and 
other supportive care therapy per institutional standards for potential anaphylaxis. 
Rimiducid should be diluted with normal saline as described in the Pharmacy Manual.  All subjects 
will receive IV rimiducid at a fixed dose of 0.4 mg/kg.  Prior to administration, rimiducid should 
be diluted in normal saline to a volume that supports infusion over 2 hours.  Rimiducid may be 
administered using either central or peripheral venous access devices.  The start and stop time for 
the infusion will be recorded. 
Rimiducid must be administered in an inpatient setting.  Subjects will be observed for at least 
4 hours after infusion and discharged once considered clinically stable.  The minimum expected 
inpatient stay is 1 night, but the length of admission will depend on response to rimiducid and time 
to symptom resolution. 
Rimiducid will be used in this study to mitigate uncontrolled toxicity induced by BPX-701. 
Therefore, rimiducid administration is limited to qualifying subjects who experience specific, 
treatment-related side effects in response to BPX-701 therapy.  Refer to Section 7.6 for detailed 
criteria and guidelines for rimiducid infusion.  Because rimiducid is designed to activate the iCasp9 
safety switch, thereby initiating downstream signaling events to induce BPX-701 T cell apoptosis, 
it is expected that any potential for further TCR-dependent anti-tumor activity will be 
significantly reduced or eliminated following rimiducid infusion.  Refer to Appendix 3 for the 
frequency and timing of pre- and post-infusion for research blood samples that must be collected 
from subjects who receive rimiducid.    
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7.6 
 Toxicity Management and Supportive Care Guidelines 
All the guidelines within this section are general recommendations and investigators may use local 
institutional guidelines and clinical judgments in the management of toxicities and dose 
modifications. 
7.6.1 
Infusion Reactions / Hypersensitivity 
BPX-701 is an autologous, fully humanized TCR therapy and is therefore less likely to be 
immunogenic and induce a hypersensitivity reaction.  However, mild to severe infusion-related 
reactions have been previously reported with rimiducid (Rimiducid Investigator Brochure).   
To minimize or mitigate infusion-related toxicity associated with BPX-701 and rimiducid, all 
subjects should receive premedication as described in Section 7.4 and Section 7.5, respectively. 
Additionally, the rate of infusion may be decreased and supportive care according to local 
standards may be used as needed.  In case of infusion-related toxicity during the post-infusion 
observation period for BPX-701 T cells or rimiducid, subjects should receive symptom-directed 
supportive care (e.g., antihistamines, antipyretics, antiemetics as clinically indicated) as per 
institutional guidelines. 
7.6.2 
Management of T Cell-Related Toxicity 
As BPX-701 is a type of adoptive T-cell therapy, adverse events similar to those observed with 
other engineered cell immunotherapies (e.g., chimeric antigen receptors, bispecific 
T-cell-engaging antibodies) may be reported.  The two most commonly observed toxicities with 
T cell-based therapies are CRS and neurotoxicity (Lee 2014, Maude 2014, Brudno 2016, Hu 
2016).  Although these data are largely derived from clinical trials of CD19-targeted therapies for 
the treatment of hematologic malignancies, similar side effects have been reported in patients with 
non-hematologic cancers.   
In vitro studies showed that T cells expressing the PRAME-specific BPX-701 TCR recognized a 
variety of tumor cell lines and primary AML blasts, positive for both PRAME and HLA-A2, as 
indicated by cytokine (i.e., interferon-γ) production (Amir 2011).  Therefore, as part of the 
biological effect of BPX-701 may include cytokine modulation and as neurologic toxicity exists 
as a potential class effect for T-cell therapies, AEs of or related to CRS and neurotoxicity, 
respectively, may be anticipated. 
Cytokine Release Syndrome 
Clinical symptoms of CRS may include but are not limited to rigors, fever, nausea, chills, 
hypotension, hypoxia, and/or multiorgan toxicity.  Symptoms may have acute onset either during 
or within minutes to hours after treatment administration and may coincide with peak cytokine 
levels (Kim 1993, Lee 2014).  Alternately, symptoms may be delayed by a week or more following 
T cell infusion (Corrigan-Curay 2014).  Subjects should be closely monitored during and after the 
BPX-701 T cell infusion for signs and symptoms indicative of CRS. 
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Grading criteria for CRS are provided in Table 3.  Recommendations for the clinical management 
of CRS, including when to administer rimiducid (Section 7.5), are described in Table 4. 
CRS is considered an adverse event of special interest for this study.  Refer to Section 9.8 for 
reporting procedures. 
Table 3:  Grading Criteria for Cytokine Release Syndrome 
Grade 
Toxicity 
Grade 1 
Temperature ≥38℃ and/or Grade 1a constitutional symptoms requiring symptomatic treatment 
only 
Grade 2 
Temperature ≥38℃ and at least one of the following symptoms: 
• 
Oxygen requirement <40%; 
• 
Hypotension responsive to IV fluids or low dose of one vasopressor; or 
• 
Grade 2a organ toxicity 
Grade 3 
Temperature ≥38℃ and at least one of the following symptoms: 
• 
Oxygen requirement ≥40%; 
• 
Hypotension requiring high-dose or multiple vasopressorsb; or 
• 
Grade 3a organ toxicity or Grade 4 transaminitis 
Grade 4 
Temperature ≥38℃ and at least one of the following symptoms: 
• 
Requirement for ventilator support;  
• 
Life-threatening hypotension; or, 
• 
Grade 4a organ toxicity (except Grade 4 transaminitis) 
Adapted from Kim 1993, Lee 2014 
a. Toxicity grade according to NCI CTCAE 
b. High-dose vasopressors are defined as any of the following: noradrenaline ≥20 µg/min; dopamine 
≥10 µg/kg/min; phenylephrine ≥200 µg/min; adrenaline ≥10 µg/min; if on vasopressin, vasopressin plus 
noradrenaline equivalent of ≥10 µg/min; and if on combination vasopressors (not including vasopressin), 
noradrenaline equivalent of ≥20 µg/min.  The noradrenaline equivalent dose is calculated using the VASST 
trial vasopressor equivalent equation: [noradrenaline (µg/min)] + [dopamine (µg/kg/min)/2] + [adrenaline 
(µg/min)] + [phenylephrine (µg/min)/10] (Russell 2008).  
 
Table 4:  Recommendations for the Management of Cytokine Release Syndrome 
Gradea 
Sign/Symptom 
Managementd 
Grade 1 
Fever or organ 
toxicity 
• Acetaminophen (or ibuprofen if not contraindicated) and hypothermia 
blanket for fever 
• Assess for infection using blood/urine cultures, chest radiography 
• Empiric broad-spectrum antibiotics and filgrastim, if neutropenic 
• Maintenance IV fluids for hydration 
• Symptomatic management of constitutional symptoms and organ toxicities 
• Consider tocilizumab 8 mg/kgb IV or siltuximab 11 mg/kg IV for persistent 
(lasting >3 days) and refractory fever 
Grade 2 
Hypotension 
• IV fluid bolus of 500-1000 mL normal saline (optional second bolus if SBP 
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Gradea 
Sign/Symptom 
Managementd 
remains <90 mmHg) 
• If refractory to fluids, administer tocilizumab 8 mg/kgb IV or siltuximab 
11 mg/kg IV (optional repeat tocilizumab after 6 hours as needed) 
• If refractory to fluids and anti-IL-6 therapy, administer vasopressors, 
consider transfer to ICU, obtain ECHO, and initiate other methods of 
hemodynamic monitoring as per institutional guidelines  
• If subject is high-riskc or if hypotension persists after 1-2 doses of anti-IL-6 
therapy, consider dexamethasone 10 mg IV every 6 hours 
o 
If refractory to anti-IL-6 therapy and corticosteroids (i.e., no 
improvement after 48 hours), rimiducid infusion as per Section 7.5 
should be considered.  The Bellicum medical monitor must be 
consulted prior to the decision to administer rimiducid. 
o 
If administered, rimiducid may be used in conjunction with continued 
corticosteroids and anti-inflammatory agents. Samples for rimiducid 
PK analysis should be collected before and after rimiducid as 
described in Section 8.3. 
o 
If there is evidence improvement (e.g. partial response) but not 
complete resolution after the first dose of rimiducid, then repeat 
infusions may be given every 48 hours up to a total of 3 doses. 
• Manage fever and constitutional symptoms as indicated for Grade 1 
Hypoxia 
• Supplemental oxygen 
• Tocilizumab or siltuximab ± corticosteroids and other BSC as recommended 
for hypotension management 
o 
If refractory to anti-IL-6 therapy and corticosteroids (i.e., no 
improvement after 48 hours), rimiducid infusion as recommended for 
hypotension management should be considered. 
Organ toxicity 
• Symptomatic management of organ toxicities as per institutional guidelines 
• Tocilizumab or siltuximab ± corticosteroids and other BSC as recommended 
for hypotension management 
o 
If refractory to anti-IL-6 therapy and corticosteroids (i.e., no 
improvement after 48 hours), rimiducid infusion as recommended for 
hypotension management should be considered. 
Grade 3 
Hypotension 
• IV fluid boluses as needed, as indicated for Grade 2 
• Tocilizumab and siltuximab as indicated for Grade 2, if not administered 
previously 
• Vasopressors as needed 
• Transfer to ICU, obtain ECHO, perform hemodynamic monitoring as for 
Grade 2 
• Dexamethasone 10 mg IV every 6 hours; if refractory, increase to 20 mg IV 
every 6 hours 
o 
If refractory to anti-IL-6 therapy and corticosteroids (i.e., no 
improvement after 48 hours), administer rimiducid as per 
Section 7.5.  The Bellicum medical monitor must be consulted prior 
to the rimiducid infusion. 
o 
Rimiducid may be used in conjunction with continued corticosteroids 
and anti-inflammatory agents. Samples for rimiducid PK analysis 
should be collected before and after rimiducid as described in 
Section 8.3. 
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Gradea 
Sign/Symptom 
Managementd 
o 
If there is evidence improvement (e.g. partial response) but not 
complete resolution after the first dose of rimiducid, then repeat 
infusions may be given every 48 hours up to a total of 3 doses. 
• Manage fever and constitutional symptoms as indicated for Grade 1 
Hypoxia 
• Supplemental oxygen including high-flow oxygen delivery and non-invasive 
positive pressure ventilation 
• Tocilizumab or siltuximab plus corticosteroids and other BSC as described 
above 
o 
If refractory to anti-IL-6 therapy and corticosteroids (i.e., no 
improvement after 48 hours), administer rimiducid as recommended 
for hypotension management. 
Organ toxicity 
• Symptomatic management of organ toxicities as per institutional guidelines 
• Tocilizumab or siltuximab plus corticosteroids and other BSC as described 
above 
o 
If refractory to anti-IL-6 therapy and corticosteroids (i.e., no 
improvement after 48 hours), administer rimiducid as recommended 
for hypotension management. 
Grade 4 
Hypotension 
• IV fluids, anti-IL-6 therapy, vasopressors, and hemodynamic monitoring as 
indicated for Grade 3 
• Methylprednisolone 1 g/day IV 
o 
If refractory to anti-IL-6 therapy and corticosteroids (i.e., no 
improvement after 48 hours), administer rimiducid as recommended 
for hypotension management. 
• Manage fever and constitutional symptoms as indicated for Grade 1 
Hypoxia 
• Mechanical ventilation 
• Tocilizumab or siltuximab plus corticosteroids and other BSC as described 
above 
o 
If refractory to anti-IL-6 therapy and corticosteroids (i.e., no 
improvement after 48 hours), administer rimiducid as recommended 
for hypotension management. 
Organ toxicity 
• As indicated for Grade 3 
Adapted from Neelapu 2018 
Abbreviations: ECHO=echocardiogram; ICU=intensive care unit; IV=intravenous; SBP=systolic blood pressure 
a. Toxicity grade according to Table 3. 
b. Maximum amount of tocilizumab per dose is 800mg. 
c. High-risk subjects include those with bulky disease, comorbidities, and those who develop early onset CRS 
(≤3 days of BPX-701 T cell infusion). 
d. If symptom management includes administration of rimiducid, refer to Section 7.6.4 for required safety blood 
samples for biomarker monitoring. 
Neurotoxicity 
Neurologic toxicity in response to T cell-based therapies encompasses a range of clinical 
symptoms including but not limited to diminished attention, language disturbance, impaired 
handwriting, confusion, disorientation, agitation, aphasia, somnolence, and tremors as well as 
seizures, motor weakness, incontinence, mental obtundation, increased intracranial pressure, 
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papilloedema, and cerebral edema (Neelapu 2018).  Based on historical evidence with other 
cellular immunotherapies, neurologic symptoms may exhibit early onset (within days to a week) 
or may be delayed several weeks following treatment.  Time to symptom resolution may be 
relatively short (hours to ~2-4 days) or prolonged for several weeks.  Symptom severity may also 
fluctuate rapidly, necessitating close safety monitoring for signs and symptoms indicative of 
neurotoxicity. 
Recommendations for the clinical management of neurotoxicity are described in Table 5.   
Neurologic toxicity is considered an adverse event of special interest for this study.  Refer to 
Section 9.8 for reporting procedures. 
Table 5:  Recommendations for the Management of Neurotoxicity 
Gradea 
Sign/Symptom 
Managemente 
Grade 
1 
Any 
• Symptomatic management as per institutional guidelines 
Grade 
≥2 
Focalb 
• Consider neurology consult and performing EEG 
• Perform daily neurological and mini-mental status examinations to evaluate for 
resolution/worsening of symptoms 
• Perform CNS imaging (MRI and/or contrast enhanced CT if MRI is not feasible or 
contraindicated) 
o For persistent symptoms, consider repeat neuroimaging  
• Consider CSF evaluation for presence of cell counts (and differential), glucose, 
protein and gram stain for bacteria 
o If negative for bacteria, consider CSF evaluations for other infectious 
etiologies (e.g., herpes viruses, JC virus, fungal, West Nile virus and 
toxoplasma) 
o CSF samples should be sent to the sponsor for research use to evaluate for 
the presence of BPX-701 T cells 
• Administer anti-viral and/or anti-fungal therapy as per institutional standard of 
care should be considered if infectious etiology is suspected (tailored for lab data 
results) 
• Consider empiric use of anticonvulsants if seizure is expected 
• Start management of stroke/ischemia per institutional guidelines if suspected 
• A brain biopsy, as per the discretion of the site clinical research team, should be 
considered if other diagnostic tests do not reveal a reasonable etiology 
• For neurological symptoms without concurrent CRS or evidence of CNS/systemic 
infection, administer dexamethasone 10 mg IV every 6 hours or 
methylprednisolone 1 mg/kg IV every 12 hours 
o Continue steroids until improvement to Grade 1 and then taper 
• If associated with concurrent CRS, administer tocilizumab 8 mg/kgd IV or 
siltuximab 11 mg/kg IV  
o If refractory to anti-IL-6 therapy, administer dexamethasone or 
methylprednisolone as above 
– If refractory to anti-IL-6 therapy and corticosteroids (i.e., no 
improvement after 48 hours), administer rimiducid as per Section 7.5.  
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Gradea 
Sign/Symptom 
Managemente 
The Bellicum medical monitor must be consulted prior to the rimiducid 
infusion. 
– Rimiducid may be used in conjunction with continued corticosteroids and 
anti-inflammatory agents. Samples for rimiducid PK analysis should be 
collected before and after rimiducid as described in Section 8.3. 
– If there is evidence improvement (e.g. partial response) but not complete 
resolution after the first dose of rimiducid, then repeat infusions may be 
given every 48 hours up to a total of 3 doses. 
• Transfer to ICU with consideration of need for mechanical ventilation as clinically 
indicated 
Grade 
≥2 
Generalizedc 
• Perform routine institutional care for subjects with altered mental 
status/obtundation (e.g., continuous vital sign monitoring, oxygen, suction, airway 
protection measurements and consideration of need for mechanical ventilation, 
ICU admission) 
• Neurology consult and EEG evaluation 
• Complete blood count analysis and peripheral blood smear to evaluate for 
thrombotic microangiopathy (TTP/HUS) 
• Evaluate for electrolyte and acid-base etiologies 
• Evaluate for liver dysfunction and evidence of hyperammonemia/veno-occlusive 
disease 
• Perform daily neurological and mini-mental status examinations to evaluate for 
resolution/worsening of symptoms 
• Perform CNS imaging (MRI and/or contrast enhanced CT if MRI is not feasible or 
contraindicated) 
o For persistent symptoms, consider repeat neuroimaging  
• Perform CSF evaluation for presence of cell counts (and differential), glucose, 
protein and gram stain for bacteria 
o If negative for bacteria, consider CSF evaluations for other infectious 
etiologies (e.g., herpes viruses, JC virus, fungal, West Nile virus and 
toxoplasma) 
o CSF samples should be sent to the sponsor for research use to evaluate for 
the presence of BPX-701 T cells 
• Consider empiric anti-viral and/or anti-fungal therapy as per institutional standard 
of care should be considered if infectious etiology is suspected (tailored for lab 
data results) 
• A brain biopsy, per the discretion of the site clinical research team, should be 
considered if other diagnostic tests do not reveal a reasonable etiology 
• For neurological symptoms without concurrent CRS or evidence of CNS/systemic 
infection, administer dexamethasone 10 mg IV every 6 hours or 
methylprednisolone 1 mg/kg IV every 12 hours 
o Continue steroids until improvement to Grade 1 and then taper 
• If associated with concurrent CRS, administer tocilizumab 8 mg/kgd IV or 
siltuximab 11 mg/kg IV  
o If refractory to anti-IL-6 therapy, administer dexamethasone or 
methylprednisolone as above 
– If refractory to anti-IL-6 therapy and corticosteroids (i.e., no 
improvement after 48 hours), administer rimiducid as recommended 
above. 
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Gradea 
Sign/Symptom 
Managemente 
Abbreviations: CNS=central nervous system; CRS=cytokine release syndrome; CSF=cerebral spinal fluid; 
CT=computed tomography; EEG=electroencephalogram; HUS=Hemolytic-uremic syndrome; ICU=intensive 
care unit; IV=intravenous; MRI=magnetic resonance imaging; SBP=systolic blood pressure; TTP=Thrombotic 
thrombocytopenic purpura 
a. Toxicity grade according to NCI CTCAE. 
b. Includes but is not limited to cranial nerve abnormalities, brachial plexopathy, ischemia, nystagmus, 
pyramidal tract syndrome, radiculitis, focal seizure, stroke, transient ischemic attack. 
c. Includes but not limited to aphonia, ataxia, cognitive disturbance, depressed level of consciousness, 
dysarthria, dysphasia, encephalopathy, headache, hypersomnia, lethargy, memory impairment, meningismus, 
seizures, somnolence, tremor, visual disturbances. 
d. Maximum amount of tocilizumab per dose is 800 mg. 
e. If symptom management includes administration of rimiducid, refer to Section 7.6.4 for required safety blood 
samples for biomarker monitoring. 
7.6.3 
Autoimmune Toxicity 
Autoimmune toxicity, so-called “on-target, off-tumor” toxicity results from antigen-specific attack 
on host tissues when the targeted tumor antigen is expressed on non-malignant tissues.  The degree 
of on-target, off-tumor toxicity is likely related to the affinity of the TCR for its cognate antigen, 
the level of antigen expression on healthy tissue, the potency of the TCR, and the relative 
functional importance of the antigen as non-tumor target.  PRAME is highly overexpressed a 
variety of malignancies, including those under investigation in this study (Epping 2006); whereas 
expression in normal tissues is primarily restricted to the testis, endometrium, ovary, and kidney 
epithelium (Ikeda 1997). 
Safety Risk Assessment for On-Target, Off-Tumor Toxicity 
At Baseline and at regular intervals following the BPX-701 T cell infusion, male subjects will be 
monitored for testicular health and function as described in Section 8.2.8 and Appendix 1.  
Similarly, male and female subjects will be offered the option to bank sperm and oocytes, 
respectively, for fertility preservation, as applicable, and if not already completed prior to 
Screening.  All uveal melanoma subjects who have not undergone definitive enucleation at the 
primary disease site at Screening will undergo an ophthalmologic assessment as part of the 
physical exam prior to the BPX-701 T cell infusion.  Subjects will be monitored following 
experimental treatment for signs and symptoms of uveitis and other ocular sequalae as described 
in Section 8.2.3 and Appendix 1.  Renal function of all subjects will be assessed by repeat serum 
creatinine assessment as shown in Appendix 1. 
If clinical signs or symptoms of anti-PRAME-directed autoimmune toxicity are suspected, subjects 
should receive symptom-directed supportive care as per institutional standards.  If corticosteroid 
therapy is indicated, consider: 
• Dexamethasone 10 mg IV every 6 hours or methylprednisolone 1 mg/kg IV every 12 hours 
o If symptoms do not improve, consider an increased corticosteroid dose (e.g., 
dexamethasone 20 mg IV every 6 hours) 
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o Continue the corticosteroid regimen until symptoms improve to Grade 1 and then 
taper 
For persistent symptoms that do not respond to corticosteroids (i.e., no improvement after 
48 hours), administer rimiducid as per Section 7.5.  The Bellicum medical monitor must be notified 
prior to the administration of rimiducid.  Rimiducid may be administered in conjunction with 
continued corticosteroids and other supportive care medications.  Samples for rimiducid PK 
analysis should be collected before and after rimiducid as described in Section 8.3.  If there is 
evidence of improvement (e.g., partial response) but not complete response after the initial dose 
of rimiducid, then repeat infusions may be given every 48 hours up to 3 doses.  
Autoimmune toxicity is considered an adverse event of special interest for this study.  Refer to 
Section 9.8 for reporting procedures. 
7.6.4 
Safety Blood Samples for Biomarker Monitoring in response to CRS or 
Neurotoxicity 
For subjects with signs or symptoms of CRS or neurotoxicity (Section 7.6.2), the following 
biomarker samples should be collected for safety monitoring at the time of the event or as soon as 
possible following diagnosis: 
• Blood sample (serum) for peripheral cytokine assessment 
• Whole blood sample for BPX-701 T cell tracking and functional activity 
If event onset coincides with a planned time point (Appendix 1 and Appendix 2), proceed with the 
scheduled collection.  Additional samples may be collected as clinically indicated for further safety 
monitoring.  Refer to the Laboratory Manual for collection instructions. 
7.6.5 
Pharmacokinetics and Biomarker Blood Samples following Rimiducid Infusion 
If rimiducid is indicated for symptomatic AE management (Section 7.6.2 and Section 7.6.3), the 
following blood samples should be collected for safety monitoring: 
• Blood sample (serum) for peripheral cytokine assessment 
• Whole blood sample for BPX-701 T cell tracking and functional activity 
• Blood sample (plasma) for rimiducid pharmacokinetics  
If more than one dose of rimiducid is administered, sample collection will be performed relative 
to the initial infusion only as detailed in Appendix 3.  Samples may be collected more frequently 
as clinically indicated.  Refer to the Laboratory Manual for collection instructions. 
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7.7 
Concomitant Therapies 
Subjects may receive concomitant medications and procedures as required or deemed necessary 
for supportive care, unless specifically restricted or prohibited in this study (Section 7.8).  
During the study, subjects should continue the use of prescribed medications identified at baseline, 
consistent with study inclusion and exclusion criteria. 
7.8 
Prohibited Therapies 
The following medications are not permitted from the Screening visit through completion of the 
EOT Visit unless otherwise indicated: 
• Approved or investigational non-study chemotherapy, small molecule, immunotherapy, 
monoclonal antibody, radiotherapy (non-palliative), medical device or other cellular 
therapy intended to treat the disease under study unless there is clinical or radiographic 
evidence of confirmed disease progression. 
o Arm 1 only: if clinically indicated to control disease, salvage standard of care 
chemotherapy may be administered after apheresis and to up 2 weeks before the 
planned BPX-701 T cell infusion upon discussion with and approval by the sponsor. 
o Ongoing bisphosphonate therapy is allowed for supportive/palliative care.  
o Palliative radiotherapy (e.g., focused radiotherapy for bone metastases) may be 
permitted upon discussion with and approval by the sponsor. 
• Systemic corticosteroids >10 mg/day of prednisone or equivalent (unless used for 
management of treatment-related toxicity) 
• Live vaccines  
• Seasonal influenza vaccines for injection are generally killed virus vaccines and are 
allowed.  
• Intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not 
permitted. 
There are no prohibited therapies or procedures once the subject has completed the EOT visit. 
 
STUDY PROCEDURES AND ASSESSMENTS 
This study consists of an initial Prescreening phase, followed by a Screening phase, a Treatment 
phase (including an EOT visit), and a Posttreatment Follow Up phase. 
 
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Prescreening 
All subjects must sign the Prescreening ICF prior to the conduct of any study-related prescreening 
procedures.  The Prescreening phase will begin after applicable ICF signature when the first 
prescreening assessment is conducted.  The includes a preliminary review of the study eligibility 
criteria (i.e., in anticipation of subsequent screening and study enrollment) and clinical evaluation 
as specified in the Schedule of Assessments (Appendix 1): 
• HLA typing (if not part of prior medical records at the time of consent; Section 8.2.8) 
• PRAME expression testing (fresh bone marrow aspirate or fresh/archived tumor tissue 
sample; Section 8.4.1) 
• Infectious disease testing (blood sample for serology; Section 8.2.8) 
Subjects who are HLA-A2.01 positive with documented PRAME tumor expression and blood test 
results that are negative or nonreactive for relevant communicable disease agents may proceed to 
the Screening phase.  Subjects with alternate HLA typing, PRAME-negative disease, and/or 
evidence of active or ongoing infectious disease are not eligible for the study.  The investigator 
should discuss with the subject alternate, non-protocol treatment options in accordance with local 
standards of care.  
Screening 
Prescreened subjects who are HLA-A2.01 positive with documented PRAME tumor expression 
and no evidence of relevant communicable disease must sign the Screening/Study Treatment ICF 
prior to conduct of any further study-related procedures.  The Screening phase will begin after 
applicable ICF signature when the first screening assessment is conducted and includes a review 
of the eligibility criteria and clinical evaluation as specified in the Schedule of Assessments 
(Appendix 1).  The following will be performed on eligible subjects up to 42 days before the 
planned BPX-701 T cell infusion: 
• Days -40 to -21: apheresis procedure at the study site (Section 7.2) with subsequent 
BPX-701 T cell manufacturing from subject-derived T cells at the sponsor’s manufacturing 
facility 
• Day -7 to Day -1: baseline clinical assessments and lymphodepletion (Day -5 to Day -3; 
Section 7.3) prior to BPX-701 T cell infusion 
The last result obtained prior to the BPX-701 T cell infusion will be used to determine eligibility 
to receive TCR therapy.  Retesting of abnormal baseline values are allowed only once to reassess 
treatment eligibility. 
Treatment 
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The Treatment phase begins on Day 0 with BPX-701 T cell infusion (Section 7.1.1).  During the 
Treatment phase, subjects will be closely monitored for AEs, laboratory abnormalities, and 
antitumor response. The frequency of study site visits and required study procedures and 
assessments to be conducted during the Treatment phase are outlined in Appendix 1.  Clinical 
evaluations and laboratory studies may be repeated more frequently, if clinically indicated. 
An EOT visit will be scheduled 12 months after BPX-701 T cell infusion or at the time disease 
progression is confirmed or the subject is discontinued per investigator discretion (Section 5.10) 
unless the subject has died, is lost to follow-up, or has withdrawn consent for study participation.  
Assessments to be performed at the EOT visit are outlined in Appendix 1.  The EOT visit should 
be completed before starting any subsequent anticancer treatment.  If a subject is unable to return 
to the site for the EOT Visit, the subject should be contacted to collect information on any 
unresolved AEs. 
Posttreatment Follow Up 
After the EOT visit, subjects will enter the Posttreatment Follow Up phase and will complete 
routine follow-up visits for long-term safety evaluation and survival assessment (vital status and 
subsequent anticancer therapy monitoring) at least twice annually for 5 years and once annually 
from years 6 to 15 after BPX-701 T cell infusion.  The frequency of study visits and required 
procedures to be conducted during the Posttreatment Follow Up phase are specified in Appendix 
1. 
• If the subject discontinued prior to disease progression, the results of disease assessments 
performed according to standard of care will be collected, if available.  Efficacy evaluations 
should be performed until disease progression, the start of new anticancer therapy, death, 
withdrawal of consent, or the subject is lost to follow-up. 
8.1 
General Assessments 
The following general assessments will be collected at Screening. 
8.1.1 
Demography 
• Date of birth, age, gender, ethnicity, and race as allowed by local regulations 
8.1.2 
Medical History 
• All active conditions, including the disease under study 
o For subjects with AML or MDS, the following disease characteristics will be 
collected:  
 Date of initial diagnosis 
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 Morphology (includes blast count and percentage in peripheral blood and 
bone marrow) 
 Genetics (includes chromosomal abnormalities and gene arrangements) 
 Molecular genetics and mutation profiling (if known) 
 Immunophenotyping 
 ELN risk category (for subjects with AML; Dohner 2017) 
 Antecedent myeloid disorder (for subjects with AML) 
 International Prognosis Scoring System category (for subjects with MDS; 
Greenberg 2012) 
o For subjects with uveal melanoma, the following disease characteristics will be 
collected: 
 Date of initial diagnosis 
 Disease stage and histology and site(s) of disease 
 Molecular genetics and mutation profiling (if known) 
 Largest diameter of largest metastasis 
 Lactate dehydrogenase, alkaline phosphatase 
 Time from treatment of primary disease to development of metastatic 
disease 
• Any past medical condition considered to be clinically significant by the investigator 
• Height (without shoes) 
8.1.3 
Prior Anticancer Therapy 
• All prior therapies, including surgery(ies), allogeneic hematopoietic stem cell transplants 
(AML and MDS only), radiation, and interventional treatment regimens for management 
of the disease under study, including start and stop dates and best response 
8.2 
Safety Assessments 
Subject safety be assessed by collection of data on ECOG performance status, vital signs, weight, 
physical examination including ophthalmologic assessments, neurological evaluation and mini-
mental status exam, cardiac function tests, AEs, concomitant medications, and routine clinical 
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laboratory assessments.  Clinically significant changes from pre-treatment values in safety 
assessments should be reported as AEs.  Safety assessments described below will be conducted 
according to Appendix 1.  In addition to the weekly clinic visits scheduled during the first two 
months after the BPX-701 T cell infusion, mid-week phone calls may be made to the subject to 
help determine whether there is an emerging, acute condition that would require immediate safety 
evaluation by the investigator on an inpatient or outpatient basis. 
8.2.1 
ECOG Performance Status 
The ECOG performance status scale (Appendix 4) will be used to grade changes in the subject’s 
daily living activities. 
8.2.2 
Vital Signs 
Vital signs, including blood pressure, heart rate, respiratory rate, and temperature will be obtained 
at each indicated visit.  On infusion days (BPX-701 and each dose of rimiducid, if applicable), 
collect prior to dosing (-60 to -5 min) and at 15 min, 30 min, 1 hr, 2 hr, and 4 hr (±5 min) after the 
start of the infusion and thereafter as clinically indicated until completion of the post-infusion 
safety monitoring period. 
8.2.3 
Physical Examination and Weight 
Comprehensive Physical Examination 
Complete physical examinations will be conducted at Screening and EOT.  The comprehensive 
physical examination will include the following organ or body system assessments: skin; head, 
eyes, ears, nose, and throat; thyroid; lungs; cardiovascular system; abdomen (liver and spleen); 
extremities; and lymph nodes.   
Uveal melanoma subjects who have not undergone definitive enucleation at the primary disease 
site will undergo a routine ophthalmic assessment according to institutional standards as part of 
the complete physical exam during Screening to establish a baseline for any treatment-emergent 
ocular toxicity. 
Symptom-directed Physical Examination 
Symptom-directed physical examinations may be conducted at all other visits as indicated.  The 
targeted physical examination will include assessment(s) of the body systems or organs, as 
indicated by subject symptoms, AEs, or other findings. 
An ophthalmologist should be consulted if uveitis is suspected or any other signs and symptoms 
of eye-related inflammation including eye redness, eye pain, light sensitivity, blurred vision, 
floating spots in the field of vision, and decreased vision are observed in uveal melanoma subjects.  
Symptom-directed supportive care (e.g., slit lamp microscopy) should be performed as clinically 
indicated (Section 7.6.3). 
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Weight 
Weight (kilograms) will be obtained at each indicated visit (prior to infusion, if applicable). The 
measurement obtained during Screening will be used in BPX-701 T cell manufacturing.  The 
measurement obtained at Baseline will be used to calculate the appropriate dose of 
lymphodepletion therapy (Section 7.3).  For qualifying subjects that receive rimiducid, the most 
recent measurement obtained prior to the infusion should be used in dose calculations. 
8.2.4 
Neurological Evaluation and Mini-Mental Status Exam 
Subjects will undergo neurologic examination according to institutional standards at the frequency 
specified in Appendix 1.  A mini-mental status examination (MMSE) should be performed in 
conjunction with all neurologic evaluations (Folstein 1975). 
8.2.5 
Cardiac Function Tests 
Echocardiogram (ECHO)/Multi-gated Acquisition (MUGA) Scan 
Routine ECHO/MUGA should be performed according to local standard practice.  Cardiac 
function including left ventricular ejection fraction quantification should be assessed by the 
investigator for clinical significance and eligibility assessment. 
Electrocardiogram (ECG) – applicable only for subjects that receive rimiducid 
Routine 12-lead ECG should be performed according to local standard practice after the subject 
has rested in a recumbent or semi-recumbent position for ≥5 minutes.  ECG parameters (e.g., heart 
rate, PR interval, QT interval, QRS duration, and corrected QT interval) should be interpreted by 
the investigator for clinical significance and eligibility assessment.  Assessment frequency is 
defined in Appendix 3. 
8.2.6 
Adverse Events 
Adverse events will be reported by the subject for the duration of the study.  Adverse events will 
be followed by the Investigator as specified in Section 9.6. 
8.2.7 
Concomitant Medications 
Medications used at the time of consent until the Baseline visit will be recorded as prior 
medications.  
All concomitant medication administered from the Baseline visit until the EOT visit will be 
recorded (including the lymphodepletion regimen [Section 7.3], infusion premedication, and all 
over the counter medications, herbal remedies and dietary supplements). The generic name, 
dosage, duration, and reason for the concomitant medication should be included.  
Following the EOT visit, concomitant medications will only be collected if associated with the 
management of an ongoing AE. 
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8.2.8 
Clinical Laboratory Tests 
Blood samples for clinical laboratory tests (Table 6) will be collected according to the frequency 
specified in Appendix 1.  More frequent clinical laboratory tests may be performed if indicated by 
the overall clinical condition of the subject or by abnormalities that warrant more frequent 
monitoring.  The investigator must review the laboratory reports, document this review, and ensure 
that any clinically relevant changes occurring during the study are recorded in the AE section of 
the eCRF.  The laboratory reports must be filed with the source documents. 
The following tests will be performed by the local laboratory: 
Table 6:  Clinical Laboratory Tests 
Hematology (eligibility and routine safety assessment) 
• White blood cell count with differential 
• Red blood cells 
• Hemoglobin 
• Hematocrit 
• Platelets 
• Absolute neutrophil count 
Chemistry (eligibility and routine safety assessment) 
• Sodium 
• Potassium 
• Chloride 
• Bicarbonate 
• Creatinine 
• Blood urea nitrogen 
• Glucose, non-fasting 
• Calcium 
• Magnesium 
• Phosphate 
• Albumin 
• ALT 
• AST 
• Bilirubin 
• Direct bilirubin 
• Alkaline phosphatase 
• LDH 
• Uric acid 
Coagulation (eligibility and routine safety assessment) 
• PT 
• PTT 
• INR 
• Fibrinogen 
• D-Dimer 
Urinalysis (screening only, as clinically indicated thereafter) 
Dipstick: 
• Specific gravity 
• pH 
• Protein 
• Glucose 
• Ketones 
• Blood 
If dipstick is abnormal, microscopy will be used to 
measure sediment: 
• Red blood cells 
• White blood cells 
• Epithelial cells 
• Crystals 
• Casts 
• Bacteria 
HLA-A Serotyping (prescreening for eligibility assessment) 
• HLA-A2.01 
Infectious Disease Panel (prescreening for eligibility assessment, collected ≤7 days of planned apheresis) 
• Anti-HIV-1 antibody 
• Anti-HIV-2 antibody 
• HIV viral load (if indicated) 
• Hepatitis B surface antigen 
• Hepatitis B core antibody 
• Hepatitis B viral load (if indicated) 
• Hepatitis C antibody 
• Hepatitis C viral load (if indicated) 
• Human T-lymphotropic Virus-1 antibody 
• Human T-lymphotropic Virus-2 antibody 
• Anti-Trypanosoma cruzi antibody 
• West Nile virus RNA 
• Syphilis 
• Cytomegalovirus antibody 
• Indirect antibody test (Coombs) 
Pregnancy (eligibility and routine safety assessment for female subjects) 
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• Serum (β-human chorionic gonadotropin [β-hCG] or urine pregnancy testing for women of childbearing 
potential 
Testicular Toxicity Monitoring (routine safety assessment for male subjects) 
• Testosterone 
• FSH 
• LH 
• Inhibin B 
Cytokines and CRP (routine safety assessment) 
• IFNγ 
• GM-CSF 
• TNFα 
• IL-2 
• IL-6 
• CRP 
Flow Cytometry (routine safety assessment) 
• CD3+Vβ1+ T cells to determine the number of transduced cells (absolute count and percent of total 
lymphocytes) 
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; CRP=C-reactive protein; 
FSH=follicle-stimulating hormone; HIV=human immunodeficiency virus; HLA=human leukocyte antigen; 
HTLV=human 
T-lymphotropic 
virus; 
GM-CSF=granulocyte-macrophage 
colony-stimulating 
factor; 
IFN=interferon; IL=interleukin; INR=international 
normalized ratio; 
LDH=lactate dehydrogenase; 
LH=luteinizing hormone; PT=prothrombin time; PTT=partial thromboplastin time; TNF=tumor necrosis factor 
8.3 
Rimiducid Concentration Measurements (Pharmacokinetics) 
Blood samples (plasma) for analysis of rimiducid concentrations will be obtained from qualifying 
subjects to characterize the PK profile of rimiducid.  Samples will be collected at time points 
indicated in Appendix 3.  If more than one dose of rimiducid is administered, PK sample collection 
will be performed relative to the initial infusion only.  For all planned PK time points up to 8 hours 
post-infusion, blood must be collected from a peripheral vein contralateral to the arm/location into 
which rimiducid is administered.  The time and date of each sample must be recorded; samples 
will be collected and processed by sites as outlined in the Laboratory Manual.  All analyses will 
be conducted by the sponsor or designee. 
8.4 
Research Laboratory Assessments 
Research laboratory assessments will be conducted to characterize the pharmacodynamics and 
mechanism of action of BPX-701 T cells as well as the effect of rimiducid, as applicable, on these 
parameters.  The results may help to inform dose selection, characterize on-treatment immune 
responses and cancer progression, evaluate the efficacy of rimiducid as a safety switch, as well as 
monitor long-term safety.  Research assessments planned for this study include: 
• PRAME expression in bone marrow (fresh aspirate) from subjects with AML/MDS; or 
tumor tissue (archival or fresh biopsy) from subjects with uveal melanoma as determined 
by quantitative polymerase chain reaction (qPCR) 
• T-cell phenotyping and functional activity (transduced and non-transduced) using standard 
markers via flow cytometry analysis of whole blood and PBMCs 
• Persistence of peripheral BPX-701 T cells by qPCR (vector copy analysis) and flow 
cytometry (cell counts) 
• Serum cytokine analysis using a multiplex analysis technique  
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• Gene expression changes in peripheral blood or bone marrow (AML/MDS) or the tumor 
microenvironment (uveal melanoma) 
• Bone marrow or tumor microenvironment assessment of markers associated with immune 
infiltrate including BPX-701 T cells for AML/MDS or uveal melanoma, respectively 
• Gene therapy monitoring for vector and replication competent retrovirus (RCR) 
Peripheral blood and tumor (bone marrow biopsy/aspirate or tissue biopsy as appropriate for the 
disease under study) samples will be collected at the visits and time points indicated in Appendix 
1 and further detailed in Appendix 2.  Detailed information regarding sample collection, 
processing, and shipment is outlined in the Laboratory Manual. 
All analyses will be conducted by the sponsor or designee.  Blood samples, bone marrow 
biopsies/aspirates, tumor tissue biopsies, and available archival tumor tissue may also be used for 
exploratory evaluation of DNA, RNA, and/or proteins as potential tumor and immune-associated 
biomarkers. 
Based on emerging data, site-specific collection feasibility, or for other operational reasons, the 
timing for sample collection may be adjusted, or certain samples may not be collected.  Biomarker 
analysis may be deferred or not performed, if during or at the end of the study, it becomes clear 
that the analysis will not have sufficient scientific value for biomarker evaluation, or if there are 
not enough samples or responders to allow for adequate biomarker evaluation. In the event the 
study is terminated early or shows poor clinical efficacy, completion of biomarker assessments is 
based on justification and intended utility of the data and/or analyzed.  No pharmacogenomic 
analyses will be conducted on the biomarkers samples. 
8.4.1 
PRAME Evaluation 
A requirement for trial inclusion is documented positive myeloid blast or solid tumor expression 
of PRAME, as appropriate for the disease under study, as determined by central qPCR assessment 
of an available bone marrow aspirate or tumor tissue biopsy.  For subjects with AML or MDS, a 
fresh bone marrow aspirate will be collected during the Prescreening phase for PRAME testing 
(Appendix 1).  For subjects with uveal melanoma, PRAME expression will be evaluated using 
formalin-fixed, paraffin embedded (FFPE) tumor tissue.  During the Prescreening phase, all 
potential uveal melanoma subjects will be required to provide archived tumor tissue (FFPE block, 
preferred, or scrolls) or to undergo tumor biopsy if an archived sample is not available (Appendix 
1).  From the time of sample receipt by the central analysis vendor, it is anticipated that PRAME 
expression results should be available within 7 to 14 days. 
8.4.2 
BPX-701 T cell Tracking and Functional Activity 
Persistence of genetically modified BPX-701 T cells in PBMCs isolated from whole blood will be 
assessed by flow cytometry (e.g., absolute count of CD3+Vβ1+ T cells and percentage within the 
total lymphocyte population) and qPCR.  Flow cytometry using standard activation markers may 
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also be used for immunophenotyping of both BPX-701-engineered and patient-derived T cells.  In 
addition, T cell functional activity may be analyzed in PBMC samples using appropriate 
techniques such as intracellular cytokine staining or a PRAME-specific cytotoxicity assay, if 
sufficient material is available for testing.  
8.4.3 
Cytokines 
In addition to local serum testing for time-sensitive routine safety monitoring (Table 6), blood 
(serum) will also be collected for centralized pharmacodynamic assessment using a multiplexed 
cytokine assay that includes evaluation of IFNγ, GM-CSF, TNFα, IL-2, and IL-6. 
8.4.4 
Immunogenicity Assessment 
Based on emerging data, residual blood (serum) samples collected for centralized cytokine 
assessment (Section 8.4.3) may be explored for the presence of anti-BPX-701 antibodies.  
Anti-BPX-701 antibodies will be assessed using a validated method. 
8.4.5 
Pretreatment and On-Treatment Tumor Sampling  
AML or MDS 
Subjects with AML and MDS will undergo repeat bone marrow aspirate and peripheral blood 
sampling prior to as well as after BPX-701 T cell infusion as part of routine disease evaluations to 
determine response to treatment (Appendix 1). 
Uveal Melanoma 
Subjects with uveal melanoma are required to provide a pretreatment (tissue collected at Baseline) 
as well as on-treatment, fresh tumor biopsy following BPX-701 T cell therapy (tissue sample 
collected between Days 14 and 21; Appendix 1). 
The investigator should select a representative lesion amenable to post-infusion fresh biopsy.  The 
biopsy should be obtained from appropriate tumor site(s) using standard techniques to yield 
adequate tissue for analysis.  Fine needle aspirations will not be acceptable.  A second 
post-treatment biopsy may also be collected from all subjects at the time of disease progression, 
provided the lesion for biopsy is accessible and tissue collection is clinically feasible. 
8.4.6 
Gene Therapy Monitoring 
Per FDA guidelines, subjects will undergo blood testing for vector and RCR prior to BPX-701 
T cell infusion and then every 6 months from the date of infusion (i.e., Day 0) for 5 years (Table 
7).  Beginning with year 6, blood samples will be drawn annually for another 10 years (total of 
15-year follow-up).  All samples collected at pre-infusion and during the initial 12 months after 
BPX-701 T cell therapy will be analyzed for RCR. If a result is positive during this time, all 
remaining samples for that subject collected during the 15-year follow up period will also be 
analyzed.  If all results are negative during the initial 12 months of RCR testing, samples will 
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continue to be collected but will be centrally archived by the sponsor or designee for analysis at a 
future date. 
Table 7:  Gene Therapy Monitoring Schedule 
Time Point of Collection 
Clinical Evaluation 
Blood 
Prior to lymphodepletion 
Xb 
X 
Month 3a 
Xb 
X 
Month 6 a 
Xb 
X 
Month 12 a 
Xb 
X 
Every 6 Months up to Year 5 a 
Xc 
Xd 
Every 12 Months up to Year 15 a 
Xc 
Xd 
a. 
After the BPX-701 T cell infusion 
b. Includes ECOG performance status, vital signs, symptom-directed physical exam, and 
adverse event monitoring.  Refer to Appendix 1. 
c. 
Includes adverse event monitoring. 
d. If blood samples collected during the initial 12 months after BPX-701 T cell infusion 
are negative, remaining blood samples collected will be archived. 
 
8.5 
Efficacy Assessments for Subjects with AML or MDS 
Disease evaluation will include clinical examination, routine peripheral blood and bone marrow 
sampling (aspirate or biopsy), and appropriate radiographic imaging techniques.  The latter should 
be used to characterize known or suspected extramedullary disease sites.  CNS imaging is required 
at Baseline for subjects with associated clinical signs or symptoms; if positive, a confirmatory 
lumbar puncture should be performed. Subjects without extramedullary or CNS disease do not 
require on-study body or brain imaging, respectively, unless clinically indicated.   
Refer to Appendix 1 for detailed information regarding the schedule and frequency for peripheral 
blood and bone marrow sampling.  Samples may be collected more frequently if clinically 
indicated.  If a subject discontinues the study for reasons other than progression or relapse, 
continue 
marrow 
assessments 
per 
standard 
of 
care 
frequency 
until 
documented 
progression/relapse, withdrawal, or study end.   
Response assessment will be determined locally by the investigator using ELN criteria for AML 
(Appendix 9) or IWG criteria for MDS (Appendix 10). 
8.6 
Efficacy Assessments for Subjects with Uveal Melanoma 
Radiographic tumor evaluation will include clinical examination and appropriate imaging 
techniques, preferably computed tomography (CT) scans with contrast of the chest, abdomen, and 
pelvis with ≤5 mm slice thickness.  Magnetic resonance imaging (MRI) is required at Baseline to 
document known or suspected liver as well as CNS metastases.  Subjects without brain lesions do 
not require brain imaging on study unless clinically indicated.  A bone scan should be conducted 
for known or suspected bone metastases.  
If CT scan is contraindicated (e.g. allergy to contrast dye), MRI should be performed.  Tumor 
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imaging will be performed using the same assessment technique throughout the study.  Refer to 
Appendix 1 for detailed information regarding the schedule and frequency for tumor imaging.  If 
a subject discontinues study treatment for reasons other than progressive disease, continue imaging 
per standard of care frequency until documented disease progression, withdrawal, or study end.   
Radiographic imaging will be evaluated locally by the investigator for response assessment using 
RECIST v1.1 (Appendix 7).  The investigator/local radiology review will also use irRC (Appendix 
8) to assess tumor response and progression and make treatment decisions. 
If an initial complete response (CR) or partial response (PR) is noted, confirmatory scans must be 
performed at least 4 weeks later.  In the case of stable disease (SD), follow-up imaging must have 
met the SD criteria at least once after study entry and no less than 4 weeks.  
If radiographic disease progression is observed, another scan should be performed no less than 
4 weeks later to confirm disease progression prior to treatment discontinuation. Subjects 
discontinued after confirmation of progression should complete the EOT Visit and enter the 
Posttreatment Follow-Up Period. 
 
ADVERSE EVENT REPORTING 
9.1 
Safety Parameters and Definitions 
Safety assessments will consist of monitoring and recording protocol-defined AEs and SAEs; 
measurement of protocol-specified hematology, clinical chemistry variables vital signs and other 
protocol-specified tests that are deemed critical to the safety evaluation of the study drug(s). 
The sponsor or its designee is responsible for reporting relevant SAEs to the FDA, other applicable 
regulatory authorities, and participating investigators, in accordance with ICH guidelines, FDA 
regulations, European Clinical Trials Directive, and/or local regulatory requirements. 
9.2 
Adverse Events 
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with 
the use of an investigational medicinal product or other protocol-imposed intervention, regardless 
of attribution. 
This includes the following: 
1. AEs not previously observed in the subject that emerge during the protocol-specified AE 
reporting period, including signs or symptoms that were not present prior to the AE 
reporting period 
2. Pre-existing medical conditions judged by the investigator to have worsened in severity or 
frequency or changed in character during the protocol-specified AE reporting period 
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Abnormal laboratory values or test results that induce clinical signs or symptoms and are 
considered clinically significant. 
9.3 
Serious Adverse Events (SAE) 
An SAE is any AE that is any of the following: 
1. Fatal (i.e., the AE actually causes or leads to death) 
2. Life threatening (i.e., the AE, in the view of the investigator, places the subject at 
immediate risk of death) 
3. Requires or prolongs in subject hospitalization 
4. Results in persistent or significant disability/incapacity (i.e., the AE results in substantial 
disruption of the subject’s ability to conduct normal life functions) 
5. A congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the 
investigational product(s) 
6. Considered a significant medical event by the investigator (e.g., may jeopardize the subject 
or may require medical/surgical intervention to prevent one of the outcomes listed above) 
All AEs that do not meet any of the criteria for serious should be regarded as non-serious AEs. 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an AE 
(as in mild, moderate, or severe pain); the event itself may be of relatively minor medical 
significance (such as severe headache). “Serious” is a regulatory definition and is based on subject 
or event outcome or action criteria usually associated with events that pose a threat to a subject’s 
life or vital functions. Seriousness (not severity) serves as the guide for defining regulatory 
reporting obligations. 
Severity and seriousness should be independently assessed when recording AEs and SAEs on the 
CRF. 
The investigator is responsible for ensuring that all AEs and SAEs are recorded on the CRF and 
reported to the sponsor in accordance with protocol instructions. 
9.4 
Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each AE and the potential relationship 
(causality) between the AE and the study treatment. 
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9.4.1 
Assessment of Severity 
The severity of all AEs except CRS will be graded according to the NCI CTCAE v. 4.03 
(http://ctep.cancer.gov/reporting/ctc.html).  Grading criteria for CRS are provided in Table 3.  For 
AEs not listed in the CTCAE, the following grading system will be used: 
• Mild (CTCAE Grade 1):  Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated 
• Moderate (CTCAE Grade 2): Moderate; minimal, local or noninvasive intervention 
indicated; limiting instrumental activities of daily living 
• Severe (CTCAE Grade 3): Severe or medically significant but not immediately 
life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care activities of daily living 
• Life-threatening (CTCAE Grade 4): Life-threatening consequences; urgent intervention 
indicated  
• Death (CTCAE Grade 5): Death related to AE 
9.4.2 
Assessment of Causality 
The Investigator will estimate the relationship between the study treatment (BPX-701 T cells, 
rimiducid, or both) and the occurrence of each AE or SAE. The relationship (synonym: causality) 
is based on the Investigator’s clinical judgment regarding the likelihood that the event may 
(certainly, probably, possibly) or may not be (unlikely, unrelated) attributed to the study treatment. 
9.5 
Disease-Related Events Not Qualifying as AEs 
An event which is part of the natural course of the disease under study (i.e., disease progression, 
death due to disease progression) should not be recorded as an AE or serious AE term; instead, 
signs and symptoms of clinical sequelae resulting from disease progression/lack of efficacy will 
be reported if they fulfill the definition of an AE or SAE (Section 9.2 and Section 9.3).   
For events associated with disease progression, the relevant signs and symptoms should be 
reported using a diagnosis whenever possible rather than individual underlying signs and 
symptoms.  When a clear diagnosis cannot be identified, each sign or symptom should be reported 
as a separate AE or SAE as applicable. 
9.6 
Adverse Event Reporting Period 
Safety reporting periods for this study are defined in Table 8. 
 
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Table 8:  Safety Reporting Periods 
Event Type 
Reporting Period 
Additional Requirements 
SAEs  
(screening) 
Date of informed consent and prior to 
BPX-701 infusion 
• Report new SAE only if caused by a 
protocol-mandated intervention during 
Screening 
AEs  
(treatment-emergent) 
No less than 30 days following 
infusion of BPX-701 or the last dose of 
rimiducid, as applicable, whichever 
occurs later  
• Report new AEs for up to 15 years if 
assessed as related to BPX-701 or 
rimiducid 
SAEs  
(treatment-emergent) 
No less than 180 days following 
infusion of BPX-701 or the last dose of 
rimiducid, as applicable, whichever 
occurs later 
• Report new SAEs for up to 15 years if 
assessed as related to BPX-701 or 
rimiducid 
• Report diagnosis of any new secondary 
malignancy regardless of relationship to 
study treatment for up to 15 years 
Adverse events of 
special interest 
(treatment-emergent) 
No less than 180 days following 
infusion of BPX-701 or the last dose of 
rimiducid, as applicable, whichever 
occurs later 
• Report new AESI for up to 15 years if 
assessed as related to BPX-701 or 
rimiducid 
Pregnancy of subjects 
or partner 
No less than 12 months following the 
last dose of cyclophosphamide in the 
lymphodepletion regimen 
• As per Section 9.10 
• Report diagnosis of any congenital 
abnormality in offspring from a study 
participant for up to 15 years  
 
9.7 
Reporting Requirements for SAEs 
9.7.1 
Initial Reports 
An SAE report will be completed for each observed SAE.  The Investigator will submit SAE 
information to the sponsor or designee within 24 hours of learning about the initial event.  The 
initial report will contain all available details about the event.  If the Investigator does not have all 
information about an SAE within the submission window, the Investigator will not wait to receive 
additional details before notifying the sponsor of the event.  Relevant follow-up information should 
be submitted to the sponsor or designee within 24 hours of awareness of the new information 
and/or upon request. 
9.7.2 
Expedited Reporting Requirements 
The sponsor or designee will report all events qualifying as Suspected Unexpected Serious 
Adverse Reactions (SUSARs) to the relevant health and regulatory authorities and Investigators 
in the form of an expedited safety report.  SUSARs will be submitted as follows: 
• Within 7* calendar days for unexpected life-threatening or fatal SAEs that are unexpected 
and considered related to study treatment 
• Within 15* calendar days for all other SAEs that are unexpected and considered related to 
study treatment  
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*Note: These timeframes begin with the first notification of the SUSAR from the investigator 
to the sponsor or designee. 
In addition to safety reporting requirements of the sponsor, the investigator must also comply with 
all applicable requirements related to the reporting of SAEs to local health and regulatory 
authorities. 
9.8 
Adverse Events of Special Interest 
The following events are considered adverse events of special interest (AESI) and should be 
reported following SAE reporting procedures (Section 9.7).  These events have been identified as 
serious risks associated with approved T-cell-based therapies and can result in severe and fatal 
reactions. The following AEs (irrespective of severity, attribution, or seriousness) will therefore 
be monitored as AESI in this study: 
• Cytokine release syndrome 
• Neurologic toxicity 
• Autoimmune toxicity 
• Any event that satisfies the definition of DLT (Section 5.3) 
• Any event (other than the above) for which rimiducid is administered as supportive care 
9.9 
Adverse Event Follow-Up Reporting 
The Investigator should follow all unresolved AEs and SAEs until the events are resolved or 
stabilized (in the case of persistent impairment), the subject dies or is lost to follow-up, or it has 
been determined that the study treatment or participation is not the cause of the AE/SAE.  
Resolution of AEs and SAEs (with dates) should be documented on the case report form and in 
the subject’s medical record to facilitate source data verification (SDV). 
For SAEs, the sponsor or designee may utilize telephone, fax, or electronic mail communications 
as well as monitoring visits to obtain additional case details deemed necessary to appropriately 
evaluate the SAE report (e.g., hospital discharge summary, consultant report, or autopsy report).  
Within 24 hours of receipt of new follow-up information, the Investigator must update the SAE 
report and submit any supporting documentation to the sponsor or designee. 
9.10 
Pregnancy Reporting 
The investigator should report to the sponsor or designee all instances of pregnancy in female 
subjects or partners of male subjects within 24 hours of their knowledge of the pregnancy using 
the Pregnancy Form.  In addition, abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal 
death, stillbirth, congenital anomalies, and ectopic pregnancy) are considered SAEs and must be 
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reported using the SAE Form.  Follow-up information regarding the outcome of the pregnancy and 
any postnatal sequelae in the infant will be required. 
9.11 
Safety Reporting Contact Information 
SAE and pregnancy reporting contact information are provided below.  All reports (initial and 
follow-up) for screening and treatment-emergent SAEs, AESI, and pregnancy should be directed 
to the electronic SAE reporting mailbox (primary route of submission) or facsimile (back-up): 
Email:
  
Fax (back-up): 
 
Sites should contact the sponsor medical monitor for any safety concerns or questions.   
Primary Medical Monitor: 
 
Email: 
 
Telephone No (direct): 
 
Alternate Telephone No (mobile):  
 
Back-up Medical Monitor: 
 
Email: 
 
Telephone No (direct): 
 
Alternate Telephone No (mobile):  
 
 
 
STATISTICAL METHODS 
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below. Specific details will be provided in the Statistical Analysis Plan. 
No formal hypothesis testing will be conducted. Data will be summarized using descriptive 
statistics by dose level/Part and tumor type (i.e., Arm 1 reported separately from Arm 2). 
Continuous variables will be summarized using the number of observations, mean, standard 
deviation, coefficient of variation, median, and range as appropriate. Categorical values will be 
summarized using the number of observations and percentages as appropriate.  Descriptive 
summaries of time to event data from Kaplan Meier estimates will include the number of events, 
number censored, medians, quartiles and 95% confidence intervals. Graphical summaries of the 
data may be presented. All data will be listed for all subjects. 
The sponsor will establish a clinical data cutoff date for clinical study report analysis reporting 
12 months after the last subject has received BPX-701 or after all subjects have discontinued the 
study, whichever comes first. 
10.1 
Sample Size Determination 
Part 1 (Phase 1): Cell Dose Escalation 
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One or more dose cohorts of 3 to 6 subjects will be enrolled at a cell dose level including at least 
6 subjects at the RDE.  The total number of subjects enrolled in Part 1 will depend on the frequency 
of DLT and when RDE is determined for each disease indication. 
Parts 2 and 3 (Phase 2): Dose Expansion 
The dose expansion phase of this study is not designed to make explicit power and Type I error 
considerations for a hypothesis test.  Instead, it is designed to obtain preliminary efficacy and 
additional safety and PK/PD data on the PRAME-TCR therapy, BPX-701, administered at the 
respective RDE to subjects with either AML/MDS or uveal melanoma that express sufficient levels 
of PRAME.  Preliminary efficacy will be assessed as follows: 
• For AML and MDS combined: the proportion of AML subjects with complete* or partial 
remission per ELN criteria pooled together with the proportion of MDS subjects with 
complete* or partial remission per IWG criteria during Part 2 as well as Part 3 (provided a 
minimum, cumulative 20% remission rate is observed in Part 2 and that the sponsor deems 
as having a promising risk/benefit profile) 
*Note: Complete remission includes CRMRD-, CR, and CRi (for AML) and CR and 
CR marrow (for MDS) 
• For uveal melanoma: the proportion of subjects with an objective response (CR or PR) 
per RECIST v1.1 during Part 2 as well as Part 3 (provided a minimum 10% ORR is 
observed in Part 2 and that the sponsor deems as having a promising risk/benefit profile) 
Given the exploratory nature of this study, it is anticipated that at least one interim analysis per 
arm will be conducted during the dose expansion phase when 10 patients have been enrolled and 
completed at least one post-baseline disease evaluation (Part 2).  A posterior probability will be 
used to guide further enrollment based on observed clinical activity in each disease indication 
compared to historical control response rates (i.e., ≤20% for AML/MDS; ≤10% for uveal 
melanoma).  If the interim analysis suggests that the clinical activity in an experimental arm is 
higher than that observed in historical reports, up to 30 additional subjects may be enrolled for a 
total of 40 subjects (Parts 2 and 3 combined).  Accrual of up to 30 additional uveal melanoma 
subjects may also proceed if the median time to next treatment (defined as the time from BPX-701 
T cell infusion to initiation of next systemic therapy for the disease under study) observed in the 
initial 10 subjects is ≥4 months.   
If the remission rate is ≤10% for the first AML/MDS subjects in both Parts 2 and 3 (at least 
20 subjects), further enrollment in Part 3 will be stopped.  Similarly, if the disease control rate, 
defined as the proportion of uveal melanoma subjects with an objective response (CR or PR) or 
stable disease per RECIST v1.1 is <15% for the first subjects in both Parts 2 and 3 (at least 10-
15 subjects), further enrollment in Part 3 will be stopped.  Interim analyses will be performed and 
interpreted by the sponsor. 
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10.2 
Analysis Sets 
The following analysis sets will be used for this study.  Each analysis set will be applied to Arm 1 
and Arm 2. 
All treated: all subjects with AML or MDS who were infused with any quantity of BPX-701 T cells 
(this is the safety population) 
Intent-to-treat (ITT): all subjects who were infused with the planned dose of BPX-701 T cells 
Efficacy: all ITT subjects in Parts 2 and 3 with at least one evaluable post-baseline tumor response 
assessment 
DLT evaluable: all ITT subjects in Part 1 who complete through Day 28 or who had a DLT during 
the DLT evaluation period 
PK: all ITT subjects with at least 1 evaluable concentration measurement of rimiducid 
10.3 
Subject Disposition 
Subject disposition summaries will include the number of enrolled subjects, the number of subjects 
receiving BPX-701 T cells, the number of subjects receiving rimiducid, the number of subjects 
completing the study, the number of subjects withdrawing prematurely, and the reasons for study 
discontinuation. 
Demographics, baseline disease characteristics, prior disease related therapies, and concomitant 
medications will be summarized using descriptive statistics. 
10.4 
Safety Analyses 
All safety analyses will be performed on data from the all treated analysis sets (Arm 1 and Arm 2 
separately) according to BPX-701 T cell dose level. The baseline value for safety assessment is 
defined as the value collected at the time closest to, but prior to, BPX-701 T cell infusion. The 
safety parameters to be evaluated are the incidence, severity, and type of AEs, clinically significant 
changes in the subject’s physical examination findings, vital signs measurements, and clinical 
laboratory results. Exposure to study treatment and reasons for discontinuation will be tabulated. 
All adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA) and assessed for severity by the investigator using the NCI CTCAE v4.03.  AEs will 
be summarized by system organ class and preferred term and presented in decreasing order of 
frequency. Incidences of AEs and SAEs will be summarized overall and with respect to CTCAE 
grade and relationship to study drug.  AEs leading to treatment discontinuation, infusion 
interruption, and with an outcome of death will also be summarized. Incidences of SAEs and 
AESIs will be summarized overall and with respect to relationship to study treatment.  
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Clinically significant changes from baseline in ECOG and changes from baseline in CTCAE 
grading for vital signs and safety laboratory parameters will be examined and presented in shift 
tables.  All abnormal laboratory parameters will be listed. 
10.5 
Pharmacokinetic Analyses 
Pharmacokinetic analyses will be described separately outside the context of this protocol and in 
the SAP. 
10.6 
Efficacy Variables and Analyses 
Clinical response to study treatment will be determined by the investigator’s assessment.   
For AML and MDS, all efficacy endpoints will be defined and analyzed according to the ELN or 
IWG criteria, respectively (Dohner 2017; Cheson 2006). The following efficacy endpoints will be 
derived and summarized descriptively according to study Part and BPX-701 T cell dose level: 
Remission Rate is defined as the combined portion of AML subjects with CRMRD-, CR, 
CRi, or PR plus MDS subjects with CR or marrow CR 
Morphologic leukemic-free state (MLFS) defined as the proportion of AML subjects 
with bone marrow blasts <5%, absence of blasts with Auer rods, and no extramedullary 
disease but with no hematologic recovery 
Time to next treatment is defined as the date of BPX-701 T cell infusion to the initiation 
of next systemic therapy for the disease under study. 
Relapse-free survival (RFS) is measured from the date of achievement of a remission (as 
defined above) until the date of relapse or death from any cause.  Subjects who do not 
experience disease relapse and are alive will be censored at the time of last evaluable tumor 
assessment. 
Event-free survival (EFS) subjects measured from the date of BPX-701 T cell infusion to 
the date of primary refractory disease, disease relapse following remission (as defined 
above), or death from any cause.  Subjects who do not experience disease progression or 
relapse and are alive will be censored at the time of last evaluable tumor assessment. 
Overall survival (OS) subjects measured from the date of BPX-701 T cell infusion to the 
date of death from any cause.  Subjects without documentation of death at the time of 
analysis will be censored as of the date the subject was last known to be alive. 
For uveal melanoma, all efficacy endpoints will be defined and analyzed according to RECIST 
v1.1 (Eisenhauer 2009) and irRC (secondary evaluation; Wolchok 2009).  The following efficacy 
endpoints will be derived and summarized descriptively according to study Part and BPX-701 
T cell dose level: 
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Objective Response Rate (ORR) is defined as the proportion of subjects with a best 
overall response of partial response (PR) or complete response (CR).  
Duration of response (DOR) is defined as the date from the first tumor assessment that 
supports the subject’s objective disease response to the date of disease progression or death 
due to any cause.  
Disease control rate (DCR) is defined as subjects with CR, PR, or stable disease (SD).  
Time to next treatment is defined as the date of BPX-701 T cell infusion to the initiation 
of next systemic therapy for the disease under study.  
Progression-free survival (PFS) is defined as the date of BPX-701 T cell infusion to the 
first documentation of disease progression or death due to any cause. Subjects who do not 
experience progressive disease and are alive will be censored at the time of last evaluable 
tumor assessment.  
OS defined as the date of BPX-701 T cell infusion until date of death due to any cause. 
Subjects without documentation of death at the time of analysis will be censored as of the 
date the subject was last known to be alive. 
10.7 
Research Laboratory Analyses 
Analyses of research laboratory samples, tumor markers, samples for gene therapy monitoring, 
tumor biopsies, and immune response data will be described separately outside the context of this 
protocol and in the SAP. 
10.8 
Interim Analysis 
For each dose expansion arm (Arm 1 and Arm 2 separately), one interim analysis is planned to 
evaluate the clinical activity of BPX-701 T cells.  The analysis will be performed after 
approximately 10 subjects have been enrolled and have at least 1 post-baseline disease assessment.  
The interim analysis will follow the rules outlined in Section 5.4.2.  Review and communication 
of results will be addressed by the SRC as described in Section 5.5. 
10.1. 
Data Monitoring Committee 
There will be no formal Data Monitoring Committee for this study.  Treatment emergent safety 
and efficacy data will be reviewed by the SRC comprised of participating investigators in the 
study, the medical monitor, and sponsor representatives (Section 5.5). 
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REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
11.1 
Institutional and Ethical Review 
The study will be conducted according to the ethical principles of the declaration of Helsinki, the 
ICH-GCP Guidelines, the EU Clinical Trial Directive (2001/120/EG), FDA and other international 
regulatory agencies. 
11.2 
Investigator Responsibilities 
By signing this document, the investigator agrees to carry out this research in accordance with the 
protocol approved by the IRB/EC, ICH GCP and all applicable regulatory requirements.  The 
investigator is responsible for ensuring that site personnel involved in conducting this trial will be 
qualified by education, training, and experience to perform their respective task(s).   
11.3 
Subject Informed Consent and Human Subject Protection 
Consent forms describing in detail the study intervention, study procedures, and risks are given to 
the participant and written documentation of informed consent is required prior to initiation of any 
study-related procedures. 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation.  Consent forms will be 
approved by all applicable local regulatory authorities and the participant will be asked to read and 
review the document.  The investigator will explain the research study to the participant and answer 
any questions that may arise.  A verbal explanation will be provided in terms suited to the 
participant’s comprehension of the purposes, procedures, and potential risks of the study and of 
their rights as research participants.  As part of this discussion, the investigator should clarity 
alternate therapy options and the associated risks/benefits. 
Participants will have the opportunity to carefully review the written consent form and ask 
questions prior to signing.  The participants should have the opportunity to discuss the study with 
their family or surrogates or think about it prior to agreeing to participate. 
The participant will sign the informed consent document prior to any procedures being done 
specifically for the study.  Participants must be informed that participation is voluntary and that 
they may withdraw from the study at any time, without prejudice.  A copy of the informed consent 
document will be given to the participants for their records. 
The informed consent process will be conducted and documented in the source document 
(including the date), and the form signed, before the participant undergoes any study-specific 
procedures.  The rights and welfare of the participants will be protected by emphasizing that the 
quality of medical care will not be adversely affected if they decline to participate in this study. 
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11.4 
Confidentiality and Privacy 
Participant confidentiality and privacy is held in trust by the participating investigators, their staff, 
and the sponsor.  This confidentiality is extended to cover testing of biological samples in addition 
to the clinical information relating to participants.  Therefore, the study protocol, documentation, 
data, and all other information generated will be held in strict confidence.  No information 
concerning the study or data will be released to any unauthorized third party without prior written 
approval of the sponsor. 
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
EC, or regulatory agencies may inspect all documents and records required to be maintained by 
the investigator, including but not limited to, medical and pharmacy records for the participants in 
this study.  The clinical study site will permit access to such records. 
The subject’s contact information will be securely stored at each clinical site for internal use during 
the study.  At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
Subject research data, which is for purposes of statistical analysis and scientific reporting, will be 
entered into an electronic clinical study database maintained by the sponsor or designee.  This will 
not include the subject’s contact or identifying information.  Rather, individual participants and 
their research data will be identified by a unique study identification number.  The study data entry 
and study management systems used by clinical sites will be secured and password protected.  At 
the end of the study, all study databases will be de-identified and archived according to the 
sponsor’s standard policies. 
11.5 
Clinical Monitoring 
Clinical site monitoring will be conducted by the sponsor or designee to ensure that the rights and 
well-being of trial participants are protected, that the reported trial data are accurate, complete, and 
verifiable, and that the conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), with International Conference on Harmonization Good Clinical Practice 
(ICH GCP), and with applicable regulatory requirement(s). 
The investigational site will provide direct access to all trial-related information, source 
data/documents, and reports for the purpose of monitoring by the sponsor, and inspection by local 
and national regulatory authorities. 
11.6 
Data Handling and Record Keeping 
11.6.1 
Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
investigator.  The investigator is responsible for ensuring the accuracy, completeness, legibility, 
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and timeliness of the data reported.  The investigator will review all the case report forms for each 
subject and confirm the completeness, medical correctness, and plausibility of the documented 
data by his/her electronic signature. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. 
Study data will be entered by the site staff into a 21 CFR Part 11-compliant electronic data capture 
system maintained by the sponsor or designee.  The data system includes password protection and 
internal quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate.  Clinical data will be entered directly into the electronic CRF from the 
source documents and should be consistent with the latter. 
11.6.2 
Study Records Retention 
Study documents should be retained by the site for a minimum of 2 years after the last approval of 
a marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal discontinuation 
of clinical development of the study intervention.  These documents should be retained for a longer 
period, however, if required by local regulations.  No records will be destroyed without the written 
consent of the sponsor, if applicable.  It is the responsibility of the sponsor to inform the 
investigator when these documents no longer need to be retained. 
11.7 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol or ICH GCP.  The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff.  
As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly.  Protocol deviations must be sent to the reviewing IRB/EC per local regulations.
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APPENDICES 
13.1 
Appendix 1:  Schedule of Assessments 
Study Period 
Prescreen 
Screening4 
Baseline 
Treatment 
EOT22 
Post 
treatment 
Follow Up 
Month 
-- 
-- 
-- 
1 
2 
3 
4 
5 
6 
9 
12 
-- 
Q6M 
x823 
Q12M 
x1024 
Day 
-- 
-42 
to -8 
-7  
to -1 
0 
1 
2 
4 
7 
11 
14 
21 
28 
56 
84 
112 
140 
168 
252 
336 
-- 
-- 
-- 
Visit Window (days) 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
±2 
±2 
±2 
±3 
±3 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
-- 
±14 
±14 
Informed consent (Prescreen) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HLA typing1  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PRAME expression2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infectious disease monitoring3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent (Screening/Treatment)4 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography5 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history5 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior medications 
(includes anticancer therapy)5 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam (complete)6 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Weight 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Apheresis7 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lymphodepletion8 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY TREATMENT 
BPX-701 T cell infusion10 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rimiducid infusion12 
 
 
 
 
As indicated to treat uncontrolled treatment-emergent toxicity; see Appendix 3 
SAFETY ASSESSMENTS 
ECOG performance status 
 
X 
X9 
X11 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs13 
 
 
X9 
X13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical exam (symptom-directed)6 
 
 
X 
X11 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
Neurological exam, MMSE14 
 
 
 
X14 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
ECHO/MUGA15 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse events16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
LABORATORY ASSESSMENTS 
Hematology 
 
X 
X9 
X11 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Chemistry 
 
X 
X9 
X11 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
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Study Period 
Prescreen 
Screening4 
Baseline 
Treatment 
EOT22 
Post 
treatment 
Follow Up 
Month 
-- 
-- 
-- 
1 
2 
3 
4 
5 
6 
9 
12 
-- 
Q6M 
x823 
Q12M 
x1024 
Day 
-- 
-42 
to -8 
-7  
to -1 
0 
1 
2 
4 
7 
11 
14 
21 
28 
56 
84 
112 
140 
168 
252 
336 
-- 
-- 
-- 
Visit Window (days) 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
±2 
±2 
±2 
±3 
±3 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
-- 
±14 
±14 
Coagulation 
 
X 
X9 
X11 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Urinalysis 
 
X 
X9 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test 
 
X 
X9 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Testicular toxicity monitoring17 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
Cytokines18 
 
 
X9 
X18 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
X 
 
 
BPX-701 T cell tracking and functional 
activity19 
 
 
X9 
X19 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
Gene therapy monitoring20 
 
 
X9 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
X 
Tumor biopsy (Arm 2 only)21 
 
 
X9 
 
 
 
 
 
 
X21 
 
 
 
 
 
 
 
 
X21 
 
 
EFFICACY ASSESSMENTS 
ARM 1 (AML/MDS) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor analysis – peripheral blood25 
 
X26 
X9,27 
X11 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X25 
 
 
 
Tumor analysis – bone marrow 
 
X26 
X9,27 
 
 
 
 
 
 
 
 
X28 
 
X28 
 
 
X28 
 
X28 
 
 
 
ARM 2 (Uveal melanoma) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Radiographic tumor imaging and 
response assessment 
 
X29 
X9,30 
 
 
 
 
 
 
 
 
X31 
 
X31 
 
 
 
 
 
 
 
 
ARM 1 & ARM 2 (All subjects) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital status 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Subsequent anticancer therapy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
1. 
If not part of prior medical records at the time of consent for Prescreening. 
2. 
Centralized testing for PRAME expression in a fresh bone marrow aspirate (AML/MDS) or FFPE tumor tissue biopsy (uveal melanoma).  Refer to Section 8.4.1. 
3. 
Blood sample for infectious disease evaluation must be collected within 7 days of planned apheresis.  Refer to Section 8.2.8 for panel scope. 
4. 
Only for HLA-A2.01+ subjects with documented positive PRAME expression and no evidence of active infectious disease per Prescreening evaluation. 
5. 
As described in Section 8.1. 
6. 
As described in Section 8.2.3.  Obtain standing height at Screening only.    
7. 
Perform as described in Section 7.2 between Day -40 and Day -21 or as approved by the sponsor.  Subjects (Arms 1 and 2) must have adequate bone marrow 
function and subjects (Arm 1 only) must be ≥14 days since the last dose of ongoing or prior anticancer therapy at the time of apheresis. 
8. 
Cyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV on Day -5, Day -4, and Day -3 prior to the planned BPX-701 infusion on Day 0.  Refer to Section 
7.3. 
9. 
Must be performed prior to initiation of lymphodepletion. 
10. Administer by IV infusion over 15-30 minutes as described in Section 7.4 and the Pharmacy Manual.  Subjects should be monitored for safety ≥4 hours after the 
end of the infusion and released once clinically stable. 
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11. Must be performed prior to BPX-701 infusion. 
12. FOR QUALIFYING SUBJECTS ONLY (as defined in Section 7.6): Administer by IV infusion over 2 hours as described in Section 7.5 and the Pharmacy Manual.  
Subjects should be monitored for safety ≥4 hours after the end of the infusion and released once clinically stable.  All required post-infusion time points for blood 
sample collection, electrocardiogram assessments, and clinic visits will be performed relative to rimiducid administration.  Refer to Appendix 3 for additional 
details.    
13. As described in Section 8.2.2.  On infusion days (Day 0 for BPX-701 and each dose of rimiducid, if applicable), collect prior to infusion (-60 to -5 min) and at 15 
min, 30 min, 1 hr, 2 hr, and 4 hr (± 5 min) after the start of the infusion, and thereafter as clinically indicated until completion of the post-infusion safety monitoring 
period. 
14. As described in Section 8.2.4.  On Day 0, perform prior to the BPX-701 infusion (-60 to -5 min) and 4hr (± 30 min) after the start of the infusion.  Additional 
assessments may be performed on infusion days or at any time thereafter as clinically indicated; all neurological exams should be accompanied by an MMSE. 
15. LVEF determination by ECHO or MUGA as described in Section 8.2.5.  Historical results may be obtained from medical records if performed within 6 weeks of 
Screening.    
16. Collect from date of informed consent (Prescreen) according to safety reporting periods defined in Section 9.6.  Refer to Section 9.2 for the definition of an AE.   
17. As described in Section 8.2.8.  Additional time points should be collected as clinically indicated. 
18. Refer to Section 8.2.8 and Section 8.4.3 for panel scope.  On Day 0, collect blood samples (serum) prior to the BPX-701 infusion and at 1, 4, and 24 hr after the 
start of the infusion; for each time point, duplicate samples should be collected for local and central assessment, respectively.  Refer to Appendix 2 and Appendix 
3 for additional details.   
19. Refer to Section 8.2.8 and Section 8.4.2 for panel scope.  On Day 0, collect whole blood samples prior to the BPX-701 infusion and at 1, 4, and 24 hr after the start 
of the infusion; for each time point, duplicate samples should be collected for local and central assessment, respectively.  Refer to Appendix 2 and Appendix 3 for 
additional details. 
20. As described in Section 8.4.6. 
21. As described in Section 8.4.5.  Required pretreatment and on-treatment tumor biopsy for subjects with uveal melanoma.  Collect pretreatment sample at Baseline 
prior to lymphodepletion.  Collect on-treatment sample between Days 14 and 21. An additional biopsy at disease progression (EOT visit) is requested, if feasible.  
Refer to the Laboratory Manual for sample collection procedures. 
22. Twelve months after the BPX-701 infusion, or at the time disease progression is confirmed or the subject is discontinued unless the subject has died, is lost to 
follow-up, or has withdrawn consent for study participation.  Visit should be completed before starting any subsequent anticancer treatment.  If a subject is unable 
to return for EOT, the subject should be contacted to collect information on any unresolved AEs.  Serum pregnancy test (female subjects) or testicular toxicity 
monitoring (male subjects) is required if not performed within the past 28 days.  
23. Months 18, 24, 30, 36, 42, 48, 54, and 60 from the BPX-601 T cell infusion.  Refer to Section 8.4.6. 
24. Years 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15 from the BPX-701 T cell infusion.  Refer to Section 8.4.6. 
25. Complete blood count including white blood cell differential and myeloid blast percentage.  Samples may be collected more frequently if clinically indicated.  
Following Month 12, peripheral blood sample are required every 4 weeks (±7 days) for 12 months then every 12 weeks (±7 days) until disease progression or 
relapse, the start of new anticancer therapy, withdrawal, or study end.  If a subject discontinues the study for reasons other than progression or relapse, continue 
peripheral blood assessments per standard of care frequency until documented progression/relapse, withdrawal, or study end.  Response assessment by the 
investigator using ELN criteria for AML (Appendix 9) or IWG criteria for MDS (Appendix 10). 
26. Screening peripheral blood sample as well as aspirate or biopsy to assess bone marrow morphology including myeloid blast count, genetics and mutation profiling, 
and immunophenotyping.  Standard of care assessments if performed within 6 weeks of Screening may be used to characterize disease status.  Refer to Section 
8.1.2. 
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27. Baseline peripheral blood sample as well as aspirate or biopsy within 14 days of BPX-701 infusion and following the last dose of any salvage chemotherapy 
administered after apheresis.  Imaging required to document known or suspected CNS involvement; if positive, perform lumbar puncture.  Perform additional 
imaging techniques as appropriate to document other known or suspected sites of extramedullary disease. 
28. Serial aspirate or biopsy samples at the indicated time points after BPX-701 infusion.  Samples may be collected more frequently if clinically indicated.  Assess of 
bone marrow morphology including myeloid blast count relative to Baseline.  Perform additional marrow analyses (genetics, immunophenotyping) as well as CNS 
and/or extramedullary disease imaging, as appropriate, to confirm complete or partial remission.  Following Month 12, marrow sample are required every 24 weeks 
(±7 days) until disease progression or relapse, the start of new anticancer therapy, withdrawal, or study end.  If a subject discontinues the study for reasons other 
than progression or relapse, continue marrow assessments per standard of care frequency until documented progression/relapse, withdrawal, or study end.  Response 
assessment by the investigator using ELN criteria for AML (Appendix 9) or IWG criteria for MDS (Appendix 10).   
29. Radiologic evidence of measurable disease required at Screening to confirm subject eligibility.  Standard of care assessments if performed within 6 weeks of 
Screening may be used to assess disease status. 
30. CT scan with contrast of the chest, abdomen, and pelvis plus MRI to document known or suspected liver and CNS metastases (all subjects) within 28 days of 
BPX-701 infusion.  Bone scan required to document known or suspected bone metastases, if applicable.  Refer to Section 8.6. 
31. Use the same assessment technique for tumor imaging throughout the study.  Radiographic assessments required at Day 28, followed by every 8 weeks (±7 days) 
for the first year following BPX-701 T cell infusion, then every 12 weeks (±7 days) for the second year, then annually until confirmed disease progression, the start 
of new anti-cancer therapy, withdrawal, or study end. If a subject discontinues the study for reasons other than progressive disease, continue imaging per standard 
of care frequency until documented disease progression, withdrawal, or study end.  Response assessment by the investigator using RECIST v1.1 (Appendix 7).  
Confirmation of response or disease progression is required as described in Section 8.6.
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13.2 
Appendix 2:  Biomarker Sampling Schedule during Treatment Month 1 (Day 0 thru Day 28) 
Study Period: 
Treatment 
Month: 
1 
Day: 
0 
1 
2 
4 
7 
11 
14 
21 
28 
Scheduled collection time 
Pre-infusion1 
Post-infusion start2 
During visit 
1hr 
4hr 
24hr 
Sample collection window (min) 
-60 to -5 
±5 
±5 
±60 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sample (serum) for cytokines3, 4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Whole blood sample for BPX-701 T cell tracking and 
functional activity3, 4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1. 
BPX-701 T cell infusion. 
2. 
Scheduled time points are relative to the start of the infusion. 
3. 
Refer to Laboratory Manual for detailed sample collection, processing, and shipment instructions. 
4. 
Samples may be collected more frequently as clinically indicated. For subjects with signs or symptoms of CRS or neurotoxicity (Section 7.6.2), collect at the time of event as 
described in Section 7.6.4. 
 
13.3 
Appendix 3:  Pharmacokinetics, ECG, and Safety Biomarker Sampling Schedule for Subjects that receive Rimiducid 
Study Period: 
Treatment   
Scheduled collection time 
Pre-infusion1 
Post-infusion start2 
Every 24hr thereafter until 
symptom resolution 
1hr 
2hr 
4hr 
8hr 
24hr 
Sample collection window (min) 
-60 to -5 
±5 
-54 
±5 
±5 
±60 
±60 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sample (plasma) for rimiducid PK6 
X3 
X3 
X3 
X3 
X3 
X 
 
Electrocardiogram5 
X 
X 
X 
X 
X 
X 
 
Blood sample (serum) for cytokines6,7 
X 
X 
X 
X 
 
X 
X 
Whole blood sample for BPX-701 T cell tracking and 
functional activity6,7 
X 
X 
X 
X 
 
X 
X 
1. 
Rimiducid infusion FOR QUALIFYING SUBJECTS ONLY (as defined in Section 7.6).  Administer by IV infusion over 2 hours as described in Section 7.5 and the Pharmacy 
Manual.  Subjects should be monitored for safety ≥4 hours after the end of the infusion and released once clinically stable. 
2. 
Scheduled time points are relative to the start of the FIRST rimiducid infusion ONLY. 
3. 
For all planned PK time points up to 8 hours post-infusion, blood must be collected from a peripheral vein contralateral to the arm/location into which rimiducid is administered. 
4. 
Collect sample just prior to the end of the rimiducid infusion. 
5. 
Prior to each blood sample collection, obtain a time-matched ECG; triplicate assessments no more than 5 mins apart are required if the initial tracing is abnormal, clinically 
significant. 
6. 
Refer to Laboratory Manual for detailed sample collection, processing, and shipment instructions. 
7. 
Samples may be collected more frequently as clinically indicated. For subjects with signs or symptoms of CRS or neurotoxicity (Section 7.6.2), collect at the time of event as 
described in Section 7.6.4. 
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13.4 
Appendix 4:  Eastern Cooperative Oncology Group Performance Status 
Grade 
Eastern Cooperative Oncology Group Performance Status 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about 
more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
5 
Dead 
Adapted from Oken 1982 
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13.5 
Appendix 5:  New York Heart Association Criteria 
The following table presents the New York Heart Association Classification of Functional 
Capacity and Objective Assessment:  
Class Functional Capacity 
Objective Assessment 
I 
Patients with cardiac disease but without resulting limitations of physical 
activity. Ordinary physical activity does not cause undue fatigue, 
palpitation, dyspnea, or anginal pain. 
No objective evidence of 
cardiovascular disease. 
II 
Patients with cardiac disease resulting in slight limitation of physical 
activity. They are comfortable at rest. Ordinary physical activity results in 
fatigue, palpitation, dyspnea, or anginal pain. 
Objective evidence of minimal 
cardiovascular disease. 
III 
Patients with cardiac disease resulting in marked limitation of physical 
activity. They are comfortable at rest. Less than ordinary activity causes 
fatigue, palpitation, dyspnea, or angina pain. 
Objective evidence of 
moderately severe 
cardiovascular disease. 
IV 
Patients with cardiac disease resulting in inability to carry on any physical 
activity without discomfort. Symptoms of heart failure or the anginal 
syndrome may be present even at rest. If any physical activity is 
undertaken, discomfort is increased. 
Objective evidence of severe 
cardiovascular disease. 
 
Classification of Functional Capacity and Objective Assessment. Available at 
http://my.americanheart.org/professional/StatementsGuidelines/ByPublicationDate/PreviousYears/Classification-of-
Functional-Capacity-and-Objective-Assessment_UCM_423811_Article.jsp. Accessed 18 June 2018 
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13.6 
Appendix 6:  Common Corticosteroids and Conversion Half-Lives 
 
 
 
Glucocorticoid 
Approximate 
equivalent 
dose (mg) 
 
 
Half‐life 
(hr) 
 
 
Clearance/ 
7 half- lives 
(DAYS) 
Short‐Acting 
Cortisone 
25 
8-‐12 
3.5 
Hydrocortisone 
20 
8-‐12 
3.5 
Intermediate‐Acting 
Methylprednisolone 
4 
18-‐36 
10.5 
Prednisolone 
5 
18-‐36 
10.5 
Prednisone 
5 
18-‐36 
10.5 
Triamcinolone 
4 
18-‐36 
10.5 
Long‐Acting 
Betamethasone 
0.6 – 0.75 
36-‐54 
15.75 
Dexamethasone 
0.75 
36-‐54 
15.75 
Hunter J. (1992). “Second line agents in the treatment of rheumatic diseases.” Ann Rheum Dis 51: 1192. 
 
Meikle AW, Tyler FH. (1977). “Potency and duration of action of glucocorticoids. Effects of hydrocortisone, 
prednisone and dexamethasone on human pituitary function.” Am J Med 63: 200-207. 
 
Singer M, Webb A. (2009). Oxford Handbook of Critical Care, 3rd Edition, Oxford University Press. 
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13.7 
Appendix 7:  Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 
Quick Reference 
Eligibility 
Only patients with measurable disease at baseline should be included in this protocol. 
  
Measurable disease - the presence of at least one measurable lesion. If the measurable disease is restricted to a 
solitary lesion, its neoplastic nature should be confirmed by cytology/histology. 
  
Measurable lesions: 
• 
Tumor lesions must be accurately measured in at least one dimension with longest diameter  ≥10mm 
by CT scan (slice thickness ≤5 mm), ≥10mm caliper measurement by clinical exam, ≥20mm by chest 
x-ray. 
• 
Malignant lymph nodes must be considered pathologically enlarged and measurable with a diameter 
≥15mm in the short axis when assessed by CT scan (slice thickness ≤5 mm) 
 
Non-measurable lesions - all other lesions, including small lesions (longest diameter <10mm or pathological 
lymph nodes with ≥10 to <15mm short axis) as well as truly non-measurable lesions, i.e., leptomeningeal 
disease, ascites, pleural/pericardial effusion, inflammatory breast disease, lymphangitis cutis/pulmonis, cystic 
lesions, and also abdominal masses that are neither confirmed nor followed by reproducible imaging 
techniques. 
 
All measurements should be taken and recorded in metric notation, using a ruler or calipers. All baseline 
evaluations should be performed as closely as possible to the beginning of treatment and never more than 4 
weeks before the beginning of the treatment.  
 
The same method of assessment and the same technique should be used to characterize each identified and 
reported lesion at baseline and during follow-up.  
 
Clinical lesions will only be considered measurable when they are superficial and ≥10mm diameter as assessed 
using calipers. For the case of skin lesions, documentation by color photography, including a ruler to estimate 
the size of the lesion, is suggested.  When lesions can be evaluated by both clinical exam and imaging, imaging 
is preferred. 
 
Methods of Measurement 
CT is the best currently available and reproducible method to measure lesions selected for response assessment. 
CT should be performed with cuts of 5mm or less in slice thickness contiguously. MRI is also acceptable in 
certain situations (e.g., for body scans). 
 
Lesions on chest X-ray are acceptable as measurable lesions when they are clearly defined and surrounded by 
aerated lung. However, chest CT is preferable.  
 
Ultrasound is not a useful assessment of lesion size and should not be used as a method of measurement as they 
are not reproducible and operator dependent. If new lesions are identified by ultrasound, confirmation by CT or 
MRI is advised.  If there is concern about radiation exposure at CT, MRI may be used instead of CT in selected 
instances.  
 
The utilization of endoscopy and laparoscopy for objective tumor evaluation is not advised. However, such 
techniques can be useful in confirming complete pathological response when biopsies are obtained or to 
determine relapse in trials where recurrence following complete response or surgical resection is an endpoint. 
 
Tumor markers alone cannot be used to assess response.  If markers are initially above the upper normal limit, 
they must normalize for a patient to be considered in complete response. 
 
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Cytology and histology can be used to differentiate between PR and CR in rare cases (e.g., after treatment to 
differentiate between residual benign lesions and residual malignant lesions in tumor types such as germ cell 
tumors). 
 
Baseline documentation of Target and Non-Target Lesions 
All measurable lesions up to a maximum of two lesions per organ and 5 lesions in total, representative of all 
involved organs should be identified as target lesions and recorded and measured at baseline.  
 
Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their 
suitability for accurate repeated measurements (either by imaging techniques or clinically). 
 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target lesions will be 
calculated and reported as the baseline sum diameters. The baseline sum diameters will be used as reference by 
which to characterize any objective tumor regression in the measurable dimension of the disease. 
 
All other lesions (or sites of disease) including pathological lymph nodes should be identified as non-target 
lesions and should also be recorded at baseline. Measurements of these lesions are not required, but these 
lesions should be followed as ‘present’, ‘absent’, or ‘unequivocal progression’.  
 
Response Criteria 
Evaluation of Target Lesions 
 
Complete Response (CR): 
Disappearance of all target lesions.  Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to 
<10mm. 
 
Partial Response (PR): 
At least a 30% decrease in the sum of diameters of target lesions, taking 
as reference the baseline sum diameters 
 
Progressive Disease (PD): 
At least a 20% increase in the diameters of target lesions, taking as 
reference the smallest sum on study.  In addition to the relative increase of 
20%, the sum must also demonstrate an absolute increase of ≥5mm.  The 
appearance of 1 or more new lesions is also considered progression 
 
Stable Disease (SD): 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters since 
treatment started 
 
Evaluation of Non-Target Lesions 
 
Complete Response (CR): 
Disappearance of all non-target lesions and normalization of tumor 
marker level.  All lymph nodes must be non-pathological in size (<10mm 
short axis) 
 
Non-CR/Non-PD: 
Persistence of one or more non-target lesion(s) or/and maintenance of 
tumor marker level above the normal limits 
 
Progressive Disease (PD): 
Appearance of one or more new lesions and/or unequivocal progression 
of existing non-target lesions 
 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until the end of 
treatment considering any requirement for confirmation. In general, the patient's best response assignment 
will depend on findings of both target and non-target disease and will also take into consideration the 
appearance of new lesions. 
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Target lesions 
Non-Target lesions 
New Lesions 
Overall response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all evaluated 
No 
PR 
SD 
Non-PD or not all evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
Unevaluable 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
 
Patients with a global deterioration of health status requiring discontinuation of treatment without objective 
evidence of disease progression at that time should be classified as having “symptomatic deterioration”. Every 
effort should be made to document the objective progression even after discontinuation of treatment. 
 
In some circumstances it may be difficult to distinguish residual disease from normal tissue. When the evaluation 
of complete response depends on this determination, it is recommended that the residual lesion be investigated 
(fine needle aspirate/biopsy) to confirm the complete response status. 
 
Confirmation 
The main goal of confirmation of objective response is to avoid overestimating the response rate observed.  In 
cases where confirmation of response is not feasible, it should be made clear when reporting the outcome of such 
studies that the responses are not confirmed. 
 
To be assigned a status of confirmed PR or confirmed CR, changes in tumor measurements must be confirmed 
by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. 
Longer intervals as determined by the study protocol may also be appropriate.  
 
In the case of SD, follow-up measurements must have met the SD criteria at least once after study entry at a 
minimum interval (in general, not less than 6-8 weeks) that is defined in the study protocol. 
 
Adapted from Eisenhauer 2009
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13.8 
Appendix 8:  Immune-Related Response Criteria (irRC) 
Under immune-related Response Criteria (irRC), antitumor response is based on the total 
measurable tumor burden. For irRC, only index and measurable new lesions are considered. To 
calculate baseline tumor burden, the sum of the products of the two largest perpendicular diameters 
(SPD) of all index lesions is obtained. All index lesions include up to 5 lesions per organ, up to 10 
visceral lesions and 5 cutaneous index lesions. At each subsequent tumor assessment, the SPD of 
index lesions and of new, measurable lesions (≥5 x 5mm; up to 5 new lesions per organ: 5 new 
cutaneous lesions, and 10 visceral lesions) are added together to provide the total tumor burden: 
Tumor Burden = SPDindex lesions + SPDnew, measurable lesions 
Time-point response assessment using irRC involves percentage changes in tumor burden per 
assessment time point which describes the size and growth kinetics of both conventional and new, 
measurable lesions upon their appearance. At each tumor assessment, the response in index and 
new, measurable lesions is defined and based on the change in tumor burden (after ruling out irPD). 
Decreases in tumor burden must be assessed in relation to baseline measurements (i.e. the SPD of 
all index lesions at screening). 
Overall response assessment (according to irRC) is derived from the time-point assessments, 
which is based on tumor burden, and as listed below: 
Measurable Response 
Non-Measurable Response 
Overall Response 
Index and new, measurable 
lesions (tumor burden), *% 
Non-index lesions 
New, non-measurable 
lesions 
Using irRC 
↓100 
Absent 
Absent 
irCR† 
↓100 
Stable 
Any 
irPR† 
↓100 
Unequivocal progression 
Any 
irPR† 
↓≥50 
Absent/Stable 
Any 
irPR† 
↓≥50 
Unequivocal progression 
Any 
irPR† 
↓<50 to <25↑ 
Absent/Stable 
Any 
irSD 
↓<50 to <25↑ 
Unequivocal progression 
Any 
irSD 
≥25? 
Any 
Any 
irPD† 
* Decreases assessed are relative to baseline, including measurable lesions only (>5 x 5 mm). 
† Assuming response (irCR) and progression (irPD) are confirmed by a second, consecutive assessment at least 4 weeks apart. 
 
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Response/Lesion 
Categories 
irRC Response definition 
 
New, measurable 
lesions (i.e. ≥5 x 5 mm) 
Incorporated into tumor burden 
New, measurable 
lesions (i.e. <5 x 5 mm) 
Do not define progression (but preclude irCR) 
Non-index lesions 
Changes contribute to defining irCR (complete disappearance required) 
irCR 
Complete disappearance of all lesions (whether measurable, or not), and no new 
lesions, in two consecutive observations not less than 4 weeks apart 
irPR 
≥50% decrease in tumor burden, compared with baseline, in two consecutive 
observations at least 4weeks apart 
irSD 
Not meeting criteria for irCR or irPR, in the absence of irPD 
irPD 
At least 25% increase in tumor burden relative to nadir (minimum recorded tumor 
burden), confirmed by a repeat, consecutive assessment no less than 4 weeks from 
the date first documented 
 
Adapted from Wolchok 2009 
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13.9 
Appendix 9:  ELN Response Criteria for AML 
CATEGORY 
DEFINITION 
RESPONSE 
CR without MRD (CRMRD-) 
If studied pretreatment, CR with negativity for a genetic marker by RT-PCR, or 
CR with negativity by MFC 
CR 
• Bone marrow blasts <5% 
• Absence of circulating blasts and blasts with Auer rods 
• Absence of extramedullary disease 
• ANC ≥1.0 x 109/L 
• Platelets ≥100 x 109/L 
• MRD+ or unknown 
CR with incomplete 
hematologic recovery (CRi) 
All CR criteria except: 
o 
Residual neutropenia (<1.0 x 109/L); or, 
o 
Thrombocytopenia (<100 x 109/L) 
Morphologic leukemia-free 
state (MLFS) 
• Bone marrow blasts <5% 
• Absence of circulating blasts and blasts with Auer rods 
• Absence of extramedullary disease 
• No hematologic recovery required 
• Marrow should not merely be aplastic; at least 200 cells should be enumerated, 
or cellularity should be ≥10% 
PR 
• All hematologic criteria of CR 
• Decrease of bone marrow blast percentage to 5% to 25% 
• Decrease of pretreatment bone marrow blast percentage by ≥50% 
Stable disease 
Absence of CRMRD-, CR, CRi, PR, MLFS; and criteria for progressive disease not 
met for ≥3 months 
Progressive disease 
Evidence for an increase in bone marrow blast percentage and/or increase of 
absolute blast counts in blood: 
o 
>50% increase in marrow blasts over baseline (a minimum 15%-point 
increase is required in cases with <30% blasts at baseline; or persistent 
marrow blast percentage >70% over ≥3 months; without at least a 100% 
improvement in ANC to an absolute level (>0.5 x 109/L, and/or platelet 
count to >50 x 109/L nontransfused); or 
o 
>50% increase in peripheral blasts (WBC x % blasts) to >25 x 109/L (in 
the absence of differentiation syndrome1); or, 
o 
New extramedullary disease 
RELAPSE 
Hematologic relapse (after 
CRMRD-, CR, CRi) 
• Bone marrow blasts ≥5%; or,  
• Reappearance of blasts in the blood; or, 
• Development of extramedullary disease 
Molecular relapse (after 
CRMRD-) 
If studied pretreatment, recurrence of MRD as assessed by RT-PCR or MFC 
TREATMENT FAILURE 
Primary refractory disease 
No CR or CRi after 2 courses of intensive induction treatment; excluding patients 
with death in aplasia or death due to indeterminate cause 
Death in aplasia 
Deaths occurring ≥7 days following completion of initial treatment while 
cytopenic; with an aplastic or hypoplastic bone marrow obtained within 7 days of 
death, without evidence of persistent leukemia 
Death from indeterminate 
cause 
Death occurring before completion of therapy, or <7 days following its 
completion; or death occurring ≥7 days following completion of initial therapy 
with no blasts in the blood, but no bone marrow examination available 
ANC=absolute neutrophil count; CR=complete remission; MFC=multiparameter flow cytometry; MRD=minimal 
residual disease; PR=partial remission; RT-PCR=reverse transcription polymerase chain reaction 
1. Transient increase in percentage of bone marrow blasts and an absolute increase in blood blasts 
Adapted from Dohner 2017
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13.10 
Appendix 10:  IWG Response and Hematological Improvement Criteria for 
Myelodysplasia 
CRITERIA FOR RESPONSE 
Category 
Description (responses must be last ≥4 weeks) 
Complete remission 
Bone Marrow: ≤5% blasts with normal maturation of cell lines1 
Peripheral Blood: 
• 
Hgb ≥11 g/dL 
• 
Platelets ≥100 x 109/L 
• 
Neutrophils ≥1.0 x 109/L 
• 
Blasts 0% 
Partial remission 
Same as complete response except bone marrow blasts decreased by ≥50% 
over pretreatment but still >5% 
Cellularity and morphology not relevant 
Marrow CR 
Bone Marrow: ≤5% blasts and decrease ≥50% over pretreatment 
Peripheral Blood: if HI responses, note in addition to marrow CR 
Stable disease 
Failure to achieve at least PR, but no evidence of progression for >8 weeks 
Failure 
Death during treatment or disease progression characterized by worsening of 
cytopenias, increase in bone marrow blast %, or progression to a more 
advanced MDS FAB subtype than pretreatment 
Relapse after CR or PR 
At least 1 of the following: 
• 
Return to pretreatment bone marrow blast % 
• 
Decrement of ≥50% from maximum remission/response levels in 
granulocytes or platelets 
• 
Reduction in Hgb ≥1.5 g/dL or transfusion dependence 
Cytogenetic response 
Complete: disappearance of the chromosomal abnormality without the 
appearance of new ones 
Partial: ≥50% reduction of the chromosomal abnormality 
Disease progression 
For subjects with: 
• 
<5% blasts: ≥50% increase in blasts to >5% blasts 
• 
5%-10% blasts: ≥50% increase to >10% blasts 
• 
10-20% blasts: ≥50% increase to >20% blasts 
• 
20-30% blasts: ≥50% increase to >30% blasts 
Any of the following: 
• 
≥50% decrement from maximum remission/response in granulocytes 
or platelets 
• 
Reduction in Hgb by ≥2 g/dL 
• 
Transfusion dependence 
CRITERIA FOR HEMATOLOGICAL RESPONSE 
Hematologic improvement2 
Description (responses must be last ≥8 weeks) 
Erythroid response 
(pretreatment <11 g/dL) 
Hgb increase by ≥1.5 g/dL 
Relevant reduction of units of RBC transfusions by an absolute number of ≥4 
RBC transfusions/8 weeks compared with the pretreatment transfusion number 
in the previous 8 weeks.  Only RBC transfusions given for a Hgb of ≤9.0 g/dL 
pretreatment will count in the RBC transfusion response evaluation. 
Platelet response 
(pretreatment <100 x 109/L) 
Absolute increase ≥30 x 109/L for patients starting with >20 x 109/L platelets 
Increase from <20 x 109/L to >20 x 109/L and by at least 100% 
Neutrophil response 
(pretreatment <1.0 x 109/L) 
≥100% increase and an absolute increase >0.5 x 109/L 
Progression or relapse after HI3 
At least one of the following: 
• 
≥50% decrement from maximum response levels in granulocytes or 
platelets 
• 
Reduction in Hgb by ≥1.5 g/dL 
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• 
Transfusion dependence 
CR=complete remission; FAB=French American British; Hgb=hemoglobin; HI=hematological improvement; 
PR=partial response; RBC=red blood cell 
1. Persistent dysplasia will be noted; dysplastic changes should consider the normal range of dysplastic changes. 
2. Pretreatment counts average of at least 2 measurements (not influenced by transfusions) ≥1 weeks apart. 
3. In the absence of another explanation, such as acute infection, repeated courses of chemotherapy, 
gastrointestinal bleeding, hemolysis, and so forth.  It is recommended that 2 kinds of erythroid and platelet 
responses be reported overall as well as by the individual response pattern. 
Adapted from Cheson 2006 
 
Bellicum Pharmaceuticals, Inc., BPX-701
IND 
 SN 0006