A Phase 1, Open-label, Dose Finding Study of CC-95251 Alone and in Combination With Antineoplastic Agents in Subjects With Acute Myeloid Leukemia and Myelodysplastic Syndromes
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
Sponsor: Bristol-Myers Squibb

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
1
A PHASE 1, OPEN-LABEL, DOSE FINDING STUDY OF CC-95251 ALONE AND IN 
COMBINATION WITH ANTINEOPLASTIC AGENTS IN SUBJECTS WITH ACUTE 
MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROMES
PROTOCOL NUMBER:
CA059-001
COMPOUND CODE:
CC-95251
(also known as BMS-986351)
DATE FINAL:
16 Jun 2021
AMENDMENT 1.0 FINAL:
17 Aug 2021
AMENDMENT 2.0 FINAL:
19 Dec 2022
AMENDMENT 3.0 FINAL:
19 May 2023
EudraCT NUMBER:
2021-002799-38
IND NUMBER:
154328
SPONSOR NAME/ ADDRESS:
Celgene Corporation
86 Morris Avenue
Summit, NJ 07901
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or 
consultant for review by you, your staff, and ethics committee/institutional 
review board.  The information contained in this document is regarded as 
confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by 
law or regulations.  Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
2
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION
Contact Information:
Name: 
Title: 
Address: 400 Dexter Ave N, Suite 1200, Seattle, WA 98109
Phone:  
E-mail: 
 
Note: The back-up 24-hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24-hour Global Emergency Contact Call Center: +1-877-501-7738
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
3
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
4
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
By my signature, I agree to personally supervise the conduct of this study at my study site 
and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, International Council for
Harmonisation (ICH) Good Clinical Practices Guidelines, and local regulations governing 
the conduct of clinical studies.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
5
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good Clinical 
Practices guidelines and agree to offer guidance throughout the study as needed.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
6
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 3.0:
The purpose of global amendment 3.0 is to add cohorts to evaluate the safety and preliminary 
efficacy of the investigational product CC-95251 (also known as BMS-986351) administered in 
combination with injectable azacitidine and venetoclax in eligible subjects with relapsed/refractory
(R/R) (Part A) and treatment-naïve (TN) acute myeloid leukemia (AML) (Part D).
CC-95251 is a first-in-class, high-affinity, fully human antibody, designed to bind to signal 
regulatory protein alpha (SIRPα) and block its interaction with cluster of differentiation 47 
(CD47), interrupting a macrophage inhibitory signaling pathway providing a mechanism for 
immune escape in AML. Preclinical studies including those conducted using SIRPα-positive tumor 
cells such as AML cell lines and patient-derived xenograft cultures have demonstrated anti-tumor 
activity of CC-95251 as monotherapy or in combination with azacitidine. Clinical experience in 
subjects with R/R AML and R/R myelodysplastic syndromes (MDS) has demonstrated 
preliminary safety and efficacy with CC-95251 as monotherapy and in combination with 
azacitidine. 
The B-cell lymphoma-2 inhibitor venetoclax (Venclexta) is approved by the US Food and Drug 
Administration and European Commission in combination with injectable azacitidine for adults 
with newly diagnosed (ND) AML ineligible for standard induction, and this regimen has improved
response rates and overall survival in this population compared to azacitidine monotherapy. 
Despite this improvement, prognosis in patients treated with this regimen remains poor, and the 
addition of agents with different mechanisms of action may confer added benefit. Currently, other 
agents targeting the CD47-SIRPα axis such as magrolimab (Hu5F9G4, an anti-CD47 monoclonal 
antibody) and ALX148 (SIRPα fusion protein CD47 blocker) are under clinical study in subjects 
with AML and MDS including in combinations with azacitidine or azacitidine and venetoclax.
Preliminary results from these studies have primarily demonstrated signs of improved clinical 
efficacy in the front-line TN setting. However, in contrast to the clinical experience with 
CC-95251, CD47-targeting agents have been noted to have associated hematologic toxicities
including significant anemia due to off-tumor, on-target activity on CD47-expressing red blood 
cells and may compound cytopenias seen with venetoclax. Therefore, the addition of CC-95251to 
azacitidine and venetoclax may provide additional clinical benefit with a more favorable safety 
profile. The updated protocol design enables evaluation of this triplet in the front-line setting, 
where clinical benefit is most likely to be derived.
In addition to the cohorts described above, additional revisions and clarifications based on the 
clinical trial experience to date have been incorporated into this amendment. Other clarifications, 
corrections of minor typographical errors, and incidental formatting changes were made 
throughout the document, including removal of the 
 
deficiency test from the Table of Events in 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
7
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 3.0
Section Number & Title
Description of Change
Brief Rationale
Medical Monitor / 
Emergency Contact 
Information
Updated personnel and contact information.
Changes in study personnel.
Protocol Summary
The Protocol Summary was updated to reflect 
changes made throughout the protocol.
Updated to include rationale for 
Protocol Amendment 3.0.
Introduced triplet combinations of 
CC-95251 with injectable 
azacitidine and venetoclax in 
relapsed/refractory (R/R) and 
newly diagnosed (ND) acute 
myeloid leukemia (AML)
subjects.
Section 1.1.1: Acute 
Myeloid Leukemia
Section 1.2.3: Venetoclax
Section: 1.3.1: Study 
Rationale and Purpose 
Section 1.3.4.2: Rationale 
for Combination of 
CC-95251 with 
Azacitidine Venetoclax
Section 1.3.5: Rationale 
for Pharmacodynamics 
and Potential Predictive 
Biomarkers
Section 1.3.2: Rationale 
for the Study Design 
Section 3.1: Study Design 
Section 3.1.1: Part A
Section: 3.1.4 Part D
Section: 3.1.5 Study 
Treatments
 
Section 4.1: Number of 
Subjects
Section 4.2: Inclusion 
Criteria, 6a-6d.
Section 4.3: Exclusion
criteria
Section: 4.4 Lifestyle 
Restrictions
Section 4.4.1: Meals and 
Dietary Restrictions
Added background, mechanism of action for 
venetoclax, and clinical and safety data in 
AML subjects treated with venetoclax plus
azacitidine.
Added a new cohort of CC-95251 in 
combination with azacitidine plus venetoclax
(triple combination) in study design, Part A 
dose escalation, and Part D dose expansion, 
foot note e, f, and g. Clarified roles of the 
Safety Review Committee.
Updated study population to include a new 
cohort of CC-95251 in combination with 
azacitidine plus venetoclax (triple 
combination). Added definition for treatment-
naïve (TN) AML; added language regarding 
venetoclax use in subjects of childbearing 
potential; added venetoclax-specific exclusion 
criteria including recent use of strong 
cytochrome P450 (CYP)3A inhibitors, lifestyle
and dietary restrictions, and conditions limiting 
absorption of orally administered drugs.
To permit addition of triplet 
combinations of CC-95251 with 
azacitidine and venetoclax, which 
is supported by data from recent 
study. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
8
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 3.0
Section Number & Title
Description of Change
Brief Rationale
Section 1.3.3: Rationale 
for Dose Schedule, and 
Regimen Selection
Section 3.1.5: Study 
Treatments
 
 
 
Section 7.1.3: Venetoclax
Section: 7.2.1.3:
Venetoclax
Section: 7.2.7.8.3 
Monitoring and 
Management of 
 
 
 
Section 6.4: Efficacy 
Assessment
 
 
 
 
 
 
 
 
Added new sections for drug description, 
preparation and administration, dosing, 
schedules, and supply information for 
venetoclax. Added dose modification 
guidelines including adjustments due to 
hematologic toxicity in triple combination 
cohorts
Addition of background and guidance for 
monitoring and management of 
 to 
this section
 
Added venetoclax-related data collection: 
venetoclax administration; medication diary; 
whole blood for T-cell. B-cell, and natural 
killer cell; disease assessment,
 
 bone marrow (BM) assessment 
specific to subjects receiving venetoclax; 
adjusted timing of 
 
 
 
 
 
 
 
Added dose modification guidelines for 
CC-95251 in combination with azacitidine plus 
venetoclax (triple combination).and footnotes a 
and b
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
9
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 3.0
Section Number & Title
Description of Change
Brief Rationale
7.2.7.10: Definition of 
Overdose
7.6: Investigational 
Product Compliance
Section 6.2: Treatment 
Period
Section: 7.2.7.8.2: 
Prophylaxis and 
Management of Tumor 
Lysis Syndrome
Section 7.2.7.8.4:
Hematological Toxicity
Section 8.2: Prohibited 
Concomitant Medications 
and Procedures
Section 8.3: Required 
Concomittent 
Medications and 
Procedures
Section 9.10: Safety 
Review Committee
Table 12: Management of 
Potential Venetoclax 
Interaction with CYP3A 
and P-gp Inhibitors
Clarification of criteria for overdose of IV (CC-
95251 and azacitidine) and SC (azacitidine) 
administration of study drugs and addition of 
PO overdose criteria (venetoclax)
Added description of venetoclax compliance 
monitoring to this section.  
Added venetoclax-related toxicity management 
including tumor lysis syndrome and 
hematological toxicity.
Added premedication guidelines for azacitidine 
and venetoclax.
Provided updated language regarding BMS 
safety process. Added venetoclax related 
prohibited concomitant medication. Added 
table to describe venetoclax dose modifications 
in subjects receiving CYP3A or P-gp 
inhibitors.
Table 1: Risk Assessment
Table 2: Study Objectives
Table 3: Study Endpoints 
 
 
 
Adapted the language to align with addition of
a new cohort of CC-95251 in combination with 
azacitidine plus venetoclax (triple combination) 
in Part A dose escalation and Part D Dose 
expansion.
 
To align language throughout 
protocol.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
10
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 3.0
Section Number & Title
Description of Change
Brief Rationale
Section 7.5 
Investigational Product 
Accountability and 
Disposal
Section 7.2.7.3: Permitted 
Study Drug Adjustments
Section 7.2.3: Definition 
of a Subject Evaluable for 
DLT
Section 7.3: Method of 
Treatment Assignment
Section 9.1 Overview
Section 9.7 Safety 
Analysis
Section 9.9.6
Figure 4: Overall Study 
Design
Clarified that PK of CC-95251 will be 
characterized as a single agent and in 
combination with antineoplastic agents.
Section: 1.4 Risk/Benefit 
Assessment
Section 1.4.1: Benefit 
Assessment
Section 1.4.2: Risk 
Assessment
Table 1: Risk Assessment
Section 1.4.3: Overall 
Risk/Benefit Conclusion
Added language regarding the risk/benefit 
assessment, including risk of venetoclax.
Section 1.4 Risk/Benefit Assessment and Table 
1 replaces prior section 1.4 Safety Monitoring 
Plan
To permit addition of triple 
combination arm.
With the integration of Celgene
and Bristol-Myers Squibb 
Company's protocol development 
and risk-benefit assessment 
process, the information on 
relevant/potential risks and 
mitigation strategy has been 
summarized in Table 1: Risk 
Assessment, and benefit 
assessment and overall 
assessments have been added. 
Sections 3.1.5.2:
Treatment Period
Sections 7.2.1.1:
CC-95251
Section 7.2.1.3:
Venetoclax
 
 
Clarification that subjects are going observed 
for 
 between administrations when 
receiving azacitidine and CC-95251
To comply with 
 
 
 mg per vial 
presentation as detailed in the 
CC-95251 Pharmacy Manual.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
11
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 3.0
Section Number & Title
Description of Change
Brief Rationale
 
 
 
 
 
Section 7.2.7.1: Criteria 
for Stopping a Dose 
Cohort
Section 9.3: Sample Size 
and Power Considerations
Table 13: Definition of 
study population
 
 
 
 
 
 
Added statistical consideration including 
sample size and power considerations and 
safety stopping rules for triple combination for 
Part A Dose escalation and Part D Dose 
expansion.
To permit addition of triple 
combination arm.
 
 
 
 
Removal of erroneous 
deficiency test.
In Protocol amendment 2.0
mandatory requirement for
 
testing was removed as an 
exclusion criterion, and the 
screening assessment was deleted 
from 
 
 
 
 
 
 
 
 
Screening for all
potential schedules in the Table 
of Events were correctly 
removed.
Section 1.2.1.5: Clinical 
Experience with 
CC-95251
Updated clinical experience for CC-95251.
To align with the most current 
version of CC-95251
Investigator’s Brochure
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
12
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 3.0
Section Number & Title
Description of Change
Brief Rationale
Section 6.2.6: Clinical 
Laboratory Tests
Updated 
 
as an optional test.
C-reactive protein was 
determined to be a more globally 
utilized and specific test and 
therefore, due to limitations of 
 availability, this test was 
deemed optional.
All
Minor typographical and formatting errors 
were corrected, and minor edits and 
clarifications were made.
Minor; therefore, have not been 
summarized.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
13
PROTOCOL SUMMARY
Study Title
A Phase 1, Open-label, Dose Finding Study of CC-95251 Alone and in Combination with 
Antineoplastic Agents in Subjects with Acute Myeloid Leukemia and Myelodysplastic Syndromes
Indication
Relapsed or refractory (R/R) and treatment-naïve (TN) intensive chemotherapy ineligible acute 
myeloid leukemia (AML)
R/R and TN myelodysplastic syndromes (MDS)
Primary Objectives

To determine the safety and tolerability of CC-95251 (also known as BMS-986351) alone and 
in combination with antineoplastic agents

To define the recommended Phase 2 dose (RP2D) of CC-95251 alone and in combination with 
antineoplastic agents in subjects with AML and MDS
Secondary Objectives

To assess the preliminary efficacy of CC-95251 as a single agent and in combination with 
antineoplastic agents in AML and MDS

To characterize the pharmacokinetics (PK) of CC-95251

To evaluate the presence, frequency, and functional impact of anti CC-95251 antibodies (anti-
drug antibodies [ADA])
Exploratory objectives and endpoints for the study are outlined in Section 2.
Study Design
Study CA059-001 is an open-label, multicenter, Phase 1 study testing the safety and efficacy of 
CC-95251, a monoclonal antibody directed against signal regulatory protein alpha (SIRPα), alone 
and in combination with antineoplastic agents in subjects with R/R or TN AML and R/R or TN
MDS. This protocol is intended to evaluate various drug combinations with CC-95251, as separate 
arms, over the life of the protocol, using the same objectives. CC-95251 as a single agent and as 
part of each of the combinations will be evaluated separately (ie, the intention is not to compare 
between monotherapy or combinations) for the purposes of the objectives, trial design, and 
statistical analysis.
The study will consist of 4 parts with a dose escalation (Part A) and dose expansions (Parts B, C,
and D) as detailed below

Part A: Dose escalation with CC-95251 alone and in combination with injectable azacitidine
in subjects with R/R AML and R/R intermediate, high or very high risk (ie, Revised 
International Prognostic Scoring System score [IPSS-R]
 MDS. Dose escalation with 
CC-95251 in combination with injectable azacitidine and venetoclax (triple combination) in 
subjects with R/R AML.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
14

Part B: Dose expansion testing CC-95251 alone and in combination with injectable azacitidine 
in R/R AML and R/R intermediate, high, or very high risk (ie, IPSS-R
) MDS. 

Part C: CC-95251 dose expansion in combination with injectable azacitidine in TN subjects 
with intermediate, high or very high risk (ie, IPSS-R
 MDS.

Part D: CC-95251 dose expansion in combination with injectable azacitidine and venetoclax
(triple combination) in subjects with TN AML ineligible for intensive chemotherapy.

Other combinations of CC-95251 and antineoplastic agents in subjects with R/R or TN AML
and/or R/R or TN MDS may be explored at the recommendation of the Safety Review 
Committee (SRC) and will be added by subsequent protocol amendment.
Part A
Part A will evaluate the safety and tolerability of escalating doses of CC-95251 administered 
intravenously (IV) as a single agent (monotherapy) to determine the preliminary recommended 
Phase 2 dose (RP2D) of single agent CC-95251 in subjects with R/R AML or R/R MDS. An 
additional dose escalation evaluating the safety and tolerability of CC-95251 administered IV in 
combination with azacitidine administered IV or subcutaneously (SC) (double combination) will
also take place in Part A with the aim of determining the preliminary RP2D of CC-95251 plus
injectable azacitidine in subjects with R/R AML or R/R MDS. Further dose escalation evaluating 
the safety and tolerability of CC-95251 administered IV in combination with azacitidine 
administered IV or SC and venetoclax administered orally (triple combination) will also take place 
in Part A with the aim of determining the preliminary RP2D of CC-95251 plus injectable 
azacitidine and venetoclax in subjects with R/R AML.
will be utilized to guide 
CC-95251 dose escalation/de-escalation decisions for monotherapy, double combination, and 
triple combination, with the final decisions being made by the SRC. The SRC membership will be 
comprised of Investigators (and/or designated representatives), the Sponsor’s Medical Monitor, 
safety physician, clinical scientist, and the study manager. Ad hoc attendees may include the study 
PK scientist, biostatistician, and translational research scientist. Other internal and external experts 
may be consulted by the SRC, as necessary.
The proposed dose levels for testing the CC-95251 monotherapy include a starting dose 
 
20 mg/kg weekly (QW) and 
 30 mg/kg to be administered by IV infusion. A 20 mg/kg QW 
dose of CC-95251 has been demonstrated to be tolerated in subjects with advanced solid cancers
in the CC-95251-ST-001 study (NCT03783403). In the event that 
 is not tolerated in the 
CC-95251 monotherapy cohort, a lower dose 
of 10 mg/kg CC-95251 may be recommended 
by the SRC. 
The proposed starting dose (DL1a) for CC-95251 in combination with azacitidine (double 
combination) is 10 mg/kg QW, 
. The Part A dose 
escalation may enroll subjects in the CC-95251 plus azacitidine cohorts in parallel with the 
CC-95251 monotherapy cohorts. 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
15
 
The proposed starting dose (DL1b) for CC-95251 in combination with azacitidine and venetoclax
(triple combination) is 20 mg/kg QW, 
 
. Dose 
de-escalation to dose level 
 (10 mg/kg QW of CC-95251 in combination with azacitidine and 
venetoclax) may be recommended by the SRC if the starting dose is not tolerated or to explore a 
lower dose level based on the available safety, PK, and pharmacodynamic (PD) data. The Part A 
dose escalation may enroll subjects in the CC-95251 plus azacitidine and venetoclax cohorts in 
parallel with the CC-95251 monotherapy and double combination cohorts. 
 
 
 
All subjects within each dose level will be observed 
 
 before 
initiation of the next dose level. Subject treatment on Cycle 1 Day 1 (C1D1) will be staggered with 
 between subjects in a given cohort during Part A.
A decision table (
based on 
 
 
 are provided to guide CC-95251 dose escalation/de-escalation 
decisions for monotherapy, double combination cohorts, and triple combination cohorts. The SRC 
will make dose escalation/de-escalation recommendations based on real-time integrated 
assessment of available safety, efficacy, PK and pharmacodynamics (PD) in each dose cohort. 
After enrollment has been completed in the corresponding Part A cohorts, the SRC will undertake 
an evaluation of the available safety, PK, PD, and preliminary efficacy data to make a 
determination of the preliminary RP2D of CC-95251 to test in the expansion cohorts (Parts B, C,
and D). 
 
 
. The preliminary 
 
, and may 
differ based on indication (ie, MDS versus AML). For a dose level to be selected by the SRC for 
dose expansions (Part B, C, and D), at least  subjects should be evaluable for DLT in Part A to 
declare a tolerable dose level. Subjects non-evaluable for DLT may be replaced.
During dose escalation, the decision to evaluate additional subjects within a dose cohort, a higher 
dose level, intermediate dose levels, an alternate dosing interval, or declare the RP2D will be 
determined by the SRC, based on their review of available safety, PK, PD, and preliminary efficacy 
data for a given dose level. The investigation of any other alternate dosing schedule beyond those 
stipulated in the current protocol version will be submitted in a protocol amendment.
Part B
Part B will further evaluate the safety and efficacy of CC-95251 alone and in combination with 
injectable azacitidine in R/R AML and R/R MDS (IPSS-R 
 The expansion cohorts of each 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
16
individual treatment may start after a dose and schedule is shown to be tolerated in the 
corresponding Part A cohort and the SRC has selected the Part B dose and schedule. 
Approximately 
 subjects per cohort will be enrolled to further evaluate the safety and assess the 
efficacy of:
1. CC-95251 alone in R/R AML
2. CC-95251 in combination with injectable azacitidine in R/R AML
3. CC-95251 alone in R/R MDS (IPSS-R 
 
4. CC-95251 in combination with injectable azacitidine in R/R MDS (IPSS-R 
at the preliminary RP2D of CC-95251 monotherapy or RP2D of CC-95251 in combination with 
injectable azacitidine established in Part A. The SRC may choose 
 based on review of the available safety, PK, PD and preliminary 
efficacy data from Part A and will regularly review safety and emerging response data during 
expansion to make recommendations about continuation and dose modification, as appropriate
(Section 7.2.7). 
Additional cohorts of subjects testing CC-95251 in combination with additional antineoplastic 
agents in subjects with R/R AML or R/R MDS may be considered at the recommendation of the 
SRC and will be included by protocol amendment.
Part C
Part C will evaluate subjects with treatment-naïve (ie, previously untreated), intermediate, high or 
very high risk (ie, IPSS-R 
) MDS with CC-95251 in combination with standard of care 
azacitidine. 
 
 
 The SRC will review the safety data from this group of 
subjects utilizing
 prior to the 
opening of the Part C expansion. The dose of CC-95251 selected for Part C may occur at the 
preliminary RP2D established in dose escalation, or at an alternative tolerable dose based on 
review of available safety, PK, PD, and preliminary efficacy data.
The Part C expansion will initially evaluate at least 
 with TN MDS 
 
 
The SRC will review the available safety utilizing 
 
, PK, PD and preliminary efficacy data in the initial 
to determine 
if the dose and schedule is tolerated prior to escalating the CC-95251 dose to the proposed Part C 
expansion dose and schedule.
 may be selected for
continued enrollment in the expansion based on SRC review of the available data from the initial 
 Thereafter, a total of approximately 
 additional subjects with TN MDS 
may be enrolled in Part 
 
. During enrollment in Part C the SRC will review available safety data from Cycle 1 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
17
of every  subjects treated in the cohort to evaluate for excessive toxicity. Enrollment in Part C
may proceed concurrently with enrollment in the Part B expansion cohorts. 
The SRC will continue to review safety data regularly throughout the study and make 
recommendations about study continuation, dose modification and establishment of a RP2D as 
appropriate.
Part D
The Part D expansion will evaluate CC-95251 in combination with azacitidine and venetoclax in 
subjects with TN AML and who are not candidates to receive IC due to comorbidities or age (ie, 
≥ 75 years)
Enrollment in Part D 
 
 
 The SRC will review the safety data from this group of subjects 
utilizing 
 prior to the opening 
of the Part D expansion. The dose of CC-95251 selected for Part D may occur at the preliminary 
RP2D established in dose escalation, or at an alternative tolerable dose based on review of 
available safety, PK, PD, and preliminary efficacy data.
The Part D expansion will initially evaluate at least  subjects with TN AML treated 
 
 
 
 
 Subject treatment on C1D1 will be staggered with at 
least one day between subjects for the initial 
subjects. 
 
 
An additional 
 subjects may be enrolled 
based on the response seen in the initial 
 subjects (
and Section 9.3: Sample Size and 
Power Considerations). During enrollment in Part D, the SRC will review available safety data 
from Cycle 1 of every  subjects treated in the cohort to evaluate for excessive toxicity. 
The SRC will continue to review safety data regularly throughout the study and make 
recommendations about study continuation, dose modification and establishment of a RP2D as 
appropriate.
Study Population
Up to approximately 
subjects (
in Part A dose escalation, 
 in Part B expansion,
 in 
Part C expansion, and 
in Part D expansion) may be enrolled.
The Study Population will be subjects ≥ 18 years of age and defined as follows:

R/R AML (Parts A and B): AML as defined by the 2016 World Health Organization (WHO) 
Classification (Appendix B) who have failed or who are ineligible for all available therapies 
for AML which may provide clinical benefit
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
18

R/R MDS (Parts A and B): MDS as defined by the 2016 WHO Classification (Appendix D)
with intermediate, high or very high risk by IPSS-R (IPSS-R 
 and who have failed or who 
are ineligible for all available therapies for MDS which may provide clinical benefit.

TN MDS (Part C): Treatment-naïve MDS as defined by the 2016 WHO Classification 
(Appendix D) with intermediate, high or very high risk by IPSS-R (IPSS-R 
).

TN AML (Part D): Treatment-naïve AML as defined by the 2016 WHO Classification
(Appendix B), including secondary AML and therapy-related AML in subjects who are IE for 
IC and allogeneic
due to having one of the following:
Severe cardiac comorbidities (including congestive heart failure, left ventricular 
ejection fraction <45%, and chronic stable angina)
Pulmonary comorbidity (diffusing capacity of the lung for carbon monoxide ≤ 65% or 
forced expiratory volume in 1 second ≤ 65%) 
Any other comorbidity incompatible with intensive chemotherapy upon approval of the 
Sponsor Medical Monitor 
Aged ≥ 75 years, regardless of the presence of any of the above comorbidities

Subjects must have a projected life expectancy of ≥ 12 weeks.

Additionally, TN AML subjects who have not received hypomethylating agents, 
venetoclax, or chemotherapy in the setting of antecedent MDS are eligible. Prior treatment 
for antecedent MDS including, but not limited to, growth factors (eg, erythropoiesis-
stimulating agents), hydroxyurea, and lenalidomide is allowed. 
Length of Study
The full length of the study is expected to be approximately 36 to 48 months including recruitment, 
screening, treatment, and follow up. Approximately 16 to 19 months will be required to enroll 
subjects in the dose escalation portion of the study (Part A). Approximately 12 to 18 months will 
be required to enroll and evaluate subjects in the dose expansion portion of the study (Parts B, C, 
and D). 
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date.
Study Treatments
CC-95251 will be administered intravenously in two phases starting with a more frequently dosed
induction phase followed by a maintenance phase. 

During induction phase, subjects will be dosed weekly for Cycles 1 through 4 (QW, eg, on 
Day 1, Day 8, Day 15, and Day 22 of each cycle).  After Cycle 4, subjects will enter the 
maintenance phase. 

During the maintenance phase, CC-95251 will be administered every two weeks (Q2W, eg, on 
Day 1 and Day 15 of each cycle).
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
19
The SRC may change the frequency of dosing
 
 based on review of the available safety, PK, PD, and 
preliminary efficacy data 
The investigation of any other alternate 
dosing schedule beyond those stipulated in the current protocol version will be submitted in a 
protocol amendment.
In combination cohorts, azacitidine will be administered at 75 mg/m2 on Days 1-7 (or Days 1-5 
and 8-9) of each 28-day cycle as an IV or SC injection throughout the course of the study treatment
per local prescribing information and institutional standard of care.  
In triple combination cohorts, venetoclax will be administered orally once daily on Days 1 through 
28 of each 28-day cycle. A brief dose ramp-up occurs during Cycle 1, with the dosing of 100 mg 
on Day 1, 200 mg on Day 2, and 400 mg on Day 3. Venetoclax will be administered at 400 mg on 
subsequent days. Doses may be adjusted for subjects receiving concurrent P-glycoprotein or
cytochrome P450 3A inhibitors.
Parts A, B, C, and D will consist of 3 periods: Screening, Treatment, and Follow-up (refer to
Figure 4).
Screening Period
The Screening Period starts 28 days prior to first dose of study intervention. The informed consent 
form (ICF) must be signed and dated by the subject and the administering staff prior to the start of 
any other study procedures. All screening tests and procedures must be completed within the 28 
days prior to the first dose of study treatments.
Treatment Period
Upon confirmation of eligibility, subjects will be enrolled and begin treatment in the assigned dose 
level cohort.
The Sponsor will supply the investigational product (IP), CC-95251, for IV administration 
(Section 7.1.1).
Azacitidine will be supplied or obtained according to local clinical study agreement and in 
accordance with local guidelines. When provided by the Sponsor, azacitidine for injection will be 
supplied as a lyophilized powder in 100 mg single-dose vials for reconstitution and administration.
Venetoclax will be supplied or obtained according to local clinical study agreement and in 
accordance with local guidelines. When provided by the Sponsor, venetoclax will be supplied as 
tablets in 10 mg, 50 mg, and 100 mg blister/bottles for administration.
In Part A, subjects with AML in the monotherapy and double combination cohorts will be 
hospitalized for at least 24 hours after the first dose of CC-95251 (C1D1) for IV hydration and 
 and to monitor for adverse events. Subjects with AML 
in triple combination cohorts in Part A or Part D will be hospitalized during venetoclax ramp-up 
(3-5 days) for IV hydration,
, and to monitor for adverse events based on the 
ongoing risk of TLS (see Section 7.2.7.8.2). 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
20
 
 Subjects with 
 
 Full emergency resuscitation facilities should 
be immediately available, and subjects should be under close supervision of the Investigator or 
designated staff during and for
 
following CC-95251 administration with serial vital signs obtained and pulse oximetry performed. 
 
 
 
 
 
CC-95251 infusion will be started at 
 mg/hr 
 
mg/hr 
 mg/hr. Further changes to the rate of 
infusion may be considered during the course of the trial based on review of clinical data and 
approval from the SRC. 
For subjects receiving azacitidine in combination with CC-95251, subjects will receive azacitidine 
prior to starting CC-95251 infusion on days receiving both treatments. Subjects should be observed 
for 
  
For subjects receiving triple combination, on Day 1 of each cycle, CC-95251, azacitidine, and 
venetoclax will be administered on the same day. Azacitidine should be administered prior to 
starting CC-95251 infusion. Subjects should be observed 
 between 
administrations. Venetoclax should be taken orally at least 
 after CC-95251 infusion.
Subjects should be instructed to take their daily dose at approximately the same time each day 
 
hours.
 
 
 
 
 
 
 
Thus, in Part A dose escalation, the window for evaluation of DLT during Cycle 1 will be up to 
 days (
 days); Cycles 2 and higher will be 28 days in length. In dose expansion, all cycles 
will be 28 days in length. 
 
 Subjects will only be 
considered DLT evaluable during the first cycle of their initial enrollment in Part A (dose 
escalation).
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
21
All treatments will be administered in 28-day cycles. To optimally benefit from the treatment, 
Investigators should aim to treat subjects for at least 
cycles, although subjects can be 
discontinued from the protocol earlier if they demonstrate documented relapse from CR or partial 
remission (PR), disease progression, unacceptable adverse event(s), intercurrent illness that 
prevents further administration of treatment, investigator’s decision to withdraw the subject, 
subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or 
procedure requirements, or administrative reasons. Subjects may continue treatment if they are 
deriving benefit from treatment without unacceptable toxicity (any CR, MLFS, PR, or stable 
disease [SD] with demonstrated clinical benefit eg, reduction in transfusion burden), as judged by 
the Investigator, 
 
 or until disease progression, loss of clinical benefit, unacceptable 
toxicity, or decision to withdraw by subject or Investigator. Subjects who discontinued one study 
treatment in a combination arm for reasons other than relapse or resistant disease may continue on 
the non-discontinued drug(s) if the subjects are receiving benefit as per Investigator’s discretion 
until there is evidence of relapse or resistant disease, or until they are no longer able to tolerate 
treatment due to an adverse event (AE). Retreatment (within 
 from last dose of CC-95251
in the prior study treatment period) will be permitted (refer to Section 7.2.7.9 for details). Subjects 
may be retreated only once during the study and the total duration in the study will be no longer 
than 4 years from the original C1D1.
Follow-up Period
All subjects will be followed for 
days after the last dose of study drug for AE reporting. 
In addition, serious adverse events (SAEs) made known to the Investigator at any time thereafter 
that are suspected of being related to study drug are to be reported until such SAEs have recovered 
(returned to baseline), recovered with sequelae, or death (due to the SAE). Subjects will also be 
followed for all AEs (SAEs and non-serious AEs) associated with confirmed or suspected severe 
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until resolution, the condition 
stabilizes, the event is otherwise explained, the event is deemed irreversible, the subject is lost to 
follow-up, or for suspected cases, until SARS-CoV-2 infection is ruled-out (Section 6.3.1).
Subjects who discontinue treatment for reasons other than disease progression (or relapse) or start 
of a new anticancer therapy will have efficacy evaluations (refer to Section 6.3.2) up to a maximum 
of 
 or until progression of disease (or relapse), initiation of a new anticancer therapy, 
withdrawal from the study, death, or the End of Trial, whichever comes first. 
All subjects will be followed starting from the end of treatment according to the schedule for the 
efficacy long term follow-up (refer to Section 6.3.2), for survival for up to 
 or until death, 
lost to follow-up, or the End of Trial, whichever occurs first. Survival follow-up may be conducted 
by record review (including public records) and/or telephone contact with the subject, family, or 
the subject’s treating physician.
During follow-up, information (including dates) on new anticancer therapies will be collected until 
withdrawal from the study, death, or the End of Trial, whichever comes first.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
22
The study will be conducted in compliance with International Conference on Harmonisation (ICH) 
Good Clinical Practices (GCPs).
Overview of Key Efficacy Assessments
Efficacy assessments include (Section 6.4):

Clinical findings (eg, physical examinations, constitutional symptoms)

Complete blood counts (CBC) and peripheral blood smears (PBS)

Bone marrow examination (biopsy and/or aspiration)
Bone marrow (BM) aspiration and/or biopsy for disease burden assessments will be collected to 
be evaluated for 
 at Screening, end 
of 
 
 
 
 In addition, bone marrow 
aspirates (BMA) or biopsies (BMB) are performed to confirm CR or CRi or morphologic CR with 
partial hematologic recovery (CRh), relapse after CR/CRi/CRh (as assessed by the Investigator 
based on CBC with white blood cell [WBC] differential results), or disease progression. Additional 
aspirates and/or biopsies will be collected as clinically indicated, based on Investigator’s medical 
judgement.
Complete blood count and peripheral blood smear (PBS) will be performed at the time of each 
bone marrow collection. Starting with 
 subjects will be monitored for disease status using 
CBC and PBS 
 for the 
second year or until progression of disease (or relapse).
Response to treatment will be assessed by Investigator using local laboratory results according to 
modified 2017 European Leukemia Network (ELN) AML Response Criteria (Döhner, 2017) for 
AML and modified International Working Group (IWG) Response Criteria (Cheson, 2006) for 
MDS. Hematologic response/transfusion dependence will also be evaluated. In addition, CRh will 
be reported for both AML and MDS (Bloomfield, 2018).
AML response criteria will be summarized by best overall response categories: complete remission
rate (CRR) defined as CR + CRi + CRh, and objective response rate (ORR) defined as all responses 
of CR (ie, CRMRD-, morphologic CR, CRh, CRi) + MLFS + PR. For MDS, the complete remission 
rate (CRR) is defined as CR rate, objective response rate (ORR) includes all responses (CR + CRh
+ marrow CR + PR). The efficacy variable of focus will be complete remission rate (CRR) and 
ORR. Other measures of clinical activity include duration of remission, duration of response, 
stable disease rate (MDS only), relapse-free survival, event-free survival, progression-free survival
(PFS), time to remission/response, transfusion independence, time to AML transformation for 
MDS subjects, and overall survival (OS) rates at 6 and 12 months.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
23
Secondary and exploratory endpoints include evaluation of CC-95251 PD and predictive 
biomarkers in blood and/or bone marrow, and exploration of PK, PD, toxicity and activity 
relationships.
Overview of Key Safety Assessments
The safety variables for this study include:

Dose-limiting toxicities

AE and SAE

Physical examination

Vital signs/weight

Eastern Cooperative Oncology Group Performance Status (ECOG PS)

Safety clinical laboratory assessments (including hematology, clinical chemistry, coagulation 
studies, and urinalysis)

Cardiac monitoring:

Exposure to study treatment

Assessment of concomitant medications/procedures
Overview of Pharmacokinetic Assessments
All subjects will be required to participate in PK sampling in the study, and serial blood samples 
will be collected at specified times for measurement of CC-95251. All post-dose assessments 
should be timed from the end of CC-95251 infusion (EOI). If an infusion is terminated early, EOI 
sampling should still be performed. PK sampling is performed as indicated in
, 
).
PK parameters (Cmax, Cmin, tmax, AUC(0-T), AUC(TAU), Ctrough, CLT) of CC-95251, where feasible,
will be calculated from the serum concentration-time data of CC-95251 using non-compartment 
methods. The sponsor may conduct additional PK and PK/PD analyses to follow up on the safety 
of the study treatment or to better understand the progression of the disease or the response to 
study treatment.
Overview of Pharmacodynamic Assessments
Pharmacodynamic biomarkers will be collected in all subjects on study to further explore 
CC-95251 activity and identify potential predictors of response. Pharmacodynamic biomarker 
assessments include but are not limited to, 
 
 
 
 
Pharmacodynamic sampling is performed as indicated in 
Reflecting the molecular diversity of AML, different minimal residual disease (MRD) platforms 
are available for detecting MRD. As per ELN recommendation, MRD assessments will be 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
24
performed in BM aspirates using either or both, multiparameter flow cytometry and molecular 
MRD by next generation sequencing. 
The sponsor may conduct additional analyses on the PD samples to further evaluate the safety of 
the study treatment, to better understand the progression of the disease or to assess response to the 
study treatment.
Overview of Key Immunogenicity Assessments
The development of ADA may impact drug exposure in subjects on the study. Serum will be 
collected for analysis of ADA during study treatment prior to study drug infusion (pre-dose) and 
during the follow-up phase. ADA sampling is performed as indicated in the Table of Events
(
) and Section 6.5.
Statistical Methods
Dose escalation/de-escalation decisions for monotherapy, double combination, and triple 
combination will be guided per the 
 
 
. Preliminary estimation of the 
 
will be based on the estimation of the 
 
 
 The final determination of RP2D will be decided by the SRC.
Statistical analyses will be performed by dose level or dose schedule and a combination product 
as needed or applicable. Study data will be summarized for disposition, demographic and baseline 
characteristics, exposure, efficacy, safety, PK, and PD per respective analysis population defined 
in Section 9 and Table 13 as applicable. All analyses will be descriptive in nature.
AEs, including treatment-emergent adverse events, will be summarized by National Cancer 
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 grades, 
except for cytokine release syndrome (CRS) and TLS, which will be graded according to the 
revised CRS grading system ([Lee, 2014] and Cairo-Bishop TLS grading system [Cairo, 2004], 
respectively). The frequency of AEs will be tabulated by Medical Dictionary for Regulatory 
Activities (MedDRA) system organ class and preferred term. Grade 3 or higher AEs, AEs leading 
to discontinuation of study treatment or to death, study intervention-related AEs, and SAEs will 
be tabulated separately. Changes from baseline in selected laboratory analytes for example 
transfusion dependence (platelet count or red blood cell [RBC] transfusion units), vital signs, and 
 will be summarized.
For dose expansion, efficacy variables to be analyzed include complete remission rate (CRR) and 
ORR, duration of remission, duration of response, stable disease rate (MDS only), relapse-free 
survival, event-free survival, PFS, time to remission/response, transfusion independence, time to 
AML transformation for MDS subjects, and overall survival (OS) rates at 6 and 12 months. Point 
estimates and 2-sided 90% exact Clopper-Pearson confidence intervals of CRR and ORR will be 
reported. For time to event endpoints, Kaplan-Meier survival analyses will be performed. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
25
During the dose expansion (Parts B, C, and D), a non-binding Bayesian safety monitoring method 
will be utilized to continuously monitor for excessive toxicities defined as the occurrence of AEs 
that would fulfill the DLT criteria defined at any time during study treatment (Section 9.9.2). 
Weakly informative priors [eg, beta 
 will be constructed for estimating the stopping 
boundaries. After a minimum of subjects have enrolled and completed at least one cycle of study 
treatment, the non-binding Bayesian stopping criterion based on the posterior distribution of 
excessive toxicity will be calculated (refer to
 The study may pause when there is a 
greater than 
 chance that toxicity rate is over 
. The excessive toxicity rate 
 is 
established to be consistent with the target toxicity rate specified in dose escalation. If the stopping 
rule is triggered, the SRC will conduct a comprehensive review of available safety, PK, PD, and 
preliminary efficacy data to make continuation decisions.
In Parts B, C, and D, a 
 analysis based on CRR will be performed. In Part B, 
at least 
 efficacy evaluable subjects who complete at least one cycle of study treatment for each 
cohort will initially be accrued; 
 
 In Part C, at least 
 efficacy evaluable subjects who complete at 
least one cycle of study treatment at RP2D will initially be accrued; 
 
. In Part D, at least 20 efficacy 
evaluable subjects who complete at least one cycle of study treatment at RP2D will initially be 
accrued; 
.
The 
 decision will be made by the SRC upon reviewing all available safety, PK, PD, 
and any efficacy results in dose expansion phase, including considerations on adjustment of the 
RP2D dose. Otherwise, the cohort will be expanded to up to approximately 
 evaluable subjects 
in Part B. approximately 
 evaluable subjects in Part C, and approximately 
 evaluable subjects 
in Part D (Section 9.9.2).  
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
26
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 3.0:............................................6
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 3.0.........................................7
PROTOCOL SUMMARY ........................................................................................................13
TABLE OF CONTENTS..........................................................................................................26
LIST OF TABLES....................................................................................................................31
LIST OF FIGURES ..................................................................................................................33
1
INTRODUCTION..................................................................................................34
1.1
Disease Background ...............................................................................................34
1.1.1
Acute Myeloid Leukemia.........................................................................................34
1.1.2
Myelodysplastic Syndromes ....................................................................................35
1.2
Compound Background ..........................................................................................36
1.2.1
CC-95251...............................................................................................................36
1.2.1.1
Nonclinical Pharmacology .....................................................................................37
1.2.1.3
Nonclinical Toxicology...........................................................................................41
1.2.1.4
Nonclinical Pharmacokinetics ................................................................................41
1.2.1.5
Clinical Experience with CC-95251........................................................................42
1.2.2
Azacitidine..............................................................................................................44
1.2.3
Venetoclax..............................................................................................................45
1.3
Rationale ................................................................................................................46
1.3.1
Study Rationale and Purpose..................................................................................46
1.3.2
Rationale for the Study Design................................................................................48
1.3.3
Rationale for Dose, Schedule and Regimen Selection..............................................51
1.3.4
Rationale for Choice of Combination Compounds ..................................................53
1.3.4.1
Rationale for Combination of CC-95251 with Azacitidine.......................................53
1.3.4.2
Rationale for Combination of CC-95251 with Azacitidine Plus Venetoclax.............53
1.3.5
Rationale for Pharmacodynamics and Potential Predictive Biomarkers..................54
1.4
Risk/Benefit Assessment ........................................................................................55
1.4.1
Benefit Assessment..................................................................................................55
1.4.2
Risk Assessment......................................................................................................56
1.4.3
Overall Risk/Benefit Conclusion .............................................................................60
2
STUDY OBJECTIVES AND ENDPOINTS...........................................................61
3
OVERALL STUDY DESIGN ................................................................................66
3.1
Study Design ..........................................................................................................66
3.1.1
Part A.....................................................................................................................69
3.1.2
Part B.....................................................................................................................70
3.1.3
Part C.....................................................................................................................71
3.1.4
Part D ....................................................................................................................72
3.1.5
Study Treatments ....................................................................................................72
3.1.5.1
Screening Period ....................................................................................................73
3.1.5.2
Treatment Period....................................................................................................73
3.1.5.3
Follow-up Period....................................................................................................77
3.2
Study Duration for Subjects....................................................................................78
3.3
End of Trial ............................................................................................................78
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
27
4
STUDY POPULATION.........................................................................................78
4.1
Number of Subjects ................................................................................................78
4.2
Inclusion Criteria....................................................................................................78
4.3
Exclusion Criteria...................................................................................................81
4.4
Lifestyle Restrictions..............................................................................................83
4.4.1
Meals and Dietary Restrictions...............................................................................83
6
PROCEDURES......................................................................................................94
6.1
Screening Period.....................................................................................................94
6.2
Treatment Period ....................................................................................................96
6.2.1
Prior and Concomitant Medications and Procedures..............................................97
6.2.2
Adverse Event Monitoring ......................................................................................97
6.2.3
Vital Signs and Oxygen Saturation..........................................................................97
6.2.4
Physical Examination and ECOG Performance Status............................................97
6.2.5
Pregnancy Test.......................................................................................................98
6.2.6
Clinical Laboratory Tests .......................................................................................98
6.2.7
12-Lead Electrocardiograms ..................................................................................99
6.2.8
Left Ventricular Ejection Fraction ........................................................................100
6.2.9
End of Treatment..................................................................................................100
6.3
Follow-up Period..................................................................................................100
6.3.1
Safety Follow-up...................................................................................................100
6.3.2
Efficacy Long Term Follow up..............................................................................100
6.3.3
Survival Follow up................................................................................................101
6.4
Efficacy Assessment.............................................................................................101
6.5
Pharmacokinetics..................................................................................................104
6.6
Biomarkers, Pharmacodynamics, Pharmacogenomics...........................................108
6.7
Additional and Optional Research.........................................................................109
6.7.1
Additional Research .............................................................................................109
6.7.2
Optional Research................................................................................................110
6.8
Subject Reported Outcomes..................................................................................110
7
DESCRIPTION OF STUDY TREATMENTS......................................................110
7.1
Description of Investigational Products.................................................................110
7.1.1
CC-95251.............................................................................................................110
7.1.2
Azacitidine............................................................................................................110
7.1.3
Venetoclax............................................................................................................110
7.2
Treatment Administration and Schedule ...............................................................111
7.2.1
Study Drug Preparation and Administration.........................................................111
7.2.1.1
CC-95251.............................................................................................................111
7.2.1.2
Azacitidine............................................................................................................112
7.2.1.3
Venetoclax............................................................................................................113
7.2.2
Dose Escalation Criteria ......................................................................................114
7.2.3
Definition of a Subject Evaluable for DLT ............................................................114
7.2.4
Definition 
.....................................................115
7.2.5
Definition of Dose-Limiting Toxicity (DLT) ..........................................................115
7.2.6
Criteria for Dose Escalation in the Next Cohort of Subjects..................................117
7.2.7
Definition of Stopping Criteria .............................................................................117
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
28
7.2.7.1
Criteria for Stopping a Dose Cohort.....................................................................117
7.2.7.2
Criteria for Pausing or Stopping the study............................................................118
7.2.7.3
Permitted Study Drug Adjustments .......................................................................118
7.2.7.4
Criteria for Dose Reduction..................................................................................119
7.2.7.5
Criteria for Dose Increase ....................................................................................119
7.2.7.6
Treatment Interruption for Adverse Events ...........................................................120
7.2.7.7
Dose Modification Guidelines...............................................................................121
7.2.7.8
Management of Select Adverse Events ..................................................................125
7.2.7.9
Retreatment or Increased Dose Intensity of CC-95251..........................................132
7.2.7.10
Definition of Overdose..........................................................................................132
7.3
Method of Treatment Assignment.........................................................................133
7.4
Packaging and Labeling........................................................................................133
7.5
Investigational Product Accountability and Disposal ............................................133
7.6
Investigational Product Compliance......................................................................133
8
CONCOMITANT MEDICATIONS AND PROCEDURES..................................134
8.1
Permitted Concomitant Medications and Procedures.............................................134
8.2
Prohibited Concomitant Medications and Procedures............................................135
..............................................137
9
STATISTICAL CONSIDERATIONS ..................................................................138
9.1
Overview..............................................................................................................138
9.2
Study Population Definitions ................................................................................139
9.3
Sample Size and Power Considerations.................................................................139
9.4
Background and Demographic Characteristics......................................................141
9.5
Subject Disposition...............................................................................................141
9.6
Efficacy Analysis..................................................................................................141
9.7
Safety Analysis.....................................................................................................142
...................................................................................................142
9.9
Other Topics.........................................................................................................142
9.9.1
Statistical Method for Dose Escalation .................................................................142
9.9.2
Stopping Rules Regarding Toxicity in Dose Expansion .........................................144
9.9.3
Assessment of Pharmacokinetics...........................................................................145
9.9.4
Assessment of Immunogenicity..............................................................................146
9.9.5
Assessment of Pharmacodynamics and Exploratory Biomarkers...........................146
9.9.6
Assessment of Other Exploratory Endpoints .........................................................146
9.10
Safety Review Committee ....................................................................................146
10
ADVERSE EVENTS............................................................................................147
10.1
Monitoring, Recording and Reporting of Adverse Events .....................................147
10.2
Evaluation of Adverse Events...............................................................................148
10.2.1
Seriousness...........................................................................................................148
10.2.2
Severity/Intensity ..................................................................................................149
10.2.3
Causality ..............................................................................................................150
10.2.4
Duration...............................................................................................................150
10.2.5
Action Taken.........................................................................................................150
10.2.6
Outcome ...............................................................................................................150
10.3
Abnormal Laboratory Values................................................................................150
10.4
Pregnancy.............................................................................................................151
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
29
10.4.1
Subjects of Childbearing Potential........................................................................151
10.4.2
Subjects Who Are Able to Impregnate Their Partner .............................................151
10.5
Reporting of Serious Adverse Events....................................................................152
10.6
Expedited Reporting of Adverse Events................................................................152
11
DISCONTINUATIONS .......................................................................................153
11.1
Treatment Discontinuation....................................................................................153
11.2
Study Discontinuation ..........................................................................................153
11.3
Emergency Contact...............................................................................................154
11.4
Emergency Identification of Investigational Products ...........................................154
12
REGULATORY CONSIDERATIONS.................................................................154
12.1
Good Clinical Practice..........................................................................................154
12.2
Investigator Responsibilities .................................................................................154
12.3
Subject Information and Informed Consent...........................................................155
12.4
Confidentiality......................................................................................................155
12.5
Protocol Amendments...........................................................................................156
12.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval ..............................................................................................................156
12.7
Ongoing Information for Institutional Review Board/ Ethics Committee ..............157
12.8
Termination of the Study ......................................................................................157
13
DATA HANDLING AND RECORDKEEPING...................................................157
13.1
Data/Documents ...................................................................................................157
13.2
Data Management.................................................................................................157
13.3
Record Retention..................................................................................................157
14
QUALITY CONTROL AND QUALITY ASSURANCE......................................158
14.1
Study Monitoring and Source Data Verification....................................................158
14.2
Audits and Inspections..........................................................................................159
14.3
Investigational Medicinal Product Quality Issues..................................................159
15
PUBLICATIONS .................................................................................................159
16
REFERENCES.....................................................................................................160
APPENDIX A
TABLE OF ABBREVIATIONS...........................................................167
APPENDIX B
THE WORLD HEALTH ORGANIZATION (WHO) 
CLASSIFICATION OF ACUTE MYELOID LEUKEMIA (AML) ......174
APPENDIX C
RESPONSE CRITERIA FOR ACUTE MYELOID LEUKEMIA 
(AML)..................................................................................................175
APPENDIX D
THE WORLD HEALTH ORGANIZATION (WHO) 
CLASSIFICATION OF THE MYELODYSPLASTIC 
SYNDROMES (MDS) .........................................................................176
APPENDIX E
RESPONSE CRITERIA FOR MYELODYSPLASTIC 
SYNDROMES (MDS) .........................................................................178
APPENDIX F
RISK STATUS BASED ON CYTOGENETICS FOR ACUTE 
MYELOID LEUKEMIA......................................................................180
APPENDIX G
REVISED INTERNATIONAL PROGNOSTIC SCORING
SYSTEM    FOR MDS.........................................................................182
APPENDIX H
PERFORMANCE STATUS CRITERIA ..............................................184
APPENDIX I
TUMOR LYSIS SYNDROME PROPHYLAXIS 
RECOMMENDATIONS......................................................................185
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
30
APPENDIX M
RECOMMENDATIONS FOR THE MANAGEMENT OF 
TREATMENT-INDUCED DIARRHEA ..............................................211
APPENDIX N
PROTOCOL AMENDMENT SUMMARY OF CHANGE 
HISTORY ............................................................................................212
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
31
LIST OF TABLES
Table 1:
Risk Assessment.....................................................................................57
Table 2:
Study Objectives ....................................................................................61
Table 3:
Study Endpoints .....................................................................................63
.84
Table 5:
Pharmacokinetic Parameters.................................................................104
.105
.106
.109
.121
.121
.124
Table 12:
Management of Potential Venetoclax Interactions with CYP3A 
and P-gp Inhibitors ...............................................................................137
Table 13:
Definition of study population ..............................................................139
144
145
145
Table 17:
Abbreviations and Specialist Terms......................................................167
Table 18:
WHO classification of AML.................................................................174
Table 19:
Hematologic/Molecular Response According to ELN Criteria for 
AML ....................................................................................................175
Table 20:
WHO classifications for MDS ..............................................................176
Table 21:
Modified IWG Response Criteria for MDS...........................................178
Table 22:
Risk Stratification by Genetics in Non-APL AML................................180
Table 23:
IPSS-R Cytogenetic Risk Groups .........................................................182
Table 24:
IPSS-R Prognostic Score Values...........................................................182
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
32
Table 25:
IPSS-R Prognostic Risk Categories/Scores...........................................182
Table 26:
IPSS-R: Prognostic Risk Category Clinical Outcomes..........................183
Table 27:
Eastern Cooperative Oncology Group (ECOG) Performance Status 
(PS)......................................................................................................184
Table 28:
Tumor Lysis Syndrome (TLS) Prophylaxis Recommendations 
Based on TLS Risk...............................................................................185
Table 29:
Cairo-Bishop Definition of Laboratory Tumor Lysis Syndrome............186
Table 30:
Cairo-Bishop Grading System for Tumor Lysis Syndrome ...................186
.188
.189
.191
.201
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
33
LIST OF FIGURES
...38
...40
...68
Figure 4:
Overall Study Design..............................................................................73
...76
.188
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
34
1
INTRODUCTION
1.1
Disease Background
1.1.1
Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a genetically heterogeneous cancer of bone marrow (BM) 
myeloid progenitors that, when untreated or unresponsive to treatment, leads to death within weeks 
to months due to BM failure or effects of leukemia cells on circulation or organ function. AML is 
the most commonly reported type of acute leukemia in adults in the United States (US). Based on 
Surveillance, Epidemiology, and End Results (SEER, 2023) estimates, approximately 20,380 
people will be diagnosed with AML in 2023 in the US and 11,310 will die from the disease. It 
remains a challenging disease to treat with an estimated relative 5-year survival of 31.7% for AML 
patients diagnosed in the years 2013 to 2019. AML remains a disease primarily of older adults, 
with a median age at diagnosis of 69 years (SEER, 2023). 
Standard curative treatment for AML consists of intensive induction chemotherapy followed by 
consolidation chemotherapy, allogeneic stem cell transplantation, or both. Elderly patients with 
AML have significant comorbidities, an increased frequency of adverse cytogenetic abnormalities, 
poor performance status, a higher incidence of AML arising from myelodysplastic syndromes 
(MDS), and resistance to conventional treatments (Dombret, 2008). For these reasons, elderly 
patients may not be candidates for standard intensive chemotherapy induction regimens (DiNardo, 
2019). Furthermore, treatment options are few for patients who choose not to or are considered
ineligible by their physician to receive intensive induction chemotherapy. Patients considered 
ineligible for intensive induction chemotherapy are generally patients older than 75 years of age 
or those 60 to 75 years old with significant comorbidities, poor performance status, or with 
complex cytogenetic abnormalities (Milligan, 2006). Though there have been promising 
developments in the use of lower-intensity therapies in this population such as low-dose cytarabine 
or recently approved combination regimens with the B-cell lymphoma-2 (BCL-2) inhibitor 
venetoclax (Venclexta Package Insert, 2020), the durability of response and overall prognosis 
remains poor. Targeted therapies may also be utilized in distinct subpopulations of AML patients. 
For individuals with FMS-like tyrosine kinase 3 (FLT3) mutated AML, tyrosine kinase inhibitors 
including midostaurin, gilteritinib or sorafenib (with HMAs [hypomethylating agents]) have a 
therapeutic role; ivosidenib or enasidenib can be used for patients
with isocitrate 
dehydrogenase-1/isocitrate dehydrogenase-2 mutations, respectively; gemtuzumab ozogamicin 
can be used for patients with CD33-positive AML (NCCN, 2021a).
For the majority of patients with relapsed or refractory (R/R) AML with unfavorable prognostic 
features, intensive chemotherapy or other standard treatment options have poor outcomes with 
complete remission rate (CRR) no higher than 15% and median overall survival (mOS) less than 
6 months (Estey, 1996; Ritchie, 2013; Roboz, 2014; Perl, 2019). Among AML patients who 
relapsed after having achieved a first complete remission (CR1), about 45% do so within 6 months, 
75% within 12 months and 85% within 18 months (Breems, 2005; Estey 1996). While the minority 
of patients who experience relapse after more than 1 or 2 years in CR1 generally fare better, 
chances to achieve long term disease control for the majority of patients with R/R AML are dismal, 
exemplified by 3-year survival of 11% for adults up to 55 years old and 6% for patients above age 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
35
55 determined by analysis of eight pooled Eastern Cooperative Oncology Group (ECOG) studies 
for relapsed AML (Rowe, 2010). More recently, Onureg, an oral formulation of the 
hypomethylating agent azacitidine, in AML maintenance demonstrated improvement in both 
progression free survival (PFS) and overall survival (OS) for patients in CR1 that are ineligible for 
allogeneic stem cell transplantation (SCT) (Wei, 2020). While this is encouraging, the experience 
needs to be built upon (Reville, 2021). Although the approved combination regimen of venetoclax 
and azacitidine (DiNardo, 2020) has improved response rates and survival in this patient
population compared with prior regimens (see Section 1.2.3), complete remission (CR) rates 
remain low and rates of eventual relapse are high, and this remains a population with a high unmet 
need. Continuing research efforts are needed to develop new agents and treatment regimens that 
are tolerable and effective in R/R AML patient population, and the addition of investigational 
agents to the combination of venetoclax and azacitidine may increase the remission rate and 
prolong survival, therefore addressing an important unmet medical need in patients with newly 
diagnosed (ND) and R/R AML.
1.1.2
Myelodysplastic Syndromes
Myelodysplastic syndromes are an umbrella term for a heterogeneous collection of hematopoietic 
stem cell disorders primarily affecting older adults. It is estimated that between 2 and 4 cases per 
100,000 persons per year are diagnosed with MDS. The elderly are particularly vulnerable with 
annual incidence rates between 15 and 50 cases per 100,000 persons per year (Steensma, 2003). 
The prognosis depends on the individual’s risk factors, with a median survival ranging from 
5.3 years in low-risk patients to 1.6 and 0.8 years in high- and very high-risk patients, respectively
(Greenberg, 2012). 
Myelodysplastic syndromes are typically characterized by ineffective hematopoiesis in the BM 
and peripheral blood (PB) leading to cytopenias that manifest clinically as anemia, neutropenia, 
and/or thrombocytopenia of variable frequency and severity. Other less common presenting 
clinical features related to the cytopenias are an increased risk of infection or hemorrhage and a 
propensity to progress to AML (Catenacci, 2005). 
For certain subtypes of MDS, excess blast cells are present (Bennett, 1982). Progress in 
understanding the pathobiology of MDS has evolved rapidly, as have an increasing number of 
myeloablative and supportive care strategies. The mainstay of therapy has been supportive care, 
which includes the use of red cell or platelet transfusions, treatment of infections, and the use of
epoetin alfa or myeloid growth factors when needed (NCCN, 2021b; Silverman, 2000; Lübbert, 
2000). Vidaza (azacitidine) has been shown to increase overall survival (OS) in patients with 
higher-risk MDS (HR-MDS) relative to conventional care, but it is not curative (Fenaux, 2009). 
Bone marrow transplantation has been effective both in patients under the age of 50 and in those 
older than 50 years who are in good health. However, this approach has limited value since most 
patients with MDS are older than 65 years of age and have significant comorbidities (Silverman, 
2000). 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
36
The International Prognostic Scoring System (IPSS) is a validated standard for assessing the 
prognosis of primary untreated adult patients with MDS. The IPSS-R is a revision to the original 
IPSS which is particularly notable for the incorporation of prognostic cytogenetic features of MDS. 
For patients with HR-MDS who have failed hypomethylating therapy, the prognosis is comparable 
to R/R AML with mOS between 4.5 and 11 months dependent on prognostic factors of age, 
performance status, cytogenetics, myeloblast percentage, platelet count and red cell transfusion 
dependency (Nazha, 2017; Bewersdorf, 2020a). 
Relapsed or refractory HR-MDS patients are a high-unmet need population for which there is no 
standard of care and novel therapies are needed.
1.2
Compound Background 
1.2.1
CC-95251
The investigational product CC-95251 (also known as BMS-986351) is a first-in-class, high
affinity, fully human antibody, designed to bind to and modulate the biology of the macrophage 
inhibitory receptor signal regulatory protein alpha (SIRPα) by blocking the binding of SIRPα to 
cluster of differentiation (CD) 47. CD47 binding to SIRPα on macrophages and other phagocytes 
triggers a signaling pathway that inhibits phagocytosis, thus enabling CD47-expressing cells to 
avoid phagocytic removal. CC-95251 has an immunoglobulin G1 (IgG1) framework 
 
 
 CC-95251 did not 
 
 induce cytokine release from human
 in immobilized or soluble formats, with or without 
myeloid or T cell pre-activation, nor does it have antibody-dependent cellular phagocytosis 
(ADCP) activity against autologous T cells or monocytes. In combination with effector-competent, 
tumor-targeting antibodies (eg, cetuximab, rituximab), CC-95251 enhances macrophage-mediated 
phagocytosis of tumor cells in in vitro phagocytosis assays. CC-95251 is being developed as an 
injectable intravenous (IV) treatment for solid tumors and hematological malignancies and to date 
has been administered in subjects as a single agent or in combination with effector-competent 
tumor targeting antibodies (eg, cetuximab, an anti-epidermal growth factor receptor [anti-EGFR] 
monoclonal antibody; rituximab, an anti-cluster of differentiation 20 [anti-CD20] monoclonal 
antibody). 
 
 
 
 
 
Please refer to the CC-95251 IB (Investigator Brochure) (for detailed information concerning the 
available pharmacology, toxicology, drug metabolism, clinical studies, and adverse event (AE)
profile of CC-95251 (CC-95251 IB).
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
37
1.2.1.1
Nonclinical Pharmacology
1.2.1.1.1
Mechanism of Action
SIRPα is an immunoglobulin (Ig)-like family member and is expressed on monocytic and neuronal 
lineage cells. Macrophage phagocytic receptors can discriminate altered self-molecules on aged or 
dying cells from normal self-markers on healthy cells, resulting in either activation or inhibition 
of the phagocytosis response (Taylor, 2005). CD47 is a transmembrane protein ubiquitously 
expressed on human cells but may also be overexpressed by many different tumor cells (Chao, 
2012; Edris, 2012; Willingham, 2012).  The inhibitory CD47-SIRPα ligand-receptor pair has been 
identified as an important, but not universal, innate immune negative checkpoint regulator in the 
homeostatic clearance of apoptotic cells by macrophage-mediated phagocytosis (Matlung, 2017). 
The biology of SIRPα is differentiated from its related family members SIRP beta (β) and SIRP 
gamma (γ) due to the identified interactions and downstream signaling with its cognate ligand 
CD47 as a negative regulator of phagocytosis (Matlung, 2017). In the context of cancer, several 
types of neoplastic cells have been reported to overexpress CD47, providing an immune evasion 
mechanism by enhancing this “don’t-eat-me” signal (Majeti, 2009; Chao, 2010; Willingham, 
2012). Extensive preclinical in vitro and in vivo models disrupting the CD47-SIRPα interaction 
have demonstrated that hematologic and solid tumor clearance can be promoted by targeting either 
CD47 or SIRPα (Russ, 2018). Examples of CD47-SIRPα checkpoint blockade, either alone or in 
combination with well-known cancer opsonizing therapeutic antibodies, have been shown to 
effectively promote anti-tumor activity (Chao, 2010; Zhao, 2011). 
The potential mechanisms of action of CC-95251 alone and in combination with azacitidine 
against AML include the following (numbers correspond to

CC-95251 binds to SIRPα on macrophages and other phagocytes disrupting the CD47-SIRPα 
“don’t eat me” signaling and thus promoting phagocytosis of AML.

Hypomethylating agents including azacitidine increase the expression of “eat me” signals such 
as calreticulin on AML, further promoting phagocytosis of the AML by macrophages via “eat 
me” receptors.

 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
38
1.2.1.1.2
In Vitro Pharmacology
1.2.1.1.2.1 Distribution of SIRPα and CD47
The distribution of SIRPα in normal and cancerous human tissues was investigated using 
immunohistochemistry (IHC). SIRPα expression was limited to the normal resident cells of 
monocyte origin in many tissues including spleen, lymph nodes, lung, gastrointestinal tract, and 
liver. Strong immunoreactivity was also observed in neural tissue of brain and spinal cord. Staining 
of lesser intensity was observed in transitional epithelium, glandular epithelia (mammary and 
prostate glands), kidney glomeruli, and pancreatic ductal epithelium.
In cancerous tissues, expression of SIRPα was confirmed on infiltrating macrophages in most 
tumor types including AML. Notably, SIRPα expression was evident in the neoplastic cells of 
several tumor types including melanoma, renal cell carcinoma, squamous cell carcinoma of the 
head and neck (SCCHN), AML, and diffuse large B-cell lymphoma. In AML, expression of SIRPα 
was evident in all cases, but was most prominent in those exhibiting monocytic differentiation as 
determined by the French-American-British (FAB) classification of acute myelomonocytic 
leukemia or M4.
In AML, CD47 expression is present across the bulk leukemia population but is increased in the 
self-renewing leukemia stem cell (LSC) fraction (Majeti, 2009). Increased CD47 expression 
portends a poor prognosis in AML (Majeti, 2009). Similarly, expression of CD47 in MDS is 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
39
increased in high-risk patients (by IPSS) compared with low-risk MDS and normal controls (Jiang, 
2013).
1.2.1.1.2.2 CC-95251-mediated phagocytosis of AML
Azacitidine treatment of an AML cell line has been shown to increase the surface expression of
the pro-phagocytic ligand calreticulin, which correlated with an increase in phagocytosis 
by monocyte-derived macrophages. Blockade of CD47 further augmented the phagocytosis of
azacitidine-treated AML cells (Chao, 2020). 
 
 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
40
 CC-95251 did not induce cytokine release from multiple human 
donor PBMCs in either platebound or soluble formats, with or without myeloid or T cell pre-
activation.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
41
1.2.1.3
Nonclinical Toxicology
All in vivo toxicity studies were conducted in the cynomolgus monkey as it is the 
pharmacologically relevant species identified for evaluation of potential CC-95251-related toxic 
effects. The highest dose evaluated in the 3 repeat-dose toxicity studies was
 mg/kg CC-95251. 
Although ADAs were detected in individual monkeys, exposure to circulating free CC-95251 was 
achieved and maintained throughout the dosing phases in all studies at all dose levels, enabling 
appropriate evaluation of potential toxicities. All CC-95251-related effects were considered 
nonadverse due to their low severity.
In the 28-day exploratory toxicity study, the effects of CC-95251 were evaluated following 
separate administration to female cynomolgus monkeys twice (Days 1 and 15) as bolus IV 
injections at dose levels of 
mg/kg/dose. No test article-related changes were 
observed; therefore, the no observed effect level for both molecules was 
mg/kg/dose, the 
highest dose evaluated in this study.
In the pivotal GLP-compliant toxicity study, CC-95251 was also well-tolerated when administered 
to male and female cynomolgus monkeys via IV injection at doses of 
 mg/kg/dose 
weekly for a total of 5 doses. Six of 10 animals in the 
 mg/kg dose group were positive for anti-
drug antibodies (ADA) by Dose 4, but exposure to CC-95251 was maintained in all animals 
negative for ADA in this low-dose group, and in all animals in the mid- and high-dose groups, 
throughout the study. CC-95251 was well tolerated with CC-95251--related findings limited to 
minimal to mild decreases in eosinophils at doses
 mg/kg, with partial to complete recovery 
at the end of the 4-week treatment-free period. Due to the low severity, these findings were 
considered nonadverse. Therefore, the no observed adverse effect level and the highest 
non-severely toxic dose were the highest dose evaluated in this study, 
mg/kg/dose.
In a GLP-compliant human tissue cross-reactivity study, CC-95251 demonstrated a pattern of 
staining generally consistent with the reported expression of SIRPα. Specifically, cell membrane 
staining was noted in mononuclear cells across a variety of tissues where these cells may normally 
be found (eg, lymphoid tissues), as well as in macrophages (alveolar and Kupffer cells), blood 
neutrophils, and marrow hematopoietic cells. Some epithelial cell types also stained (tonsil, 
thymus, intestine, prostate, pancreas, salivary glands). In some tissues (eg, pituicytes, 
spermatogenic cells, cardiomyocytes), only cytoplasmic elements stained; however, antibody 
binding to cytoplasmic sites in tissue cross-reactivity studies generally is considered of little to no 
toxicologic significance due to the inability of antibody drugs to access the cytoplasmic 
compartment in vivo (Hall, 2008; Leach, 2010). Staining of the neuropil of the brain and spinal 
cord was also observed; however, due to the inability of antibody drugs to cross blood-tissue 
barriers (eg, brain, spinal cord, eye) in vivo (Garbuzova-Davis, 2014; Ghate, 2006; Palmer, 2013;
Pardridge, 2015), binding to these tissues in vitro is also generally considered of little to no 
toxicologic significance.
1.2.1.4
Nonclinical Pharmacokinetics
The pharmacokinetics (PK) parameters of CC-95251 were characterized after single and multiple 
IV doses. Systemic exposure to CC-95251 in
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
42
1.2.1.5
Clinical Experience with CC-95251
A summary of the clinical experience with CC-95251 as of 14 Feb 2022 is provided in the 
CC-95251 IB (CC-95251 IB). There are 2 clinical trials with CC-95251 currently ongoing: 
CC-95251-ST-001, with 
subjects enrolled as of the IB data cutoff date of 14-Feb-2022 and 
CA059-001,
 AML/MDS specific data were available at the time of clinical data cutoff for the 
CC-95251 IB. Please refer to the IB for additional details and interim summary of 
pharmacodynamic, PK, and safety data (CC-95251 IB).
First-in-human (FIH) clinical study CC-95251-ST-001 is a Phase 1, open-label, dose escalation
(Part A) and dose expansion (Parts B and C) study in subjects with advanced solid and hematologic 
cancers. As of 14 Feb 2022, 
 received at least one intravenous dose of 
CC-95251
 
 
 
 
The safety and tolerability of single agent CC-95251 
 was evaluated in subjects with 
advanced solid cancers who have progressed on standard anticancer therapy or for whom no other 
approved conventional therapy exists and is summarized below. 
The results of preliminary clinical safety assessments of the treated subjects in the CC-95251 
monotherapy show the most frequently reported treatment-emergent adverse events (TEAEs) were 
 
 
 
 who had TEAEs that were suspected by the Investigator to be
related to CC-95251. 
 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
43
Investigator to be related to CC-95251
 
 
One subject in the 
 
 
 
 
 
 
 
 
 
 
 
 
 
In the monotherapy settings of CC-95251, 
 
 
 
 
 
 
 
 
 
  
Study CA059-001 is an open-label, Phase 1 dose-finding study of CC-95251 alone and in
combination with antineoplastic agents in subjects with AML and MDS. No study-specific data
were available at the time of clinical data cutoff for the CC-95251 IB. Please refer to the CC-95251
IB for detailed information concerning the available pharmacology, toxicology, drug metabolism, 
clinical studies, and adverse event profile of CC-95251.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
44
1.2.2
Azacitidine
Azacitidine, an analog of the pyrimidine nucleoside cytidine, has effects on cell differentiation, 
gene expression, deoxyribonucleic acid (DNA) synthesis and metabolism, and causes cytotoxicity. 
Vidaza (azacitidine for injection) is approved by the United States Food and Drug Administration 
(US FDA) for the following 5 subtypes of the French-American-British (FAB) classification 
system of MDS: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if 
accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia
with excess blasts, refractory anemia with excess blasts in transformation , and chronic
myelomonocytic leukemia (CMMoL) (Vidaza package insert, 2022). Vidaza is also approved by
the European Commission for the treatment of adult patients who are not eligible for hematopoietic
stem cell transplantation with intermediate-2 (int-2) and high-risk MDS according to the IPSS,
CMMoL with 10% to 29% marrow blasts without myeloproliferative disorder, AML with 20% to
30% blasts and multilineage dysplasia, and AML with > 30% marrow blasts according to the 
World Health Organization (WHO) classification. As of 18 May 2020, Vidaza has received 
marketing authorization in 86 countries worldwide, including the US and those in the EU. Current 
approved routes of administration include subcutaneous (SC) and IV (approvals vary by country).
Azacitidine has been extensively studied in MDS and has been shown in a large, randomized Phase 
3 trial ofhigher-risk MDS patients to provide a survival advantage of 9.4 months over conventional 
care regimens (CCRs), thus altering the natural course of MDS. The median OS of azacitidine-
treated patients was 24.5 months compared with 15.0 months for the combined CCR group, which 
included best supportive care, low-dose cytarabine, and intensive chemotherapy (Fenaux, 2009).
In a subset of 113 patients with WHO-defined AML (mean age 70 years, 24% with unfavorable 
karyotype, median bone marrow blasts 23%) from the larger MDS study discussed above, the 
median OS was 24.5 months (N = 55) in the azacitidine arm compared with 16.0 months (N = 58)
in the CCR arm (Fenaux, 2008; Fenaux, 2010). Additionally, the outcome was not significantly
different in patients with an unfavorable karyotype, although the sample size was small. Silverman
et al, using WHO AML criteria for diagnosis, reported a median OS of 19.3 months (N = 27) in 
azacitidine treated patients compared with 12.9 months (N = 25) in patients who received best 
supportive care (Silverman, 2006).
Additionally, Goldberg et al, reported on 33 patients who received azacitidine (N = 11, median 
age 74) or 7 + 3 intensive chemotherapy (N = 22, median age 67 years). Median blast counts at 
baseline were 42% in the azacitidine group and 65% in the intensive chemotherapy group. The 
median OS was 13.2 months in azacitidine treated patients compared with 9.2 months in intensive 
chemotherapy patients (Goldberg, 2006).
The efficacy of SC azacitidine to treat AML was evaluated in a controlled Phase 3 study 
(azacitidine [N = 241] vs CCR [N = 247]) in 488 patients age ≥ 65 years with newly diagnosed 
AML with > 30% blasts (Dombret, 2015). Azacitidine increased median OS by 3.8 months vs 
CCR arm (10.4 vs 6.5 months; P = .1009). One-year survival rates with azacitidine and CCR were 
46.5% and 34.2%, respectively. A prespecified analysis that censored patients who received AML 
treatment after discontinuing study drug showed median OS with azacitidine vs CCR was 12.1 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
45
months vs 6.9 months. Azacitidine safety in patients age ≥ 65 years with AML (> 30% blasts) was 
consistent with its known safety profile in other trials.
The most commonly observed adverse reactions (SC or IV route) treated with azacitidine include 
nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, injection site 
erythema, constipation, neutropenia, ecchymosis. Most common adverse reactions by IV route 
also included petechiae, rigors, weakness and hypokalemia. Cytopenias were the most common 
reason for dose reduction or discontinuation (Vidaza package insert, 2022).
Please refer to the current local prescribing information for detailed information concerning the 
available pharmacology, toxicology, drug metabolism, clinical studies, and adverse event profile 
of azacitidine.
1.2.3
Venetoclax
Venetoclax is a selective and orally bioavailable small-molecule inhibitor of B-cell lymphoma-2
(BCL-2), an anti-apoptotic protein. Overexpression of BCL-2 has been demonstrated in chronic
lymphocytic leukemia and AML cells where it mediates tumor cell survival and has been
associated with resistance to chemotherapeutics. Venetoclax helps restore the process of apoptosis
by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BCL-2-interacting
mediator of cell death, triggering mitochondrial outer membrane permeabilization and the
activation of caspases. In nonclinical studies, venetoclax has demonstrated cytotoxic activity in
tumor cells that overexpress BCL-2.
In a Phase 1b study, the preliminary safety and efficacy of venetoclax in combination with HMA 
(either decitabine or azacitidine) in elderly patients with newly diagnosed (ND) AML was 
demonstrated (DiNardo, 2019). In VIALE-A (NCT02993523), a confirmatory Phase 3 study, 
patients with ND AML not eligible for intensive chemotherapy (IC) were randomized to receive
venetoclax plus azacitidine (n = 286) or placebo plus azacitidine (n = 145) (DiNardo, 2020). 
Efficacy was established based on an improvement in OS with median OS of 14.7 months (95% 
confidence interval [CI]: 11.9, 18.7) in patients treated with venetoclax plus azacitidine compared 
to 9.6 months (95% CI: 7.4, 12.7) in those receiving placebo plus azacitidine (hazard ratio [HR] 
0.66; 95% CI: 0.52, 0.85; p < 0.001). Patients treated with venetoclax plus azacitidine also 
demonstrated an improvement in CR rate: 37% (95% CI: 31%, 43%) versus 18% (95% CI: 12%, 
25%) (FDA, 2020).
The incidence of the composite CR (CR or complete remission with incomplete blood recovery 
[CRi]) was 66.4% (95% CI, 60.6 to 71.9) in the azacitidine and venetoclax group versus 28.3% 
(95% CI, 21.1 to 36.3) in the control group (p < 0.001). (Dinardo, 2020). Based on this data, in 
October 2020 the FDA granted regular approval to venetoclax in combination with injectable 
azacitidine for adults with ND AML aged > 75 years or who have comorbidities precluding IC, 
followed by approval in May 2021 by the European Commission.  
Data on R/R AML are scarce and heterogenous. Outcomes in patients with R/R AML are dismal,
with a median OS of 3 to 7 months, and there is no approved standard of care (SOC). A systematic
literature review and meta-analysis assessed overall response rate (ORR), and rates of CR/CRi for
R/R AML subjects treated with venetoclax or venetoclax plus HMA/low-dose cytarabine (LDAC)
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
46
(Bewersdorf, 2020b). This systematic review and meta-analysis of venetoclax treatment in R/R 
AML included 7 studies with a total of 224 subjects and demonstrated an ORR of 38.7% and a CR 
rate of 19% for R/R AML subjects treated with venetoclax plus HMA/LDAC. Moreover, the meta-
analysis showed that prior treatment with HMA did not preclude a response to subsequent 
venetoclax-based treatment.
The safety of venetoclax in combination with azacitidine (N = 283) versus placebo in combination
with azacitidine (N = 144) was evaluated in the VIALE-A study. Subjects were randomized to
receive venetoclax 400 mg orally once daily (QD) after completion of the ramp-up phase in
combination with azacitidine (75 mg/m2 either IV or SC on Days 1 through 7 of each 28-day cycle) 
or placebo in combination with azacitidine. Serious adverse reactions were reported in 83% of 
subjects who received venetoclax in combination with azacitidine, with the most frequent (≥ 5%) 
being febrile neutropenia (30%), pneumonia (22%), sepsis (excluding fungal; 19%), and 
hemorrhage (6%). Fatal adverse reactions occurred in 23% of subjects who received venetoclax in 
combination with azacitidine, with the most frequent (≥ 2%) being pneumonia (4%), sepsis 
(excluding fungal; 3%), and hemorrhage (2%).
In subjects with AML who followed the current 3-day ramp-up dosing schedule and the tumor
lysis syndrome (TLS) prophylaxis and monitoring measures, the rate of TLS was 1.1% in subjects
who received venetoclax in combination with azacitidine (VIALE-A). In subjects with AML,
baseline neutrophil counts worsened in 95% to 100% of subjects treated with venetoclax in
combination with azacitidine, decitabine, or low-dose cytarabine. Neutropenia can recur with
subsequent cycles.
A detailed description of the chemistry, pharmacology, efficacy, and safety of venetoclax in
combination with azacitidine is provided in the Summary of Product Characteristics (SmPC)
and/or package insert approved in the local country (venetoclax Package Insert, 2020) (venetoclax 
SmPC, 2022).
1.3
Rationale
1.3.1
Study Rationale and Purpose
The study will explore the safety, tolerability, and preliminary clinical activity of CC-95251 as a 
single agent and in combination with antineoplastic agents in subjects with relapsed or refractory
and treatment-naïve (TN) AML, relapsed or refractory and TN higher risk MDS (ie, IPSS-R 
 
There is strong rationale for evaluating CC-95251 as a single agent, in combination with injectable 
azacitidine (double combination), and in combination with injectable azacitidine and venetoclax
(triple combination) in the previously mentioned indications. 
In the context of cancer, several types of neoplastic cells have been reported to overexpress CD47, 
providing an immune evasion mechanism by enhancing the “don’t-eat-me” signal. In AML, CD47 
expression is present across the bulk leukemia population but is increased in the self-renewing 
leukemic stem cell (LSC) fraction. Additionally, increased CD47 expression portends a poor 
prognosis in AML (Majeti, 2009). Similarly, expression of CD47 in MDS is increased in high-risk
patients compared with low-risk MDS and normal controls (Jiang, 2013).
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
47
Azacitidine treatment of an AML cell line has been shown to increase the surface expression of 
the pro-phagocytic ligand calreticulin which correlated with an increase in phagocytosis 
by monocyte-derived macrophages. Blockade of CD47 further augmented the phagocytosis 
of azacitidine-treated AML cells (Chao, 2020).
 
 
 
 
In vitro phagocytosis assays reported in the literature demonstrated that treatment with venetoclax
or azacitidine induced phosphatidylserine in MOLM-13 cells, which may function as a pro-
phagocytic signal and contribute to the enhanced phagocytosis. The mechanisms of increased 
phagocytosis and the induction of “eat-me signals” by combination treatment with venetoclax
andazacitidine are currently under investigation (Jia, 2021). 
Additionally, recent clinical data targeting the CD47-SIRPα pathway has shown anti-cancer 
activity across a variety of solid cancers and hematologic malignancies. Magrolimab (Hu5F9-G4), 
an anti-CD47 monoclonal antibody in combination with azacitidine demonstrated preliminary
clinical activity in an ongoing Phase 1b trial evaluating previously untreated subjects with 
chemotherapy ineligible AML and intermediate to very high risk MDS (Sallman, 2020a, Sallman, 
2020b). 
More recent studies are evaluating the combination of azacitidine and venetoclax with agents 
targeting the CD47/SIRPα axis including magrolimab (NCT04435691) and ALX148, a high 
affinity CD47 blocker fusion protein (NCT04755244) in both R/R and TN AML. These studies 
have demonstrated limited response in the R/R setting, particularly in subjects previously exposed 
to venetoclax; however, they have demonstrated promising results in the front-line setting, notably 
in subjects with TP53-mutated AML (Daver, 2022, Garcia-Manero, 2022). 
Taken together, this evidence highlights a strong biological rationale for the evaluation of 
CC-95251 as monotherapy and in combination with either azacitidine or azacitidine and 
venetoclax in the treatment of subjects with AML and higher risk MDS. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
48
A cumulative benefit and risk assessment for this study is provided below (Section 1.4). Please 
refer to the CC-95251 IB for additional details regarding the physical and chemical properties, 
nonclinical studies, and toxicology data for CC-95251.
1.3.2
Rationale for the Study Design
Part A
The dose escalation part (Part A) of the study will be conducted using 
 
 to guide CC-95251 dose escalation / de-
escalation decisions, with the final decisions being made by the SRC, whose members include 
Investigators (and/or designated representatives), the Sponsor’s Medical Monitor, safety 
physician, clinical scientist, and the study manager. Ad hoc attendees may include the study PK 
scientist, biostatistician, and translational research scientist. Other internal and external experts 
may be consulted by the SRC, as necessary. 
 
 
After enrollment has been completed in the corresponding Part A cohorts, the SRC will undertake 
an evaluation of the available safety, PK, PD, and preliminary efficacy data to make a 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
49
determination of the preliminary dose and schedule of CC-95251 to test in the expansion cohorts 
(Parts B, C, and D).
Part B
Additional cohorts of subjects testing CC-95251 in combination with additional antineoplastic 
agents in subjects with R/R AML or R/R MDS may be considered at the recommendation of the 
SRC and will be included by protocol amendment.
Part C
The heterogeneous collection of clonal hematopoietic stem cell disorders that broadly make up 
MDS remain a challenging clinical scenario with very limited therapeutic options in the front-line
setting. The elderly are particularly vulnerable to the development of MDS with annual incidence 
rates between 15 and 50 cases per 100,000 persons per year (Steensma, 2003). The prognosis 
depends on the individual’s risk factors, with a limited median survival of only 0.8 to 1.6 years in 
patients with high or very high-risk presentations, respectively (Greenberg, 2012). 
While hypomethylating agents such as azacitidine have been shown to increase OS in patients with 
high-risk MDS relative to conventional care, they do not represent a curative option (Fenaux, 
2009) and the majority of these patients continue to experience only a limited extent and duration 
of benefit with this class of drugs. Furthermore, potentially curative bone marrow transplantation 
has limited applicability to the broader MDS population in light of advanced age and comorbidities 
(Silverman, 2000). There also remains both a significant risk of transformation of MDS into AML 
and no approved agents that impact survival in those who have failed to respond or progressed on 
hypomethylating agents, highlighting the need to attain better disease control in the front-line
setting. In conclusion, there remains a significant need to expand on therapeutic options available 
to the treatment-naïve HR-MDS patient population. The safety profile of CC-95251 to date and 
the potential to combine this differentiated mechanism of action with that of standard-of-care 
azacitidine supports evaluating this combination in the treatment -naïve (ie, previously untreated), 
intermediate, high or very high risk (ie, IPSS-R 
) MDS population in the Part C dose 
expansion. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
50
Part D
Part D expansion will evaluate CC-95251 in combination with injectable azacitidine and 
venetoclax in subjects with TN AML and who are not candidates to receive IC due to comorbidities 
or age (ie, ≥ 75 years). Venetoclax is approved by the FDA and European Commission in this 
setting; however, while this regimen has improved response rates and OS in this population 
compared to azacitidine monotherapy, prognosis remains poor, and this remains an area of high 
unmet need. The addition of agents with different mechanisms of action to this combination may 
confer added benefit. Currently, other agents targeting 
 
 
 
 
 
 
 
 
 
 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
51
 
 
 
 
The SRC will continue to review safety data regularly throughout the study and make 
recommendations about study continuation, dose modification, and establishment of a RP2D as 
appropriate. Enrollment in Part D may proceed concurrently with enrollment in the Part B and C 
expansion cohorts. 
Other combinations of CC-95251 and antineoplastic agents in subjects with R/R AML and/or R/R 
or TN MDS may be explored at the recommendation of the SRC and will be added by subsequent 
protocol amendment.
1.3.3
Rationale for Dose, Schedule and Regimen Selection
The ongoing, Phase 1 study CC-95251-ST-001 has evaluated escalating doses of CC-95251 up to 
a dose level 
 mg/kg 
 administered as monotherapy, in combination with cetuximab in 
subjects with colorectal cancer and SCCHN and in combination with rituximab 
non-Hodgkin’s Lymphoma (NHL).
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
52
As the demonstrated mechanism of action of CC-95251 involves
 
 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
53
 based on review of the available safety, PK, PD, and preliminary efficacy data
The investigation of any other alternate dosing schedule beyond 
those stipulated in the current protocol version will be submitted in a protocol amendment.
The dosing of azacitidine will follow local prescribing information and institutional standard of 
care at 75 mg/m2 with an exception to allow flexibility on the dosing schedule, either Days 1-7 or 
Days 1-5 and 8-9 in each 28-day cycle. 
 
 
 
1.3.4
Rationale for Choice of Combination Compounds
1.3.4.1
Rationale for Combination of CC-95251 with Azacitidine
The safety and clinical profile of azacitidine have been well-characterized in the setting of both 
AML and MDS. As detailed in Section 1.2.2, the use of azacitidine in the therapeutic treatment 
landscape for these myeloid malignancies makes it a preferred agent to pair in combination with 
CC-95251. 
Preclinically, azacitidine treatment of an AML cell line has been shown to increase the surface 
expression of the pro-phagocytic ligand calreticulin which correlated with an increase in 
phagocytosis by monocyte-derived macrophages. Blockade of CD47 further augmented the 
phagocytosis of azacitidine-treated AML cells (Chao, 2020). 
 
 
 
Magrolimab (Hu5F9-G4), an anti-CD47 monoclonal antibody, in combination with azacitidine 
demonstrated preliminary clinical activity in a Phase 1b trial evaluating untreated patients with 
intermediate to very high risk MDS and chemotherapy ineligible AML and several additional trials 
are now underway which target the CD47/SIRPα axis in AML and MDS (Sallman, 2020a,
Sallman, 2020b, Sallman, 2023). The early signals of clinical activity in AML and MDS seen by 
targeting of the CD47/SIRPα axis lend further support to the potential for CC-95251 plus 
azacitidine in these disease settings. 
1.3.4.2
Rationale for Combination of CC-95251 with Azacitidine Plus 
Venetoclax
The safety and clinical profile of injectable azacitidine in combination with venetoclax has been 
well characterized in the setting of AML. As detailed in Section 1.2.3, injectable azacitidine and 
venetoclax has demonstrated improved OS and CR rates compared to azacitidine alone, and this 
combination is now approved by the FDA and European Commission as a standard of care (SOC) 
for adults with ND AML not eligible for intensive induction chemotherapy. Despite this 
improvement over prior regimens, CR rates and OS remain low, and this is not a curative therapy. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
54
Outcomes of subjects with R/R AML are dismal, with a median OS of 3 to 7 months, and while 
there is no approved SOC, the combination of venetoclax with injectable azacididine has been 
used successfully in this population, albeit with low OR and CR rates. Therefore, these remain 
areas of high unmet therapeutic need, and the addition of agents to this regimen with a different 
mechanism of action may confer additional benefit. Preliminary results from recent studies 
combining agents targeting the CD47/SIRPα axis such as magrolimab and ALX148 in R/R and 
TN AML have demonstrated limited response, though with more promising results in the front-
line setting (Daver, 2022, Garcia-Manero, 2022). These early results lend further support to the 
potential for CC-95251 plus azacitidine and venetoclax in these settings.
1.3.5
Rationale for Pharmacodynamics and Potential Predictive Biomarkers
The antitumor function of CC-95251 depends on the binding of SIRPα on monocytes, neutrophils, 
and dendritic cells, and some tumor cells (eg, AML blasts), promoting phagocytosis and killing of 
tumor cells. PD biomarkers will help to inform the appropriate dose and schedule of CC-95251 by 
providing measures of target engagement, immune activation status, cytokine release, disease 
progression, and tumor burden. Additionally, the sampling plan and downstream analyses of the 
exploratory endpoints aim to address open questions centered on the biology governing the activity 
and durability of the CC-95251 antitumor response, as well as potential resistance mechanisms 
that could include underlying immune status, the tumor microenvironment, or direct resistance by 
the tumor.
Multiple pharmacodynamic biomarkers will be explored to characterize dose-dependent 
CC-95251 activities as a single agent and in combination with azacitidine or azacitidine and
venetoclax. These may include:

Frequencies of leukemic blasts and monocytes in the bone marrow and periphery

SIRPα target expression levels and coverage (receptor occupancy) 

 
Potential predictive markers of efficacy of CC-95251 alone or in combination with azacitidine or 
in venetoclax and azacitidine will be explored for correlates of response. Samples may be 
characterized using molecular and cellular assays potentially including, but not limited to:

Baseline SIRPα expression on tumor and/or immune cells and presence of immune cell subsets 


 
Resistance to the SIRP-CD47 axis has not been characterized, although changes in the tumor
microenvironment and acquired mutations within the tumor could be factors that drive resistance
to therapeutic drugs. Potential pharmacodynamic biomarkers will be evaluated from samples 
collected pre- and post-treatment from bone marrow and peripheral blood, as applicable. 
Assessments will explore biomarkers related to safety, efficacy, and resistance to treatment with 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
55
CC-95251 alone or in combination. Biomarker assessments may include, but are not limited to, 
the following:

SIRPα expression levels and spatial localization of immune cells from paired bone marrow 
biopsies; single cell expression levels on bone marrow aspirates 

Minimal residual disease (MRD) may be measured on bone marrow samples at time of 
response assessments, end of treatment (EOT) and/or time of CR using flow cytometry and/or 
molecular analyses (eg, next generation sequencing [NGS]).

 
 

 

 
 
Other biomarkers of interest may be evaluated as determined by additional data.
Genetic variation may impact a subject’s response to study intervention, susceptibility to disease, 
and severity and progression of disease. Variable response to study intervention may be due to 
genetic determinants that impact intervention absorption, distribution, metabolism, and excretion; 
mechanism of action of the intervention; disease etiology; and/or molecular subtype of the disease 
being treated.
DNA samples will be used for research related to the study intervention(s) and/or disease/condition
under study and related conditions. The samples may also be used to develop tests/assays,
including diagnostic tests related to the study intervention(s) and/or disease/condition under study
and related conditions. Genetic research may consist of the analysis of 1 or more candidate genes
or the analysis of genetic markers throughout the genome or analysis of the entire genome.
Biomarker samples may also be used for research to develop methods, assays, prognostics, and/or
diagnostics.
The biomarker assessments will be conducted according to the laboratory manual.
1.4
Risk/Benefit Assessment
1.4.1
Benefit Assessment
Patients with intermediate to very high-risk MDS and AML have a poor prognosis overall with a 
limited number of therapeutic options available to modify the course of the disease. As a result, 
there remains a significant need to develop novel therapeutics that can generate clinically 
meaningful responses in these therapeutic indications. Multiple lines of preclinical evidence and 
now emerging clinical trial data suggest the potential for therapeutic efficacy via targeting of the 
CD47-SIRPα macrophage checkpoint axis in the setting of HR-MDS and AML. 
Azacitidine has an established role in the therapeutic management of both HR-MDS and AML and 
a well-characterized safety profile. As a result, it is commonly utilized as a core component of 
multi-drug regimens with partnered agents that carry distinct and potentially synergistic 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
56
mechanisms of action. CC-95251 is a first-in-class, 
 
 
. The combination of CC-95251 with
azacitidine provides the opportunity to 
 
 
. In the Part C expansion, 
administration of CC-95251 in combination with azacitidine to newly diagnosed (IPSS-R 
) 
MDS subjects ensures that study subjects are receiving the clinical standard-of-care 
hypomethylating agent with the added potential benefit for more robust disease-modifying activity 
due to the addition of CC-95251. 
Recently, a randomized trial (VIALE-A) of injectable azacitidine plus either venetoclax or placebo 
in untreated AML subjects who were ineligible for standard induction therapy because of 
coexisting conditions, or because they were ≥ 75 years of age, demonstrated a 5.1-month increase 
in OS and higher CR rate (36.7% vs 17.9%) among subjects who received venetoclax in 
combination with injectable azacitidine compared to those who received azacitidine alone
(DiNardo 2020). Systematic review and meta-analysis of venetoclax treatment in R/R AML, which 
included 7 studies with a total of 224 subjects, demonstrated an ORR of 38.7% and CR rate of 
19% for R/RAML subjects treated with venetoclax plus HMA/LDAC (Bewersdorf 2020b). 
Moreover, the meta-analysis showed that prior treatment with HMA did not preclude a response 
to subsequent venetoclax-based treatment
(Bewersdorf 2020b). Although the approved 
combination regimen of venetoclax and azacitidine has improved response rates in the above-
mentioned AML populations compared with prior regimens, this remains a population without a 
curative treatment option. It is hypothesized that adding an investigational third agent such as 
CC-95251 which targets a different mechanistic pathway may increase remission rates and prolong 
survival, therefore addressing an important unmet medical need.
1.4.2
Risk Assessment
The proposed study design includes various components aimed at limiting potential risks to study 
subjects. The subject population will not include individuals, such as children or mentally disabled 
adults, who are not capable of expressing themselves in the same way as mentally competent 
adults, in order to detect any potential harm to the subjects as early as possible. Standard eligibility 
criteria are included to ensure acceptable baseline organ function (including hematopoietic 
function) and lack of clinically significant comorbid diseases. Specific precautions for early 
development include use of a study design with dose escalation and subsequent expansion, a 
defined DLT observation period and DLT monitoring, staggered enrollment, hospitalization for 
observations as specified in the study protocol, as well as SRC oversight built into the protocol. 
Subjects will be monitored for possible toxicity throughout the study by physical examination, 
vital sign and AE collection, through standard and specialized laboratory tests including complete 
blood counts, serum chemistries, and electrocardiogram (ECG), and observed for survival follow-
up starting from the last dose of the investigational agent for up to 
 or until death, lost to 
follow-up, or the end of study, whichever occurs first. Study subject monitoring and guidelines for 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
57
management for select AEs of interest for the study drug are included in the study protocol (Section 
7.2.7.8).
The 
 will be utilized to guide CC-95251 dose escalation/de-escalation 
decisions, with the final recommendation being made by the SRC. Additionally, the protocol 
defines the criteria in the dose escalation (Part A) that must be met prior to opening enrollment to 
cohorts testing CC-95251 in combinations with azacitidine or with venetoclax and azacitidine in 
the relapsed/refractory setting. The protocol also specifies that testing of combinations in newly 
diagnosed MDS or AML populations in dose expansion may only occur 
 
 
Furthermore, the protocol also defines rules for monitoring of excess toxicities during the dose 
expansion cohorts outlined in the study.  Review of the TEAEs to date with monotherapy 
CC-95251 does not suggest a high likelihood of overlapping toxicity with common AEs attributed 
to azacitidine or the combination of venetoclax and azacitidine. Furthermore, there is low potential 
for drug-drug interactions in this proposed pairing of a biologic monoclonal antibody with a 
nucleoside analog and small molecule inhibitor. Well-defined discontinuation criteria are 
established in the protocol for individual subjects for both safety and treatment futility with clear 
criteria for study intervention discontinuation, dose delay, and toxicity management. 
The risks associated with treatment with CC-95251 are detailed in Table 1. 
Table 1:
Risk Assessment
Potential Risk of 
Clinical Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
Study Intervention: CC-95251

This study protocol
includes prophylaxis, 
monitoring and management guidance for 
 in Section 7.2.7.8

 
in this 
study as described in the study protocol. See
Section 7.2.1.1

Subjects are being monitored for possible 
toxicity throughout the study by standard and 
specialized laboratory tests as described in the 
study protocol, Section 6.2.6, Table of Events
(Section 5)

Management 
guidance 
including 
dose 
modification guidelines included in this study 
protocol (Section 7.2.6 and Section 7.2.7.7)
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
58
Table 1:
Risk Assessment
Potential Risk of 
Clinical Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy

Subjects are being monitored for possible 
toxicity throughout the study by physical 
examination, vital signs and AE collection, and 
through standard and specialized laboratory tests 
as indicated in this study protocol (Section 5 and 
Section 6.2.6)

Dose modification guidelines included in this
study protocol (Section 7.2.7.7)

Permitted antimicrobial prophylaxis is described 
in Section 7.2.7.8.5 and Section 8.1

Subjects are being monitored for possible 
toxicity throughout the study by physical 
examination, vital signs and AE collection, and 
through standard and specialized laboratory tests 
as indicated in this study protocol (Sections 5 and
10.1)

Dose modification guidelines included in this
study protocol (Section 7.2.7.7)

Subjects are being monitored for possible 
toxicity throughout the study by physical 
examination and AE collection, and through 
standard 
and 
specialized 
laboratory 
tests 
(Sections 5 and Section 6.2.6)

Eligibility criteria 
 and
dose modification guidelines included in this
study protocol (Section 4.2 and 7.2.7.7)

This study protocol includes monitoring and 
management of CRS
and
MAS (Section
7.2.7.8.3)

Full emergency resuscitation facilities should be
immediately available, and subjects should be
under close supervision of the Investigator or
appropriately trained staff at all times (Section
7.2.7.8.3)

 
 

Subjects with AML will be hospitalized for at
 
after the first dose of CC-95251 (C1D1) for IV
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
59
Table 1:
Risk Assessment
Potential Risk of 
Clinical Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
extensive bone marrow
involvement/bone marrow blast
percentage.
hydration
to monitor
for adverse events (Sections 7.2.1.1, 8.1, and 8.2)

Subjects will be closely monitored for
by
laboratory tests as described in Sections 5 and
Section 6.2.6

 monitoring and management guidelines 
included in 
Section
7.2.7.8.2,
and dose 
modification guidelines in
Study Intervention: Venetoclax
Neutropenia
Lymphopenia
Anemia
Thrombocytopenia
Serious and fatal 
infections
These events were commonly
reported and are considered
important identified risks. 
results from on-target effects and 
occurs during the initial
dosing/ramp-up period.
Low starting dose followed by gradual dose ramp-
up
Subjects with AML receiving venetoclax will be 
hospitalized during ramp-up
for
IV hydration
and to monitor
for adverse events (See Sections 7.2.1.1, 8.1, and
8.2)
Subjects will be closely monitored for
by
laboratory tests as described in Sections 5 and
6.2.6

 monitoring and management guidelines 
included in Section 7.2.7.8.2, and dose modification 
guidelines in  
Serious/Fatal Infections
Physical examination, vital sign and laboratory 
assessments, and monitoring for infections. Use of
as needed to treat infections.
Neutropenia/Lymphopenia/Anemia/Thrombocytopenia
Dose modification guidelines included in this study 
protocol in Section7.2.7.7, 
 and 
Monitor for infections and bleeding
Hematologic toxicity monitoring and management 
guidance included in Section 7.2.7.8.4,  
Hematological Toxicity
Study Intervention: Azacitidine
Anemia
Bleeding
Bone marrow suppression 
Neutropenia
Febrile neutropenia 
Infections
Leukopenia 
Pancytopenia  
Serious and fatal hemorrhagic
events (GI, intracranial), and
serious and fatal infections have
been reported.
Laboratory monitoring. Monitor for infections and
bleeding. Use of
as needed to treat infections
Azacitidine dose adjustment recommendations are 
provided in
as well as in the
product label (note: dose increases will not be allowed)
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
60
Table 1:
Risk Assessment
Potential Risk of 
Clinical Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
Study Procedures
BMA or BMB,
venipuncture
Planned study procedures (BMA
or BMB, venipuncture) are
consistent with routine care for
AML subjects and do not pose
additional risk to study subjects.

Routine medical evaluation and AE assessment
Other
Susceptibility of
immunocompromised
subjects with AML and 
MDS to SARS-CoV-2
infections
The global COVID-19 pandemic
has been identified as a potential
risk to clinical trial subjects in 
general. Immunocompromised
subject populations, such as
those with AML and MDS, may
be more susceptible to infections,
including SARS-CoV-2
infections. In addition, the
potential impact of venetoclax
and azacitidine administration on
the frequency or severity of
SARS-CoV-2 infections in
subjects with AML or MDS is
currently unknown.

To mitigate this potential risk, RT-PCR testing for
SARS-CoV-2 infection will be mandatory for all
subjects. Subjects with recent or acute

SARS-CoV-2 infections will be excluded or delay
the start of treatment as defined in Section 4.3 and
7.2.7.8.5.1

If a subject has a confirmed

SARS-CoV-2 infection while on study intervention,
dose delay or interruption of study intervention is
required as described in Section 7.2.7.8.5.1

Testing for COVID-19 should follow local
standard practice

None-live COVID-19 vaccination is a simple
concomitant medication within the study
(Section 8.1)
Abbreviations: AE = Adverse event; 
; AML = Acute myeloid leukemia; 
 
 BMA = Bone marrow aspirate; BMB = Bone marrow biopsy; C = cycle;
 
; D = day;
 GI = Gastrointestinal, 
; IV =intravenous; 
; 
 
; MDS = Myelodysplastic Syndromes; RT-PCR  = Reverse transcription-polymerase chain 
reaction; 
 SARS-CoV-2 = Severe acute respiratory syndrome coronavirus 2; 
 
 
 
1.4.3
Overall Risk/Benefit Conclusion
As demonstrated by the clinical data summarized in Section 1.2.1.5, CC-95251 is well tolerated 
as monotherapy and in combination with cetuximab or rituximab in solid tumors, with a toxicity 
profile that supports its use in combination with azacitidine or in triple combination with 
venetoclax and azacitidine. Given the poor prognosis for MDS and AML subjects with R/R 
disease, and limited, noncurative therapeutic options for ND AML subjects not eligible for 
chemotherapy and ND MDS subjects ineligible for stem cell transplant, there remains a significant 
need to develop novel therapeutics that can generate clinically meaningful responses in these 
therapeutic indications. Multiple lines of preclinical evidence and now emerging clinical trial data 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
61
suggest the potential for therapeutic efficacy via targeting of the CD47-SIRPα macrophage 
checkpoint axis in the setting of HR-MDS and AML. Clinical experience with CC-95251 to date 
suggests a manageable safety profile with low expected risk to the subject populations while 
having a strong rationale for enhanced therapeutic activity in this difficult clinical setting. In 
summary, the benefits of CC-95251 alone and in combination with either azacitidine or venetoclax 
and azacitidine are expected to outweigh the risks for subjects treated with these compounds. The 
Sponsor will evaluate the benefit/risk profile of the study on an ongoing basis. This evaluation will 
be based on all available data with particular attention regarding (i) AEs or other safety trends in 
clinical studies involving CC-95251 in combination with azacitdine or venetoclax plus azacitidine, 
whose character, severity, and/or frequency suggest that subjects would be exposed to an 
unreasonable and significant risk of illness or injury; (ii) new nonclinical data suggesting 
unreasonable and significant risk of illness or injury. If such evaluation suggests that the 
benefit/risk profile of the study has become unfavorable to subjects, the Sponsor will take 
appropriate action to optimize and ensure study subjects safety. 
Overall, based on the current available data, the defined safety management/monitoring plan 
specified in the protocol, the low expectation for overlapping toxicities, and the current therapeutic 
benefit versus risk ratio, there is an acceptable level of risk and potential therapeutic benefit to 
proceed with the current study in the subject population at the dose regimen specified in the 
protocol.
2
STUDY OBJECTIVES AND ENDPOINTS
Table 2:
Study Objectives
Primary Objective(s)
The primary objectives of the study are:

To determine the safety and tolerability of CC-95251 alone and in combination with 
antineoplastic agents

To define the recommended Phase 2 dose (RP2D) of CC-95251 alone and in combination 
with antineoplastic agents in subjects with AML and MDS
Secondary Objective(s)
The secondary objectives are:

To assess the preliminary efficacy of CC-95251 as a single agent and in combination with 
antineoplastic agents in AML and MDS

To characterize the pharmacokinetics (PK) of CC-95251 as a single agent and in combination 
with antineoplastic agents in AML and MDS

To evaluate the presence, frequency and functional impact of anti-CC-95251 antibodies 
(anti-drug antibodies [ADA])
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
62
Table 2:
Study Objectives
Exploratory Objective(s)
The exploratory objectives are:

To explore the relationship between dose and systemic exposure of CC-95251 and measures 
of toxicity, efficacy, and PD biomarkers. 

To evaluate molecular and/or cellular biomarkers in the bone marrow and blood that may be 
associated with efficacy of CC-95251

To evaluate the minimal residual disease (MRD) status, by flow cytometry and/or relevant 
gene sequencing methods
Abbreviations: ADA = anti-drug antibodies; AML = acute myeloid leukemia; MDS = myelodysplastic syndromes; 
MRD = minimal residual disease; PD = Pharmacodynamics; PK = pharmacokinetics.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
63
Table 3:
Study Endpoints
Endpoint
Name
Description
Timeframe
Primary
Safety
DLTs evaluated using the NCI 
CTCAE criteria, Version 5.0. 
Adverse events, including TEAEs, 
laboratory assessments, ECG results, 
ECOG performance status, and vital 
signs
Dose escalation and dose 
expansion
Screening to 
 after the last 
dose of study treatment
Secondary 
Preliminary efficacya
Complete remission rate (CRR) (as 
assessed by the Investigator) for 
AML according to the modified 
European Leukemia Net (ELN) 
response criteria (CR + CRh + CRi), 
ORR (CR + CRMRD- + CRh + CRi +
MLFS + PR)
CRR (as assessed by the 
Investigator) for MDS according to 
the modified IWG Response Criteria
(CR), ORR (CR + CRh + marrow 
CR + PR)
Duration of remission, duration of 
response, stable disease rate (MDS 
only), relapse-free survival, event-
free survival, progression-free 
survival, time to remission/response, 
transfusion independence, time to 
AML transformation for MDS 
subjects, OS rates at 6 and 12 
months
Dose expansion
Day 1 to end of follow up
Secondary
Pharmacokinetics
(PK)
Estimate parameters including but 
not limited to Cmax, Cmin, Ctrough,
AUC(0-T), AUC(TAU), tmax, CLT, and 
accumulation index of CC-95251, 
when feasible as a single agent and 
in combination with antineoplastic 
agents in AML and MDS
Dose escalation and dose 
expansion
Day 1 to 8 weeks post-dose of 
CC-95251
Secondary
Anti-drug Antibody 
(ADA)
Determine the presence and 
frequency of anti CC-95251
antibodies (ADAs) using a validated 
electrochemiluminescence (ECL) 
assay
Dose escalation and dose 
expansion
Day 1 to 8 weeks post-dose of 
CC-95251
Exploratory
Pharmacodynamics
(PD)
Potential pharmacodynamic 
biomarkers will be explored in blood 
at baseline and on study treatment 
and may include:

 
 

 
 
 
Dose escalation and dose 
expansion
Day 1 to end of follow up
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
64
Table 3:
Study Endpoints
Endpoint
Name
Description
Timeframe

 
 
 

 
 
Exploratory
PD
Potential pharmacodynamic 
biomarkers will be explored in bone 
marrow at baseline and on study 
treatment and may include:

 
 

 
 
 

 
 
 

 

 
 
Dose escalation and dose 
expansion
Day 1 to end of follow up
Exploratory
Mechanisms of 
Response/Resistance
Molecular and/or cellular biomarkers 
in the bone marrow will be explored 
as potential predictors of response to 
CC-95251
 
 
 
Dose escalation and dose 
expansion Day 1 to end of follow 
up
Exploratory
Preliminary efficacy 
(MRD)b
Proportion of subjects achieving 
MRD negativity at any time on/after 
treatment with CC-95251 alone and 
in combination with azacitidine or 
azacitidine and venetoclax
Dose escalation and dose 
expansion
Day 1 to end of follow up
Abbreviations: ADA = anti CC-95251 antibodies; AML = acute myeloid leukemia; AUC(0-T) = area under the 
concentration time-curve from time zero to time of last quantifiable concentration; AUC(TAU) = area under the 
concentration-time curve in a dosing interval; CLT = total body clearance of the drug from the serum; Cmax = 
maximum serum concentration of drug; Cmin = minimum serum concentration of drug; CR = complete remission; 
CRh = morphologic complete remission with partial hematologic recovery; CRi = morphologic complete remission 
with incomplete blood recovery; CRMRD- = Morphologic complete remission without minimal residual disease; 
CRR = complete remission rate; Ctrough = trough observed serum concentration; DLT = dose-limiting toxicity; ECG = 
electrocardiogram; ECL = electrochemiluminescence; ECOG = Eastern Cooperative Oncology Group; ELN = 
European Leukemia Net; IWG = International Working Group;
MDS = myelodysplastic syndromes; 
MLFS = morphologic leukemia-free state; MRD = minimal residual disease; NCI CTCAE = National Cancer Institute 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
65
common terminology criteria for adverse events; 
; ORR = objective response rate; 
OS = overall survival; PD = pharmacodynamics; PK = pharmacokinetics; 
 
TEAE = treatment-emergent adverse events; tmax = time to peak (maximum) serum concentration.
a
 
 
b
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
66
3
OVERALL STUDY DESIGN
3.1
Study Design
Study CA059-001 is an open-label, multicenter, Phase 1 study testing the safety and efficacy of 
CC-95251, a monoclonal antibody directed against SIRPα, alone and in combination with 
antineoplastic agents in subjects with R/R AML and R/R or treatment-naïve MDS. This protocol 
is intended to evaluate various drug combinations with CC-95251, as separate arms, over the life 
of the protocol, using the same objectives. CC-95251 as a single agent and as part of each of the 
combinations will be evaluated separately (ie, the intention is not to compare between 
monotherapy or combinations) for the purposes of the objectives, trial design, and statistical 
analysis.
The study will consist of 4 parts with a dose escalation (Part A) and dose expansion (Parts B, C,
and D) as detailed below

Part A: Dose escalation with CC-95251 alone and in combination with injectable azacitidine 
in subjects with relapsed/refractory (R/R) AML and R/R intermediate, high or very high risk 
(ie, IPSS-R 
 MDS.

Dose escalation with CC-95251 in combination with injectable azacitidine and venetoclax
(triple combination) in subjects with R/R AML.

Part B: Dose expansion testing CC-95251 alone and in combination with injectable azacitidine 
in R/R AML and R/R intermediate, high or very high risk (ie, IPSS-R 
 MDS. 

Part C: CC-95251 dose expansion in combination with injectable azacitidine in treatment-naïve
subjects with intermediate, high or very high risk (ie, IPSS-R
) MDS.

Part D: CC-95251 dose expansion in combination with injectable azacitidine and venetoclax
(triple combination) in subjects with TN AML ineligible (IE) for intensive chemotherapy (IC).

Other combinations of CC-95251 and antineoplastic agents in subjects with R/R AML and/or 
R/R or treatment-naïve MDS may be explored at the recommendation of the SRC and will be 
added by subsequent protocol amendment.
The Study Population will be subjects ≥ 18 years of age and defined as follows:

R/R AML (Parts A and B): AML as defined by the 2016 World Health Organization (WHO) 
Classification (Appendix B) who have failed or who are ineligible for all available therapies 
for AML which may provide clinical benefit.

R/R MDS (Parts A and B): MDS as defined by the 2016 WHO Classification (Appendix D)
with intermediate, high or very high risk by IPSS-R (IPSS-R 
 and who have failed or who 
are ineligible for all available therapies for MDS which may provide clinical benefit.

TN MDS (Part C): Treatment-naïve (TN) MDS as defined by the 2016 WHO Classification 
(Appendix D) with intermediate, high or very high risk by IPSS-R (IPSS-R 
).

TN AML (Part D): Treatment-naïve/ND AML as defined by the 2016 WHO Classification, 
including secondary AML and therapy-related AML in subjects who are ineligible (IE) for 
intensive chemotherapy (IC) and allogeneic
due to 
having one of the following:
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
67
Severe cardiac comorbidities (including congestive heart failure, left ventricular
ejection fraction [LVEF] <45%, and chronic stable angina)
Pulmonary comorbidity (diffuse capacity of the lung for carbon monoxide [DLCO] 
≤ 65% or forced expiratory volume in 1 second [FEV1] ≤ 65%) 
Any other comorbidity incompatible with intensive chemotherapy upon approval of the 
Sponsor Medical Monitor.
Age ≥ 75 years, regardless of the presence of any of the above comorbidities

Subjects must have a projected life expectancy of ≥ 12 weeks.

TN AML subjects who have not received HMA, venetoclax, or chemotherapy in the setting 
of antecedent MDS are eligible.  Prior treatment for MDS including, but not limited to,
growth factors (eg, erythyropoiesis-stimulating agents), hydroxyurea, and lenalidomide is 
allowed.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
68
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
69
3.1.1
Part A
 will be utilized to guide 
CC-95251 dose escalation/de-escalation decisions, with the final decisions being made by the 
SRC.
The proposed dose levels for testing the CC-95251 monotherapy include a starting dose 
 
20 mg/kg QW and 
 of 30 mg/kg to be administered by IV infusion. A 20 mg/kg QW dose of 
CC-95251 has been demonstrated to be tolerated in subjects with advanced solid cancers in the 
CC-95251-ST-001 study (NCT03783403). In the event that 
 is not tolerated in the CC-95251
monotherapy cohort, 
 of 10 mg/kg CC-95251 may be recommended by the 
SRC. 
The proposed starting dose (DL1a) for CC-95251 in combination with injectable azacitidine is 10 
mg/kg QW, 
. The Part A dose escalation may enroll 
subjects in the CC-95251 plus azacitidine- cohorts in parallel with the CC-95251 monotherapy
cohorts. However, cohorts of CC-95251 plus azacitidine will only open to enrollment after the 
corresponding or a higher dosing cohort of CC-95251 monotherapy is determined to be tolerated
by the SRC.
The proposed starting dose (DL1b) for CC-95251 in combination with azacitidine and venetoclax
(triple combination) is 20 mg/kg QW, 
 
 
(10 mg/kg QW) may be recommended by the SRC if the starting dose is 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
70
not tolerated or to explore a lower dose level based on the available safety, PK, and PD data. The 
Part A dose escalation may enroll subjects in the CC-95251 plus azacitidine and venetoclax cohorts 
in parallel with the CC-95251 monotherapy and double combination cohorts. 
 
 
 
All subjects within each dose level will be observed 
 
 
initiation of the next dose level. Subject treatment on Cycle 1 Day 1 (C1D1) will be staggered with 
 between subjects in a given cohort during Part A.
A decision table (
) based on 
 
 are provided to guide CC-95251 dose escalation/de-escalation 
decisions for monotherapy, double combination cohorts, and triple combination cohorts. The SRC 
will make dose escalation/de-escalation recommendations based on real-time integrated 
assessment of available safety, efficacy, PK and PD in each dose cohort. For a dose level to be 
selected by the SRC for dose expansions (Part B, C, or D), 
 should be evaluated 
for DLT in Part A to declare a tolerable dose level. Additional subjects may be enrolled in 1 or 
more cohorts at the recommendation of the SRC. Subjects non-evaluable for DLT may be replaced. 
After enrollment has been completed in the corresponding Part A cohorts, the SRC will undertake 
an evaluation of the available safety, PK, PD, and preliminary efficacy data to make a 
determination of the preliminary RP2D of CC-95251 within a respective indication to test in the 
expansion cohorts (Parts B, C, and D).
 
 
 The preliminary
 
and may differ based on indication (ie 
MDS versus AML). An intermediate dose level of CC-95251 or a variable dose schedule 
 
 may be evaluated to 
accurately determine the RP2D at the recommendation of the SRC. The investigation of any other 
alternate dosing schedule beyond those stipulated in the current protocol version will be submitted 
in a protocol amendment.
3.1.2
Part B
 
 The expansion cohorts of each 
individual treatment may start after a dose and schedule is shown to be tolerated in the 
corresponding Part A cohort and the SRC has selected the Part B dose and schedule.  
Approximately 
 subjects per cohort will be enrolled to further evaluate the safety and assess the 
efficacy of:
1) CC-95251 alone in R/R AML
2) CC-95251 in combination with azacitidine in R/R AML
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
71
3) CC-95251 alone in R/R MDS (IPSS-R 
 
4) CC-95251 in combination with azacitidine in R/R MDS (IPSS-R 
at the preliminary RP2D of CC-95251 monotherapy or RP2D of CC-95251 in combination with 
azacitidine established in Part A. 
 
 
and will regularly review safety and emerging response data during expansion to make 
recommendations about continuation and dose modification, as appropriate (Section 7.2.7). The 
subjects will be assigned to treatment cohorts (monotherapy vs double combination with 
azacitidine) based on the slot availability, not based on randomization. 
Additional cohorts of subjects testing CC-95251 in combination with additional antineoplastic 
agents in subjects with R/R AML or R/R MDS may be considered at the recommendation of the 
SRC and will be included by protocol amendment.
3.1.3
Part C
Part C will evaluate subjects with treatment-naïve (ie, previously untreated), intermediate, high or 
very high risk (ie, IPSS-R 
 MDS with CC-95251 in combination with standard of care 
injectable azacitidine. 
Enrollment in Part C 
 
 
 The SRC will review the safety data from this group of 
subjects utilizing
 prior to the 
opening of the Part C expansion. The dose of CC-95251 selected for Part C may occur 
 
 based on 
review of available safety, PK, PD, and preliminary efficacy data.
The Part C expansion will initially evaluate at 
 with treatment-naïve MDS treated 
 of CC-95251 plus 
azacitidine. The SRC will review the available safety utilizing 
 
 PK, PD and preliminary efficacy data in the initial 
 
to determine if the dose and schedule is tolerated prior to escalating the CC-95251 dose to the 
proposed Part C expansion dose and schedule. 
 
 
 Thereafter, a total of approximately 
 additional subjects with 
treatment-naïve MDS may be enrolled in Part 
 
 During enrollment in Part C the SRC will review available safety data 
from Cycle 1 of every  subjects treated in the cohort to evaluate for excessive toxicity. Enrollment 
in Part C may proceed concurrently with enrollment in the Part B expansion cohorts. 
The SRC will continue to review safety data regularly throughout the study and make 
recommendations about study continuation, dose modification and establishment of a RP2D as 
appropriate.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
72
3.1.4
Part D
Part D will evaluate subjects with TN AML with CC-95251 in combination with standard of care 
azacitidine and venetoclax. Enrollment in Part D may start 
 
 of 
CC-95251 plus azacitidine and venetoclax. The SRC will review the safety data from this group 
of subjects utilizing the
 prior to 
the opening of the Part D expansion.
The Part D expansion will initially evaluate
 
 
 
 
 
 
 
An additional 
 subjects may be enrolled based on the response seen 
in the initial 
 subjects (
 and Section 9.3: Sample Size and Power Considerations). 
During enrollment in part D, the SRC will review available safety data from Cycle 1 of every  
subjects treated in the cohort to evaluate for excessive toxicity.  
The SRC will continue to review safety data regularly throughout the study and make 
recommendations about study continuation, dose modification, and establishment of a RP2D as 
appropriate.
3.1.5
Study Treatments
CC-95251 will be administered intravenously in two phases starting with a more frequently dosed
induction phase followed by a maintenance phase. 

During induction phase, subjects will be dosed weekly for Cycles 1 through 4 (QW, eg, on 
Day 1, Day 8, Day 15, and Day 22 of each cycle).  After Cycle 4, subjects will enter the 
maintenance phase. 

During the maintenance phase, CC-95251 will be administered every two weeks (Q2W, eg, on 
Day 1 and Day 15 of each cycle).
The SRC may change the frequency of dosing 
 
 based on review of the available safety, PK, PD, and 
preliminary efficacy data
The investigation of any other alternate 
dosing schedule beyond those stipulated in the current protocol version will be submitted in a 
protocol amendment.
Azacitidine will be administered at 75 mg/m2 on Days 1-7 (or Days 1-5 and 8-9) of each 28-day 
cycle as an IV or SC injection throughout the course of the study treatment per local prescribing 
information and institutional standard of care.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
73
 
 
 
  Subjects will be admitted as inpatients during venetoclax dose ramp-up for 
IV hydration and monitoring of toxicities including TLS. 
 
(Table 12). The duration of venetoclax dosing may 
be shortened based on evaluation of a bone marrow aspirate and biopsy on 
 
 to evaluate clearance of blasts and overall cellularity (see Section 
7.2.7.7 and 
 In subsequent cycles, the shortened venetoclax dosing may be continued at 
the discretion of the investigator. The investigator may also choose to follow the algorithm in 
in 
Parts A, B, C, and D will consist of 3 periods: Screening, Treatment, and Follow-up (refer to
Figure 4). 
Figure 4:
Overall Study Design
Abbreviations: SRC = safety review committee.
3.1.5.1
Screening Period
The Screening Period starts 28 days prior to first dose of study intervention. The informed consent 
form (ICF) must be signed and dated by the subject and the administering staff prior to the start of 
any other study procedures. All screening tests and procedures must be completed within the 28 
days prior to the first dose of study treatments.
3.1.5.2
Treatment Period
Upon confirmation of eligibility, subjects will be enrolled and begin treatment in the assigned dose 
level cohort.
The Sponsor will supply the investigational product (IP), CC-95251, for IV administration
(Section 7.1.1). 
Treatment Period
Part A: Dose escalation
Parts B, C, and D: Dose expansion
CC-95251 administered in 28-day cycles 
according to protocol- or SRC-approved 
dosing schedule. Treatment may continue 
, or until disease 
progression, loss of clinical benefit, 
unacceptable toxicity, or decision to 
withdraw by subject or Investigator.
Screening Period
Day -28 to Day -1
Follow-up Period
Safety follow-up occurs 
 
(± 3 days) after the last dose of 
CC-95251.
Survival follow-up will be every  
 (± 1 week) for the first year 
and every 
 weeks (± 2 weeks)
for the 
 
 or until death, lost to follow-
up, or the End of Trial, whichever 
occurs first.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
74
Azacitidine will be supplied or obtained according to local clinical study agreement and in 
accordance with local guideline. When provided by the Sponsor, azacitidine for Injection will be 
supplied as a lyophilized powder in 100 mg single-dose vials for reconstitution and administration.
Venetoclax will be supplied or obtained according to local clinical study agreement and in 
accordance with local guidelines. When provided by the Sponsor, venetoclax will be supplied as 
tablets in 10 mg, 50 mg, and 100 mg blister/bottles for administration.
In Part A, subjects with AML in CC-95251 monotherapy and double combination (CC-95251 and 
azacitidine) cohorts will be hospitalized for 
 after the first dose of CC-95251
(C1D1) for IV hydration 
 and to monitor for adverse events. Subjects with 
AML in triple combination (CC-95251 plus azacitidine and venetoclax) cohorts will be 
hospitalized during venetoclax dose ramp-up (
) for hydration 
 and to 
monitor for adverse events. 
 
 
 
 Full emergency resuscitation facilities should be 
immediately available, and subjects should be under close supervision of the Investigator or 
designated staff during and for 
 
following CC-95251 administration with serial vital signs obtained and pulse oximetry performed. 
 
 
 
 
 
 
CC-95251 infusion will be started at
mg/hr 
 
mg/hr 
 mg/hr. Further changes to the rate of 
infusion may be considered during the course of the trial based on review of clinical data and 
approval from the SRC. 
For subjects receiving azacitidine in combination with CC-95251, subjects will receive azacitidine 
prior to starting CC-95251 infusion on days receiving both treatments. Subjects should be observed 
for at least 
 between administrations.
For subjects receiving triple combination, on Day 1 of each cycle, CC-95251, azacitidine, and 
venetoclax will be administered on the same day. 
 
 
 
 
For subjects receiving CC-95251 monotherapy and double combination (CC-95251 and 
azacitidine), in the absence of residual morphologic leukemia and in the presence of ongoing 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
75
cytopenias at the completion of the DLT evaluation period, study interventions could be 
interrupted for up to 
 to allow for hematologic recovery. 
 
 
 
 
For subjects receiving triple combination (CC-95251 plus azacitidine and venetoclax), 
 
 
 
 
 
 
 
If the venetoclax dosing schedule is shortened based on bone marrow evaluation and the algorithm 
above, the shortened schedule may be continued in subsequent cycles at the discretion of the 
investigator. The investigator may also choose to follow the algorithm in 
 
 
Dose modification guidance is provided in Section 7.2.7.7, 
and 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
76
Thus, in Part A dose escalation, the window for evaluation of DLT during Cycle 1 will be up to 
 Cycles 2 and higher will be 28 days in length. In dose expansion, all cycles 
will be 28 days in length. 
 
 Subjects will only be 
considered DLT evaluable during the first cycle of their initial enrollment in Part A (dose 
escalation).
In dose expansion (Parts B, C, and D), a non-binding
 safety monitoring method will be 
used to continuously monitor for excess toxicities defined as the occurrence of AEs 
 
 (Section 9.9.2). After a minimum of  
subjects have enrolled and completed at least one cycle of study treatment, the non-binding 
 stopping criterion 
 will be 
calculated (refer to
). If the stopping rule is triggered, the SRC will conduct a 
comprehensive review of available safety, PK, PD, and preliminary efficacy data to make 
continuation decisions.
In both Parts B, C, and D, a 
 will be performed. In Part 
B, at least 
 efficacy evaluable subjects who complete at least one cycle of study treatment for 
each cohort will initially be accrued;
 
 In Part C, at least 
efficacy evaluable subjects who complete at 
least one cycle of study treatment at RP2D will initially be accrued;
 
. In Part D, at least 
 
evaluable subjects who complete at least one cycle of study treatment at RP2D will initially be 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
77
accrued;
The
 decision will be made by the SRC upon reviewing all available safety, PK, PD, 
and any efficacy results in dose expansion phase, including considerations on adjustment of the 
RP2D dose. Otherwise, the cohort will be expanded to up to approximately 
 evaluable subjects
in Part B, approximately 
evaluable subjects in Part C, and approximately 
evaluable subjects
in Part D (Section 9.9.2).
All treatments will be administered in 28-day cycles. Subjects may continue treatment if they are 
deriving benefit from treatment without unacceptable toxicity (any CR, MLFS, partial remission 
(PR), or stable disease (SD) with demonstrated clinical benefit eg, reduction in transfusion 
burden), as judged by the Investigator, 
 
), or until disease progression, loss of 
clinical benefit, unacceptable toxicity, or decision to withdraw by subject or Investigator. Subjects 
who discontinued one study treatment in a combination arm for reasons other than relapse or 
resistant disease may continue on the non-discontinued drug(s) if they are receiving benefits as per 
Investigator’s discretion until there is evidence of relapse or resistant disease, or until they are no 
longer able to tolerate treatment due to an adverse event.
 
 
 
The subject cannot have had another systemic anti-cancer therapy upon relapse. 
 
 
 
 
 
 
 
 
 The subject will not be re-considered in the efficacy evaluation.
3.1.5.3
Follow-up Period
All subjects will be followed for 
 after the last dose of study drug for AE reporting. 
In addition, serious AEs (SAEs) made known to the Investigator at any time thereafter that are 
suspected of being related to study drug are to be reported until such SAEs have recovered 
(returned to baseline), recovered with sequelae, or death (due to the SAE). Subjects will also be 
followed for all AEs (SAEs and non-serious AEs) associated with confirmed or suspected SARS-
CoV-2 infection until resolution, the condition stabilizes, the event is otherwise explained, the 
event is deemed irreversible, the subject is lost to follow-up, or for suspected cases, until SARS-
CoV-2 infection is ruled-out (Section 6.3.1). 
Subjects who discontinue treatment for reasons other than disease progression (or relapse) or start 
of a new anticancer therapy will have efficacy evaluations of CBC and PBS performed every 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
78
subsequent 
 up 
to a 
 
. A bone 
marrow evaluation will be completed 
 and as clinically indicated 
during the Follow-up Period.
All subjects will be followed starting from the end of treatment according to the schedule for the 
efficacy long term follow-up (refer to Section 6.3.2) for survival for 
 or until death, 
lost to follow-up, or the End of Trial, whichever occurs first. Survival follow-up may be conducted 
by record review (including public records) and/or telephone contact with the subject, family, or 
the subject’s treating physician.
During follow-up, information (including dates) on new anticancer therapies will be collected until 
withdrawal from the study, death, or the End of Trial, whichever comes first.
The study will be conducted in compliance with the International Council on Harmonisation (ICH) 
of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical 
Practice (GCP) and applicable regulatory requirements.
3.2
Study Duration for Subjects 
Enrollment is expected to take approximately 24 to 36 months to complete (approximately 16 to 
19 months for dose escalation and approximately 12 to 18 months for dose expansion). The entire 
study is expected to last up to approximately 3 to 4 years.
An individual subject will be in the study for 
 including treatment and 
follow up unless, the SRC decides to extend the treatment period.
3.3
End of Trial
The end of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date. Survival Follow-up may be terminated at the Sponsor’s discretion. 
4
STUDY POPULATION
4.1
Number of Subjects 
This is a multicenter, open-label study which will enroll approximately 
subjects. 
Approximately
subjects will be enrolled in Part A dose escalation, 
 subjects in Part B dose 
expansion (
 per cohort),
subjects in Part C dose expansion, and 
subjects in Part D dose 
expansion.  
4.2
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1) Subject is ≥ 18 years of age, at the time of signing the ICF.
2) Subject must understand and voluntarily sign an ICF prior to any study-related 
assessments/procedures being conducted.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
79
3) Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements.
4) Parts A and B: 
a.
R/R AML: AML as defined by the 2016 WHO Classification (Appendix B) who have 
failed or who are ineligible for all available therapies for AML which may provide clinical 
benefit.
b. R/R MDS: MDS as defined by the 2016 WHO Classification (Appendix D) with 
intermediate, high or very high risk by IPSS-R (IPSS-R 
 and who have failed or who 
are ineligible for all available therapies for MDS which may provide clinical benefit.
5) Part C: Treatment-naïve (ie, previously untreated) MDS as defined by the 2016 WHO 
Classification (Appendix D) with intermediate, high or very high risk by IPSS-R (IPSS-R 
. Prior administration of erythroid or myeloid growth factors and/or supportive transfusions 
is permitted unless otherwise specified (eg, in Section 4.3 and Section 8).
6) Part D: TN AML as defined by the 2016 WHO Classification (APPENDIX B), including 
secondary AML and therapy-related AML in subjects who are IE for IC and allogeneic
due to having one of the following:
a.
Severe cardiac comorbidities (including congestive heart failure, left ventricular ejection 
fraction [LVEF] <45%, and chronic stable angina).
b. Pulmonary comorbidity (diffuse capacity of the lung for carbon monoxide [DLCO] ≤ 65% 
or forced expiratory volume in 1 second [FEV1] ≤ 65%).
c.
Any other comorbidity incompatible with intensive chemotherapy upon approval of the
Sponsor Medical Monitor.
d. Aged ≥ 75 years, regardless of the presence of any of the above comorbidities.
i. Subjects must have a projected life expectancy of ≥ 12 weeks.
ii. TN AML subjects who have not received HMA, venetoclax, or chemotherapy in the 
setting of antecedent MDS are eligible. Prior treatment for MDS including, but not 
limited to growth factors (eg, erythropoiesis-stimulating g agents), hydroxyurea, and 
lenalidomide is allowed. 
7) Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2. 
8) Subjects must have the following laboratory values: 
Total White Blood Cell Count (WBC) 
 
 
 
Potassium and magnesium within normal limits or correctable with supplements.
Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT)
and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT)
 
, unless considered due to leukemic organ 
involvement, in which case AST and ALT can be
Uric acid 
 mg/dL (
 µmol/L). Prior and/or concurrent treatment with 
hypouricemic agents (eg, allopurinol, rasburicase) are allowed. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
80
Serum bilirubin 
, or primary unconjugated bilirubin 
 if 
individual has a documented history of Gilbert’s syndrome  (eg, a gene mutation in 
UGT1A1) or genetic equivalent.
Estimated serum creatinine clearance of 
 mL/min using the Cockcroft-Gault 
equation. Measured creatinine clearance from a 24-hour urine collection is acceptable 
if clinically indicated.

 and partial thromboplastin time 
(PTT)
.
9) Subject of childbearing potential (SCBP)1 must:
Either commit to true abstinence2 from heterosexual contact (which must be reviewed 
on a monthly basis and source documented) or agree to use, and be able to comply with, 
at least one highly effective contraceptive methods (oral, injectable, or implantable 
hormonal contraceptive; tubal ligation; intra-uterine device; or vasectomized partner), 
from signing the ICF, while participating in the study, during dose interruptions, and 
for up to 
 following the last dose of CC-95251 and 6 months (or longer if 
required by local regulations) after the last dose of azacitidine, and 30 days after the 
last dose of venetoclax (It is currently unknown whether venetoclax may reduce the 
effectiveness of hormonal contraceptives, and therefore women using hormonal 
contraceptives should add a barrier method.); and
Have two negative quantitative serum or urine pregnancy tests as verified by the 
Investigator, one must be at Screening and one performed within 72 hours prior to 
starting study treatment (Section 6.1). Subject must agree to ongoing pregnancy testing 
during the course of the study, and 
 after end of CC-95251 and 6 months (or 
longer if required by local regulations) after azacitidine, and 30 days for venetoclax.
This applies even if the subject practices true abstinence2 from heterosexual contact. 
The subject may not receive study treatment until the Investigator has verified that the 
result of the pregnancy test is negative; and 
Have a negative quantitative serum pregnancy test (sensitivity of at least 25 mIU/mL) 
at Screening.
Have a negative serum or urine pregnancy test (Investigator’s discretion) within 
72 hours prior to C1D1 of study treatment, and within 72 hours prior to Day 1 of every 
subsequent cycle. A serum or urine pregnancy test (Investigator’s discretion) must also 
be performed at the end of study for each SCBP; and 
Avoid conceiving and blood or egg donation from signing the ICF, while participating 
in the study, during dose interruptions, and for 
 after the last dose of CC-95251
and 6 months (or longer if required by local regulations) after the last dose of 
azacitidine, and 30 days after the last dose of venetoclax.
                                                       
1 A subject of childbearing potential is a sexually mature individual who 1) has not undergone a hysterectomy (the 
surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been 
naturally postmenopausal for at least 24 consecutive months (eg, has had menses at any time during the preceding 
24 consecutive months).
2 True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. (Periodic 
abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable 
methods of contraception.)
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
81
10) Subjects who are able to impregnate their partner must practice true abstinence2 (which must 
be reviewed on a monthly basis and source documented) or agree to use a condom (a latex 
condom is recommended) during sexual contact with a pregnant partner or a partner with 
childbearing potential and must avoid blood or semen or sperm donation from signing the ICF, 
while participating in the study, during dose interruptions, and for at least 
 following 
CC-95251 discontinuation and 3 months (or longer if required by local regulations) after the 
last dose of azacitidine, even if subject has undergone a successful vasectomy.
4.3
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1)
 
 Evaluation of cerebrospinal fluid is only required if there is clinical 
suspicion of CNS involvement by leukemia during screening.
2) Subjects with immediately life-threatening, severe complications of leukemia such as 
disseminated/uncontrolled infection, uncontrolled bleeding, and/or uncontrolled disseminated 
intravascular coagulation (DIC).  
5) Subjects who have received prior treatment with a 
6) An exception is subjects who are considered for retreatment in the study. Impaired cardiac 
function or clinically significant cardiac diseases, including any of the following:  
8) Prior autologous 
 
prior to starting study 
treatment, or who, in the Investigator’s judgment, have not fully recovered from the effects of 
the last transplant.
9) Prior allogeneic 
 with either standard or reduced 
intensity conditioning 
 prior to starting study treatment.
10) Subjects on 
 
 The use of topical steroids for ongoing 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
82
skin or ocular 
is permitted. 
 
 
11) Subject is on chronic systemic immunosuppressive therapy or corticosteroids
 
 mg 
). Intranasal, inhaled, 
topical, or local corticosteroid injections (eg, intra-articular injection), or steroids as
premedication
for
hypersensitivity reactions
(eg,
computed
tomography [CT] scan 
premedication) are exceptions to this criterion.
12) Prior systemic cancer-directed treatments or investigational modalities 
 
 
 
13) Major surgery 
 prior to starting CC-95251. Subjects must have recovered from any 
clinically significant effects of recent surgery.
14) Pregnant or nursing subjects.  
15) Subject has active 
 infection.

 
 
16) Subject has active 
 infection.
17)
 
18) History of concurrent second cancers requiring active, ongoing systemic treatment.
19) Subject has any significant medical condition, laboratory abnormality, or psychiatric illness 
that would prevent the subject from participating in the study.
20) Subject has any condition including, active or uncontrolled infection, or the presence of 
laboratory abnormalities, which places the subject at unacceptable risk if he/she were to 
participate in the study.
21) Subject has any condition that confounds the ability to interpret data from the study.
22) Previous SARS-CoV-2 infection 
 for mild or asymptomatic infections or 20 
days for severe/critical illness prior to C1D1.

Acute symptoms must have resolved and based on Investigator assessment in 
consultation with the Sponsor’s Medical Monitor, there are no sequelae that would 
place the subject at a higher risk of receiving study treatment.
23) Previous non-live COVID-19 vaccine 
. For vaccines requiring more 
than one dose, the full series (eg, both doses of a two-dose series) should be completed at least 
 when feasible and when a delay in C1D1 would not put the study subject 
at risk.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
83
24) Previous live COVID-19 vaccine 
 of C1D1. For live vaccines requiring more 
than one dose, the full series (eg, both doses of a two-dose series) should be completed at least 
 to C1D1 when feasible and when a delay in C1D1 or study treatment would not 
put the study subject at risk.
25) Treatment-naïve MDS subjects who are determined by the investigator 
 
26) Subjects with known dysphagia, short-gut syndrome, gastroparesis, or other conditions/surgery 
that limit the ingestion or gastrointestinal absorption of drugs administered orally.
27) Prior/Concomitant Therapy Treatment naive/ND AML subjects:
4.4
Lifestyle Restrictions
4.4.1
Meals and Dietary Restrictions
No restrictions are required for CC-95251. 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
84
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
85
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
86
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
87
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
88
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
89
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
90
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
91
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
92
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
93
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
94
6
PROCEDURES
Any questions regarding the protocol should be directed to the Sponsor’s Medical Monitor (MM) 
or designee. The procedures conducted for each subject enrolled in the study are outlined in 
, and Section 6.2.
All study treatment visits/procedures will have a 
 
unless otherwise specified (eg, PK sampling) below or in 
,
and 
 All laboratory blood samples should be drawn predose unless otherwise specified 
(eg, PK samples). Specific laboratory tests that must be completed 
 prior to the first 
dose of study drug are identified in Section 6.1.
The study procedures should be recorded in the source document and the electronic case report 
forms (eCRF). In the event subjects fail screening, minimal information will be documented on 
the eCRFs, per database instructions.
6.1
Screening Period
For all treatment arms, the Screening window starts 
 prior to first dose of study drug. Refer 
to
, and Section 6.2 through Section 6.7 for detailed information on 
procedures performed and the schedule.  
Waivers to the protocol will not be granted during the conduct of this trial, under any 
circumstances.
Safety laboratory analyses will be performed locally. Screening laboratory values must 
demonstrate subject eligibility, but may be repeated within the screening window, if necessary.
The ICF will be administered at the Screening visit to all subjects by qualified study staff. It must
be signed and dated by the subject and the administering staff prior to the start of any other study 
procedures and its completion documented in source documents and in the eCRF. All screening 
tests and procedures must be completed within 
 prior to the first dose of study drug
according to the schedule shown in
. 
The following will be performed at Screening (as specified in 
) 
after informed consent has been obtained.
Inclusion and exclusion criteria will be assessed at Screening and recorded in the source documents 
and the eCRF.  

Medical
 
 
 will be collected during Screening as consistent with local regulations. 
If full date of birth will not be collected, year of birth and age are required. Oncologic history 
will include a detailed history of the primary diagnosis and date, therapies and responses and 
transfusion dependence history if applicable.  

Information on prior and concomitant medications and procedures will be collected (refer to 
Section 6.2.1).

Registration in the interactive response technology system (IRT)
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
95

Adverse event (AE) monitoring (refer to Section 6.2.2).

Vital signs assessed (refer to Section 6.2.3)

Physical examination (source documented only), height, weight, and ECOG performance 
status (refer to Section 6.2.4).

Viral serologies for 
 will be collected at Screening. 
 

Pregnancy testing (refer to Section 6.2.5) for SCBP. Appropriate methods of contraception will 
be discussed with subjects during Screening.  One highly effective contraceptive method for 
SCBP (eg, oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine
device; or vasectomized partner) and a single contraceptive method (a condom [a latex condom 
is recommended]) for subjects who are able to impregnate their partner must be used from the 
time the ICF is signed, throughout the study by subjects, and for 
 after the last dose of 
CC-95251 and 6 months (or longer if required by local regulations) for SCBP or 3 months (or 
longer if required by local regulations) for subjects who are able to impregnate their partner,
after the last dose of azacitidine.

True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the 
subject. This will be documented in the source documents.  
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
96

Pregnancy β-subunit of human chorionic gonadotropin (β-hCG) test for SCBP (refer to Section 
6.2.5).

A SCBP must have two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior 
to starting study treatment. The first pregnancy test must be performed at Screening and 
the second pregnancy test performed within 72 hours prior to the start of study treatment. 
The results must be confirmed to be negative prior to dosing. 

Clinical laboratory tests (refer to Section 6.2.6).

Single
 (refer to Section 6.2.7) will be performed to fulfill eligibility criteria.

Left Ventricular Ejection Fraction (LVEF) assessment (refer to Section 6.2.8).

Disease (efficacy) assessments (refer to Section 6.4) with the bone marrow aspiration and 
biopsy, peripheral blood smear (PBS), and complete blood count (CBC) are collected during 
 prior to the first dose of study drug. 
Pharmacodynamic bone marrow biomarker samples should be obtained at the same time (refer 
to Section 6.6).
6.2
Treatment Period
Procedures in this section occur during treatment and specific timing is described in
 
The subject will begin treatment upon confirmation of eligibility. The
subject must start treatment 
 of signing the ICF (refer to Section 7.2). If screening
assessments are performed 
 of C1D1, safety laboratory (except hematology) and
physical examinations need not be repeated at C1D1. Subjects with AML receiving CC-95251
monotherapy or double combination (CC-95251 with azacitidine) 
 
 
Subjects with AML receiving triple combination (CC-95251 with 
azacitidine and venetoclax) 
 
 
 
 
 
 
All subjects who fulfill the inclusion/exclusion criteria who are continuing in the study will be 
registered in the IRT system prior to receiving study drug(s) on C1D1.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
97
6.2.1
Prior and Concomitant Medications and Procedures
All prior and concomitant medications and procedures taken or conducted beginning when the 
subject signs the ICF, throughout the study, and 
 after the last dose of study drug will 
be recorded in the source documents and eCRF.
Packed red cell and platelet transfusion history 
 
6.2.2
Adverse Event Monitoring
Adverse events and serious adverse events (SAEs) will be recorded from the time a subject signs
the ICF 
after the last dose of study drug. Refer to Section 10 for detailed information.
Subjects experiencing AEs will be monitored with relevant clinical assessments and laboratory 
tests, as determined by the Investigator. Every attempt will be made to document resolution dates 
for ongoing AEs. The AE will be recorded on the AE page of the eCRF and in the subject’s source 
documents. Photographs of skin rashes should be obtained whenever possible, anonymized, and 
stored appropriately for future retrieval.
6.2.3
Vital Signs and Oxygen Saturation
Vital signs include body temperature, blood pressure, pulse rate, and respiration rate will be 
recorded at screening and during the study at various time points for safety monitoring as described 
in the Table of Events
Serial vital signs will be obtained during each CC-95251
 
 
 
 
 
 and at 30 (± 10 minutes) 
after the EOI and recorded with vital signs time points. 
 
Additional vital signs should be obtained as clinically indicated per the Investigator’s assessment. 
All measurements will be captured in the source documents and eCRF.
6.2.4
Physical Examination and ECOG Performance Status
Physical examination, including height and weight, and Eastern Cooperative Oncology Group 
(ECOG) performance status will be performed at the visits listed in 
, and 
. Results for both will be recorded in the source documents and results for height, weight 
and the ECOG PS will also be collected on the eCRF.
Physical examination findings will be classified as either normal or abnormal. If abnormal, a 
description of the abnormality and clinical significance will be provided in the source documents. 
Clinically significant changes from baseline will be recorded in the AE section of the eCRF.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
98
6.2.5
Pregnancy Test
All subjects will be informed about pregnancy-related risks prior to the first dose of study drug to 
ensure compliance with all requirements for pregnancy prevention.
A SCBP is defined as a sexually mature individual who has: 

Not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy
(the surgical removal of both ovaries), or 

Not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out 
childbearing potential) for at least 24 consecutive months (eg, has had menses at any time in 
the preceding 24 consecutive months).  
The Investigator will classify a subject as a SCBP according to this definition. Pregnancy testing 
is not required for non-SCBP subjects, but justification must be recorded in the eCRF and the 
source document. Pregnancy testing will be conducted by the local laboratory.
For a SCBP, pregnancy testing will be conducted at the visits listed in 
 
A serum pregnancy (β-hCG) test with sensitivity of at least 25 mIU/mL is to be obtained at 
Screening and serum or urine pregnancy test (based on Investigator’s discretion) within 72 hours 
prior to C1D1 of study treatment. The subject may not receive study drug until the Investigator 
has verified the two screening pregnancy tests to be negative. 

A quantitative serum or urine pregnancy test (based on Investigator’s discretion and minimum 
test sensitivity [25 mIU/mL]) should be done within 72 hours prior to Day 1 of every cycle, 
and at the EOT visit. The subject may not receive study drug until the Investigator has verified 
the pregnancy test to be negative.

A SCBP or a subject who is able to impregnate their partner
must avoid 
blood/egg/semen/sperm donation and activities that could lead to conception for at least 
 after the last dose of CC-95251 and 6 months (or longer if required by local regulations) 
for SCBP or 3 months (or longer if required by local regulations) for subject who is able to 
impregnate their partner, after the last dose of azacitidine. 
Results for pregnancy tests will be recorded in the source document and eCRF.  
6.2.6
Clinical Laboratory Tests
The following laboratory assessments will be performed at the Screening visit and/or during the 
study at the time points as described in
All samples on dosing 
days should 
. Laboratory assessments 
will be recorded in the source document and eCRF and are the following:

Hematology: 
 
 

Serum chemistry: 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
99

For an individual subject, the type of sample drawn (either serum or plasma) for chemistry 
assessment should be consistent across all collection time points.

Special chemistry: 
 

Coagulation: 
 

Urinalysis or dipstick

microscopy in the event of a positive (1+ or greater) blood or protein

24-hour collection for creatinine clearance and protein quantification in the event of 2+ or 
greater protein

Creatinine clearance determination using the Cockcroft-Gault equation required at Screening 
to fulfill inclusion criteria (refer to Section 4.2).
6.2.7
12-Lead Electrocardiograms
 
 
When subjects are being
treated with CC-95251 in combination with azacitidine, the ECG will be done prior to CC-95251
administration.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
100
 
 
 
Investigators will make clinical decisions based on their interpretation of the ECG results and 
provide their overall assessment of the ECG in the eCRF. Clinically significant changes from 
baseline will be recorded in the AE section of the eCRF.
6.2.8
Left Ventricular Ejection Fraction
 
 will be conducted at Screening in all subjects, and as clinically 
indicated. If clinically indicated, follow-up assessments should use the same procedure used at the 
screening assessment. 
 
Clinically significant changes for these 
 
assessments will be documented on the AE section of the eCRF.
6.2.9
End of Treatment
An EOT evaluation (refer 
for procedures) should be performed 
for subjects who are discontinued from treatment for any reason as soon as possible after the 
decision to permanently discontinue treatment has been made
 
.
6.3
Follow-up Period
6.3.1
Safety Follow-up
All subjects will be followed for 
 after the last dose of study drug for AE reporting. 
In addition, concomitant medication use, SAEs made known to the Investigator at any time 
thereafter that are suspected of being related to study drug are to be reported until such SAEs have 
recovered (returned to baseline), recovered with sequelae, or death (due to the SAE) as described 
in Section 10.1. Subjects will also be followed for all AEs (SAEs and non-serious AEs) associated 
with confirmed or suspected SARS-CoV-2 infection until resolution, the condition stabilizes, the 
event is otherwise explained, the event is deemed irreversible, the subject is lost to follow-up, or 
for suspected cases, until SARS-CoV-2 infection is ruled-out.
The 
 safety follow-up contact may be done by telephone if the subject is unable 
or unwilling to come in for the PK and ADA sampling.  
6.3.2
Efficacy Long Term Follow up
After EOT visit, subjects without documented progression of disease (or relapse) or start of a new 
anticancer therapy will have efficacy evaluations 
 
 
 or until 
progression of disease (or relapse), initiation of a new anticancer therapy, withdrawal from the 
study, death, or the End of Trial, whichever comes first. A bone marrow evaluation will be 
completed 
 and as clinically indicated during the Follow-up Period.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
101
Information (including dates) on new anticancer therapies initiated will be collected until 
withdrawal from the study, death, or the End of Trial, whichever comes first.
6.3.3
Survival Follow up
After EOT visit, all subjects will be followed according to the schedule for the efficacy long term 
follow-up (refer to Section 6.3.2) for survival 
 or until death, lost to follow-up, or 
the End of Trial, whichever occurs first. Survival follow-up 
 
 
The Follow-up Period will document survival and new anticancer therapies 
 
6.4
Efficacy Assessment
Blood and Bone Marrow Aspirate and/or Biopsy
Bone marrow (BM) aspiration and/or biopsy for disease burden assessments will be collected to 
be evaluated for 
 at Screening, end 
 
 
 
  In addition, bone marrow 
aspirates (BMA) or biopsies (BMB) are performed to confirm complete remission (CR) or 
morphologic CR with incomplete hematologic recovery (CRi) or morphologic CR with partial 
hematologic recovery (CRh), relapse after CR, CRi, or CRh (as assessed by the Investigator based 
on CBC with WBC differential results), or disease progression. Additional aspirates and/or 
biopsies will be collected as clinically indicated, based on Investigator’s medical judgement. Both 
bone marrow aspirate and biopsy samples are mandatory at Screening
 
thereafter, a bone marrow aspirate alone is sufficient, but a biopsy must be collected if the aspirate 
is not available and may be collected in addition to the aspirate per institutional practice.   
 
 
 
 
 
 
 
 
 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
102
Response to treatment will be assessed by Investigator using local laboratory results according to 
modified 2017 European Leukemia Network (ELN) AML Response Criteria (Döhner, 2017) for 
AML and modified IWG Response Criteria (Cheson, 2006) for MDS based on reported 
hematology laboratory parameters, peripheral blood smear, bone marrow aspirates and/or biopsies. 
Hematologic response/transfusion dependence will also be evaluated. In addition, CR with partial 
hematologic recovery (CRh) will be reported for both AML and MDS (Bloomfield, 2018). 
AML response criteria will be summarized by best overall response categories: complete remission 
rate (CRR) defined as CR + CRi + CRh, and objective response rate (ORR, all responses of CR 
[ie, CRMRD-, morphologic CR, CRh, CRi] + morphologic leukemia free state [MLFS] + partial 
remission [PR]). For MDS, the CRR is defined as CR, ORR includes all responses (CR + CRh +
marrow CR + PR). The efficacy variable of focus will be CRR and ORR. Other measures of 
clinical activity include duration of remission, duration of response, stable disease rate (MDS 
only), 
relapse-free 
survival, 
event-free 
survival, 
progression-free 
survival, 
time 
to 
remission/response, transfusion independence, time to AML transformation for MDS subjects, and 
overall survival (OS) rates at 6 and 12 months.
The site will ensure peripheral blood, plasma and BMA/ BMB samples are collected and sent to 
the central lab for exploratory testing at the time of each bone marrow collection as detailed in the 
Biomarkers Section 6.6.
Progressive disease for AML will be defined as:

A > 50% increase in bone marrow blast count percentage from the baseline (screening) bone 
marrow blast count (a minimum 15% point increase is required in cases with <30% blasts at 
baseline; or persistent bone marrow blast count > 70%, over at least 3 months; without at least 
a 100% improvement in ANC to an absolute level (> 0.5 x 109/L) and/or platelet count > 50 x 
109/L non-transfused), or

A > 50% increase in peripheral blasts (WBC × % blasts) to > 25 x 109/L (> 25,000/μL) (in the 
absence of differentiation syndrome), or

New extramedullary disease.
The date of progressive disease is defined as the first date that there was either a > 50% increase 
in BM blast count from baseline, a persistence of BM blasts > 70% in subjects with a baseline BM 
blast count of > 70%, or a doubling of the peripheral blood (PB) blast count.
Treatment failure will be defined as progressive disease or not achieving at least partial remission 
(PR) by the end of the treatment period. Subjects may continue treatment if they are deriving 
benefit from treatment without unacceptable toxicity (any CR, MLFS, PR, or SD with 
demonstrated clinical benefit eg, reduction in transfusion burden), as judged by the Investigator, 
, or until disease progression, loss of clinical benefit, unacceptable toxicity, or 
decision to withdraw by subject or Investigator. Failure to achieve a response while simultaneously 
not meeting the criteria for progressive disease will be considered stable disease.
Subjects who discontinue study treatment for reasons other than disease progression (or relapse) 
or start of a new anticancer therapy will have disease assessments according to the specified 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
103
assessment schedule (refer to Section 6.3.2) until progression (or relapse) and/or initiation of new 
anticancer therapies. For subjects who have discontinued study treatment due to relapse or 
progression or start of a new anticancer therapy, follow up can be performed by site visits or phone 
calls. Subjects will be followed 
 they have died, are lost to follow up, 
withdraw consent for further data collection, or until study closure.
Molecular and cytogenetic studies in BM may be omitted:

At the Screening, if they were completed within the 
 and the results are available 
to enter on the eCRFs.

 
The bone marrow aspiration and core sampling (biopsy) should be performed according to the 
standard of care and analyzed at the local site’s laboratory in accordance with the International 
Council for Standardization in Hematology Guidelines (Lee, 2008). 
Minimal residual disease
The minimal residual disease (MRD) response rate and MRD conversion rate will also be assessed 
as efficacy variables. MRD negative CR (CRMRD-), combined rate of CRs (cCRR = CR + CRMRD-
+ CRi  + CRh in AML and CR + CRMRD- in MDS) will be assessed (Bloomfield, 2018).
MRD assessments will be performed in BMA or BMB at disease assessment timepoints using a 
flow cytometry-based and/or NGS-based method performed by central laboratory (refer to 
Biomarkers Section 6.6).
Testing for MRD will be performed locally, as applicable, per institutional guidelines in AML 
subjects with complete response in order to permit efficacy assessment according to ELN response 
criteria (Dohner, 2017).
Packed red blood cell and platelet transfusions
Transfusion dependence is defined as 
 
Transfusion independence for hematologic response 
 
 
Packed red cell and platelet transfusion history 
 before beginning the 
study treatment, continuous, and until End of Treatment or efficacy follow-up, whichever occurs 
later will be collected.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
104
6.5
Pharmacokinetics
Samples will be collected for PK and immunogenicity assessment for subjects at the time points 
indicated in
(
 
for each study part.
All on-treatment PK time points are intended to align with days on which study treatment is 
administered. All predose samples should be taken prior to the start of CC-95251 infusion. If it is 
known that a dose is going to be delayed, then collect the predose sample just prior to the delayed 
dose. However, if a predose sample is collected but the dose is subsequently delayed, do not collect 
an additional predose sample.
 
 
 
 
 
 
Dosing and sample collection information, including CC-95251 dose level, dosing date, dosing 
time, infusion time, and actual PK blood sampling time, should be accurately documented on the 
appropriate source documents and eCRF (refer to Table 5). If the infusion was interrupted, the 
interruption details will also be documented on the eCRF.
Pharmacokinetics of CC-95251 will be derived from serum concentration versus time. The 
pharmacokinetic parameters including but not limited to the ones shown in Table 5 will be assessed 
where feasible.
Table 5:
Pharmacokinetic Parameters
Cmax
Maximum observed serum concentration
Cmin
Minimum observed serum concentration 
Tmax
Time of maximum observed serum concentration
AUC(0-T)
Area under the concentration-time curve from time zero to time of last quantifiable 
concentration
Ctrough
Trough observed serum concentration
AUC(TAU)
Area under the concentration-time curve in a dosing interval
CLT
Total body clearance
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
105
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
106
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
107
Concentration analyses for CC-95251 will be performed by validated bioanalytical method(s).
 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
108
Additionally, residual bioanalytical samples will be archived and may be used for potential 
exploratory bioanalysis (including but not limited to: 
 
Detailed instructions for the PK and immunogenicity blood collection, labeling, processing, 
storage, and shipping will be provided to the site in the laboratory manual.
6.6
Biomarkers, Pharmacodynamics, Pharmacogenomics
Biomarker assessments will include analyses of peripheral blood and a portion of bone marrow 
tissue (aspirate and biopsy), collected before treatment and at several times after treatment has 
begun. Assessments will be performed centrally to evaluate potential associations with safety and 
efficacy, and to explore mechanisms of resistance and response to the specified treatment. 
 
 
 
Minimal residual disease has been proposed as a marker of potential relapse; therefore, we will
assess MRD in bone marrow using next generation sequencing and/or flow cytometry methods.
 
Sample specimens will be collected for these studies as indicated in
and outlined in 
. Biomarker specimens will be collected predose of study treatment 
unless otherwise specified to evaluate the following:

Frequencies of bone marrow and peripheral blast cells and monocytes and SIRPα target 
expression levels and coverage (receptor occupancy) 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
109
Consent for biomarker sampling procedures will be obtained through signature of a biomarker
specific component of the informed consent form. All subjects participating in this study will
consent to biomarker sampling procedures, as described. The sponsor may conduct additional
analyses on the PD samples to evaluate the safety of the study treatment or to better understand
the progression of the disease or the disease’s response to the study treatment. See the Laboratory 
Manual for sample collection, labeling, processing, storage, and shipping instructions.
6.7
Additional and Optional Research
Additional and optional research as described below may be performed using left-over samples 
originally collected for another test required in this study or using samples collected specifically 
for biomarker testing. The research may involve genetic tests using DNA or RNA and may lead to 
the development of new diagnostic tests.
6.7.1
Additional Research
Additional research related to the study drug and/or disease may be performed. The results of this 
additional research could help to improve the diagnosis and/or the treatment of this disease in the 
future. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
110
6.7.2
Optional Research
Optional research not related to the study drug or the subject’s disease may be performed. The 
subject’s decision to participate in this optional research will not impact their ability to participate 
in the main study. 
6.8
Subject Reported Outcomes
Not Applicable.
7
DESCRIPTION OF STUDY TREATMENTS
7.1
Description of Investigational Products
7.1.1
CC-95251
CC-95251 (as also known as BMS-986351) will be supplied as investigational product by the 
sponsor in 2 presentations: 
 
 
 
 
 
 
 
 
 CC-95251 should be prepared according to the CC-95251
Pharmacy Manual and local practice regulations.
7.1.2
Azacitidine
Azacitidine will be supplied or obtained according to local clinical study agreement and in 
accordance with local guidelines. 
When provided by the Sponsor, azacitidine for Injection will be supplied as a lyophilized powder 
in 100 mg single-dose vials for reconstitution and administration.
Material supplied by the Sponsor will be labeled appropriately for investigational use as per the 
regulations of the relevant country health authority.
Please refer to the locally approved azacitidine label or Pharmacy Manual for preparation, 
administration, and storage information.
7.1.3
Venetoclax
Venetoclax will be supplied or obtained according to local clinical study agreement and in 
accordance with local guidelines. When provided by the Sponsor, venetoclax will be supplied as 
tablets in 10 mg, 50 mg, and 100 mg blister/bottles for administration.  Material supplied by the 
Sponsor will be labeled appropriately for investigational use per the regulations of the relevant 
country health authority.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
111
7.2
Treatment Administration and Schedule
7.2.1
Study Drug Preparation and Administration
7.2.1.1
CC-95251
 
 
 
 
 
 Subjects with 
 
 Full emergency resuscitation facilities should 
be immediately available, and subjects should be under close supervision of the Investigator or 
designated staff during and 
 
 
following CC-95251 administration. For subjects receiving injectable azacitidine in combination 
with CC-95251, subjects will receive azacitidine prior to starting CC-95251 infusion on days 
receiving both treatments. Subjects should be observed 
between 
administrations.
CC-95251 preparation and infusion will be described in the Pharmacy Manual.
 
 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
112
The initial CC-95251 infusion will be started at 
 mg/hr 
 
 mg/hr 
 mg/hr. Further changes to 
the rate of infusion may be considered during the course of the trial based on review of clinical 
data and approval from the SRC.
Serial vital signs and oxygen saturation should be measured as described in Section 6.2.3.
After the end of each CC-95251 infusion, IV access should be maintained and the subject should 
remain under close supervision 
 
 
CC-95251 will be administered intravenously in two phases starting with a more frequently dosed 
induction phase followed by a maintenance phase. Treatments will be administered in 28-day 
cycles. During induction phase, subjects will be dosed weekly for Cycles 1 through 4 (eg, on Day 
1, Day 8, Day 15, and Day 22 of each cycle).  
After Cycle 4, subjects will enter the maintenance phase. During the maintenance phase, 
treatments will be administered in 28-day cycles with dosing every two weeks (eg, on Day 1 and 
Day 15 of each cycle). 
An intermediate dose level of CC-95251 or a variable dose schedule 
 
 may be evaluated to accurately determine 
the RP2D at the recommendation of the SRC. The investigation of any other alternate dosing 
schedule beyond those stipulated in the current protocol version will be submitted in a protocol 
amendment.
Subjects may continue CC-95251 for 
 
 
, or until disease progression, loss of clinical 
benefit, unacceptable toxicity, or decision to withdraw by subject or Investigator.
7.2.1.2
Azacitidine
Azacitidine at 75 mg/m2 is administered on Days 1-7 (or Days 1-5 and 8-9) of each 28-day cycle 
as an IV or SC injection per local prescribing information and institutional standard of care.
BSA for subject dosing should be calculated on the first day of each dosing cycle. BSA should be 
calculated per institutional standard, however, the Dubois formula 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
113
is preferred. If a subject’s body weight changes by more than 10% compared 
with baseline body weight, or compared with a previous body weight value that required a dose 
adjustment, then the dose of azacitidine should be recalculated. The dose during a treatment cycle 
should not be amended.
Subjects may receive best supportive care as needed (please refer to local prescribing information 
and local therapeutic guidelines for more details on available formulations, preparation, storage 
conditions [eg, refrigeration], the approved indications, known precautions, warnings, and adverse 
reactions of best supportive care; see current version of Prescribing Information), including 
antibiotics and transfusions, per Investigator’s discretion. 
 
 
 
 
7.2.1.3
Venetoclax
 
 
 
 (Table 12). Subjects should 
be instructed to take their daily dose at approximately the same time each day 
On Day 1 of each cycle, CC-95251, azacitidine, and venetoclax will be administered 
 
 and subjects should 
be observed for 
 between infusions. 
will be taken orally 
 
hours 
 
 
Each dose should be taken with a meal and water and consumed over as short of a time as possible. 
Subjects should be instructed to swallow tablets whole and to not chew or crush the tablets. 
 
 
 
Subjects will be given a medication diary to record the time of venetoclax administration for at-
home administration. All efforts should be made to administer venetoclax on all scheduled days 
of each 28-day treatment cycle. 
 
 
 Any 
missed doses should be documented in the subject’s medication diary and not be taken beyond the 
last scheduled day of venetoclax administration.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
114
If vomiting occurs shortly after a dose of venetoclax is administrated, that dose should not be made 
up later that day. The subject should continue with the dosing schedule on the next day and inform 
the investigator about the vomiting event at the next visit and document this in the subject
medication diary. Dosing and dosing modifications should follow the approved labels, as 
summarized in the dose modification guidance,
and Table 12. Subject-specific 
factors for level of risk of 
 should be assessed, and 
 and anti-
hyperuricemics to subjects prior to first dose of venetoclax should be given, per locally approved 
label (see Section 7.2.7.8.2: Prophylaxis and Management of Tumor Lysis Syndrome).
Material supplied by Bristol-Myers Squibb Company (BMS) will be labeled appropriately for 
investigational use per the regulations of the relevant country health authority. Please refer to the 
locally approved venetoclax package insert, SmPC, or Pharmacy Manual for dosing and storage 
information
7.2.2
Dose Escalation Criteria
In Part A, CC-95251 will be given at doses that will increase according to the dose levels in
 The number of cohorts depends on incidence of DLT. 
 
 
 
 The initial dose of CC-95251 will be 20 mg/kg
 
A sample decision table is shown in 
 
.
The SRC may decide to evaluate a higher dose cohort (
 mg/kg), 
additional subjects within a dose cohort, intermediate dose cohorts, smaller dose increments, 
alternate dosing schedules, and/or declare the RP2D based on their review of available clinical and 
laboratory safety data, efficacy, PK profiles, and PD findings. For a dose level to be selected by 
the SRC for dose expansion (Parts B, C, and D), 
 should be evaluated for DLT 
in Part A to declare a tolerable dose level.
In the event that an alternate dosing schedule is evaluated, 
 
 
Dose reduction and temporary delay of CC-95251 and combination agents due to toxicity is 
allowed, 
 
7.2.3
Definition of a Subject Evaluable for DLT
All subjects who receive at least one dose of CC-95251 and/or combination drug(s) will be 
evaluable for safety. After the first dose is administered in any cohort of subjects during dose 
escalation, subjects in each cohort are observed 
 
 
A subject evaluable for a DLT is defined as one who:
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
115
In the absence of persistent AML blasts in the bone marrow, 
 
 
 
 
7.2.4
Definition of 
The 
 is defined 
 
. An 
intermediate dose level of CC-95251 or a variable dose schedule 
 
 may be evaluated to accurately determine 
the RP2D at the recommendation of the SRC. The investigation of any other alternate dosing 
schedule beyond those stipulated in the current protocol version will be submitted in a protocol 
amendment.
7.2.5
Definition of Dose-Limiting Toxicity (DLT)
Toxicity severity will be graded according to NCI CTCAE Version 5 except for CRS and TLS, 
which will be graded according to the revised CRS grading system (Lee, 2014) and Cairo-Bishop 
TLS grading system (Cairo, 2004), respectively. DLTs during dose escalation will be based on 
adverse events that occur during the DLT observation period. 
 
and subjects will be evaluated at the 
completion of each cohort at a given dose level. 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
116
Any reduced dose level of CC-95251 will be jointly defined by the Investigator and the Sponsor’s
Medical Monitor. The dose may be increased thereafter upon joint determination of the 
Investigator and the Sponsor’s Medical Monitor (see Section 7.2.7.5). All decisions regarding 
continued dosing for individual subjects with DLT will be medically managed by the Investigator, 
and per discussion with the Sponsor’s Medical Monitor, as appropriate.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
117
 
 
 
 
7.2.6
Criteria for Dose Escalation in the Next Cohort of Subjects
Subjects considered evaluable for dose escalation decisions are outlined in Section 7.2.3. Dose 
escalation decisions will be made by the SRC. Decisions will be based on a synthesis of all relevant 
data available from all dose levels evaluated in the ongoing study 
 
 
 
PK data from subjects will be made available on an on-going basis throughout the study and dosing 
will be adapted accordingly. 
 
 
 
 
 
 
. For a dose level to be selected by the SRC for dose expansion (Part B, C, and D), at 
least 
 should be evaluated for DLT in Part A to declare a tolerable dose level. 
The number of dose levels depends on incidence of DLT. A subject may experience more than one
DLT. Dose escalation decisions are based on the number of subjects experiencing DLT events.
7.2.7
Definition of Stopping Criteria
7.2.7.1
Criteria for Stopping a Dose Cohort
During dose escalation (Part A), dose escalation stops when the preliminary RP2D is declared by 
the SRC, based on the number of subjects experiencing DLT events during the DLT evaluation 
period or when CC-95251 escalates to the highest planned dose of 
 mg/kg. The preliminary 
RP2D is declared by the SRC based on a cumulative review of the available safety, tolerability, 
PK, PD, and preliminary efficacy data. 
 
 
 
 
 
During the dose expansion (Parts B, C, and D), a non-binding 
 safety monitoring method 
will be utilized to continuously monitor for excessive toxicities defined 
 
. In Parts B, C, and D, after a 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
118
minimum 
 have enrolled, the non-binding 
 stopping criterion 
 
The 
 decision will be made by the SRC upon reviewing all available safety, PK, PD, 
and any efficacy results in dose expansion phase, including considerations on adjustment of the 
RP2D dose. Otherwise, the cohort will be expanded to up to approximately 
evaluable subjects
in Part B, approximately 
 evaluable subjects in Part C, and approximately 
 evaluable subjects 
in Part D (Section 9.9.2).
7.2.7.2
Criteria for Pausing or Stopping the study
Further enrollment and treatment in the study will be paused pending review and recommendations 
of the SRC and immediate notification to all Investigators and appropriate regulatory authorities 
Adverse events and SAEs are expected to occur frequently in this study based on the subject 
population being accrued and on the nature of the advanced hematologic malignancy under study. 
Regular systematic review of SAEs will serve as the basis for pausing or prematurely stopping the 
study. Unexpected SAEs that are related to study treatment will be the primary criteria for pausing 
or stopping the study. Review of these SAEs, and any decision to pause enrollment or terminate 
the study, will be determined by the SRC. Decisions to pause enrollment or terminate the study 
will be communicated promptly to Investigators, to the Institutional Review Boards (IRBs)/Ethics 
Committees (ECs), Institutional Biosafety Committees (IBCs) (if applicable), and to the 
appropriate regulatory authorities.
7.2.7.3
Permitted Study Drug Adjustments
Dose reductions of CC-95251 are permitted in any cycle, including Cycle 1. 
 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
119
When a dose reduction of CC-95251 is indicated, 
 
 Dose omission and reduction are allowed after consultation with 
the Sponsor’s Medical Monitor. 
 
 
 
 
Modifications to the administration of azacitidine and venetoclax are allowed per local prescribing 
information and institutional standard of care. (eg, United States Prescribing Information [USPI] 
or Summary of Product Characteristics [SmPC]).
7.2.7.4
Criteria for Dose Reduction
Any study drug AE meeting the definition of DLT (refer to Section 7.2.5) will require dose 
interruption and/or reduction. 
Dose reductions of azacitidine for management of toxicities are allowed per local prescribing 
information and institutional standard of care. (eg, United States Prescribing Information [USPI] 
or Summary of Product Characteristics [SmPC]). Recommended dosing adjustments to venetoclax 
due to toxicity are summarized below (Section 7.2.7.7).  
7.2.7.5
Criteria for Dose Increase
In Part A, intra-subject dose escalation beyond the dose initially assigned to a subject is 
 
. However, 
 
 
 
 
 
In expansion phases, no dose escalation beyond the RP2D is 
allowed.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
120
7.2.7.6
Treatment Interruption for Adverse Events
Treatment may be interrupted 
 
. CC-95251 should also be 
delayed if subject has confirmed SARS-CoV-2 infection (see Section 7.2.7.8.5). 
If treatment is interrupted and not given in the visit window 
 
 treatment may restart at the next scheduled visit for CC-95251 administration. 
Treatment may restart either at the same, or a reduced dose, at the Investigator’s discretion or as 
described in Section 7.2.7.3. In Part A during Cycle 1, 
 
 
 
 
 
 
Treatment 
interruption of azacitidine for adverse events are allowed per local prescribing information and 
institutional standard of care. Refer to 
for dose modification 
guidance for venetoclax and azacitidine-related toxicities.  
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
121
7.2.7.7
Dose Modification Guidelines 
The criteria for dose modifications are presented in 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
122
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
123
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
124
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
125
7.2.7.8
Management of Select Adverse Events
7.2.7.8.1
Prophylaxis, Monitoring, and Management of Infusion Reactions
Infusion of a biologic product may cause severe and life-threatening infusion reactions. 
 
 
 Symptoms may include hypotension, tachycardia, dyspnea and respiratory symptoms 
(eg, bronchospasm, throat irritation, wheezing, laryngeal edema). Other possible symptoms 
include nausea, vomiting, diarrhea, hypertension, flushing, skin rash, headache, fever and chills. 
Full emergency resuscitation facilities should be immediately available, and subjects should be 
under close supervision of the Investigator or appropriately trained staff at all times.
 
 
Medical management of infusion reactions should be instituted according to standard medical 
practice using glucocorticoids, epinephrine, oxygen, IV fluids and other medications as medically 
indicated. 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
126
The Sponsor’s Medical Monitor should be notified of any Grade 4 or recurrent Grade 3 infusion 
reactions within 24 hours of the event.
7.2.7.8.2
Prophylaxis and Management of Tumor Lysis Syndrome
Treatment with cytolytic cancer therapies in the setting of high tumor burden may cause rapid 
tumor lysis and associated electrolyte and renal disturbance with risk of cardiac arrhythmia and 
sudden death.  
TLS is manifested by rapid release of large amounts of potassium, phosphate and nucleic acids 
into the circulation with associated hyperkalemia, hyperphosphatemia, hyperuricemia, and 
hypocalcemia. Precipitation of uric acid and calcium phosphate crystals in the renal tubules can 
result in acute kidney injury and electrolyte disturbances can trigger cardiac arrhythmias, seizures 
and sudden death.
 
 
 
Below are the minimum requirements for TLS prophylaxis and 
management. All other prophylaxis and monitoring procedures will be done as per 
institutional/regional standards:
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
127

As part of serum chemistry laboratory tests, subjects will be monitored for TLS during the 
study 
 
 
 

Investigators are to exercise clinical judgment as to whether more frequent serum 
chemistry monitoring may be appropriate at their discretion. Subjects with laboratory 
abnormalities suspicious for clinically significant TLS should be managed as inpatients.

Abnormal chemistry tests should be corrected promptly.

Medications to treat TLS are permitted. 
 
 
 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
128

If a subject experiences blood chemistry changes or symptoms suggestive of TLS, maintaining 
the same ramp-up dose for longer duration or withholding subsequent dose of venetoclax may 
be required. 

For subjects who had a dose delay or interruption, monitor for evidence of TLS during the 
restart of treatment and manage abnormalities of serum creatinine, uric acid, and electrolytes 
promptly. Dose ramp-up of venetoclax is permissible on restart.
7.2.7.8.3
Monitoring and Management of Cytokine Release Syndrome and Macrophage 
Activation Syndrome/Hemophagocytic Lymphohistiocytosis
 
 
 
 As such, the CC-95251 clinical 
study will follow the management of CRS based on the revised CRS grading system (Lee, 2014). 
The clinical signs and symptoms of CRS include, but are not limited to: fever, nausea, vomiting, 
headache, rash, hypotension, tachycardia, tachypnea, elevated D-dimer, hypofibrinogenemia, 
bleeding, acute renal failure, hyperbilirubinemia, transaminitis, headache, mental status changes, 
and seizures. Cytokine release syndrome is associated with elevated levels of serum cytokines 
including interleukin (IL)-6 and interferon γ (IFN γ). Clinical experience with managing this 
syndrome has supported that treatment with tocilizumab, an anti-IL-6 receptor antibody, with or 
without corticosteroids, can reverse the syndrome. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
129
The SRC will review the incidence and grade of CRS during the trial and will make 
recommendations on 
 
 
 
 The Sponsor’s Medical Monitor should be notified of any episode 
of Grade ≥ 2 CRS within 24 hours of the event.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 The diagnosis of MAS/HLH (according to HLH-2004 consensus criteria, further 
revised in 2014 for HLH associated with malignancies) (Lehmberg, 2015) can be established if 
either of the 2 criteria below is fulfilled:
1. A molecular diagnosis consistent with MAS/HLH
2. Diagnostic criteria for MAS/HLH fulfilled (five out of the eight criteria below):
o
High persistent fever (≥ 38.5°C)
o
Splenomegaly
o
Cytopenias (affecting 2 of 3 lineages in the peripheral blood): Hemoglobin < 9.0 
g/dL, platelets < 100 × 109/L, neutrophils < 1.0 x 109/L
o
Triglycerides ≥ 3.0 mmol/L (ie, 265 mg/dL) or fibrinogen ≤ 1.5 g/L
o
Hemophagocytosis in bone marrow, spleen, and/or lymph nodes
o
Low or absent natural killer -cell activity (according to local laboratory reference)
o
Ferritin ≥ 500 ng/mL
o
Soluble CD25 (ie, soluble IL-2 receptor) ≥ 2400 U/mL
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
130
Effective treatment of MAS/HLH requires multiple simultaneous approaches (Ramos-Casals,
2014; Lehmberg, 2015).
1) Supportive care is essential because of frequent life-threatening severe manifestations 
at presentation.
2) The elimination of triggers (particularly infection) is crucial to remove the stimuli that 
initiate the abnormal immune system activation. Appropriate broad-spectrum 
antiviral, antibacterial, antifungal prophylaxis and treatment must be initiated.
3) Suppression of the inflammatory response and cell proliferation by immunosuppressive 
and cytotoxic drugs, respectively, is necessary. 
 
 
 
 
 
 
 
 
 
4) Newer emerging treatments include emapalumab (anti IFN-gamma antibody), which 
has been approved by the FDA for the treatment of primary refractory or recurrent 
MAS/HLH (Benedetti, 2019).
7.2.7.8.4
Hematological Toxicity
Hematopoietic growth factors or other hematologic support, such as erythropoietin, darbepoetin, 
, red blood cell- or platelet- transfusions 
are allowed in the study with therapeutic intent.
 
 
 
 
 
 
 
 
 
 
  
Baseline neutrophil counts worsened in 97% to 100% subjects treated with venetoclax in 
combination with azacitidine. Neutropenia can recur with subsequent cycles of venetoclax plus 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
131
azacitidine therapy. 
 
 
In subjects with elevated WBC, 
 
 
 
 
 
 
 
Dose reductions of azacitidine are generally not recommended. If a dose reduction in azacitidine 
is believed to be necessary, a discussion with the Sponsor Medical Monitor is required.
7.2.7.8.5
Infection
Vigilance for the signs and symptoms of infection should be practiced and managed according to 
institutional standard medical practice. Routine infectious disease 
 
 
recommended during the study according to institutional standard medical practice.
7.2.7.8.5.1 SARS-CoV-2 Infection
Subjects with confirmed SARS-CoV-2 infection following the start of study treatment should have 
treatment interrupted.
For confirmed SARS-CoV-2 infection, treatment may be resumed after:

) have passed since symptoms first appeared, 
positive RT-PCR test result, or positive viral antigen test result, 

resolution of acute symptoms 
 
 

evaluation by the Investigator with confirmation that there are no sequelae that would place 
the subject at a higher risk of receiving investigational treatment, and

consultation by the Sponsor’s Medical Monitor. 

For suspected cases, treatment may also resume if SARS-CoV-2 infection is ruled-out and 
other criteria to resume treatment are met. Prior to re-initiating on-study treatment in a subject 
with a dosing delay lasting 
 due to SARS-CoV-2 infection, the Sponsor’s Medical 
Monitor/designee must be consulted.
7.2.7.8.6
Pain
Tumor pain or treatment-induced pain can be controlled with opioid and opioid-related analgesics, 
such as codeine, meperidine, propoxyphene or morphine, administered at the clinician’s discretion, 
and as dictated by medical need. The risk of bleeding, especially in the setting of 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
132
thrombocytopenia, should be considered prior to use of non-steroidal anti-inflammatory drugs and 
aspirin.
7.2.7.8.7
Gastrointestinal Disorders
Appropriate monitoring and timely management of gastrointestinal disorders is critical in avoiding 
malnourishment and dehydration. At the discretion of the Investigator, prophylactic and/or 
therapeutic use of medications (eg, antiemetics for nausea and vomiting, antidiarrheals for 
diarrhea, laxatives and/or stool softeners for constipation) may be appropriate. Subjects 
experiencing diarrhea associated with study drugs may be managed according to the guidelines 
provided in Appendix M. Dose modifications of study drugs may be considered based on the 
severity of treatment-related gastrointestinal complications (
).
7.2.7.9
Retreatment or Increased Dose Intensity of CC-95251
Retreatment with CC-95251 may be considered, at the Investigator’s discretion and after 
discussion with the Sponsor’s Medical Monitor, if all of the following criteria are met:
Subjects who are retreated will follow the Table of Events (Section 5) 
 
 
 
 
 
7.2.7.10
Definition of Overdose
Overdose, as defined for this protocol, refers to CC-95251, azacitidine, and venetoclax.
On a per dose basis, an overdose is defined as the following amount over the protocol-specified 
dose of CC-95251 or azacitidine or venetoclax assigned to a given subject, regardless of any 
associated AEs or sequelae: 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
133
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the case report form. Refer to 
Section 10.1 for the reporting of adverse events associated with overdose.
7.3
Method of Treatment Assignment
Subjects will begin treatment upon confirmation of eligibility. 
The subject must start treatment within 
 of signing the ICF and can be rescreened if the 
Screening window lapses. An IRT system will be used to track subject assignments to the dose 
levels in dose escalation (Part A) and cohorts in dose expansion (Parts B, C, and D).
Subjects will be enrolled sequentially in Part A with no more than one subject enrolled per day 
into dose escalation cohorts.  Enrollment in dose expansion will be stratified by Parts B, C, and D, 
as applicable. Enrollment in Part C may proceed concurrently with enrollment in the Part B 
expansion cohorts. Similarly, enrollment in Part D may proceed concurrently with enrollment in 
the Part B and Part C expansion cohorts. 
7.4
Packaging and Labeling
The label(s) for IP will include Sponsor name, address and telephone number, the protocol number, 
IP name, dosage form and strength (where applicable), amount of IP per container, lot number, 
expiry date (where applicable), medication identification/kit number, dosing instructions, storage 
conditions, and required caution statements and/or regulatory statements as applicable. Additional 
information may be included on the label as applicable per local regulations.
7.5
Investigational Product Accountability and Disposal 
Accountability for study drug that is administrated during the course of the study is the 
responsibility of the Investigator or designee. Investigational clinical supplies must be received by 
a designated person at the clinical site and kept in a secure and temperature-controlled location. 
For CC-95251, azacitidine, and venetoclax, the investigational site must maintain accurate records 
demonstrating dates and amounts of study drug received or obtained from the pharmacy, to whom 
it was administered (subject-by-subject accounting), and accounts of any vials accidentally or 
deliberately damaged and/or returned to the Sponsor. 
The Sponsor (or designee) will review with the Investigator and relevant site personnel the process 
for documenting receipt of IP, as well as procedures for accounting, reconciling IP, and 
documenting this process. 
The Sponsor (or designee) will review with the Investigator and relevant site personnel the process 
for IP return, disposal, and/or destruction including responsibilities for the site versus the Sponsor
(or designee).
7.6
Investigational Product Compliance
Only the pharmacist or Investigator’s designee will dispense CC-95251 and azacitidine. A record 
of the total dose (and number of vials used) of CC-95251 and azacitidine administered to each 
subject must be maintained. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
134
The pharmacist or Investigator’s designee will document the doses dispensed/administered in the 
appropriate study records and the appropriate eCRF. Study intervention compliance will be 
periodically monitored by drug accountability, including the review of dosing diary cards. Drug 
accountability should be reviewed by the study site staff at each visit to confirm treatment 
compliance. Study sites should discuss discrepancies with the subject at each on-treatment study 
visit.

When subjects are dosed at the site, they will receive study intervention directly from the
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the 
electronic case report form (eCRF). The dose of study intervention and study subject
identification will be confirmed at the time of dosing by a member of the study site staff other 
than the person administering the study intervention.

When subjects self-administer venetoclax at home, compliance with study intervention will be 
assessed at each visit. Compliance will be assessed by direct questioning, and counting 
returned tablets during the site visits, and documented in the source documents and relevant 
form. Deviation(s) from the prescribed dosage regimen should be recorded in the eCRF.

Accountability records of study interventions in respective sub-protocols dispensed and 
administered to each subject must be maintained and reconciled with study intervention and 
compliance records. Intervention start and stop dates, including dates for intervention delays 
and/or dose reductions, will also be recorded in the eCRF.
8
CONCOMITANT MEDICATIONS AND PROCEDURES
All medications (excluding prior cancer therapy for the tumor under evaluation) taken beginning 
when the subject signs the ICF and all concomitant therapy during the study 
 
 
  
All prior chemotherapy (biologic, immunologic, or radiation therapy) and anticancer surgery prior 
to the administration of either study drug, will be recorded in the appropriate section of the eCRF. 
Packed red cell and platelet transfusion history 
 
The Investigator will instruct subjects to notify the study staff about any new medications taken 
after signing the ICF. All medications and significant non-drug therapies (herbal medicines, 
physical therapy, etc.) and any changes in dosing with existing medications will be documented 
on the eCRFs. 
8.1
Permitted Concomitant Medications and Procedures
Subject to the precautions described in Section 8.2, the use of any concomitant medication or 
therapies deemed necessary for the care of the subject should be used. Repeat PK evaluations may 
be conducted if changes are made to concomitant medications suspected of affecting drug 
absorption or metabolism.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
135
Prophylactic and/or therapeutic use of medications (eg, antiemetics for nausea and vomiting, 
antidiarrheals for diarrhea, laxatives and/or stool softeners for constipation) for gastrointestinal 
disorders are permitted.
Parenteral flu vaccination is permitted.
Routine infectious disease 
 
 
Subjects may receive authorized or approved COVID-19 vaccines while continuing on study 
treatment at the discretion of the Investigator. COVID-19 vaccines that are NOT live are allowed 
and should be handled in the same manner as other vaccines. Administration may occur during the 
study, including during the administration of the BMS study treatment and after the last 
administration of the BMS study treatment.
Treatment of active SARS-CoV-2 infections or high risk exposures, including use of 
investigational therapies, is allowed and should be discussed with the Sponsor’s medical monitor.
8.2
Prohibited Concomitant Medications and Procedures
Other investigational therapies must not be used while the subject is on the study.
Anticancer therapy (chemotherapy, biologic or investigational therapy, and surgery) other than the 
study treatments must not be given to subjects while the subject is on the study. If such treatment 
is required, the subject must be discontinued from the study. 
 
 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
136
 
 
 
 
 
 
 
 
 
 Temporary use of corticosteroids for concurrent illnesses (eg, food 
allergies, pneumonitis, etc.) are acceptable upon discussion with the Sponsor’s Medical Monitor.
The administration of investigational COVID-19 vaccines is not allowed during the study. Live 
COVID-19 vaccines should not be administered to a subject during the study, including during the 
treatment, safety follow-up period and 
 following the last dose of study drug. In 
addition, the administration of a live COVID-19 vaccine is prohibited 
 prior to 
initiation of study treatment.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
137
Table 12:
Management of Potential Venetoclax Interactions with CYP3A and 
P-gp Inhibitors
Cycle Day
Moderate CYP3A or 
P-gp Inhibitora
Strong CYP3A 
Inhibitors (Other than 
Posaconazole)b
Posaconazolec
Day 1
50 mg
10 mg
10 mg
Day 2
100 mg
20 mg
20 mg
Day 3
200 mg
50 mg
50 mg
Day 4 and beyond
200 mg
100 mg
70 mg
Abbreviations: CYP = cytochrome P450; P-gp = P-glycoprotein.
a Following discontinuation of the CYP3A or P-gp inhibitor: 2 to 3 days after the inhibitor is discontinued, resume 
the venetoclax dose that was used prior to initiating the CYP3A or P-gp inhibitor.
b For subjects who have completed dose escalation and are on a steady daily venetoclax dose, reduce the venetoclax
dose to 100 mg once daily when a strong CYP3A inhibitor (other than posaconazole) must be used concurrently.
c For subjects who have completed dose escalation and are on a steady daily venetoclax dose, reduce the venetoclax
dose to 70 mg once daily when posaconazole must be used concurrently.

Based on in vitro data, azacitidine metabolism does not appear to be mediated by CYPs; 
therefore, CYP inhibitors and inducers are unlikely to have any impact on the metabolism of 
azacitidine. Clinically relevant inhibitory or inductive effects of azacitidine on the metabolism 
of CYP substrates are unlikely.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
138
 
 
9
STATISTICAL CONSIDERATIONS
9.1
Overview
Study CA059-001 is a multi-center, open-label, three-part, Phase 1, dose finding study to 
determine the safety, tolerability, PK, and PD of CC-95251 both alone and in combination with 
antineoplastic agents in subjects with R/R AML and R/R or treatment-naïve MDS or TN AML. 
The study will consist of dose escalation (Part A) and dose expansion (Parts B, C, and D). 
 
 to determine the preliminary RP2D of 
CC-95251 both alone and in combination with azacitidine in R/R AML and R/R (IPSS-R 
 
MDS subjects , and CC-99251 in combination with axacitidine and venetoclax in RR AML. Part 
B further evaluates the safety and efficacy of CC-95251 alone and in combination with azacitidine 
in R/R AML and R/R (IPSS-R 
 MDS subjects. Part C evaluates the safety and efficacy of 
CC-95251 in combination with azacitidine in treatment-naïve MDS (IPSS-R 
 subjects. Part 
D consists of a dose expansion in combination with injectable azacitidine and venetoclax (triple 
combination) in subjects with TN AML ineligible for intensive chemotherapy. One or more dosing 
regimens from Part A may be selected for cohort expansion in Parts B, C, and D
 
.
Data from all sites will be combined for the final analysis. Results will be presented using 
descriptive statistics. Statistical analyses will be performed by drug combination and dose level 
(Part A) and by cohort (Parts B, C, and D) as needed or applicable. In the dose escalation (Part A) 
of the trial, summaries will be prepared by dose level and overall. 
 
 
 
 In the treatment-naïve MDS (IPSS-R 
 
dose expansion (Part C) and treatment-naive AML dose expansion (Part D) of the trial, summaries 
will be prepared by cohort and overall.  
All analyses will be descriptive in nature. Summary tables for continuous variables will contain 
the following statistics: n (the corresponding sample size), mean, median, standard deviation (SD), 
minimum (min), and maximum (max). Summary tables for categorical variables will include n, 
percentage, and 
confidence intervals on the percentage as appropriate. 
Unless otherwise indicated, 
 confidence intervals for 
 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
139
9.2
Study Population Definitions
Table 13:
Definition of study population
Population
Description
Enrolled 
Safety (all treated)
Efficacy Evaluable (EE)
Pharmacokinetic (PK) 
population
Biomarker evaluable (BE) 
population
Abbreviations: BE = biomarker evaluable; EE = efficacy evaluable; PK = pharmacokinetic.
9.3
Sample Size and Power Considerations
During Part A of the study (dose escalation), 
 
 evaluable subjects are treated at a dose level
The proposed dose levels for testing the CC-95251 monotherapy include a 
 20 mg/kg, 
 
30 mg/kg 
 10 mg/kg, 
, and the 
total estimated subjects will be 
for CC-95251 monotherapy
 An 
intermediate dose may be investigated if 
 is not tolerated while 
 is tolerated. In the event 
the 
 is not tolerated in the CC-95251 monotherapy cohort, 
 may be recommended by the 
SRC. 
The proposed dose levels for CC-95251 in combination with azacitidine include a 
10 
mg/kg, 
 20 mg/kg, 
 30 mg/kg, 
 3 mg/kg, 
, and the total estimated 
subjects will be 
for CC-95251 in combination with azacitidine
 In the 
event the DL1a is not tolerated in the CC-95251 plus azacitidine cohort, DL1a may be 
recommended by the SRC.
The proposed dose levels for CC-95251 in combination with azacitidine and venetoclax include a 
20 mg/kg 
 30 mg/kg QW; and 
 10 mg/kg, 
; and the total estimated subjects will be 
for CC-95251 in combination with azacitidine and venetoclax. In the event that 
DL1b is not tolerated in the CC-95251 plus azacitidine and venetoclax cohort, DL1b may be 
recommended by the SRC. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
140
In Part B, approximately 
 subjects per cohort will be enrolled to further evaluate the safety and 
assess the efficacy of CC-95251 alone and in combination with azacitidine in R/R AML and R/R
MDS (IPSS-R 
 at the preliminary RP2D established in dose escalation, or at an alternative 
tolerable dose and schedule based on review of available safety, PK, PD, and preliminary efficacy
data from Part A.
 
 
 
Enrollment in Part C may start only after 
 (cumulatively between Parts A and B) 
with relapsed/refractory MDS have been treated at the proposed Part C expansion dose and 
schedule of CC-95251 plus azacitidine. The SRC will review the safety data from this group of 
subjects utilizing 
 prior to the 
opening of the Part C expansion. The dose of CC-95251 selected for Part C may occur at the 
preliminary RP2D established in dose escalation, or at an alternative tolerable dose based on 
review of available safety, PK, PD, and preliminary efficacy data. 
The Part C expansion will initially evaluate 
 with treatment-naïve MDS treated 
 
 The SRC will review the available safety utilizing 
 
, PK, PD and preliminary efficacy data in the 
 
to determine if the dose and schedule is tolerated prior to escalating the CC-95251 dose to the 
proposed Part C expansion dose and schedule. A lower dose of CC-95251 plus azacitidine may be 
selected for continued enrollment in the expansion based on SRC review of the available data from 
. Thereafter, a total of approximately 
 additional subjects with 
treatment-naïve MDS may be enrolled in Part 
 
 During enrollment in Part C the SRC will review available safety data 
from 
 
 
 
 
 
 
Approximately 
 subjects with treatment-naïve MDS will be enrolled in the Part C expansion. 
The preliminary efficacy data for dose cohorts in Part C may be combined for analysis.
In the Part D expansion, 
 will be enrolled at the preliminary RP2D established in 
dose escalation, or at an alternative tolerable dose and schedule based on review of available safety, 
PK, PD, and preliminary efficacy data from Part A.  Thereafter, an additional approximately 
 
subjects will be enrolled for the sample size of an initial 
 response-evaluable subjects dosed at 
the proposed expansion dose to further evaluate the safety and estimate the preliminary efficacy 
of triple combination.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
141
During enrollment in Part D the SRC will review available safety data from 
 
 
 
 
 
 
If the
efficacy assessment on the 
 response-evaluable subjects provides an initial evidence for
preliminary efficacy, 
 will be enrolled to further 
evaluate safety and efficacy, Therefore, approximately 
response-evaluable subjects with 
treatment-naïve AML will be enrolled in the Part D expansion.
 
 
9.4
Background and Demographic Characteristics
In Part A, the baseline characteristics of subjects will be summarized by drug combination and 
dose level for the enrolled population. In Parts B, C, and D the baseline characteristics of subjects 
will be summarized by cohort. Subject’s age, height, weight, and baseline characteristics will be 
summarized using descriptive statistics, while sex, race and other categorical variables will be 
provided using frequency tabulations. Medical history data will be summarized using frequency 
tabulations by MedDRA system organ class and preferred term.
9.5
Subject Disposition
Subject disposition (analysis population allocation, ongoing, discontinued, along with primary 
reason) from treatment and study will be summarized using frequency and percent. A summary of 
subjects enrolled by site will be provided. Protocol deviations will be summarized using frequency 
tabulations. Supportive corresponding subject listings will also be provided.
9.6
Efficacy Analysis
The key efficacy variables are CRR (defined as CR + CRi + CRh for AML; CR for MDS) and 
ORR (all responses of CR [ie, CRMRD-, morphologic CR, CRh, CRi] + MLFS + PR for AML and 
CR + CRh + marrow CR + PR for MDS) by disease -appropriate response criteria. For dose 
expansion, efficacy variables to be analyzed include CRR and ORR, duration of remission, 
duration of response, stable disease rate (MDS only), relapse-free survival, event-free survival, 
progression-free survival, time to remission/response, transfusion independence, time to AML 
transformation for MDS subjects, and OS rates at 6 and 12 months. Point estimates and 2-sided 
90% exact Clopper-Pearson confidence intervals of CRR and ORR will be reported. For time to 
event endpoints, Kaplan-Meier survival analyses will be performed. The PFS and overall survival 
rate will be measured and reported at pre-specified time points (ie, 6 months, 12 months).
Exploration of PK, PD, safety and activity relationships may be assessed.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
142
9.7
Safety Analysis
The primary objective of this study is to define the RP2D of CC-95251 alone and in combination 
with azacitidine in eligible subjects with AML or MDS and in combination with azacitidine and 
venetoclax in eligible subjects with AML. 
 
 
 
 
 
 The 
final determination of RP2D will be decided by the SRC. 
Statistical analyses will be performed by dose level or dose schedule and a combination product 
as needed or applicable. Study data will be summarized for disposition, demographic and baseline 
characteristics, exposure, efficacy, safety, PK, and PD per respective analysis population defined 
in Section 9 as applicable. All analyses will be descriptive in nature.
Adverse events, including treatment-emergent adverse events, will be graded by NCI CTCAE 
version 5 grades, except for CRS and TLS, which will be graded according to the revised CRS 
grading system ([Lee, 2014] and Cairo-Bishop TLS grading system [Cairo, 2004], respectively). 
The frequency of AEs will be tabulated by Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class and preferred term. Grade 3 or higher AEs, AEs leading to 
discontinuation of study treatment or to death, study intervention-related AEs, and SAEs will be 
tabulated separately. Changes from baseline in selected laboratory analytes for example 
transfusion dependence (platelet count or red blood cell [RBC] transfusion units), vital signs, and 
 will be summarized.
.
9.9
Other Topics
9.9.1
Statistical Method for Dose Escalation
Dose-escalation/de-escalation decisions 
 
 
 
In
 the columns indicate numbers of evaluable subjects treated at each dose level, and 
 
 
 
 Dose escalation may be halted once a dose level with 
acceptable safety and satisfactory antitumor activity has been selected for evaluation in the dose 
expansion part.
Dose escalation (Part A) may be stopped for the following reasons:
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
143
 
 
 The final determination of RP2D will be decided 
by the SRC. Each dose level may enroll 
with the potential to expand to
approximately
 in order to further inform selection of dose and schedule for dose 
expansion. Enrollment to the highest open dose level will be prioritized if multiple dose levels are 
open for enrollment.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
144
9.9.2
Stopping Rules Regarding Toxicity in Dose Expansion
During the dose expansion (Parts B, C, and D), a non-binding
 safety monitoring method 
will be utilized to continuously monitor for excessive toxicities defined as the occurrence of AEs 
. The SRC will also utilize this method 
to monitor for excessive toxicities in subjects with relapsed/refractory MDS 
 
 prior to the opening of Part C and D expansion. 
 
 
After a 
 have enrolled and completed at least one cycle of study treatment, 
the following non-binding 
 stopping criterion to pause the trial based on the posterior 
distribution of excessive toxicity will be calculated. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
145
 
Regular systematic review of SAEs will serve as the basis for pausing enrollment or prematurely 
stopping the study. Review of these SAEs, and any decision to pause enrollment or terminate the 
study, will be determined by the SRC. Decisions to pause enrollment or terminate the study will 
be communicated promptly to Investigators, to the IRBs and to the appropriate regulatory 
authorities.
9.9.3
Assessment of Pharmacokinetics
Plasma PK parameters such as Cmax, Cmin, AUC, tmax, and CLT of CC-95251 where feasible will 
be calculated by the noncompartmental analysis
(NCA)
method from the plasma 
concentration-time profiles of CC-95251. Other PK parameters may be calculated as appropriate. 
In addition to the NCA analysis, compartmental analysis may be conducted to estimate PK 
parameters based on all cycle data for each subject and/or the cohorts.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
146
Summary statistics including number of subjects (N), mean, SD, coefficient of variation (CV%), 
geometric mean, geometric CV%, median, minimum, and maximum will be provided for 
CC-95251 concentration by nominal time point, study day, and dose cohort. Mean and individual 
plots of plasma concentrations will be presented in both original and semi-logarithmic scales. 
Summary statistics will also be provided for CC-95251 PK parameters by study day and dose 
cohort and be presented in tabular form.
9.9.4
Assessment of Immunogenicity
The incidence of ADAs will be summarized for the Safety Population. In addition, subjects who 
are positive for ADAs will also be listed. Potential relationships between ADA and safety and 
efficacy will be assessed.
9.9.5
Assessment of Pharmacodynamics and Exploratory Biomarkers
Descriptive statistics (N, mean, SD, median, min, and max) will be provided for baseline, 
post-baseline values, and changes from baseline or percent change from baseline for biomarkers 
including receptor occupancy and cytokines by dose cohort (Part A) and visit. Subjects’ biomarker 
results over time will be plotted. Comparison of biomarker levels before and during treatment will 
be performed by Wilcoxon signed rank test. If sufficient and valid results from biomarker assays 
can be obtained, the relationship between percent changes in biomarker levels and clinical 
endpoints including ORR may be explored. 
9.9.6
Assessment of Other Exploratory Endpoints
Proportion of subjects achieving MRD negativity at any time on/after treatment with CC-95251 
alone, in combination with azacitidine and in combination with azacitidine and venetoclax will be 
summarized for the Safety and Efficacy Evaluable Populations. Point estimates and 2-sided 95% 
confidence intervals of CRMRD- rates will be reported.
9.10
Safety Review Committee
The SRC membership will be comprised of Investigators (and/or designated representatives), the 
Sponsor’s Medical Monitor, safety physician, clinical scientist, and the study manager. Ad hoc 
attendees may include the study PK scientist, biostatistician, and translational research scientist. 
Other internal and external experts may be consulted by the SRC, as necessary.
The SRC will recommend dose escalation/de-escalation decisions in Part A. The decision to 
evaluate additional subjects within a dose cohort, smaller dose increments, alternate dosing 
schedules, or make a recommendation of the preliminary dose and schedule of CC-95251 to test 
in the expansion cohorts (Parts B and C) will also be at the discretion of the SRC, based on their 
review of available safety, tolerability, PK, PD, and preliminary efficacy. During dose expansion 
phase, the SRC will continue to review safety data regularly throughout the study and make 
recommendations about study continuation, dose modification and establishment of a RP2D as 
appropriate.
All decisions made by the SRC at the dose escalation meetings will be formally documented (via 
meeting minutes and memos) and circulated to all sites in writing. No dose escalation, de-
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
147
escalation, change of dosing schedule, or expansion of existing dose cohorts will commence prior 
to written notification having been sent to participating sites of the respective SRC decision(s).
The meeting frequency will depend on enrollment rate and when dosing decision milestones are 
reached in the dose escalation part and when a meaningful amount, as decided by the SRC, of 
safety/efficacy data are available after dose escalation.
The Sponsor has implemented a comprehensive safety process that is appropriate in managing 
subject safety at this stage of development: a multi-layered process to ensure safety monitoring 
through close collaboration of study site investigators, the BMS study team, and the Worldwide 
Patient Safety-led SMT. To support safety oversight, the Sponsor has established processes for 
collection, ongoing review, analysis, and submission of individual AE reports and their aggregate 
analyses. Because this is an open-label study, the BMS safety physicians, Medical Monitors, and 
the investigators will have access to all data necessary for real-time safety evaluation.
10
ADVERSE EVENTS
10.1
Monitoring, Recording and Reporting of Adverse Events
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in 
a subject during the course of a study. It may be a new intercurrent illness, a worsening 
concomitant illness, an injury, or any concomitant impairment of the subject’s health, including 
laboratory test values (as specified by the criteria in Section 10.3), regardless of etiology. Any 
worsening (ie, any clinically significant adverse change in the frequency or intensity of a 
pre-existing condition) should be considered an AE. A diagnosis or syndrome should be recorded 
on the AE page of the CRF rather than the individual signs or symptoms of the diagnosis or 
syndrome. 
Abuse, withdrawal, sensitivity, or toxicity to an investigational product should be reported as an 
AE. Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported on the overdose CRF. (See Section 7.2.7.10 for the definition of overdose). Any sequela 
of an accidental or intentional overdose of an investigational product (IP) which meets the 
definition of an adverse event, should be reported as an AE on the CRF. If the sequela of an 
overdose meets serious criteria, then it must be marked as serious on the CRF. The overdose itself
should not be reported as an AE.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for CC-95251 overdose. 
Actual treatment should depend on the severity of the clinical situation and the judgment and 
experience of the treating physician.
All subjects will be monitored for AEs during the study.  Assessments may include monitoring of 
any or all of the following parameters:  the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other tests and/or 
procedures.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
148
All AEs will be recorded by the Investigator from the time the subject signs informed consent until 
 after the last dose of study drug. In addition, SAEs made known to the Investigator at any 
time thereafter that are suspected of being related to IP will be reported until such SAEs have 
recovered (returned to baseline), recovered with sequelae, or death (due to the SAE). All adverse 
events (serious/non-serious) will be recorded on the CRF and in the subject’s source documents. 
Refer to Section 10.5 for instructions on how to report SAEs to Drug Safety. 
Subjects will be followed for all SAEs, and AEs (SAEs and non-serious AEs) associated with 
confirmed or suspected SARS-CoV-2 infection until resolution, the condition stabilizes, the event 
is otherwise explained, the event is deemed irreversible, the subject is lost to follow-up, or for 
suspected cases, until SARS-CoV-2 infection is ruled out.
10.2
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
10.2.1
Seriousness 
An SAE is any AE occurring at any dose that:

Results in death;

Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate risk of 
death from the AE);

Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization 
is defined as an inpatient admission, regardless of length of stay);

Results in persistent or significant disability/incapacity (a substantial disruption of the subject’s 
ability to conduct normal life functions);

Is a congenital anomaly/birth defect;

Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life-
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.  Medical 
and scientific judgment should be exercised in deciding whether such an AE should be considered
serious.
Events not considered to be SAEs are hospitalizations for:

a standard procedure for protocol therapy administration. However, hospitalization or 
prolonged hospitalization for a complication of therapy administration will be reported as an 
SAE. 

routine treatment or monitoring of the studied indication not associated with any deterioration 
in condition.

the administration of blood or platelet transfusion as routine treatment of studied indication. 
However, hospitalization or prolonged hospitalization for a complication of such transfusion 
remains a reportable SAE.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
149

a procedure for protocol/disease-related investigations (eg, surgery, scans, endoscopy, 
sampling for laboratory tests, bone marrow sampling). However, hospitalization or prolonged 
hospitalization for a complication of such procedures remains a reportable SAE.

hospitalization or prolongation of hospitalization for technical, practical, or social reasons, in 
absence of an AE.

a procedure that is planned (ie, planned prior to start of treatment on study); must be 
documented in the source document and the CRF. Hospitalization or prolonged hospitalization 
for a complication remains a reportable SAE.

an elective treatment of or an elective procedure for a pre-existing condition, unrelated to the 
studied indication, that has not worsened from baseline. 

emergency outpatient treatment or observation that does not result in admission, unless 
fulfilling other seriousness criteria above.
For each AE, the Investigator will provide information on severity, start and stop dates, 
relationship to the IP, action taken regarding the IP, and outcome.
10.2.2
Severity/Intensity
For each AE, the Investigator must assess the severity/ intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
current active minor version of the Common Terminology Criteria for Adverse Events (CTCAE, 
Version 5.0); 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm
AEs that are not defined in the CTCAE should be evaluated for severity/intensity according to the 
following scale:

Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required

Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be needed; 
no or minimal medical intervention/therapy required

Grade 3 = Severe – marked limitation in activity, some assistance usually required; medical 
intervention/therapy required, hospitalization is possible

Grade 4 = Life-threatening – extreme limitation in activity, significant assistance required; 
significant medical intervention/therapy required, hospitalization or hospice care probable

Grade 5 = Death – the event results in death
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.  
Seriousness, not severity, serves as a guide for defining regulatory obligations.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
150
10.2.3
Causality
The Investigator must determine the relationship between the administration of the IP and the 
occurrence of an AE as Not Suspected or Suspected as defined below:
Not suspected:
a causal relationship of the adverse event to IP administration is 
unlikely or remote, or other medications, therapeutic 
interventions, or underlying conditions provide a sufficient 
explanation for the observed event.
Suspected:
there is a reasonable possibility that the administration of IP 
caused the adverse event.  ‘Reasonable possibility’ means there 
is evidence to suggest a causal relationship between the IP and 
the adverse event.
Causality should be assessed and provided for each AE based on currently available information.  
Causality is to be reassessed and provided as additional information becomes available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP that 
has not been manufactured or provided by the Sponsor, please provide the name of the 
manufacturer when reporting the event.
10.2.4
Duration
For each AE, the Investigator will provide a record of the start and stop dates of the event.
10.2.5
Action Taken
The Investigator will report the action taken with IP as a result of each AE, as applicable (eg, 
discontinuation, interruption, or dose reduction of IP, as appropriate) and report if concomitant 
and/or additional treatments were given for the event. 
10.2.6
Outcome
The Investigator will report the outcome of the event for each AE.
All SAEs that have not resolved upon discontinuation of the subject’s participation in the study 
must be followed until recovered (returned to baseline), recovered with sequelae, or death (due to 
the SAE).
10.3
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:

results in discontinuation from the study;

requires treatment, modification/ interruption of IP dose, or any other therapeutic intervention; 
or

is judged to be of significant clinical importance, eg, one that indicates a new disease process 
and/or organ toxicity, or is an exacerbation or worsening of an existing condition.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
151
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion need 
to be documented as a serious adverse event.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded as the AE.  If the abnormality was not a part of a diagnosis or 
syndrome, then the laboratory abnormality should be recorded as the AE. If possible, the laboratory 
abnormality should be recorded as a medical term and not simply as an abnormal laboratory result 
(eg, record thrombocytopenia rather than decreased platelets).
10.4
Pregnancy
All pregnancies or suspected pregnancies occurring in either a SCBP or partner of childbearing 
potential of a subject are immediately reportable events.  
The exposure of any pregnant individual (eg, caregiver, pharmacist, study coordinator, or monitor) 
to IP is also an immediately reportable event.
10.4.1
Subjects of Childbearing Potential
Pregnancies and suspected pregnancies (including elevated βhCG or positive pregnancy test in a 
SCBP regardless of disease state) occurring while the subject is on IP, or within
 of the 
subject’s last dose of CC-95251 or 6 months of the subject’s last dose of azacitidine (or longer if 
required by local regulations), are considered immediately reportable events. Investigational 
product is to be discontinued immediately. The pregnancy, suspected pregnancy, or positive 
pregnancy test must be reported to the Sponsor’s Drug Safety immediately by email, phone or 
facsimile, or other appropriate method, using the Pregnancy Initial Report Form, or approved 
equivalent form.  
The SCBP may be referred to an obstetrician-gynecologist or another appropriate healthcare 
professional for further evaluation.
The Investigator will follow the SCBP until completion of the pregnancy and must notify the 
Sponsor’s Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form, or approved equivalent form.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator should 
report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious criteria, 
it must be reported as an SAE to the Sponsor’s Drug Safety within 24 hours of the Investigator’s 
knowledge of the event.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as an SAE. In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the IP should also be reported as an SAE to the Sponsor’s Drug 
Safety within 24 hours of the Investigator’s knowledge of the event.
10.4.2
Subjects Who Are Able to Impregnate Their Partner
If a partner of childbearing potential of a subject taking IP becomes pregnant, the subject taking 
IP should notify the Investigator, and the pregnant partner should be advised to call their healthcare 
provider immediately.  
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
152
10.5
Reporting of Serious Adverse Events
Any AE that meets any serious criterion requires reporting as an SAE within 24 hours of the 
Investigator’s knowledge of the event. This instruction pertains to initial SAE reports as well as 
any follow-up reports.
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent until 
 after the last dose of IP) or any 
SAE made known to the Investigator at any time thereafter that are suspected of being related to 
IP. Serious adverse events occurring prior to treatment (after signing the ICF) are to be recorded 
within the CRF, but do not require reporting to the Sponsor’s Drug Safety.
Where required by local legislation, the Investigator is responsible for informing the Institutional 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant initial 
and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with the Sponsor and the IRB/EC.
The SAE is recorded within the CRF, and the data is transmitted electronically to the Sponsor’s
Drug Safety. In the event electronic transmission is not available, a paper SAE Report Form will 
be completed and sent directly to the Sponsor’s Drug Safety, ensuring the event is recorded on the 
CRF as well.
10.6
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, the Sponsor’s Drug Safety will determine the expectedness 
of events suspected of being related to CC-95251 based on the Investigator Brochure and 
azacitidine based on SmPC.
In the United States, expedited reports sent to the FDA by the sponsor based on the reasonable 
possibility threshold are known as ‘IND safety reports’ and will be reported in accordance with 21 
CFR 312.32.
For reporting to the FDA, events that are not suspected to be causally related to CC-95251 and 
azacitidine by the sponsor will not be considered adverse reactions. 
For countries within the European Economic Area (EEA), the Sponsor or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics Committees 
concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance with 
Directive 2001/20/EC and the Detailed Guidance on collection, verification and presentation of 
adverse reaction reports arising from clinical trials on investigational products for human use 
(ENTR/CT3) and also in accordance with country-specific requirements.  
The Sponsor or its authorized representative shall notify the Investigator of the following 
information:

Any AE suspected of being related to the use of IP in this study or in other studies that is both 
serious and unexpected (ie, SUSAR);

Any finding from tests in laboratory animals that suggests a significant risk for human subjects 
including reports of mutagenicity, teratogenicity, or carcinogenicity.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
153
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of these 
new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with the IRB/EC. (See Section 13.3 for record retention information).
The Sponsor’s Drug Safety Contact Information:
For the Sponsor’s Drug Safety contact information, please refer to the Serious Adverse Event 
Report Form Completion Guidelines or to the Pregnancy Report Form Completion Guidelines.
11
DISCONTINUATIONS
11.1
Treatment Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the 
investigational product(s):

Adverse Event

Withdrawal by subject

Completed

Progressive disease

Treatment failure

Pregnancy

Death

Lost to follow-up

Physician decision

Other (to be specified on the CRF)
The reason for discontinuation of treatment should be recorded in the CRF and in the source 
documents.
The decision to discontinue a subject from treatment remains the responsibility of the treating 
physician, which will not be delayed or refused by the Sponsor.  However, prior to discontinuing 
a subject, the Investigator may contact the Sponsor’s Medical Monitor and forward appropriate 
supporting documents for review and discussion.
11.2
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the study:

Screen failure

Withdrawal by subject

Completed

Death

Lost to follow-up
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
154

Other (to be specified on the CRF)
The reason for study discontinuation should be recorded in the CRF and in the source documents.
11.3
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page).
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on the 
Emergency Contact Information page of the protocol (after title page). This global Emergency Call 
Center is available 24 hours a day and 7 days a week. The representatives are responsible for 
obtaining your call-back information and contacting the on-call Sponsor/contract research 
organization Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Sponsor’s Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
11.4
Emergency Identification of Investigational Products
This is an open-label study; therefore, IP will be identified on the package labeling.
12
REGULATORY CONSIDERATIONS
12.1
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that the Sponsor, its authorized representative, 
and Investigator abide by Good Clinical Practice (GCP), as described in International Conference 
on Harmonisation (ICH) Guideline E6 and in accordance with the general ethical principles 
outlined in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The Investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
12.2
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in the 
local regulations. The Sponsor’s staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions, 
including obligations of confidentiality of the Sponsor’s information. The Investigator should 
maintain a list of Sub-investigators and other appropriately qualified persons to whom he or she 
has delegated significant study-related duties.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
155
The Investigator is responsible for keeping a record of all subjects who sign an ICF and are 
screened for entry into the study. Subjects who fail screening must have the reason(s) recorded in 
the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification.  The Investigator must ensure timely and accurate completion of CRFs and queries.
The information contained in the protocol and amendments (with the exception of the information 
provided by the Sponsor on public registry websites) is considered the Sponsor’s confidential 
information.  Only information that is previously disclosed by the Sponsor on a public registry 
website may be freely disclosed by the Investigator or its institution, or as outlined in the Clinical 
Trial Agreement.  The Sponsor’s protocol, amendment and IB information is not to be made 
publicly available (for example on the Investigator’s or their institution’s website) without express 
written approval from the Sponsor.  Information proposed for posting on the Investigator’s or their 
institution’s website must be submitted to the Sponsor for review and approval, providing at least 
5 business days for review.
At the time results of this study are made available to the public, the Sponsor will provide 
Investigators with a summary of the results that is written for the lay person. The Investigator is 
responsible for sharing these results with the subject and/or their caregiver as agreed by the subject.
12.3
Subject Information and Informed Consent
The Investigator must obtain informed consent of a subject and/or a subject’s legal representative 
prior to any study related procedures.
Documentation that informed consent occurred prior to the study subject’s entry into the study and 
of the informed consent process should be recorded in the study subject’s source documents 
including the date.  The original ICF signed and dated by the study subject and by the person 
consenting the study subject prior to the study subject’s entry into the study, must be maintained 
in the Investigator’s study files and a copy given to the study subject.  In addition, if a protocol is 
amended and it impacts on the content of the informed consent, the ICF must be revised.  Study 
subjects participating in the study when the amended protocol is implemented must be re-
consented with the revised version of the ICF.  The revised ICF signed and dated by the study 
subject and by the person consenting the study subject must be maintained in the Investigator’s 
study files and a copy given to the study subject.
12.4
Confidentiality
The Sponsor affirms the subject’s right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). The Sponsor
requires the Investigator to permit the Sponsor’s representatives and, when necessary, 
representatives from regulatory authorities, to review and/or copy any medical records relevant to 
the study in accordance with local laws.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
156
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in writing 
from the appropriate individual.
12.5
Protocol Amendments
Any amendment to this protocol must be approved by the Sponsor’s Clinical Research 
Physician/Medical Monitor.  Amendments will be submitted to the IRB/EC for written approval.  
Written approval must be obtained before implementation of the amended version occurs.  The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC for 
information purposes.
12.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval
Before the start of the study, the study protocol, ICF, and any other appropriate documents will be 
submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their dates 
of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is sought. 
If applicable, the documents will also be submitted to the authorities in accordance with local legal 
requirements.
IP can only be supplied to an Investigator by the Sponsor or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by the 
Sponsor or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. Formal 
approval by the IRB/EC should mention the protocol title, number, amendment number (if 
applicable), study site (or region or area of jurisdiction, as applicable), and any other documents 
reviewed. It must mention the date on which the decision was made and must be officially signed 
by a committee member. Before the first subject is enrolled in the study, all ethical and legal 
requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised.
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by the Sponsor and the 
IRB/EC prior to use. 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
157
12.7
Ongoing Information for Institutional Review Board/ Ethics Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:

Information on serious or unexpected adverse events as soon as possible; 

Periodic reports on the progress of the study;

Deviations from the protocol or anything that may involve added risk to subjects.
12.8
Termination of the Study
The Sponsor reserves the right to terminate this study prematurely at any time for reasonable 
medical or administrative reasons. Any premature discontinuation will be appropriately 
documented according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the Investigator or the Sponsor has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as:
13
DATA HANDLING AND RECORDKEEPING 
13.1
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the study 
and the distribution of the investigational product are complete, accurate, filed and retained.  
Examples of source documents include hospital records; clinic and office charts; laboratory notes; 
memoranda; subject’s diaries or evaluation checklists; dispensing records; recorded data from 
automated instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy, and the laboratories, as well 
as copies of CRFs or CD-ROM.
13.2
Data Management
Data will be collected via CRF and entered into the clinical database per the Sponsor’s SOPs. This 
data will be electronically verified through use of programmed edit checks specified by the clinical 
team.  Discrepancies in the data will be brought to the attention of the clinical team, and 
investigational site personnel, if necessary.  Resolutions to these issues will be reflected in the 
database.  An audit trail within the system will track all changes made to the data.
13.3
Record Retention
Essential documents must be retained by the Investigator according to the period of time outlined 
in the clinical trial agreement. The Investigator must retain these documents for the time period 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
158
described above or according to local laws or requirements, whichever is longer. Essential 
documents include, but are not limited to, the following:

Signed ICFs for all subjects;

Subject identification code list, screening log (if applicable), and enrollment log;

Record of all communications between the Investigator and the IRB/EC;

Composition of the IRB/EC;

Record of all communications between the Investigator, the Sponsor, and their authorized 
representative(s);

List of Sub-investigators and other appropriately qualified persons to whom the Investigator 
has delegated significant study-related duties, together with their roles in the study, curriculum 
vitae, and their signatures;

Copies of CRFs (if paper) and of documentation of corrections for all subjects;

IP accountability records;

Record of any body fluids or tissue samples retained;

All other source documents (subject records, hospital records, laboratory records, etc.); 

All other documents as listed in Section 8 of the ICH consolidated guideline on GCP (Essential 
Documents for the Conduct of a Clinical Trial).
The Investigator must notify the Sponsor if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.  
The Investigator must obtain approval in writing from the Sponsor prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask the Sponsor
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator or institution should take measures to prevent accidental or premature destruction of 
these documents.
14
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by the Sponsor or its authorized representative 
for compliance with applicable government regulations with respect to current GCP and SOPs.
14.1
Study Monitoring and Source Data Verification
The Sponsor ensures that appropriate monitoring procedures are performed before, during and 
after the study.  All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an Investigators’ Meeting.  Prior to enrolling subjects into the study, a 
Sponsor representative will review the protocol, CRFs, procedures for obtaining informed consent, 
record keeping, and reporting of AEs/SAEs with the Investigator. 
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
159
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan.
Accuracy will be checked by performing source data verification that is a direct comparison of the 
entries made onto the CRFs against the appropriate source documentation.  Any resulting
discrepancies will be reviewed with the Investigator and/or his/her staff.  Any necessary 
corrections will be made directly to the CRFs or via queries by the Investigator and/or his/her staff. 
Monitoring procedures require that informed consents, adherence to inclusion/exclusion criteria 
and documentation of SAEs and their proper recording be verified.  Additional monitoring 
activities may be outlined in a study-specific monitoring plan.
14.2
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance unit 
exists within the Sponsor.  Representatives of this unit will conduct audits of clinical research 
activities in accordance with the Sponsor’s standard operating procedures (SOPs) to evaluate 
compliance with Good Clinical Practice guidelines and regulations.
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of study subject participation for audits 
and inspections by IRB/ECs, regulatory authorities (eg, FDA, EMA, Health Canada) and company 
authorized representatives.  The Investigator should make every effort to be available for the audits 
and/or inspections.  If the Investigator is contacted by any regulatory authority regarding an 
inspection, he/she should contact the Sponsor immediately.
14.3
Investigational Medicinal Product Quality Issues
Issues that call into question IP safety, purity, potency, quality and identity (eg, evidence of 
suspected tampering of product) must be reported as soon as possible to the study Clinical Trial 
Monitor and/or Clinical Trial Manager or designee. Report an issue or concern with all sponsor 
supplied IP suspected to have occurred before the product was transferred to the responsibility of 
the investigational site (eg, during manufacturing, packaging and labeling, storage, and/or 
distribution).
This includes suspected quality issues of components co-packaged with the drug, labelling, and IP 
device/drug combination products, and medical devices. 
In the event of a suspected product quality issue, the immediate action to be taken by site is to 
quarantine the affected product. Do not dispose of the product unless retention presents a risk to 
personnel (eg, cytotoxic, risk of injury from broken glass or sharps).
When reporting, provide as much product information as possible. Suspected IP quality issues will 
be investigated and a response will be provided back to the investigational site.
15
PUBLICATIONS
As described in Section 12.2, all protocol- and amendment-related information, with the exception 
of the information provided by the Sponsor on public registry websites, is considered the Sponsor’s
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
160
confidential information and is not to be used in any publications.  The Sponsor’s protocol-related 
information proposed for use in a publication must be submitted to the Sponsor for review and 
approval and should not be utilized in a publication without express written approval from the 
Sponsor, or as described in the Clinical Trial Agreement.
The Sponsor will ensure Sponsor-sponsored studies are considered for publication in the scientific 
literature in a peer-reviewed journal, irrespective of the results.  At a minimum, this applies to 
results from all Phase 3 clinical studies, and any other study results of significant medical 
importance.  This also includes results relating to investigational medicines whose development 
programs have been discontinued.
Study results may also be presented at one or more medical congresses and may be used for 
scientific exchange and teaching purposes.  Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as publication 
on health authority study registry websites, as required by local health authority regulations.
Eligibility for external authorship, as well as selection of first authorship, will be based on several 
considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, participation in study steering committee 
(when applicable) and contribution to abstract, presentation and/or publication development.
16
REFERENCES
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision 
to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 
2016; 127(20):2391-405. 
Benedetti FD, Brogan P, Grom A, Quartier P, Schneider R, De Graaf K, et al. OP0204 
Emapalumab, an interferon gamma (IFN-Y) blocking monoclonal antibody, in patients with 
macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis 
(SJIA). Annals of Rheumatic Diseases. 2019; 78:178.
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. Proposals for 
the classification of the myelodysplastic syndromes. Br J Haematol 1982;51(2):189-199.
Benson AB, Ajani JA, Catalano RB, Engelking C, Kornblau SM, Martenson JA, et al. 
Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol.
2004;22(14):2918-2926.
Bewersdorf JP, Carraway H, Prebet T. Emerging treatment options for patients with high-risk 
myelodysplastic syndrome. Ther Adv Hematol 2020a;11:1-22.
Bewersdorf, J. P., Giri, S., Wang, R., Williams, R. T., Tallman, M. S., Zeidan, A. M., & Stahl, M., 
et. al. Venetoclax as monotherapy and in combination with hypomethylating agents or low dose 
cytarabine in relapsed and treatment refractory acute myeloid leukemia: a systematic review and 
meta-analysis. Haematologica 2020b;105 :2659-63
Bloomfield CD, Estey E, Pleyer L, Schuh AC, Stein EM, Tallman M, et al. Time to repeal and 
replace response criteria for acute myeloid leukemia? Blood Rev 2018;32(5):416-25.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
161
Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, et al. 
Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol 
2005;23(9):1969-78.
Cairo MS, Bishop M. Tumour lysis syndrome:  new therapeutic strategies and classification. Br J 
Haematol 2004;127:3-11.
Cairo MS, Coiffier B, Reiter A, Younes A. Recommendations for the evaluation of risk and 
prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases:  an 
expert TLS panel consensus. Br J Haematol 2010;149:578-86.
Catenacci DVT and Schiller GJ. Myelodysplastic syndromes: A comprehensive review. Blood 
Rev 2005;19:301-19.
.
Chao MP, Alizadeh AA, Tang C, Myklebust JH, Varghese B, Gill S, Jan M, Cha AC, Chan CK, 
Tan BT, Park CY, Zhao F, Kohrt HE, Malumbres R, Briones J, Gascoyne RD, Lossos IS, Levy R, 
Weissman IL, Majeti R. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis 
and eradicate non-Hodgkin lymphoma. Cell. 2010 Sep 3;142(5):699-713.
Chao MP, Takimoto CH, Feng DD, McKenna K, Gip P, Liu J, Volkmer J, Weissman IL, Majeti 
R.  Therapeutic targeting of the macrophage immune checkpoint CD47 in myeloid malignancies.  
Front Immunol. 2020:9:1380.
Chao MP, Weissman IW, Majeti R. The CD47-SIRPα pathway in cancer immune evasion and 
potential therapeutic implications. Curr Opin Immunol 2012;24:225-32.
Cheson BD, Greenberg PL, Bennett JM, Löwenberg B, Wijermans PW, Nimer SD, et al. Clinical 
application and proposal for modification of the International Working Group (IWG) response 
criteria in myelodysplasia. Blood 2006;108(2):419-25.
Chen A, Harrabi O, Fong AP, Ruffner KL, Forgie AJ, Sim J, Randolph SS, et al.. Alx148 enhances 
the depth and durability of response to multiple aml therapies. Blood. 2020 Nov 5;136:15-6.
Daver, Naval, et al. "Phase I/II Study of Azacitidine (AZA) with Venetoclax (VEN) and 
Magrolimab (Magro) in Patients (pts) with Newly Diagnosed (ND) Older/Unfit or High-Risk 
Acute Myeloid Leukemia (AML) and Relapsed/Refractory (R/R) AML." Blood 140.Supplement 
1 (2022): 141-144.
DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, et al. Venetoclax combined 
with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. 
Blood 2019;133(1):7-17.
DiNardo CD, Jonas BA, Pullarkart V.et. al. Azacitidine and Venetoclax in Previously Untreated 
Acute Myeloid Leukemia, N Engl J Med 2020;383:617-29.
Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and 
management of AML in adults: 2017 ELN recommendations from an international expert panel. 
Blood 2017;129(4):424-47.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
162
Dombret H, Seymour J, Butrym A, Wierzbowska A, Selleslag D, Jang JH, et al. International phase 
3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML 
with >30% blasts. Blood 2015;126(3):291-9.
Dombret H, Raffoux E, Gardin C. Acute myeloid leukemia in the elderly. Sem Onc 
2008;35(4):430-8.
Edris B, Weiskopf K, Volkmer AK, Volkmer J-P, Willingham SB, Contreras-Trujillo H, et al. 
Antibody therapy targeting the CD47 protein is effective in a model of aggressive metastatic 
leiomyosarcoma. Proc Natl Acad Sci USA 2012;109(17):6656-61.
Estey E, Kornblau S, Pierce S, Kantarjian H, Beran M, Keating M. A stratification system for 
evaluating and selecting therapies in patients with relapsed or primary refractory acute 
myelogenous leukemia. Blood 1996;88(2):756.
Food and Drug Administration (FDA) grants regular approval to venetoclax in combination for 
untreated acute myeloid leukemia. 16 Oct 2020. Available from https://www.fda.gov/drugs/drug-
approvals-and-databases/fda-grants-regular-approvalvenetoclax-combination-untreated-acute-
myeloid-leukemia.
Fenaux P, Mufti G, Hellström-Lindberg E, Santini V, Gattermann N, Sanz G. Azacitidine prolongs 
overall survival (OS) and reduces infections and hospitalizations in patients (pts) with WHO-
defined acute myeloid leukemia (AML) compared with conventional care regimens (CCR). The 
American Society of Hematology 2008; Abstract 3636:1-2.
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of 
azacitidine compared with that of conventional care regimens in the treatment of higher-risk 
myelodysplastic syndromes: a randomized, open-label, phase III study. Lancet Oncol 
2009;10(3):223-32.
Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, et al. 
Azacitidine prolongs overall survival compared with conventional care regimens in elderly 
patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 2010;28(4): 562-
9.
Garbuzova-Davis S, Sanberg PR. Blood-CNS barrier impairment in ALS patients versus an animal 
model. Front Cell Neurosci 2014; 8:21.
Garcia-Manero, Guillermo, et al. "Evorpacept (ALX148), a CD47-Blocking Myeloid Checkpoint 
Inhibitor, in Combination with Azacitidine and Venetoclax in Patients with Acute Myeloid 
Leukemia (ASPEN-05): Results from Phase 1a Dose Escalation Part." Blood 140.Supplement 1 
(2022): 9046-9047.
Ghate D, Edelhauser HF. Ocular drug delivery. Expert Opin Drug Deliv 2006; 3(2):275-287.
Goldberg S, Hsu J, Orr A, Rowley S, Donato M. 5-Azacitidine therapy in elderly patients with 
acute myelogenous leukemia yields similar survival compared to 3+7 induction chemotherapy 
with less transfusional support, bacteremias, and hospital days. Blood 2006; 108(11). Abstract No. 
4569.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
163
Garcia-Manero, Guillermo & Przespolewski, Amanda & Abaza, Yasmin & Byrne, Michael & 
Fong, Abraham & Jin, Feng & Forgie, Alison & Tsiatis, Athanasios & Guan, Shanhong & Erba, 
Harry. (2022). Evorpacept (ALX148), a CD47-Blocking Myeloid Checkpoint Inhibitor, in 
Combination with Azacitidine and Venetoclax in Patients with Acute Myeloid Leukemia (ASPEN-
05): Results from Phase 1a Dose Escalation Part. Blood. 140. 9046-9047. Greenberg PL, Tuechler 
H, Schanz J, Sanz G, Garcia-Manero G, Solé F, et al. Revised international prognostic scoring 
system for myelodysplastic syndromes. Blood 2012;120(12):2454-65.
 
Hall WC, Price-Schiavi SA, Wicks J, Rojko JL. Tissue cross-reactivity studies for monoclonal 
antibodies:  Predictive value and use for selection of relevant animal species for toxicity testing. 
In:  Cavagnaro JA, editor. Preclinical Safety Evaluation of Biopharmaceuticals:  A Science-Based 
Approach to Facilitating Clinical Trials. Wiley-Interscience; 2008. P 208-40.
Jia Y, Zhang Q, Weng C, Ramage C.L, Nishida Y, Chao M, Maute R.., Herbrich S, Zhang W, 
Andreeff M., et al. Combined Blockade of CD47-Sirpa Interaction By 5F9 (Magrolimab) and 
Azacitidine/Venetoclax Therapy Facilitates Macrophage-Mediated Anti-Leukemia Efficacy in 
AML Pre-Clinical Models. Blood. 2021;138:510.
Jiang H, Fu R, Wang H, Li L, Liu H, Shao Z. CD47 is expressed abnormally on hematopoietic 
cells in myelodysplastic syndrome. Leuk Res 2013;37(8):907-10.
Leach MW, Halpern WG, Johnson CW, Rojko JL, MacLachlan TK, Chan CM, et al. Use of tissue 
cross-reactivity studies in the development of antibody-based biopharmaceuticals:  history, 
experience, methodology, and future directions. Toxicol Pathol. 2010 Dec;38(7):1138-66.
Lee DW, Gardner R, Porter DL, Louis CJ, Ahmed N, Jensen M, et al. Current concepts in the 
diagnosis and management of cytokine release syndrome. Blood 2014;124(2):188-95.
Lee SH, Erber WN, Porwit A, Tomonaga M, Peterson LC. ICSH guidelines for the standardization 
of bone marrow specimens and reports. Int Jnl Lab Hem 2008;30:349-64.
Lehmberg K, Nichols KE, Henter JI, et al. Consensus recommendations for the diagnosis and 
management 
of 
hemophagocytic 
lymphohistiocytosis 
associated 
with 
malignancies. 
Haematologica. 2015;100(8):997-1004.
Lübbert, M. DNA methylation inhibitors in the treatment of leukemias, myelodysplastic 
syndromes and hemoglobinopathies: clinical results and possible mechanisms of action. Curr Top 
Microbiol Immunol 2000;249:135-64.
Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, et al. CD47 is an adverse prognostic 
factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 
2009;138(2):286-99.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
164
Matlung HL, Szilagyi K, Barclay NA, van den Berg TK. The CD47-SIRPα signaling axis as an 
innate immune checkpoint in cancer. Immunol Rev 2017;276(1):145-64. 
Milligan D, Grinwald D, Cullis J, Bond L, Swirsky D, et al. Guidelines on the management of 
acute myeloid leukemia in adults. B J Hem 2006;135:450-74.
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for 
Acute Myeloid Leukemia. National Comprehensive Cancer Network website. Version 3.2021a, 
02 Mar 2021. Available from URL: https://www.nccn.org/
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for 
Myelodysplastic Syndromes. National Comprehensive Cancer Network website. Version 3.2021b, 
15 Jan 2021. Available from URL: https://www.nccn.org/
National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER). Cancer 
Stat 
Facts: 
Leukemia 
–
Acute 
Myeloid 
Leukemia 
(AML). 
2023. 
https://seer.cancer.gov/statfacts/html/amyl.html
Naval Daver, Jayastu Senapati, Abhishek Maiti, Sanam Loghavi, Tapan M. Kadia, Courtney D. 
DiNardo; Phase I/II Study of Azacitidine (AZA) with Venetoclax (VEN) and Magrolimab (Magro) 
in Patients (pts) with Newly Diagnosed (ND) Older/Unfit or High-Risk Acute Myeloid Leukemia 
(AML) and Relapsed/Refractory (R/R) AML. Blood 2022; 140 (Supplement 1): 141–144.
Nazha A, Sekeres MA, Komrokji R, Steensma DP, Kantarjian H, Roboz G, et al. Validation of a 
post-hypomethylating agent failure prognostic model in myelodysplastic syndromes patients 
treated in a randomized controlled phase III trial of rigosertib vs. best supportive care. Blood 
Cancer J 2017;7(12):644.
Oken M, Creech R, Tormey D, Horton J, Davis T, McFadden E, Carbone P. Toxicity and response 
criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5(6):649-55. 
Palmer AM. Multiple sclerosis and the blood-central nervous system barrier. Cardiovasc 
Psychiatry Neurol. 2013; 530356:1-10.
Pardridge WM. Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor 
monoclonal antibody. Expert Opin Drug Deliv. 2015 Feb;12(2):207-22.
Perl A, Martinelli G, Cortes J, Neubauer A, Berman E, Paolini S, et al. Gilteritinib or chemotherapy 
for relapsed or refractory FLT-3 mutated AML. N Engl J Med 2019;381(18):1728-40.
Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X. Adult 
haemophagocytic 
syndrome 
[published 
correction 
appears 
in 
Lancet. 
2014 
Apr 
26;383(9927):1464]. Lancet. 2014;383(9927):1503-1516.
Reville PK, Kadia TM. Maintenance therapy in AML. Front Oncol 2021;10: article 619085.
Ritchie EK, Feldman EJ, Christos PJ, Rohan SD, Lagassa CB, Ippoliti C et al. Decitabine in 
patients with newly diagnosed and relapsed acute myeloid leukemia. Leuk Lymphoma 
2013;54(9):2003-7.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
165
Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, et al. International 
randomized phase III study of elacytarabine versus investigator choice in patients with 
relapsed/refractory acute myeloid leukemia. J Clin Oncol 2014;32(18):1919-26.
Rowe JM, Tallman MS. How I treat acute myeloid leukemia. Blood 2010;116(17):3147-56.
Russ A, Hua BA, Montfort WR, Rahman B, Riaz IB, et al. Bocking the “don’t eat me” signal 
CD47-SIRPα in hematological malignancies, an in-depth review. Blood Reviews. 2018. 480-c9.
Sallman D, Asch A, Kambhampati S, Al Malki M, Zeidner J, Donnellan W, et al. The first-in-class 
anti-CD47 antibody magrolimab combined with azacitidine is well-tolerated and effective in AML 
patients: Phase 1b results. The 62nd ASH Annual Meeting and Exposition, Oral and poster 
abstracts, 2020a, Session 613-330. 
Sallman D, Al Malki M, Asch A, Lee D, Kambhampati S, Donnellan W, et al. The first-in-class 
anti-CD47 antibody magrolimab combined with azacitidine is well-tolerated and effective in MDS 
patients: Phase 1b results. European Hematology Association 25th Annual Congress, 2020b, S187. 
Sallman DA, Al Malki MM, Asch AS, et al. Magrolimab in Combination With Azacitidine in 
Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study 
[published online ahead of print, 2023 Mar 8]. J Clin Oncol. 2023;JCO2201794.
 
 
Silverman L. Section 36, Neoplasms of the hematopoietic system: myelodysplastic syndrome. In: 
Holland J, Frei EI, Bast RJ, et al, editors. Cancer Medicine. 5th ed. Hamilton, Canada: BC Decker; 
2000. P. 1931-46.
Silverman LR. Hypomethylating agents in myelodysplastic syndromes changing the inevitable: 
the value of azacitidine as maintenance therapy, effects on transfusion and combination with other 
agents. Leuk Res 2009;33 (Suppl 2): S18-21.
Silverman L, McKenzie D, Peterson B, Holland J. Further analysis of trials with azacitidine in 
patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and 
Leukemia Group B. JCO 2006;24(24);3895-903.
Steensma DP, Terfferi A. The myelodysplastic syndrome(s): a perspective and review highlighting 
current controversies. Leuk Res 2003;27(2):95-120.
Taylor PR, Martinez-Pomares L, Stacey M, Lin HH, Brown GD, et al. Macrophage receptors and 
immune recognition. Annu Rev Immunol 2005;23:901-44.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision 
of the World Health Organization (WHO) classification of myeloid neoplasms and acute myeloid 
leukemia: rationale and important changes. Blood. 2009; 114(5):937-51.
Venclexta®. [Prescribing Information]. North Chicago, IL: AbbVie Inc;2020. Available from: 
https://www.rxabbvie.com/pdf/venclexta.pdf
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
166
Venclyxto ® [Summary of Product Characteristics] . 2022. Ludwigshafen, Germany: AbbVie 
Deutschland 
GmbH 
& 
Co. 
KG 
Available 
from:
https://www.ema.europa.eu/en/documents/product-information/venclyxto-epar-product-
information_en.pdf
Vidaza® (azacitidine for injection). [Prescribing Information]. Summit, NJ: Celgene Corporation; 
Revised March 2022. Available from: https://packageinserts.bms.com/pi/pi_vidaza.pdf
Wei AH, Döhner H, Pocock C, et al. Oral Azacitidine Maintenance Therapy for Acute Myeloid 
Leukemia in First Remission. N Engl J Med. 2020;383(26):2526-2537.
Willingham SB, Volkmer JP, Gentles AJ, Sahoo D, Dalerba P, Mitra SS, et al. The CD47-signal 
regulatory protein alpha (SIRPα) interaction is a therapeutic target for human solid tumors. Proc 
Natl Acad Sci USA 2012;109(17):6662-7.
Zhao XW, van Beek EM, Schornagel K, Van der Maaden H, Van Houdt M, et al. CD47-signal 
regulatory protein-α (SIRPα) interactions form a barrier for antibody-mediated tumor cell 
destruction. Proc Natl Acad Sci USA 2011;108(45):18342-7.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
167
APPENDIX A
TABLE OF ABBREVIATIONS
Table 17:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
ADA
Anti-drug antibody
ADCP
Antibody-dependent cellular phagocytosis 
ADL
Activity of daily life
AE
Adverse event
ALT
Alanine aminotransferase (SGPT)
AML
Acute myeloid leukemia
ANC
Absolute neutrophil count
Anri-CD20
Anti-cluster of differentiation 20
Anti-EGFR
Anti-epidermal growth factor receptor
APL
Acute promyelocytic leukemia
AST
Aspartate aminotransferase (SGOT)
AUC
Area under the serum concentration time-curve
Aza
Azacitidine
β-hCG
β-subunit of human chorionic gonadotropin
BCL-2
B-cell lymphoma-2
BE
Biomarker evaluable
BLRM
Bayesian logistic regression model
BM
Bone marrow
BMA
Bone marrow aspirate
BMB
Bone marrow biopsy
BSA
Body surface area
BUN
Blood urea nitrogen
C
Cycle
C1q
Complement component 1q
CBC
Complete blood count
CCR
Conventional care regimen
cCRR
Combined rate of CRs
CD4
Cluster of differentiation 4
CD47
Cluster of differentiation 47
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
168
Table 17:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
CD8
Cluster of differentiation 8
CI
Confidence interval
CLT
Total body clearance
Cmax
Maximum plasma concentration of drug
Cmin
Minimum serum concentration
CMMoL
Chronic myelomonocytic leukemia
CNS
Central nervous system
CO2
Carbon dioxide
COVID-19
Coronavirus disease 2019
CR
Complete remission
CRA
Cytokine release assay
CRh
Morphologic complete remission with partial hematologic recovery
CRi
Morphologic complete remission with incomplete blood recovery
CRMRD-
Morphologic complete remission without minimal residual disease
CRO
Contract research organization
CRF
Case report form
CRR
Complete remission rate
CRS
Cytokine release syndrome
CS
Clinical scientist
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
D
Day
DCR
Disease control rate
DIC
Disseminated intravascular coagulation
DL
Dose level
DLT
Dose-limiting toxicity
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic acid
DOR
Duration of response
EC
Ethics Committee
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
169
Table 17:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
ECG
Electrocardiogram
ECL
Electrochemiluminescence
ECOG
Eastern Cooperative Oncology Group
ECOG PS
Eastern Cooperative Oncology Group Performance Status
eCRF
Electronic case report form
EE
Efficacy evaluable
EEA
European Economic Area
ELN
European Leukemia Net
EMD
Extramedullary disease
EOI
End of infusion
EOT
End of treatment
FAB
French-American-British
FDA
Food and Drug Administration
FIH
First-in-human
FLT3-ITD
fms-like tyrosine kinase 3 internal tandem duplication
GCP
Good Clinical Practice
GI
Gastrointestinal
Hgb
Hemoglobin
HI
Hematologic improvement
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
170
Table 17:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
HMA
Hypomethylating agent
HR
Hazard ratio
HR-MDS
Higher-risk myelodysplastic syndromes
IB
Investigator’s Brochure
IC
Intensive Chemotherapy
ICF
Informed consent form
ICH
International Council on Harmonisation
IDH
Isocitrate dehydrogenase
IFNγ
Interferon γ
IE
Ineligible
Ig
Immunoglobulin
IgG(1)
Immunoglobulin G(1)
IHC
Immunohistochemistry
IL
Interleukin
IND
Investigational New Drug
int-2
Intermediate-2
IP
Investigational product
IPSS
International Prognostic Scoring System score
IPSS-R
Revised International Prognostic Scoring System score
IRB
Institutional Review Board
IRT
Integrated Response Technology
IV
Intravenous
IWG
International Working Group
LDAC
low-dose cytarabine
LDH
Lactate dehydrogenase
LVEF
Left ventricular ejection fraction
MAS 
Macrophage Activation Syndrome
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
171
Table 17:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
MDS
Myelodysplastic syndromes
MedDRA
Medical Dictionary for Regulatory Activities
MLFS
Morphologic leukemia-free state
MM
Medical monitor
mOS
Median overall survival
MRD
Minimal residual disease
MRI
Magnetic resonance imaging
NA
Not applicable
NCI
National Cancer Institute
ND
Newly diagnosed
NGS
Next generation sequencing
NHL
Non-Hodgkins Lymphoma
NOAEL
No observed adverse effect level
NOS
Not otherwise specified
ORR
Overall response rate
OS
Overall survival
P-gp
P-glycoprotein
PB
Peripheral blood
PBMC
Peripheral blood mononuclear cell
PBS
Peripheral blood smear
PFS
Progression-free survival
PD
Pharmacodynamics
PDX
Subject-derived xenograft
PFS
Progression free survival
PK
Pharmacokinetics
PO
Orally
PR
Partial remission
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
172
Table 17:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
Q
Every
QD
Once daily 
RA
Refractory anemia
RAEB
Refractory anemia with excess blasts
RAEB-T
Refractory anemia with excess blasts in transformation
RARS
Refractory anemia with ringed sideroblasts
RBC
Red blood cell count
RECIST
Response Evaluation Criteria in Solid Tumors
RO
Receptor occupancy
RP2D
Recommended Phase 2 dose
RSV
Respiratory syncytial virus
R/R
Relapsed or refractory
RT-PCR
Reverse transcription-polymerase chain reaction
SAE
Serious adverse event
SAP
Statistical analysis plan
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SC
Subcutaneous
SCBP
Subject of childbearing potential
SCCHN
Squamous cell carcinoma of the head and neck
SCT
Stem cell transplantation
SD
Stable disease/standard deviation (based on context)
SEER
Surveillance, Epidemiology, and End Results
SIRPα
Signal regulatory protein alpha
SGOT
Serum glutamic oxaloacetic transaminase 
SGPT
Serum glutamic pyruvic transaminase
SIRPα
Signal regulatory protein alpha
SmPC
Summary of Product Characteristics
SOP
Standard operating procedure
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
173
Table 17:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
SRC
Safety Review Committee
SUSAR
Suspected unexpected serious adverse reaction
TAM
Transient abnormal myelopoiesis
TEAE
Treatment-emergent adverse events
TLS
Tumor lysis syndrome
tmax
Time to peak (maximum) serum concentration
TMDD
Target mediated drug disposition
TN
Treatment-naïve
ULN
Upper limit of normal
US
United States
USP
United States Pharmacopeia
USPI
United States Prescribing Information
VAS
Visual analog scale
WBC
White blood cell count
WHO
World Health Organization
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
174
APPENDIX B
THE WORLD HEALTH ORGANIZATION (WHO)
CLASSIFICATION OF ACUTE MYELOID LEUKEMIA (AML)
Table 18:
WHO classification of AML
AML with recurrent genetic abnormalities
AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH11
APL with PML-RARA
AML with t(9;11)(p21.3;q23.3);MLLT3-KMT2A
AML with t(6;9)(p23;q34.1);DEK-NUP214
AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM
AML (megakaryoblastic) with t(1;22)(p13.3;q13.3);RBM15-MKL1
Provisional entity: AML with BCR-ABL1
AML with mutated NPM1
AML with biallelic mutations of CEBPA
Provisional entity: AML with mutated RUNX1
AML with myelodysplasia-related changes
Therapy-related myeloid neoplasms
AML, NOS
AML with minimal differentiation
AML without maturation
AML with maturation
Acute myelomonocytic leukemia
Acute monoblastic/monocytic leukemia
Pure erythroid leukemia
Acute megakaryoblastic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis
Myeloid sarcoma
Myeloid proliferations related to Down Syndrome
Transient abnormal myelopoiesis (TAM)
Myeloid leukemia associated with Down Syndrome
Abbreviations: AML = acute myelogenous leukemia; NOS = not otherwise specified; TAM = transient abnormal 
myelopoiesis. 
Source: Arber, 2016.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
175
APPENDIX C
RESPONSE CRITERIA FOR ACUTE MYELOID LEUKEMIA
(AML)
The revised recommendations of the European Leukemia Net (ELN) for diagnosis, standardization 
of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute 
myeloid leukemia modified for this protocol.
Table 19:
Hematologic/Molecular Response According to ELN Criteria for 
AML
Response Criterion
Time of Assessment
Absolute 
Neutrophils 
(µL)
Platelets 
(µL)
BM Blasts (%)
Other
Early Treatment 
assessment 
7-10 days after 
therapy
NA
NA
< 5
Morphologic 
Leukemia-free State 
(MLFS) 
Varies by protocol 
NA
NA
< 5
Flow cytometry EMD-
Morphologic CR 
Varies by protocol 
≥ 1,000
≥100,000
< 5
Transfusion EMD-
CR without minimal 
residual disease 
(CRMRD-)
Varies by protocol 
≥ 1,000
≥100,000
< 5
Molecular/genetic 
marker - negative, 
EMD-
Morphologic CR 
with incomplete 
blood recovery 
(CRi)
Varies by protocol
Fulfill all criteria for CR except for residual neutropenia (< 1,000/µL) or 
thrombocytopenia (< 100,000/µL).
Morphologic CR 
with partial 
hematologic 
recovery (CRh)
Per protocol
>500
>50,000
< 5
Absence of peripheral 
leukemic blasts, EMD-
Partial Remission 
(PR)
Varies by protocol 
≥ 1,000
≥100,000
Decrease ≥50
resulting in 5 to 25
Blasts ≤ 5% if Auer 
rod positive 
Hematologic 
Response (HR)
Varies by protocol
≥ 500
Improvement in hematologic parameters that do not meet 
criteria for PR, ie, transfusion independence*.
Stable Disease
Varies by protocol
Absence of CRMRD-, CR, CRi, CRh, PR, MLFS; and criteria for PD not met
Hematologic relapse 
after CRMRD-, CR, 
CRi, CRh 
Varies by protocol
Reappearance of leukemic blasts in the peripheral blood or ≥ 5% blasts in the 
bone marrow not attributable to any other cause (eg, bone marrow 
regeneration after consolidation therapy) or EMD+.
Molecular relapse 
after CRMRD-
Varies by protocol
Reoccurrence of MRD as assessed by RT-qPCR or by MFC
Abbreviations: AML = acute myeloid leukemia; BM = bone marrow; CR = complete remission; CRh = morphologic CR with 
partial hematologic recovery; CRi = morphologic CR with incomplete blood recovery; CRMRD- = CR without minimal residual 
disease; ELN = European Leukemia Net; EMD = extramedullary disease; EMD- = extramedullary disease negative; EMD+ = 
extramedullary disease positive; HR = hematologic response; MFC = multiparameter flow cytometry; MLFS = morphologic 
leukemia-free state; MRD = minimal residual disease; NA = not applicable; PD = progressive disease; PR = partial remission; RT-
qPCR = quantitative reverse transcription polymerase chain reaction.
* Transfusion independence for hematologic response is defined as the absence of any red blood cell or platelet transfusion during 
any consecutive 
 during the treatment period (Silverman, 2009). Packed red cell and platelet transfusion history for up 
to 
 before beginning study treatment will be collected.
Source: Bloomfield, 2018; Dohner, 2017.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
176
APPENDIX D
THE WORLD HEALTH ORGANIZATION (WHO) 
CLASSIFICATION OF THE MYELODYSPLASTIC SYNDROMES (MDS)
Table 20:
WHO classifications for MDS
WHO myeloid neoplasm and acute 
leukemia classification
Dysplastic 
findings
Cytopeniasa
PB and BM findings and cytogenetics
MDS with single lineage dysplasia 
(MDS-SLD)
1
1 or 2
BM < 5%, PB < 1%, no Auer Rods
Any cytogenetics, unless fulfills all 
criteria for MDS with isolated del(5q)
MDS with multilineage dysplasia (MDS-
MLD)
2 or 3
1-3
BM < 5%, PB < 1%, no Auer Rods
Any cytogenetics, unless fulfills all 
criteria for MDS with isolated del(5q)
MDS with ring sideroblasts (MDS-RS)b
    MDS-RS and single lineage dysplasia
(MDS-RS-SLD)
    MDS-RS and multilineage dysplasia
(MDS-RS-MLD)
1
2 or 3
1 or 2
1-3
BM < 5%, PB < 1%, no Auer Rods
Any cytogenetics, unless fulfills all 
criteria for MDS with isolated del(5q)
MDS with isolated del(5q)
1-3
1-2
BM < 5%, PB < 1%, no Auer Rods
del(5q) alone or with 1 additional 
abnormality except -7 or del(7q)
MDS with excess blasts (MDS-EB)
     MDS-EB-1
0-3
1-3
BM 5-9% or PB 2-4%, no Auer Rods
Any cytogenetics
     MDS-EB-2
0-3
1-3
BM 10-19% or PB 5-19% or Auer 
Rods
Any cytogenetics
MDS, unclassifiable (MDS-U)
    MDS-U with 1% blood blasts
1-3
1-3
BM < 5%, PB =1%c, no Auer Rods
Any cytogenetics
    MDS-U with SLD and pancytopenia
1
3
BM < 5%, PB <1%, no Auer Rods
Any cytogenetics
    MDS-U based on defining cytogenetic 
abnormality
0
1-3
BM < 5%, PB <1%, no Auer Rods
MDS-defining abnormalityd
Abbreviations: BM = bone marrow; del = deletion; FISH = fluorescence in situ hybridization; MDS = myelodysplastic 
syndromes; MDS-EB = MDS with excess blasts; MDS-EB-1 = MDS with excess blasts-1; MDS-EB-2 = MDS with 
excess blasts-2; MDS-MLD = MDS with multilineage dysplasia; MDS-RS = MDS with ring sideroblasts; MDS-RS-
MLD = MDS-RS and multilineage dysplasia; MDS-RS-SLD = MDS-RS and single lineage dysplasia; MDS-SLD = 
MDS with single lineage dysplasia; MDS-U = MDS, unclassifiable; PB = peripheral blood; WHO = World Health 
Organization.
a Cytopenias defined as : hemoglobin, <10 g/dL, platelet count, <100 x 109/L; and absolute neutrophil count, <1.8 x 
109/L. Rarely, MDS may present with mild anemia or thrombocytopenia above these levels. Peripheral blood 
monocytes must be < 1 x 109/L.
b Cases with ≥ 15% ring sideroblasts by definition have significant erythroid dysplasia, and are classified as MDS-
RS-SLD.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
177
c One percent PB blasts must be recorded on at least 2 separate occasions.
d Abnormality must be demonstrated by conventional karyotyping, not by FISH or sequencing. The presence of +8, 
-Y, of del(20q) is not considered to be MDS-defining in the absence of diagnostic morphologic features of MDS. 
Sources: Arber, 2016 and Vardiman, 2009.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
178
APPENDIX E
RESPONSE CRITERIA FOR MYELODYSPLASTIC SYNDROMES
(MDS)
The revised recommendations of the International Working Group (IWG) for diagnosis, 
standardization of response criteria, treatment outcomes, and reporting standards for therapeutic 
trials in myelodysplastic syndromes (MDS) modified for this protocol.
Table 21:
Modified IWG Response Criteria for MDS
Category
Response criteria (responses must last at least 4 weeks)
Complete remission (CR)
Bone marrow:  ≤ 5% myeloblasts with normal maturation of all cell linesa
Persistent dysplasia will be noteda,b
Peripheral bloodc
-
Hemoglobin ≥ 11 g/dL
-
Platelets ≥ 100 × 109/L
-
Neutrophils ≥ 1.0 × 109/Lb
-
Blasts 0%
Morphologic CR with partial 
hematologic recovery (CRh)
Bone marrow:  ≤ 5% myeloblasts with normal maturation of all cell linesa
Persistent dysplasia will be noteda,b
Peripheral bloodc
-
Hemoglobin ≥ 11 g/dL
-
Platelets > 50 × 109/L
-
Neutrophils > 0.5 × 109/Lb
-
Blasts 0%
Partial remission (PR)
All CR criteria if abnormal before treatment, except:
Bone marrow blasts decreased by ≥ 50% over pretreatment but still > 5%
Cellularity and morphology not relevant
Marrow CRb
± Hematologic Improvement (HI)
Bone marrow:  ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatmentb Note: Blasts 
at baseline must be ≥ 5% in order for subject to be evaluable for Marrow CRd
Peripheral blood: if HI responses, they will be noted in addition to marrow CRb
Stable disease (SD)
Failure to achieve at least PR, but no evidence of progression for > 
Failure
Death during treatment or disease progression characterized by worsening of cytopenias, 
increase in percentage of bone marrow blasts, 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 percentage

Decrement of ≥50% from maximum remission/response levels in granulocytes or 
platelets

Reduction of Hgb concentration by ≥ 1.5 g/dL or transfusion dependence
Cytogenetic Response
Complete – Disappearance of the chromosomal abnormality without appearance of new 
ones
Partial – At least 50% reduction of the chromosomal abnormality
Disease Progression (PD)
For subjects with:

Less than 5% blasts: ≥ 50% increase in blasts to > 5% blasts

5% - 10% blasts: ≥ 50% increase in blasts to > 10% blasts

10% - 20% blasts: ≥ 50% increase in blasts to > 20% blasts
Any of the following:

At least 50% decrement from maximum remission/response levels in granulocytes 
or platelets

Reduction in Hgb concentration by ≥ 2 g/dL

Transfusion dependence
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
179
Table 21:
Modified IWG Response Criteria for MDS
Category
Response criteria (responses must last at least 4 weeks)
Disease transformation
Transformation to AML (20% or more BM or PB blasts)d
Hematologic Improvement (HI)
    Erythroid response (HI-E)
   (Pretreatment < 11 g/dL)
Hgb increase by ≥ 1.5 g/dL
Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC 
transfusions/
 compared with the pretreatment transfusion number in the previous 
. Only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment will count in 
the RBC transfusion evaluation
    Platelet response (HI-P)
    (Pretreatment < 100 × 109/L)
Absolute increase of ≥ 30 × 109/L for subjects starting with > 20 × 109/L
Increase from < 20 × 109/L to > 20 × 109/L and by at least 100%
    Neutrophil response (HI-N)
    (Pretreatment < 1.0 × 109/L)
At least 100% increase and an absolute increase of > 0.5 × 109/L
    Progression/relapse after HI
At least one of the following:

At least 50% decrement from maximum response levels in granulocytes or platelets

Reduction in Hgb by ≥ 1.5 g/dL

Transfusion dependence
Abbreviations: AML = acute myeloid leukemia; BM = bone marrow; CR = complete remission; FAB = French-
American-British; Hgb = hemoglobin; HI = hematologic improvement; HI-E = HI - erythroid response; HI-P = HI -
platelet response; HI-N = HI - neutrophil response; IWG = International Working Group; MDS = myelodysplastic 
syndromes; PB = peripheral blood; PD = Disease Progression; PR = partial remission; RBC = red blood cell; SD = 
stable disease.
a Dysplastic changes should consider the normal range of dysplastic changes (modification).
b Modification to IWG response criteria.
c In some circumstances, protocol therapy may require the initiation of further treatment (eg, consolidation, 
maintenance) before the 4-week period. Such subjects can be included in the response category into which they fit 
at the time the therapy is started. Transient cytopenias during repeated chemotherapy courses should not be 
considered as interrupting durability of response, as long as they recover to the improved counts of the previous 
course.
d Sponsor modification of IWG criteria.
Sources: Bloomfield, 2018; Cheson, 2006; Vardiman, 2009.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
180
APPENDIX F
RISK STATUS BASED ON CYTOGENETICS FOR ACUTE 
MYELOID LEUKEMIA
Table 22:
Risk Stratification by Genetics in Non-APL AML
Risk Category*
Genetic Abnormality
Favorable
t(8;21)(q22;q22.1); RUNX1-RUNX1T1
inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
Biallelic mutated CEBPA 
Mutated NPM1 without FLT3-ITD or with FLT3-ITDlow†
Intermediate
Mutated NPM1 and FLT3-ITDhigh†
Wild-type NPM1 without FLT3-ITD or with FLT3-ITDlow† (without adverse-risk genetic
lesions)
t(9;11)(p21.3;q23.3); MLLT3-KMT2A‡
Cytogenetic abnormalities not classified as favorable or adverse
Poor/Adverse
t(6;9)(p23;q34.1); DEK-NUP214
t(v;11q23.3); KMT2A rearranged
t(9;22)(q34.1;q11.2); BCR-ABL1
inv(3)(q21.3q26.32) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVl1)
-5 or del(5q); -7; -17/abn(17p)
Complex karyotype§, monosomal karyotype║
Wild-type NPM1 and FLT3-ITDhigh†
Mutated RUNX1¶
Mutated ASXL1¶
Mutated TP53#
Abbreviations: ABL1 = ABL proto-oncogene 1; abn = arm band number; ASXL1 = ASXL transcriptional regulator 
1; BCR = breakpoint cluster region protein; CBFB = core-binding factor subunit β; CEBPA = CCAAT/enhancer 
binding protein α; DEK = DEK proto-oncogene; del = deletion; FLT3-ITD = FLT3 internal tandem duplication; 
GATA2 = GATA binding protein 2; KMT2A = lysine methyltransferase 2A; inv = inversion; MECOM(EVl1) = 
MDS1 and EVl1 complex locus protein (ecotropic virus integration site 1 protein homolog) ; MLLT3 = 
myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila), translocated to, 3 ; MYH11 = myosin 
heavy chain 11; NPM1 = nucleophosmin 1; NUP214 = nucleoporin 214; p = short arm of a chromosome; q = long 
arm of a chromosome; RUNX1 = runt-related transcription factor 1; RUNX1T1 = RUNX1 partner transcriptional co-
repressor 1; t = translocation; TP53 = tumor protein 53.
* Prognostic impact of a marker is treatment-dependent and may change with new therapies.
† Low, low allelic ratio (<0.5); high, high allelic ratio (≥0.5); semiquantitative assessment of FLT3-ITD allelic ratio 
(using DNA fragment analysis) is determined as ratio of the area under the curve “FLT3-ITD” divided by area under 
the curve “FLT3-wild type”; recent studies indicate that AML with NPM1 mutation and FLT3-ITD low allelic ratio 
may also have a more favorable prognosis and patients should not routinely be assigned to allogeneic HCT. FLT3 
allelic ratio is not yet pervasively used, and IF not available, the presence of an FLT3 mutation should be considered 
high-risk unless it occurs concurrently with an NPM1 mutation, in which case it is intermediate risk. As data emerge, 
this measure will evolve.
‡ The presence of t(9;11)(p21.3;q23.3) takes precedence over rare, concurrent adverse-risk gene mutations.
§ Three or more unrelated chromosome abnormalities in the absence of 1 of the WHO-designated recurring 
translocations or inversions, that is, t(8;21), inv(16) or t(16;16), t(9;11), t(v;11)(v;q23.3), t(6;9), inv(3) or t(3;3); 
AML with BCR-ABL1.
║Defined by the presence of 1 single monosomy (excluding loss of X or Y) in association with at least 1 additional 
monosomy or structural chromosome abnormality (excluding core-binding factor AML).
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
181
¶ These markers should not be used as an adverse prognostic marker if they co-occur with favorable-risk AML 
subtypes.
# TP53 mutations are significantly associated with AML with complex and monosomal karyotype.  
Source: NCCN, 2021a.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
182
APPENDIX G
REVISED INTERNATIONAL PROGNOSTIC SCORING SYSTEM    
FOR MDS
Table 23:
IPSS-R Cytogenetic Risk Groups
Cytogenetic Prognostic Subgroups
Cytogenetic Abnormalities
Very good
-Y, del(11q)
Good
Normal, del(5q), del(12p), del(20q), double including del(5q)
Intermediate
del(7q), +8, +19, i(17q), any other single or double independent clones
Poor
-7, inv(3)/t(3q)/del(3q), double including -7/del(7q), Complex: 3 
abnormalities
Very poor
Complex: > 3 abnormalities
Abbreviations: del = deletion; inv = inversion; IPSS-R = Revised International Prognostic Scoring System score; p = 
short arm of a chromosome; q = long arm of a chromosome; t = translocation.
Source: Greenberg, 2012.
Table 24:
IPSS-R Prognostic Score Values
Prognostic variable
0
0.5
1
1.5
2
3
4
Cytogenetics
Very 
Good
-
Good
-
Inter-
mediate
Poor
Very 
Poor
Bone Marrow Blast (%)
≤ 2
-
> 2 - < 5
-
5 - 10
> 10
-
Hemoglobin (g/dL)
≥10
-
8 - < 10
<8
-
-
-
Platelets (× 109/L)
≥100
50 - < 100
< 50
-
-
-
-
ANC (× 109/L)
≥0.8
< 0.8
-
-
-
-
-
Abbreviations: ANC = absolute neutrophil count; IPSS-R = Revised International Prognostic Scoring System score.
Source: Greenberg, 2012.
The total IPSS-R score is calculated as the sum of the cytogenetics, bone marrow blast percentage, 
hemoglobin, platelets, and ANC individual scores.
Table 25:
IPSS-R Prognostic Risk Categories/Scores
Risk Category
Risk Score
Very Low
≤ 1.5
Low
> 1.5 – 3
Intermediate
> 3 – 4.5
High
> 4.5 – 6
Very High
> 6
Abbreviations: IPSS-R = Revised International Prognostic Scoring System score.
Source: Greenberg, 2012.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
183
Table 26:
IPSS-R: Prognostic Risk Category Clinical Outcomes
Prognostic variable
No. pts
Very Low
Low
Intermediate
High
Very High
Subjects, %
7012
19%
38%
20%
13%
10%
Median Overall Survival 
(years)
-
8.8
5.3
3.0
1.6
0.8
Median time to 25% 
AML evolution
-
Not 
reached
10.8
3.2
1.4
0.73
Abbreviations: AML = acute myeloid leukemia; IPSS-R = Revised International Prognostic Scoring System score.
Source: Greenberg, 2012.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
184
APPENDIX H
PERFORMANCE STATUS CRITERIA
Table 27:
Eastern Cooperative Oncology Group (ECOG) Performance Status 
(PS)
Score
Description
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light housework, 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
Abbreviations: ECOG = Eastern Cooperative Oncology Group; PS = performance status.
Source: Oken, 1982.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
185
APPENDIX I
TUMOR LYSIS SYNDROME PROPHYLAXIS 
RECOMMENDATIONS
Table 28:
Tumor Lysis Syndrome (TLS) Prophylaxis Recommendations Based 
on TLS Risk
Abbreviations: ALCL = anaplastic large cell lymphoma; ALL = acute lymphoblastic leukemia; AML = acute myeloid 
leukemia; BL = Burkitt lymphoma/leukemia; CLL = chronic lymphoid leukemia; CML = chronic myeloid leukemia; 
HL = Hodgkin lymphoma; LDH = lactate dehydrogenase; LL = lymphoblastic lymphoma; MM = multiple myeloma; 
N/A = not applicable; NH: = non-Hodgkin lymphoma; ST = solid tumor; TLS = tumor lysis syndrome; ULN = upper 
limit of normal; WBC = white blood cell count.
Source:  Cairo, 2004 and Cairo, 2010.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
186
Table 29:
Cairo-Bishop Definition of Laboratory Tumor Lysis Syndrome
Uric Acid
≥ 476 μmol/l (≥ 8.0 mg/dl) or 25% increase from baseline
Potassium
≥ 6.0 mmol/l (≥ 6.0 mEq/l) or 25% increase from baseline
Phosphorous
≥ 1.45 mmol/l (≥ 4.5 mg/dl) or 25% increase from baseline
Calcium
≤ 1.75 mmol/l (≤ 7.0 mg/dl) or 25% decrease from baseline
Notes:  Laboratory tumor lysis syndrome (LTLS) is defined as either a 25% change or level above or below normal, 
as defined above, for any 2 or more serum values of uric acid, potassium, phosphate, and calcium within 3 days before 
or 7 days after the initiation of chemotherapy.  This assessment assumes that a subject has or will receive adequate 
hydration (± alkalinization) and a hypouricemic agent(s).
Source:  Cairo, 2004 and Cairo, 2010.
The Cairo-Bishop Definition of Clinical Tumor Lysis Syndrome
The Presence of Laboratory TLS and One or More of the Following Criteria:

Creatinine: ≥ 1.5 upper limit of normal ([ULN] age > 12 years or age-adjusted)

Cardiac arrhythmia / sudden death

Seizure not directly attributable to a therapeutic agent
Table 30:
Cairo-Bishop Grading System for Tumor Lysis Syndrome
Grade
LTLS
Creatinine
Cardiac Arrhythmia
Seizure
0
-
≤ 1.5 x ULN
None
None
1
+
1.5 x ULN
Intervention not indicated
None
2
+
> 1.5 – 3.0 x ULN
Non-urgent medical 
intervention indicated
One brief generalized seizure; 
seizure(s) well controlled by 
anti-convulsants or infrequent 
focal motor seizures not 
interfering with ADL
3
+
> 3.0 – 6.0 x ULN
Symptomatic and 
incompletely controlled 
medically or controlled 
with device
Seizure in which 
consciousness is altered; 
poorly controlled seizure 
disorder; breakthrough 
generalized seizures despite 
medical intervention
4
+
> 6.0 x ULN
Life-Threatening
Seizures of any kind that are 
prolonged, repetitive, or 
difficult to control
5
+
Deatha
Death
Death
Abbreviations: ADL = Activities of Daily Living; LTLS = Laboratory Tumor Lysis Syndrome; ULN = Upper Limit 
of Normal.
a Probably or definitely attributable to clinical TLS.
Source:  Cairo, 2004.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
187
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
188
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
189
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
190
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
191
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
192
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
193
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
194
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
195
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
196
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
197
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
198
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
199
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
200
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
201
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
202
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
203
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
204
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
205
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
206
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
207
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
208
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
209
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
210
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
211
APPENDIX M
RECOMMENDATIONS FOR THE MANAGEMENT OF 
TREATMENT-INDUCED DIARRHEA
The following published guidelines (Benson, 2004) were modified in order to be consistent with 
the study protocol.
Abbreviations: CBC= complete blood count; CID= chemotherapy-induced diarrhea; CTC= Common Toxicity 
Criteria; IV= intravenous; NCI= National Cancer Institute; RT= radiotherapy; SC= subcutaneous; tid= three times per 
day. 
*For radiation-induced cases and select subjects with CID, consider intensive outpatient management, unless the 
subject has sepsis, fever, or neutropenia.  
Source: Benson, 2004.
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
212
APPENDIX N
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
Overall Rationale for Protocol Amendment 2.0, 19 Dec 2022
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
213
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
214
2.0
Approved
930197534
2.0
v
Approved
1.0
v

CC-95251 (BMS-986351)
Protocol CA059-001
Celgene Corporation
Protocol CA059-001 Amendment 3.0
Final: 19 May 2023
215
2.0
Approved
930197534
2.0
v
Approved
1.0
v

EDMS Doc. Number: 25747159 - 25747050
CC-95251 (BMS-986351)
Summary of Changes CA059-001
Celgene Corporation
Confidential and Proprietary
3
CA059-001 Amendment 1: 17 Aug 2021
1.
JUSTIFICATION FOR AMENDMENT
The main purpose of this amendment is to reflect the revisions proposed by the Sponsor
 
.
Significant changes included in this amendment are summarized below:

Modification of the Primary Objective to determine the recommended Phase 2 dose 
(RP2D)
The maximal pharmacologic activity may be reached prior to reaching the 
 
, hence the determination of the 
 is removed from the study Primary objectives. 
The study seeks to define the dose with greatest clinical benefit without exceeding an acceptable 
rate of toxicity as specified in the protocol, which is the recommended Phase 2 dose (RP2D). The 
Primary objective is updated to define the RP2D of CC-95251 alone and in combination with 
antineoplastic agents in subjects with acute myeloid leukemia (AML) and myelodysplastic 
syndromes (MDS), and not the 
. 
The Safety Review Committee (SRC) will make dose escalation/de-escalation recommendations 
 
 
Revised sections: Protocol Summary; Section 2 Study Objectives and Endpoints, Section 3.1.1 
Part A, Section 3.1.2 Part B, Section 3.1.3 Part C, Section 7.2.1.1 CC-95251, Section 7.2.2 Dose 
Escalation Criteria, Section 7.2.4 Definition of 
, Section 7.2.6 
Criteria for Dose Escalation in the Next Cohort of Subjects, Section 7.2.7.1 Criteria for Stopping 
a Dose Cohort, Section 7.2.10 Criteria for Dose Increase, Section 9.1 Overview, Section 9.3 
Sample Size and Power Considerations, Section 9.7 Safety Analysis, Section 9.9.1 Statistical 
Method for Dose Escalation; 
 
; Table 1 Study Objectives

Clarification of treatment regimen for cohorts in Part B
The protocol has been updated to specify the treatment regimen including the sample size for
CC-95251 monotherapy and in combination with azacitidine cohorts in Part B.
 
 
Additional cohorts of subjects testing CC-95251 in combination with additional 
antineoplastic agents in subjects with R/R AML or R/R MDS may be considered at the
recommendation of the SRC and will be included by protocol amendment.
Revised sections: Protocol Summary; Section 1.3.2 Rationale for the Study Design, Section 3.1 
Study Design, Section 3.1.2 Part B, Section 9.1 Overview, Section 9.3 Sample Size and Power 
Considerations, Section 9.9.2 Stopping Rules Regarding Toxicity in Dose Expansion; 
Approved
2.0
v
Approved
1.0
v

EDMS Doc. Number: 25747159 - 25747050
CC-95251 (BMS-986351)
Summary of Changes CA059-001
Celgene Corporation
Confidential and Proprietary
4
CA059-001 Amendment 1: 17 Aug 2021

Statistical justification for sample sizes greater than 
 subjects in each of the 
expansion cohorts
The protocol has been updated to provide more details of statistical justification for sample sizes 
greater than 
 subjects in each of the expansion cohorts by using a 
 
.
Revised sections: Section 9.3 Sample Size and Power Considerations

Modification of interim futility analysis for expansion cohorts
Complete remission (CR) is the response endpoint reasonably likely to predict clinical benefit in 
patients with relapsed or refractory AML. Use of responses less than CR would not be sufficient 
to claim efficacy and continue accrual to a study, since use of an ineffective therapy may be 
detrimental to patients. 
 
A 
 analysis based on CRR has been added for Part C to avoid continued 
enrollment of previously untreated MDS subjects if preliminary results are not sufficiently 
promising.
Revised sections: Protocol Summary; Section 3.1.4.2 Treatment Period, Section 7.2.7.1 Criteria 
for Stopping a Dose Cohort, Section 9.9.2 Stopping Rules Regarding Toxicity in Dose 
Expansion;
 

Modification of the Eligibility Criteria related to MDS population, calcineurin 
inhibitors, and creatinine clearance 
Specific eligibility criteria have been revised to ensure patient populations are not placed at 
excess risk. The revised International Prognostic Scoring System (IPSS-R) score for eligible 
relapsed or refractory MDS subjects has been updated to 
, the IPSS-R score for previously 
untreated MDS subjects has been updated to 
. 
 
Subjects should have creatinine clearance of 
 ml/min using the Cockcroft-Gault equation.
Revised sections: Protocol Summary; Section 1.3.1 Study Rationale and Purpose, Section 1.3.2 
Rationale for the Study Design, Section 3.1 Study Design, Section 3.1.2 Part B, Section 3.1.3 
Part C, Section 4.2 Inclusion Criteria, Section 4.3 Exclusion criteria, Section 9.1 Overview, 
Section 9.3 Sample Size and Power Considerations

Modification of the hematologic dose-limiting toxicity (DLT) definition and the DLT 
criteria exceptions
Approved
2.0
v
Approved
1.0
v

EDMS Doc. Number: 25747159 - 25747050
CC-95251 (BMS-986351)
Summary of Changes CA059-001
Celgene Corporation
Confidential and Proprietary
5
CA059-001 Amendment 1: 17 Aug 2021
Specific non-hematologic toxicity exceptions to the DLT criteria were revised to ensure patient 
populations are not placed at excess risk.
Revised sections: Protocol Summary; Section 3.1.1 Part A, Section 3.1.4 Study Treatments, 
Section 7.2.3 Definition of a Subject Evaluable for DLT, Section 7.2.5 Definition of Dose-
Limiting Toxicity (DLT); Footnote ‘l’ in Table 3, 
.  

Modification of dose modifications for hematologic toxicities
Revised sections: Section 7.2.12 Dose Modification Guidelines, Section 7.2.13.4 Hematological 
Toxicity; 
  

Addition of safety labs to monitor for the potential risk for hemolysis
Subjects with MDS and AML often have severe baseline anemia and small shifts in hemoglobin 
may pose a significant safety risk. In order to monitor for hemolytic anemia, the protocol has 
been updated to check type and screen, 
 
Revised sections: 
, Section 6.2.6 Clinical Laboratory Tests, 
 
 
 
 
Approved
2.0
v
Approved
1.0
v

EDMS Doc. Number: 25747159 - 25747050
CC-95251 (BMS-986351)
Summary of Changes CA059-001
Celgene Corporation
Confidential and Proprietary
6
CA059-001 Amendment 1: 17 Aug 2021
The amendment also includes other minor clarifications and corrections:

Removal of ‘subjects with non-progressive disease’ from text describing study treatment and 
dosing of CC-95251 (Protocol Summary, Section 3.1.4 Study Treatments, Section 7.2.1.1 
CC-95251).

Addition of the statement that investigation of any other alternate dosing schedule beyond 
those stipulated in the current protocol version will be submitted in a protocol amendment
(Protocol Summary, Section 1.3.3 Rationale for Dose, Schedule and Regimen Selection, 
Section 3.1.1 Part A, Section 3.1.4 Study Treatments, Section 7.2.1.1 CC-95251, Section 
7.2.4 Definition of Maximum Tolerated Dose).

Addition of post-dose PK samples at steady state in Cycle 2 (Section 6.5 Pharmacokinetics; 
 

Clarification of the evaluation of minimal residual disease (MRD) to apply to the whole 
study (Section 2 Study Objectives and Endpoints, Section 6.4 Efficacy Assessment, Section 
6.6 Biomarkers, Pharmacodynamics, Pharmacogenomics; Table 1 Study Objectives).

Completion of Table 17 WHO classification of AML in Appendix B.

Other clarifications including content alignment, corrections of minor typographical errors 
and incidental formatting changes were made throughout the document.
Approved
2.0
v
Approved
1.0
v