Clinical trial NCT02719574
Conditions: Acute Myeloid Leukemia Acute Myelogenous Leukemia Myelodysplastic Syndrome
Keywords: AML MDS IDH1 IDH
Sponsor: Forma Therapeutics, Inc.
Start date: 2016-04-30; Completion date: 2024-01-24
Enrollment: 336 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 (olutasidenib) as a single agent or in combination with azacitidine or cytarabine. The Phase 1 stage of the study is split into 2 distinct parts: a dose escalation part, which will utilize an open-label design of FT-2102 (olutasidenib) (single agent) and FT-2102 (olutasidenib) + azacitidine (combination agent) administered via one or more intermittent dosing schedules followed by a dose expansion part. The dose expansion part will enroll patients in up to 5 expansion cohorts, exploring single-agent FT-2102 (olutasidenib) activity as well as combination activity with azacitidine or cytarabine. Following the completion of the relevant Phase 1 cohorts, Phase 2 will begin enrollment. Patients will be enrolled across 8 different cohorts, examining the effect of FT-2102 (olutasidenib) (as a single agent) and FT-2102 (olutasidenib) + azacitidine (combination) on various AML/MDS disease states.

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None arm 4: Relapsed or Refractory (R/R) AML arm 5: AML in morphologic complete remission or complete remission with incomplete blood count recovery (CR/CRi) after prior therapy with residual IDH1-R132 mutation arm 6: R/R AML/MDS, previously treated with FT-2102 arm 7: R/R AML/MDS that are naïve to prior hypomethylating therapy and IDH1 inhibitor therapy arm 8: R/R AML/MDS that have inadequately responded to or have progressed on prior hypomethylating therapy arm 9: R/R AML/MDS that have been previously treated with single-agent FT-2102 as their last therapy prior to study enrollment arm 10: Treatment naïve AML for whom standard treatments are contraindicated arm 11: Treatment naïve AML who are candidates for azacitidine first line treatment
Interventions: intervention 1: FT-2102 (olutasidenib) intervention 2: Azacitidine intervention 3: Cytarabine
Intervention descriptions: intervention 1: FT-2102 (olutasidenib) will be supplied as 50 mg or 150 mg capsules and will be administered per the protocol defined frequency and dose level intervention 2: azacitidine will be administered per site's standard of care intervention 3: low-dose cytarabine will be administered per site's standard of care

Protocol documents:
Prot_000.pdf: 
Cover Page for Protocol 
 
Sponsor name: 
FORMA Therapeutics, Inc 
NCT number 
NCT02719574 
Sponsor trial ID: 
2102-HEM-101 
Official title of study: 
A Phase 1/2, Multicenter, Open-label Study of FT-2102 as a 
Single Agent and in Combination with Azacitidine or 
Cytarabine in Patients with Acute Myeloid Leukemia or 
Myelodysplastic Syndrome with an IDH1 Mutation 
Document date: 
20 August 2020 
*Document date refers to the date on which the document was most recently updated. 
 


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
Page 1 of 114 
Forma Therapeutics, Inc. 
 
August 20, 2020 
CLINICAL STUDY PROTOCOL 
STUDY TITLE: 
A Phase 1/2, Multicenter, Open-label Study of FT-2102 as a Single 
Agent and in Combination with Azacitidine or Cytarabine in Patients 
with Acute Myeloid Leukemia or Myelodysplastic Syndrome with an 
IDH1 Mutation 
STUDY NUMBER: 
2102-HEM-101 
STUDY SPONSOR: 
Forma Therapeutics, Inc. 
500 Arsenal Street, Suite 100 
Watertown, MA 02472 
PROTOCOL: 
FINAL: 
Version 1/ Original 
 
November 30, 2015 
Version 2/ Amendment 1 
March 30, 2017 
Version 3/ Amendment 2 
October 20, 2017 
Version 4/ Amendment 3 
May 16, 2018 
Version 5/ Amendment 4 
January 25, 2019 
Version 6/ Amendment 5 
January 27, 2020 
Version 7/ Amendment 6 
August 20, 2020 
US IND NUMBER: 
127313 
EUDRACT NUMBER: 2017-001051-32 
CONFIDENTIAL
Redacted protocol 
Includes redaction of personal identifiable information only. 
. 


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August 20, 2020 
SIGNATURE OF CLINICAL INVESTIGATOR 
Study Title: 
A Phase 1/2, Multicenter, Open-label Study of FT-2102 as a 
Single Agent and in Combination with Azacitidine or 
Cytarabine in Patients with Acute Myeloid Leukemia or 
Myelodysplastic Syndrome with an IDH1 Mutation 
Protocol Number: 
2102-HEM-101 
Study Sponsor: 
Forma Therapeutics, Inc. 
500 Arsenal Street, Suite 100 
Watertown, MA 02472 
Telephone: 617-679-1970 
Facsimile: 617-679-1976 
Protocol Version: 
Version 7/ Amendment 6 
August 20, 2020 
Declaration of the Investigator: 
I confirm that I have read the above protocol, I understand it, and I will work according 
to the principles of Good Clinical Practices (GCPs) as described in the United States 
Code of Federal Regulations (CFR) – 21 CFR parts 50, 56, and 312, and the International 
Council on Harmonisation (ICH) document “E6(R2) Good Clinical Practice: Integrated 
Addendum to ICH E6(R1)” dated March 2018. Further, I will conduct the study in 
keeping with local legal and regulatory requirements. 
______________________________________________________________________________ 
Investigator’s Signature 
Date 
________________________________________________________________ 
Investigator’s Name / Title (Please print) 
________________________________________________________________ 
Institution or Affiliation 
CONFIDENTIAL




FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
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August 20, 2020 
SERIOUS ADVERSE EVENT REPORTING 
CONTACT FORMA THERAPEUTICS PHARMACOVIGILANCE WITHIN 
24 HOURS OF LEARNING OF ANY SERIOUS ADVERSE EVENT. IF THE 
SERIOUS ADVERSE EVENT IS FATAL OR LIFE THREATENING, 
FORMA THERAPEUTICS PHARMACOVIGILANCE MUST BE 
INFORMED IMMEDIATELY. 
Contact Forma Therapeutics Pharmacovigilance as described below, and complete a 
Serious Adverse Event report form: 
EMAIL OR FAX SAE REPORT 
FORM TO: 
GLOBAL MEDICAL MONITOR 
MEDICAL MONITOR 
ASIA/PACIFIC 
Attn: Forma Therapeutics 
Pharmacovigilance 
Fax: 1-617-321-4111 
Email:  
safety@formatherapeutics.com 
 
Cell: 
 
Email: 
 
 
Office: 
 
Cell: 
 
Email: 
 
For reporting of all Serious Adverse Events, Investigators must fax all completed 
pages of the SAE report form within 24 hours to the following: 
ATTENTION: FORMA THERAPEUTICS PHARMACOVIGILANCE 
FAX #: 1-617-321-4111 / Email: safety@formatherapeutics.com 
To discuss an SAE with the Medical Monitor, contact 
 or 
 
 Donato at the numbers provided above. Follow-up information to SAEs must be 
provided to Forma Therapeutics Pharmacovigilance within 24 hours of Investigator awareness. 
CONFIDENTIAL


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
 
Page 5 of 114 
Forma Therapeutics, Inc. 
 
 
August 20, 2020 
 
SYNOPSIS 
STUDY TITLE 
A Phase 1/2, Multicenter, Open-label Study of FT-2102 as a Single Agent and in 
Combination with Azacitidine or Cytarabine in Patients with Acute Myeloid Leukemia or 
Myelodysplastic Syndrome with an IDH1 Mutation 
SPONSOR 
Forma Therapeutics, Inc.  
500 Arsenal St., Suite 100 
Watertown, MA 02472 
STUDY  
RATIONALE 
The recent identification of frequent mutations in the isocitrate dehydrogenase 1 (IDH1) 
and isocitrate dehydrogenase 2 (IDH2) genes in human cancers including acute myeloid 
leukemia (AML) and myelodysplastic syndrome (MDS) has provided novel therapeutic 
targets in these diseases (Mardis et al. 2009; Cairns and Mak 2013). IDH mutation-specific 
inhibitors have been shown to reduce aberrantly elevated levels of the oncometabolite (R)-
2-hydroxyglutarate (2-HG), resulting in antitumor efficacy in preclinical models 
(Rohle et al. 2013; Saha et al. 2014). Inhibition of mutated IDH1 has recently demonstrated 
efficacy in AML and initial proof-of-concept in MDS patients (Fan et al. 2015; de Botton 
et al. 2015; DiNardo et al. 2018). 
IDH1 and IDH2 mutations in AML and glioma result in abnormal hypermethylation of 
histones and DNA and suppression of normal cellular differentiation. Treatment with the 
hypomethylating agent azacitidine causes tumor growth inhibition in a patient-derived 
IDH1-mutated glioma model by reducing DNA methylation and inducing glial 
differentiation (Borodovsky et al. 2013). Taken together, these data support the 
combination of FT-2102 and azacitidine in the treatment of patients with AML harboring 
IDH1 mutations. 
Low-dose cytarabine (LDAC) is considered a standard of care (SOC) treatment option for 
AML patients ≥ 60 years who are not candidates for intensive therapy. In a xenograft 
model, the combination of an IDH1 inhibitor with short duration low dose cytarabine 
decreased the bone marrow tumor burden better than either treatment alone 
(Yen et al. 2013). The combination of FT-2102 with LDAC in patients harboring an IDH1 
mutation might result in additive clinical benefit. 
PRIMARY 
OBJECTIVES 
Phase 1: 
• To determine the maximum tolerated doses (MTDs) or the maximum evaluated doses 
(MEDs), dose-limiting toxicities (DLTs), and the Phase 2 dose(s) of FT-2102 as a 
single agent, in combination with azacitidine, and in combination with cytarabine in 
patients with AML or MDS, harboring the IDH1-R132 mutation  
Phase 2: 
• To evaluate the antileukemic and antimyelodysplastic activity of FT-2102 as a single  
agent or in combination with azacitidine in patients with AML or MDS, harboring an 
IDH1-R132 mutation  
SECONDARY 
OBJECTIVES 
Phase 1: 
• To determine the pharmacokinetics (PK) of FT-2102 as a single agent and in 
combination with azacitidine or cytarabine 
• To observe patients for any evidence of antileukemic or antimyelodysplastic activity 
of FT-2102 as a single agent and in combination with azacitidine or cytarabine 
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Phase 2: 
• To confirm the safety of FT-2102 as a single agent and in combination with
azacitidine
• To evaluate additional measures of the antileukemic or antimyelodysplastic activity of
FT-2102 as a single agent and in combination with azacitidine
• To determine the PK of FT-2102 as a single agent and in combination with azacitidine
EXPLORATORY 
OBJECTIVES 
Phase 1 and Phase 2: 
•
To assess on-target activity of FT-2102, as determined by changes in a
pharmacodynamic (PD) biomarker in plasma
•
To determine the frequency of cancer-associated mutations and/or genetic alterations
in responding and nonresponding patients
•
To evaluate PK/PD and clinical response relationships in each cohort
Phase 2:
•
To evaluate the health-related quality of life (QOL) of patients receiving FT-2102 as a
single agent or in combination with azacitidine
STUDY 
ENDPOINTS 
Primary Endpoints 
Phase 1: 
•
Incidence and severity of adverse events (AEs), clinical laboratory abnormalities and
changes in electrocardiogram (ECG) parameters
Phase 2: 
• All cohorts except Cohort 2: Complete Response rate (best overall response [BOR] of
complete remission [CR]/ complete remission with partial hematological recovery
[CRh]) as determined by the investigator per disease-specific criteria. Refer to
Appendix 7 for AML and Appendix 8 for MDS response criteria
•
Cohort 2: Four-month relapse free survival (RFS) rate
Secondary Endpoints 
Phase 1: 
•
PK parameters derived from FT-2102 concentrations
•
Antileukemic or antimyelodysplastic activity as determined by CR, CRh, CRi, MLFS,
Marrow CR, PR, and SD
Phase 2: 
•
Evidence of clinical benefit (complete remission with incomplete blood count
recovery [CRi], morphologic leukemia-free state [MLFS], Marrow CR, Overall
Response [OR], Time to Response [TTR], Duration of Response [DOR], event free
survival [EFS], RFS, overall survival [OS], and other definitions of response,
including Stable Disease [SD])
•
Incidence and severity of adverse events (AEs), clinical laboratory abnormalities and
changes in ECG parameters
•
PK parameters derived from plasma FT-2102 concentrations
Exploratory Endpoints 
Phase 1 and Phase 2: 
•
Changes in 2-HG levels (PD biomarker) in plasma
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•
Cancer-associated mutations and/or genetic alterations
•
PK/PD in relationship with clinical safety and clinical activity
Phase 2: 
Health-related QOL of patients as assessed by a patient-reported questionnaire 
STUDY DESIGN 
This is a multicenter, open-label Phase 1/2 study of FT-2102 administered orally to 
patients with AML or MDS. Patients will be given FT-2102 daily in continuous 28-day 
cycles, alone or in combination with azacitidine or low dose cytarabine until treatment 
discontinuation. 
This study is comprised of 3 stages: a Phase 1 dose-escalation stage, a Phase 1 Dose-
expansion stage, and a Phase 2 stage. 
Phase 1 Dose-escalation Stage: 
Dose escalation will be initiated using FT-2102 as a single agent in patients with AML or 
MDS harboring an IDH1-R132 mutation, as determined by local mutation testing. It is 
planned that doses of 150 and 300 mg FT-2102 once daily (QD) will be tested. Twice daily 
(BID) dosing and/or dosing with food to improve on bioavailability may be explored when 
indicated. 
On the initial schedule (Schedule 1), FT-2102 will be given orally QD in continuous 
28-day cycles. An alternative schedule (Schedule 2) of FT-2102 administered orally BID
may be initiated based upon observed PK and clinical observations.
This study will utilize a 3+3 dose escalation design, whereby three patients will be treated 
and if a DLT occurs, then the cohort will be expanded to six patients to determine a non-
tolerated dose and MTD. The dose-escalation portion of the study will allow dose increases 
of up to 50% between cohorts above the 300 mg total daily dose level until the MTD or an 
MED is determined. Initiation of Schedule 2 will occur following analysis of PK/PD 
parameters and clinical observations, and may be independent of an MTD in Schedule 1. 
Dose escalation will stop if an intolerable dose is identified. 
During the course of dose escalation, a parallel escalation arm will be initiated for  
FT-2102 in combination with azacitidine in patients with AML or MDS harboring an 
IDH1-R132 mutation. Dose escalation in the azacitidine combination will initiate 
following determination of a pharmacodynamically active dose of FT-2102 (single-agent 
[SA] schedule). The starting dose of FT-2102 in the combination agent is a dose level at 
which ≤ Grade 2 toxicities (i.e., no Grade 3 or higher toxicities) were observed when FT-
2102 was administered as a single agent. This escalation will also enroll patients on a 3+3 
design, whereby three patients will be treated and if one DLT occurs, then the cohort will 
be expanded to six patients; if more than one DLT occurs, escalation will stop at that dose 
level (or schedule). 
Phase 1 Dose-expansion Stage: 
Once the MTD or MED has been identified for the SA or azacitidine combination cohorts, 
up to 14 additional patients may be enrolled in up to 2 expansion cohorts each of SA  
FT-2102 or in combination with azacitidine in selected populations of patients with 
AML/MDS harboring IDH1-R132 mutations. These dose-expansion cohorts will evaluate 
FT-2102 or the combination at doses of FT-2102 ≤ MTD/MED to 1) further define the 
safety profile of SA FT-2102 or the azacitidine combination and 2) to provide an initial 
assessment of antileukemic or antimyelodysplastic activity. From these dose expansion 
cohorts, a recommended Phase 2 dose (RP2D) of FT-2102 as a single agent or in 
combination with azacitidine will be selected for subsequent evaluation in Phase 2.  
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After dose-expansion is complete for FT-2102 as a single agent and FT-2102 in 
combination with azacitidine, a cohort of 6 patients with AML harboring IDH1 mutation 
will be treated with FT-2102 in combination with cytarabine 20 mg BID for 10 days, and 
then cytarabine will be stopped for 18 days. FT-2102 will be given in accordance with 
dosing schedule × 28 days out of 28 days.  
The starting dose of FT-2102 will be the 150 mg BID dose. Further dose-escalation of FT-
2102 in combination with LDAC will not occur beyond 150 mg BID.  
If > 1 DLTs are observed at the 150 mg BID dose in combination with cytarabine, a lower 
dose level may be explored. 
Recommended Phase 2 dose 
FT-2102 150 mg BID is the RP2D confirmed for single-agent and azacitidine combination 
treatment.  
Phase 2:  
Phase 2 cohorts may include the following: 
Cohort 1 (SA FT-2102): approximately 173 evaluable patients with R/R AML. To account 
for potential discordance between local and central mutation testing, approximately 
190 patients may be enrolled into this cohort. 
Cohort 2 (SA FT-2102): approximately 53 patients with AML in morphologic CR/CRi 
after prior therapy (+/- hematopoietic stem cell transplantation [HSCT]) with residual 
IDH1-R132 mutation (≥ 0.01%) detected in the bone marrow.  
Cohort 3 (SA FT-2102): approximately 20 patients with R/R AML/MDS that have been 
previously treated with FT-2102. Patients who undergo HSCT on-study then relapse post-
HSCT are allowed in this cohort.  
Cohort 4 (FT-2102 in combination with azacitidine): approximately 20 patients with R/R 
AML/MDS that are naïve to prior hypomethylating therapy and IDH1 inhibitor therapy. 
Cohort 5 (FT-2102 in combination with azacitidine): approximately 20 patients with R/R 
AML/MDS that have inadequately responded to or have progressed on prior 
hypomethylating therapy. 
Cohort 6 (FT-2102 in combination with azacitidine): approximately 44 patients with R/R 
AML/MDS who have been previously treated with SA FT-2102 as their last therapy prior 
to study enrollment. The actual number of patients in this cohort may be larger, since 
patients from the FT-2102 SA cohorts of this study are allowed to be enrolled in Cohort 6 
after their disease progression. 
Cohort 7 (SA FT-2102): approximately 54 treatment naïve AML patients for whom 
standard treatments are contraindicated. 
Cohort 8 (FT-2102 in combination with azacitidine): approximately 28 treatment naïve 
AML patients who are candidates for azacitidine first line treatment. 
Safety will be assessed throughout the study. Safety variables assessed will include AEs, 
concomitant medications, clinical laboratory tests, vital signs measurements, physical 
examination findings, and ECG readings (see manual for details of Holter monitoring 
procedures). 
Efficacy/determination of clinical benefit will be based on investigator’s assessment using 
disease-specific criteria, i.e., derived from the IWG/modified IWG criteria for AML 
(2003) and MDS (2006). 
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Plasma concentrations of FT-2102 will be determined by validated and sensitive 
bioanalytical methods. The PD biomarker is the change in 2-HG levels in plasma. 
Assessment of the presence and frequency of cancer-associated mutations and/or genetic 
alterations will be performed at a central laboratory. 
Health-related QOL of patients will be assessed by the EuroQol-5D (EQ-5D-5L). 
The study Schedule of Events are provided in Appendix 1 and Appendix 2. 
DURATION 
It is estimated that this study will last approximately 48 months. The total duration of study 
treatment for each patient is expected to be approximately 26 weeks. Study drug will be 
taken orally and daily (either QD or BID) in 28-day continuous cycles from Day 1 until 
treatment discontinuation criteria are met. 
Study treatment should be discontinued if any of the following events occur: 
•
Unacceptable AE or failure to tolerate study therapy
•
Delay in dosing of > 28 days, without approval of Sponsor
•
Treatment failure (i.e., progression or relapse) (see Section 4.3, Table 3 for
definition)
•
Hematopoietic Stem Cell Transplant (HSCT)
•
Withdrawal of consent (no further study participation)
•
Patient decision to discontinue study treatment
•
Discretion of the Investigator
•
Major protocol violation
•
Pregnancy
•
Lost to follow-up
•
Death
•
Termination of the study by Sponsor
Patients will be followed for safety after treatment discontinuation (last dose of study drug) 
to monitor for AEs for 28 days, or until resolution or stabilization of AEs, except for 
patients who withdraw consent. 
Patients who discontinue for reasons other than disease progression/relapse or withdrawal 
of consent will continue to be followed for response until progression/relapse occurs. 
Patients who achieve an adequate response to study treatment and meet other criteria 
required to undergo HSCT may proceed to HSCT after discontinuation of study treatment 
and will be followed on study for disease evaluation and any new HSCT conditioning or 
other new antineoplastic therapies received until disease relapse, death, withdrawal of 
consent, lost to follow-up, or end of study. Additional detail on follow-up for patients who 
undergo HSCT is provided in Section 4. 
Patients participating in Phase 1 may be followed for survival for up to 12 months from 
C1D1 or for 28 days after treatment discontinuation (whichever is longer). 
Patients participating in Phase 2 may be followed for survival for up to 36 months from 
C1D1 or for 28 days after treatment discontinuation (whichever is longer). 
PLANNED TOTAL 
SAMPLE SIZE 
Phase 1: Approximately 110 patients may be enrolled in the dose-escalation and 
dose-expansion stages. 
Phase 2: Approximately 429 patients may be enrolled in the 8 proposed Phase 2 cohorts. 
CONFIDENTIAL


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TEST ARTICLE, 
ADMINISTRATION 
AND DOSE 
ESCALATION 
SCHEME 
This study may explore multiple potential schedules for FT-2102. On the initial schedule 
(Schedule 1), FT- 2102 will be given orally QD in continuous 28-day cycles as shown in 
the following table.  
An alternative schedule (Schedule 2) of FT-2102 administered orally BID may be initiated 
based on observed PK and clinical observations in Schedule 1 (e.g., half-life of FT-2102); 
the establishment of a MTD in Schedule 1 is not a prerequisite to initiating Schedule 2. 
The starting dose in Schedule 2 will be calculated from the projected dose level on 
Schedule 1. 
Single-Agent (FT-2102) 
Schedule 1a (Complete) 
Dose Level 
% Increments from prior dose level 
Dose (mg) 
1 
— 
150 mg QD 
2 
Up to 100% 
≤ 300 mg QD 
3 
Up to 50% 
≤ 450 mg QD 
4 
Up to 50% 
TBD 
Single-Agent (FT-2102) 
Schedule 2b (Complete) 
Dose Level 
% Increments from prior dose level 
Dose (mg) 
1 
— 
TBD BID 
2 
TBD based on safety experience 
TBD 
3 
TBD based on safety experience 
TBD 
4 
TBD based on safety experience 
TBD 
Combination Agent (FT-2102 + Azacitidinec) 
Schedule 1a (Complete) 
Dose Level 
% Increments from prior dose level 
Dose (mg) 
FT-2102 
Azacitidine 
1 
— 
QDd 
75 mg/m2 
2 
TBD based on safety experience 
TBD 
75 mg/m2 
3 
TBD based on safety experience 
TBD 
75 mg/m2 
4 
TBD based on safety experience 
TBD 
75 mg/m2 
Combination Agent (FT-2102 + Azacitidinec) 
Schedule 2b (Complete) 
Dose Level 
% Increments from prior dose level 
Dose (mg) 
FT-2102 
Azacitidine 
1 
— 
BIDd 
75 mg/m2 
2 
TBD based on safety experience 
TBD 
75 mg/m2 
3 
TBD based on safety experience 
TBD 
75 mg/m2 
4 
TBD based on safety experience 
TBD 
75 mg/m2 
Combination Agent (FT-2102 + LDACe) 
Schedule 2 onlyb 
Dose Level 
% Increments from prior 
dose level 
Dose (mg) 
FT-2102 
LDAC 
1 
— 
150 mg BID 
20 mg BID 
AML = acute myeloid leukemia; BID = twice daily; LDAC = low-dose cytarabine; N/A = not 
applicable; QD = once daily; SA = single agent; TBD = to be determined. 
a
Schedule 1 is QD dosing of FT-2102 on a 28-day schedule. 
b
Schedule 2 is BID dosing of FT-2102 on a 28-day schedule. 
Note: Due to a 24-hour PK collection on Cycle 1 Day 2 (C1D2), the second dose of FT-2102 
should not be administered on Cycle 1 Day 1 (C1D1).  
c
Combination agent (FT-2102 + azacitidine): azacitidine will be administered via subcutaneous 
injection or intravenous infusion in combination with FT-2102 for seven days, and then 
azacitidine will be stopped for 21 days. A 48-hour dose-interruption of the azacitidine for 
weekends or holidays is allowed. FT-2102 will be given in accordance with dosing schedule × 
28 days out of 28 days. 
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d
The starting dose of FT-2102 in the combination agent is a dose level at which ≤ Grade 2 
toxicities (i.e., no Grade 3 or higher toxicities) were observed when FT-2102 was administered 
as a single agent. 
e
After dose-expansion is complete for FT-2102 as a single agent and FT-2102 in combination 
with azacitidine, a cohort of 6 patients with AML harboring IDH1 mutation will be treated 
with FT-2102 in combination with cytarabine 20 mg BID for 10 days, and then cytarabine will 
be stopped for 18 days. FT-2102 will be given in accordance with dosing schedule × 28 days 
out of 28 days. 
If the PK analysis indicates that absorption/bioavailability of FT-2102 dosed either QD or 
BID does not increase with increasing dose levels, dose escalation of FT-2102 in the 
presence of food will be explored. The starting dose of FT-2102 dose-escalation in the 
presence of food will be a QD dose intended to approximate the FT-2102 exposures 
already achieved in the clinic and found to be tolerable. Intra-patient dose escalation/dose 
adjustment within this initial dosing cohort may be considered if the observed exposures 
fall below the predicted target range. 
The DLT dose level is defined as the lowest dose level at which DLT is experienced in two 
or more patients at the same dose level. The MTD is the highest dose level that does not 
meet the DLT dose level definition. The MED is defined as the highest dose level 
evaluated when an MTD is not defined.  
Dose escalation will utilize a 3+ 3 design to define a MTD/MED in one or more selected 
schedules. For the 3+3 dose escalation design, three patients will be treated at the current 
dose level. The first cohort of patients will initiate treatment at dose level 1. If no patient 
experiences a DLT during the Cycle 1 28-day post-dose DLT monitoring period, 
subsequent dose escalation will proceed as described in the previous table. 
Dose escalation in the azacitidine combination will initiate following determination of the 
pharmacodynamically active dose of FT-2102 (single-agent schedule).  
The starting dose of FT-2102 in the combination agent is a dose level at which ≤ Grade 2 
toxicities (i.e., no Grade 3 or higher toxicities) were observed when FT-2102 was 
administered as a single agent. This escalation will also enroll patients on a 3+3 design, 
whereby three patients will be treated and if a DLT occurs, then the cohort will be 
expanded to up to six patients. 
After dose-expansion is complete for FT-2102 as a single agent and FT-2102 in 
combination with azacitidine, a cohort of 6 patients with AML harboring IDH1 mutation 
will be treated with FT-2102 in combination with cytarabine. The starting dose of FT-2102 
will be the 150 mg BID dose. Further dose-escalation of FT-2102 in combination with 
LDAC will not occur beyond 150 mg BID.  
If > 1 DLTs are observed at the 150 mg BID dose in combination with cytarabine, a lower 
dose level may be explored. The dose-escalation portion of the study will allow dose 
increases of up to 50% between cohorts above the 300 mg total daily dose level until the 
MTD or a MED is determined. Additional intermediate dose levels may be explored as 
clinically indicated. After discussion between the Investigators and Sponsor, it may be 
recommended that additional patients be enrolled in one or more cohorts. 
Patient entry and dose escalation will be based upon occurrence of DLTs in all patients at 
each dose level. Adverse events will be reviewed with the Investigators and the medical 
monitor at specific timepoints during the conduct of the study. A review will be performed 
in the dose-escalation portion of the protocol prior to the opening of a new dose level and 
to discontinue dose escalation if the MTD has been reached. 
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In the 3+3 portion of the dose-escalation phase, three patients will be enrolled in each 
cohort. 
•
A patient will not be enrolled at the next higher dose level until all patients at the
current dose level have completed the 28-day DLT monitoring period.
•
If one of the initial three patients has a DLT before the end of Cycle 1, the cohort
will be expanded to up to six patients. If five of a total of six patients complete the
full Cycle without a DLT, escalation may continue.
INCLUSION 
CRITERIA 
1.
Pathologically proven AML (except acute promyelocytic leukemia with the t(15;17)
translocation) or intermediate, high risk or very high risk MDS as defined by the
World Health Organization (WHO) criteria or Revised International Prognostic
Scoring System (IPSS-R) harboring IDH1-R132 mutations, and one of the
following based on enrollment stage or treatment cohort:
a.
Single Agent Phase 1 Cohorts including Dose-Escalation/Dose-
Expansion: AML/MDS either R/R to standard therapy, or for whom
standard treatments are contraindicated
b.
Combination (FT-2102 + azacitidine) Phase 1 Dose-Escalation/
Dose-Expansion (patients must meet one of the following):
i.
Patients with AML that is either R/R to standard therapy, or for
whom standard treatments are contraindicated
ii.
Patients that have MDS that is either R/R to standard therapy, or are
treatment-naïve, who are eligible for azacitidine therapy
c.
Combination (FT-2102 + Cytarabine) Phase 1 Dose-Escalation/Dose-
Expansion Cohort: Patients ≥ 60 years with treatment-naïve AML for
whom standard treatments are contraindicated
d.
Phase 2 Cohort 1 (Single Agent) only: AML R/R to standard therapy
e.
Phase 2 Cohort 2 (Single Agent) only: AML in morphologic CR/CRi
after prior therapy (+/- HSCT) with residual IDH1-R132 mutation
(≥ 0.01%) detected in the bone marrow
f.
Phase 2 Cohort 3 (Single Agent) only: R/R AML/MDS that have been
previously treated with FT-2102 AND for whom standard treatments are
contraindicated
g.
Phase 2 Cohort 4 (FT-2102 + Azacitidine) only: Patients < 60 years old
with R/R AML/MDS with no prior hypomethylating agent therapy AND
no prior IDH1 inhibitor therapy
h.
Phase 2 Cohort 5 (FT-2102 + Azacitidine) only: R/R AML/MDS that
have inadequately responded to or have progressed on prior treatment with
a hypomethylating agent
i.
Phase 2 Cohort 6 (FT-2102 + Azacitidine) only: R/R AML/MDS that
have been previously treated with single agent FT-2102 as their last
therapy prior to study enrollment
j.
Phase 2 Cohort 7 (Single Agent) only: Treatment naïve AML patients for
whom standard treatments are contraindicated
k.
Phase 2 Cohort 8 (FT-2102 + Azacitidine) only: Treatment naïve AML
patients who are candidates for azacitidine first line treatment.
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•
Note for Phase 2 Cohort 7 and Phase 2 Cohort 8: Treatment naïve is
defined as no prior treatment for AML. Patients may have received a
prior treatment for another hematologic malignancy.
2.
Patients must have documented IDH1-R132 gene-mutated disease as evaluated by
the site
3.
Patients ≥ 18 years old
4.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
(see Appendix 3)
5.
Signed informed consent prior to beginning study and undergoing procedures
6.
No prior solid organ allograft
7.
Acceptable liver function:
a.
Bilirubin ≤ 2 times upper limit of normal (ULN) (≤ 3 times ULN in
patients with Gilbert Syndrome)
b.
Aspartate transaminase (AST, also referred to as SGOT), alanine
transaminase (ALT, also referred to as SGPT) and alkaline phosphatase
(ALP) ≤ 3 times ULN
8.
Acceptable renal function:
a.
Serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance
≥ 50 mL/min (Cockcroft and Gault 1976)
9.
Recovery from the non-hematologic toxic effects of prior treatment to Grade ≤ 1,
or baseline value according to NCI CTCAE classification (excluding infertility,
alopecia, or Grade 1 neuropathy)
10. Baseline QTcF ≤ 450 msec (average of the QTcF values of screening triplicate
ECGs)
Note: This criterion does not apply to patients with a bundle branch block (BBB);
for patients with BBB, a cardiology consult is recommended to ensure that QTcF is
not prolonged.
11. Negative serum pregnancy test if female of childbearing potential
12. For fertile men and women, agreement to use highly effective contraceptive methods
for the duration of study participation and 90 days after the last dose of study
medication (Section 5.6.1).
13. Agreement for male patients not to donate sperm and for female patients of
childbearing potential not to donate ova during the study and for 90 days after the
final dose of study drug (Section 5.6.2).
14. Phase 2 Cohorts 1 - 8 (SA and combination) only: Pre-treatment peripheral blood
and bone marrow aspirate available for retrospective central confirmation of IDH1-
R132 mutation is required
Note: Central confirmation of IDH1-R132 mutation is not required for study
enrollment.
EXCLUSION 
CRITERIA 
1.
Phase 1 Single Agent Dose-escalation/Dose-expansion Cohorts and Phase 2
Cohorts 1, 4, 5, 7 and 8 only: Patients who have been treated with an IDH1 targeted
therapy are excluded
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2.
Phase 2 Single Agent Cohorts 1-3 and 7 only: Patients with IDH2 mutation
detection at baseline or history of IDH2m inhibitor treatment are excluded
3.
History of prior malignancy unless disease-free for ≥ 12 months or considered
surgically cured; patients with nonmelanoma skin cancers or with carcinomas in situ
are eligible regardless of the time from diagnosis (including concomitant diagnoses)
4.
Patients with symptomatic central nervous system (CNS) metastases or other tumor
location (such as spinal cord compression, other compressive mass, uncontrolled
painful lesion, bone fracture, etc.) necessitating an urgent therapeutic intervention,
palliative care, surgery or radiation therapy
5.
Patients with previous allogeneic HSCT if they meet any of the following criteria:
< 100 days from time of HSCT; active acute or chronic graft vs. host disease
(GvHD); or receiving immunosuppressive therapy as treatment or prophylaxis
against GvHD
Note: Doses < 20 mg methylprednisolone (or its equivalent) daily are not an
exclusion criterion.
6.
Treatment with radiation therapy, major surgery (requiring general anesthesia) within
one month prior to study drug dosing
7.
Treatment with chemotherapy or small molecule anticancer therapeutic within five
half-lives of the agent or within 21 days if the half-life is unknown. Patients re-
enrolling in Cohort 6 after relapse/progression on Cohort 1 are exempt from this
washout requirement (i.e. can continue FT-2102 treatment until re-enrollment)
8.
Treatment with an anticancer therapeutic antibody less than four weeks before first
dose of study drug
9.
Treatment with other experimental therapies or participation in another clinical trial
within a period of time that is less than the cycle length or within 21 days prior to
starting study drug, whichever is shorter
10. Patients unable to swallow oral medications, or patients with gastrointestinal
conditions (e.g., malabsorption, resection, etc.) deemed by the Investigator to
jeopardize intestinal absorption
11. Congestive heart failure (New York Heart Association Class III or IV) or unstable
angina pectoris; previous history of myocardial infarction within one year prior to
study entry, uncontrolled hypertension, or uncontrolled arrhythmias (see
Appendix 5)
12. Patients with a family history of QT prolongation
13. Concomitant medication(s) known to cause Torsades de Pointes (TdP) initiated less
than the duration required to reach steady-state plasma concentration (approximately
five half-lives) before first dose of study drug (see Appendix 6) (medications used as
needed [PRN] (e.g. Zofran) are exempt)
14. Concurrent treatment with chronic corticosteroids except if chronic treatment with
< 20 mg of methylprednisolone daily or equivalent (pulse steroids for treatment or
prophylaxis are allowed [e.g., for transfusion or medication reactions])
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15. Known HIV positivity
16. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
(prophylactic systemic antimicrobials permitted)
17. Uncontrolled disease-related metabolic disorder (e.g., hypercalcemia)
18. Pregnant or nursing women or women of childbearing potential not using highly
effective contraception; male patients not using highly effective contraception
Note: Women of childbearing potential (see Section 5.6) and men must agree to use
highly effective contraception (see Section 5.6.1) prior to study entry and for the
duration of study participation and 90 days after.
Should a woman become pregnant or suspect she is pregnant while participating in
this study, she should inform her treating physician immediately.
19. Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions)
that could compromise protocol objectives in the opinion of the Investigator and/or
the Sponsor
20. Unwillingness or inability to comply with procedures either required in this protocol
or considered standard of care
21. Medical, uncontrolled disease-related metabolic disorder, psychiatric, cognitive, or
other conditions that may compromise the patient’s ability to understand the patient
information, give informed consent, comply with the study protocol, or complete the
study
22. History of severe allergic reaction to azacitidine (if patient enrolling into azacitidine
combination cohort) or low-dose cytarabine (if patient enrolling into cytarabine
combination cohort)
23. Prisoners or patients who are involuntarily incarcerated or are compulsorily detained
for treatment of either a psychiatric or physical (e.g. infectious disease) illness
Note: Under certain specific circumstances, a person who has been imprisoned may
be included or permitted to continue as a patient, if local regulations permit. Strict
conditions apply and Forma’s approval is required.
DATA 
EVALUATION 
Standardized electronic CRFs (eCRFs) will be constructed for the study. Weekly-twice a 
month conference calls with each site will be put in place during Phase 1. 
Monthly conference calls with each site will be put in place during Phase 2. All sites will 
be monitored approximately every 4-8 weeks, depending on enrollment. 
STATISTICAL 
METHODOLOGY 
Sample Size Considerations: 
Dose-escalation stage sample sizes are determined per traditional 3+3 design. The number 
of patients in the dose-expansion stage is based on safety considerations. 
Phase 2 sample sizes are as described below. 
Cohort 1 is based on a group sequential design with one futility interim analysis at the time 
of ~33% of patients and one efficacy interim analysis at the time of ~66% of patients 
completing the first response assessments. A total of 173 evaluable patients will have 90% 
power on a 1-sided 2.5% significance level.  
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Cohort 2 is based on a Simon’s 2-stage design for a 4-month RFS rate. Overall, 
53 patients, with a futility interim at 11 evaluable patients completing the first response 
assessment, will have approximately 80% power on a 1-sided 2.5% significance level.  
Cohorts 3, 4, and 5 are designed by controlling the lower limit of the 85% confidence 
internal for the estimated rate of response to be at least 10% or more. A total of 20 
evaluable patients is anticipated to be enrolled in order to estimate the response rate to this 
degree. 
Cohort 6 is based on a Simon’s 2-stage design for a response rate. With approximately 
44 evaluable patients and a futility interim at 14 evaluable patients completing the first 
response assessment, the cohort would have 80% power on a 1-sided test with a 
significance level of 5%.  
Cohort 7 uses a Simon’s 2-stage design to test whether the response rate of patients 
receiving FT-2102 is greater than 25%. Seventeen (17) patients will be enrolled into stage 
1, and 37 into Stage 2, for a total of 54 evaluable patients. Assuming the response rate of 
FT-2102 treated patients is 45%, this design has 80% power on a 1-sided test using a 2.5% 
significance level. 
Cohort 8 uses a Simon’s 2-stage design to test whether the response rate of patients 
receiving FT-2102 is greater than 25%. Seven (7) patients will be enrolled into stage 1, and 
21 into Stage 2, for a total of 28 evaluable patients. Assuming the response rate of FT-2102 
+ azacitidine treated patients is 55%, this design has 80% power on a 1-sided test using a
2.5% significance level.
Analysis Populations: 
DLT-Evaluable Set will include all Phase 1 patients who enrolled in the dose escalation 
cohorts and who have received at least one dose of FT-2102 and completed at least 75% of 
doses in the first cycle during the DLT evaluation period or have discontinued / interrupted 
due to adverse events meeting the DLT evaluation criteria. This set will be used for DLT 
analyses only, unless otherwise specified. 
Safety Analysis Set will include all patients who have received at least one dose of study 
drug (FT-2102, azacitidine, or cytarabine). All safety analyses will be based on the Safety 
Set unless otherwise specified. Patients will be analyzed under the first dose level received 
by the patient. 
Full Analysis Set (FAS) will include all patients who were enrolled in the study and 
received at least one dose of FT-2102. This analysis set will be used for efficacy analyses. 
Patients will be analyzed under the assigned dose. 
Efficacy Evaluable (EE) Set will include all patients in Phase 2 Cohort 1 with confirmed 
IDH1-R132 (by central lab) who have received the first dose of FT-2102 at least 6 months 
prior to the analysis cutoff date or who have died, progressed, or discontinued study 
participation. This analysis set is the primary set for Phase 2, Cohort 1 efficacy evaluation. 
Per Protocol (PP) Analysis Set is a subset of patients in the EE set, excluding patients who 
have protocol violations that could impact the evaluation of the efficacy of FT-2102. Some 
violations that would result in exclusion from the PP Analysis Set are: not meeting all 
inclusion/ exclusion criteria for a particular cohort, having received chemotherapy not per 
protocol, received starting dose of FT-2102 other than 150 mg BID, not having at least one 
post-baseline response assessment. The full list of protocol violations will be reviewed on a 
de-identified basis by the medical, data management, and statistical leads prior to locking 
the database, and membership in the PP Analysis Set will be documented and determined 
based on that review. 
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PK Analysis Set consists of patients for whom it is possible to calculate at least one 
primary PK parameter (e.g. Cmax, AUClast and AUCinf) and who do not have any major 
protocol deviations thought to influence the absorption, distribution, metabolism and 
excretion of the FT-2102.  
PD Analysis Set consists of all patients who have received at least one dose of FT-2102 
and have completed at least one PD assessment. The PD Analysis Set will be used for 
PK/PD-related analyses unless otherwise specified. 
Efficacy Analyses: 
The analyses of response will be based on disease-specific criteria derived by the 
investigator from the IWG/ modified IWG criteria for AML (2003) and MDS (2006).   
The primary efficacy endpoint for all Phase 2 cohorts except for Cohort 2 is the complete 
response rate (CR + CRh), which will be tabulated by study phase, cohort, and dose based 
on the best overall response. Phase 2 Cohort 1 will test the complete response rate using a 
1-sided exact binomial test for one proportion, with a 2.5% significance level. Other Phase 
2 cohorts have different hypothesis tests, further described in Section 9.2.2. Additionally, 
the ORR will be calculated for each cohort, presented with the corresponding 95% 
confidence intervals, based on exact binomial methods. Number and percentage of patients 
within other response categories will also be presented by dose/dosing schedule and visit.  
The primary efficacy endpoint for Phase 2 Cohort 2 is 4-month RFS, further described in 
Section 9.2.4.3.   
Analyses of DOR, TTR, EFS, RFS, and OS will be based on Kaplan-Meier methods for 
each cohort; the median time will be tabulated along with the 95% confidence intervals. 
Safety Analyses: 
 
All safety analyses will be descriptive in nature and based on the Safety Set. 
Number of DLTs, based on the DLT-Evaluable Set, will be summarized by dose level.  
Safety data, including adverse events, safety laboratory values, vital signs, physical 
examination findings, and ECG results, will be based on the Safety Set, summarized by 
study stage and phase and by dose, and listed in the individual data listings as appropriate.  
For selected safety parameters, National Cancer Institute Common Terminology Criteria 
for Adverse Events (MedDRA version 19.1) grades and the corresponding shift from 
baseline grade may be evaluated, based on the Safety Set, if available data permit.  
Additional efficacy and safety analyses will be specified in the Statistical Analysis Plan. 
 
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TABLE OF CONTENTS 
LIST OF TABLES .........................................................................................................................23 
LIST OF FIGURES .......................................................................................................................23 
LIST OF APPENDICES ................................................................................................................23 
ABBREVIATIONS .......................................................................................................................24 
1 BACKGROUND .....................................................................................................................27 
1.1 
Pharmacology ..............................................................................................................27 
1.2 
Toxicokinetics ..............................................................................................................27 
1.3 
Enzyme-Mediated Drug-Drug Interaction Potential ....................................................28 
1.4 
Toxicology ...................................................................................................................28 
1.5 
Clinical Rationale .........................................................................................................29 
1.5.1 
Recommended Phase 2 Dose Selection and Rationale .......................................30 
2 STUDY OBJECTIVES ............................................................................................................31 
3 STUDY ENDPOINTS .............................................................................................................32 
4 STUDY DESIGN.....................................................................................................................33 
4.1 
Phase 1 Dose-Escalation Stage ....................................................................................35 
4.1.1 
Single-Agent (SA) Dose Escalation (Complete) ................................................35 
4.1.2 
FT-2102 + Azacitidine (Combination) Dose-Escalation (Complete) .................36 
4.1.3 
Definition of Dose-Limiting Toxicity.................................................................38 
4.1.4 
Phase 1 Dose-Expansion Stage ...........................................................................38 
4.2 
Phase 2 Stage ...............................................................................................................39 
4.3 
Response Assessment ..................................................................................................40 
4.4 
Eligibility Criteria ........................................................................................................42 
4.4.1 
Inclusion Criteria ................................................................................................42 
4.4.2 
Exclusion Criteria ...............................................................................................44 
4.5 
Study Assessments .......................................................................................................46 
4.6 
Replacement of Dropouts in Phase 1 Dose-Escalation Cohorts ..................................46 
5 STUDY DRUG INFORMATION AND DOSAGE ................................................................48 
5.1 
Identification and Description of Test Articles ............................................................48 
5.1.1 
FT-2102 ..............................................................................................................48 
5.1.2 
Azacitidine ..........................................................................................................48 
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5.1.3 
Cytarabine ...........................................................................................................48 
5.2 
Administration, Storage and Handling of Test Articles ...............................................48 
5.2.1 
FT-2102 ..............................................................................................................48 
5.2.2 
Azacitidine ..........................................................................................................49 
5.2.3 
Cytarabine ...........................................................................................................49 
5.3 
Drug Accountability and Return of Study Supplies ....................................................49 
5.4 
Concomitant Medications ............................................................................................50 
5.4.1 
Allowed Medications ..........................................................................................50 
5.4.2 
Prohibited Medications .......................................................................................51 
5.4.3 
Anticancer Therapy .............................................................................................51 
5.5 
Precautions ...................................................................................................................51 
5.5.1 
Differentiation Syndrome ...................................................................................51 
5.5.2 
Leukocytosis .......................................................................................................52 
5.5.3 
Hepatic Injury .....................................................................................................52 
5.5.4 
Phototoxicity .......................................................................................................53 
5.6 
Childbearing Potential .................................................................................................53 
5.6.1 
Contraception Guidelines ...................................................................................54 
5.6.2 
Guidance Against Donating Sperm or Ova ........................................................55 
6 STUDY PROCEDURES .........................................................................................................56 
6.1 
Measurements and Evaluations....................................................................................56 
6.1.1 
Pre-screening ......................................................................................................56 
6.1.2 
Informed Consent ...............................................................................................56 
6.1.3 
Screening Period (Within 14 Days Prior to Day 1) ............................................56 
6.1.4 
Cycle 1, Day 1 ....................................................................................................57 
6.1.5 
Cycle 1, Day 2 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................58 
6.1.6 
Cycle 1, Day 5 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................58 
6.1.7 
Cycle 1, Day 8 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................58 
6.1.8 
Cycle 1, Day 12 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................59 
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6.1.9 
Cycle 1, Day 15 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................59 
6.1.10 
Cycle 1, Day 19 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................59 
6.1.11 
Cycle 1, Day 22 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................60 
6.1.12 
Cycle 1, Day 26 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................60 
6.1.13 
Cycle 2, Day 1 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................60 
6.1.14 
Cycle 2, Day 2 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................61 
6.1.15 
Cycle 2, Day 4 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................61 
6.1.16 
Cycle 2, Day 8 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................62 
6.1.17 
Cycle 2, Day 15 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................62 
6.1.18 
Cycle 2, Day 22 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................62 
6.1.19 
Cycle 3, Day 1 ....................................................................................................62 
6.1.20 
Cycle 3, Day 15 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................63 
6.1.21 
Cycle 4, Day 1 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) .................................................................................63 
6.1.22 
Cycle 5 and Beyond, Day 1 (Every Other Cycle) ...............................................64 
6.1.23 
End of Treatment Assessments ...........................................................................65 
6.1.24 
Safety Follow-up Visit/Interview .......................................................................65 
6.1.25 
Disease Response Follow-up ..............................................................................65 
6.1.26 
Survival Follow-up .............................................................................................65 
6.2 
Safety ...........................................................................................................................66 
6.2.1 
Data Monitoring Committee ...............................................................................66 
6.3 
Bone Marrow Aspirate and/or Biopsy .........................................................................66 
6.4 
Pharmacokinetics .........................................................................................................67 
6.5 
Pharmacodynamics ......................................................................................................69 
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6.6 
Mutational Analysis .....................................................................................................70 
6.7 
Outcome Research Assessment ...................................................................................71 
6.8 
Dose Modifications ......................................................................................................71 
6.8.1 
FT-2102 Dose Modifications ..............................................................................71 
6.8.2 
FT-2102 Recommended Dose Reductions .........................................................73 
6.8.3 
Azacitidine Dose Modifications .........................................................................73 
6.8.4 
Cytarabine ...........................................................................................................75 
7 PROCEDURES FOR REPORTING ADVERSE EVENTS....................................................76 
7.1 
Adverse Events Definitions .........................................................................................76 
7.2 
Reporting of Adverse Events .......................................................................................76 
7.2.1 
Adverse Events ...................................................................................................76 
7.2.2 
Laboratory Abnormalities ...................................................................................77 
7.2.3 
Serious Adverse Events ......................................................................................77 
7.2.4 
Adverse Events of Special Interest .....................................................................78 
7.2.5 
Reporting of Pregnancies ....................................................................................78 
7.2.6 
Disease Progression ............................................................................................79 
7.2.7 
Overdoses............................................................................................................79 
7.3 
Classification of Adverse Events by Severity ..............................................................79 
7.4 
Classification of Adverse Events by Relationship to Study Drug Administration ......80 
7.5 
Adverse Events Qualifying for Reporting to Regulatory Authorities .........................80 
8 STUDY OR STUDY SITE TERMINATION AND PATIENT DISCONTINUATION ........81 
8.1 
Study or Study Site Termination..................................................................................81 
8.2 
Treatment and Study Discontinuation .........................................................................81 
8.2.1 
Treatment Discontinuation .................................................................................81 
8.2.2 
Study Discontinuation.........................................................................................82 
9 DATA RECORDING, CRF PROCESSING, AND STATISTICAL ANALYSIS .................83 
9.1 
Data Recording and CRF Processing ...........................................................................83 
9.2 
Statistical Analysis .......................................................................................................83 
9.2.1 
General Considerations .......................................................................................83 
9.2.2 
Sample Size.........................................................................................................83 
9.2.3 
Analysis Sets .......................................................................................................86 
9.2.4 
Analysis of Clinical Data ....................................................................................87 
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9.2.5 
Pharmacokinetic Analysis ...................................................................................89 
9.2.6 
Pharmacodynamic Analysis ................................................................................90 
9.2.7 
Genotypic Analysis .............................................................................................90 
9.2.8 
Quality of Life Analysis .....................................................................................90 
9.2.9 
Interim Analysis ..................................................................................................90 
10 ADMINISTRATIVE ASPECTS .............................................................................................91 
10.1 
Institutional Review Board/Ethics Committee ............................................................91 
10.2 
Informed Consent and Authorization for Use and Disclosure of Protected 
Health Information .......................................................................................................91 
10.3 
Delegation of Investigator Responsibilities .................................................................92 
10.4 
Study Documentation...................................................................................................92 
10.4.1 
Investigator Information .....................................................................................92 
10.4.2 
Laboratory Accreditation ....................................................................................92 
10.4.3 
Study Files ..........................................................................................................92 
10.4.4 
Source Documentation ........................................................................................93 
10.4.5 
Retention of Study Documents ...........................................................................93 
10.5 
Confidentiality .............................................................................................................93 
10.5.1 
Data .....................................................................................................................93 
10.5.2 
Patient Anonymity ..............................................................................................93 
10.6 
Protocol Compliance ....................................................................................................93 
10.7 
Monitoring Functions and Responsibility ....................................................................94 
10.8 
Drug Accountability.....................................................................................................94 
10.9 
Record Retention .........................................................................................................95 
10.10 Financial Disclosure .....................................................................................................95 
10.11 Patient Confidentiality .................................................................................................95 
10.12 Disclosure of Data ........................................................................................................95 
10.13 Publication Agreement .................................................................................................96 
10.14 General Information .....................................................................................................96 
11 REFERENCES ........................................................................................................................97 
 
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LIST OF TABLES 
Table 1 
Single-Agent Dose-Escalation Schema ..................................................................35 
Table 2 
Combination Dose-Escalation Schema ..................................................................37 
Table 3 
Response Assessment Criteria ................................................................................41 
Table 4 
Pharmacokinetic Sampling Times: FT-2102 ..........................................................68 
Table 5 
Pharmacodynamic Sampling Times: FT-2102 (Single Agent) and FT-2102 
plus Azacitidine or Low-Dose Cytarabine (Combination) .....................................70 
Table 6 
FT-2102 Recommended Dose Modifications for Adverse Events Unrelated 
to Liver Function Abnormalities ............................................................................72 
Table 7 
FT-2102 Recommended Dose Modifications for Liver Function Test 
Abnormalities .........................................................................................................72 
Table 8 
Recommended FT-2102 Dose Reduction Levels ...................................................73 
Table 9 
Azacitidine Dose Modifications: Hematology Laboratory Values ........................74 
LIST OF FIGURES 
Figure 1 
Study Design ..........................................................................................................34 
LIST OF APPENDICES 
Appendix 1 
Schedule of Events (Ongoing Patients) ..................................................................99 
Appendix 2 
Schedule of Events (Patients Enrolled After Protocol Version 7/ 
Amendment 6) ......................................................................................................103 
Appendix 3 
ECOG Performance Status ...................................................................................105 
Appendix 4 
National Cancer Institute Common Terminology Criteria for Adverse 
Events (NCI CTCAE) Version 4.03 .....................................................................106 
Appendix 5 
NYHA Classification ...........................................................................................107 
Appendix 6 
Drugs that are Generally Accepted by Authorities to have a Risk of Causing 
Torsades de Pointes ..............................................................................................108 
Appendix 7 
Response Criteria for AML ..................................................................................109 
Appendix 8 
Response Criteria for MDS ..................................................................................111 
Appendix 9 
Drugs that are Strong Inducers or Sensitive Substrates of CYP3A4 ...................114 
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ABBREVIATIONS 
Abbreviation 
Definition 
α-KG 
α-ketoglutarate 
AE 
adverse event 
AESI 
adverse event(s) of special interest 
ALP 
alkaline phosphatase 
ALT (SGPT) 
alanine transaminase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
API 
active pharmaceutical ingredient 
AST (SGOT) 
aspartate transaminase 
AUC 
area under the concentration curve 
BBB 
bundle branch block 
BID 
twice daily 
BMA 
bone marrow aspirate 
BOR 
best overall response 
BUN 
blood urea nitrogen 
Bx 
biopsy 
CBC 
complete blood count 
CL/F 
total body clearance 
Cmax 
maximum plasma concentration 
CNS 
central nervous system 
CR 
complete remission 
CRh 
complete remission with partial hematological recovery 
Cri 
complete remission with incomplete blood count recovery 
Css 
concentration at steady state 
CTCAE 
common terminology criteria for adverse events 
DLT 
dose-limiting toxicity 
DMC 
Data Monitoring Committee 
DOR 
duration of response 
eCRF 
electronic case report form 
EC 
Ethics Committee 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EE 
efficacy evaluable 
EFD 
embryo-fetal developmental 
EFS 
event-free survival 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GvHD 
graft vs. host disease 
2-HG 
(R)-2-hydroxyglutarate 
HNSTD 
highest non-severely toxic dose 
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HSCT 
hematopoietic stem cell transplantation 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation 
ICSH 
International Council for Standardization in Hematology 
IDH1 
isocitrate dehydrogenase 1 
IDH2 
isocitrate dehydrogenase 2 
IDH1m 
isocitrate dehydrogenase 1-mutant 
IND 
Investigational New Drug 
INR 
international normalized ratio 
IPSS-R 
Revised International Prognostic Scoring System 
IRB 
Institutional Review Board 
IV 
intravenous 
IWG 
International Working Group 
KM 
Kaplan-Meier 
LDAC 
low-dose cytarabine 
LH 
luteinizing hormone 
LFT 
liver function test 
MDS 
myelodysplastic syndrome 
MED 
maximum evaluated dose 
MedRA 
Medical Dictionary for Regulatory Activities 
MLFS 
morphologic leukemia-free state 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
NOAEL 
no-observed-adverse-effect-level 
NOEL 
no-observed-effect-level 
OR 
overall response 
OS 
overall survival 
PD 
pharmacodynamics 
PHI 
protected health information 
PK 
pharmacokinetics 
PP 
per protocol 
PR 
partial remission 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QD 
once daily 
QOL 
Quality of Life 
QTcF 
QT interval corrected using Fridericia’s formula 
RFS 
relapse free survival 
R/R 
relapsed/refractory 
RP2D 
recommended Phase 2 dose 
SA 
single agent 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
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SC 
subcutaneous 
SOC 
standard of care 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
terminal elimination half-life 
TBD 
to be determined 
TdP 
Torsades de Pointes  
TEAE 
treatment-emergent adverse event 
Tmax 
time to maximum plasma concentration 
TTR 
time to response 
ULN 
upper limits of normal 
US 
United States 
Vd/F 
apparent volume of distribution 
WBC 
white blood cell count 
WHO 
World Health Organization 
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FT-2102 
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August 20, 2020 
1 
BACKGROUND 
This study will evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical 
activity of the novel anticancer drug FT-2102 (olutasidenib), administered to patients with 
relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). FT-
2102 is a potent, selective, orally bioavailable, small-molecule inhibitor of mutated isocitrate 
dehydrogenase 1 (IDH1) being developed by Forma Therapeutics, Inc. and is intended for the 
treatment of patients harboring IDH1 mutations, in both hematologic and solid tumors. 
The presence of mutations at codon 132 in IDH1 imparts a neomorphic activity to the enzyme, 
resulting in the production of the “oncometabolite” (R)-2-hydroxyglutarate (2-HG), which has 
pleotropic roles in tumorigenesis. Studies in genetically engineered mouse models and models 
derived from cancer patient samples support the hypothesis that mutated IDH1 produces 2-HG, 
the downstream effects of which cause epigenetic changes that consequently block the proper 
differentiation of progenitor cells and lead to cancer. These data support the therapeutic rationale 
that inhibition of mutated IDH1 will lower (R)-2-hydroxyglutarate (2-HG) levels and restore 
normal cellular differentiation. 
The promising preclinical data for FT-2102 support its rapid progression into human AML and 
MDS trials. Additional studies in patients with hematologic malignancies are planned and studies 
in patients with solid tumors, including central nervous system (CNS) tumors, that harbor an 
IDH1 mutation, have been initiated. 
1.1 
Pharmacology 
The metabolic enzyme IDH1 catalyzes the oxidative decarboxylation of isocitrate to 
α-ketoglutarate (α-KG). In both hematologic and solid tumor malignancies, IDH1 mutations lead 
to aberrant accumulation of 2-HG. 2-HG has been proposed to act as an “oncometabolite” that 
has pleotropic effects on tumorigenesis. Excess production of 2-HG has been shown to inhibit 
α-KG-dependent enzymes involved in epigenetic regulation, collagen synthesis, and cell 
signaling, thereby leading to a block in normal differentiation of progenitor cells and the 
subsequent development of cancer (Gross et al. 2010; Cairns and Mak 2013; Losman et al. 2013). 
Therefore, inhibition of mutated IDH1 in tumor cells and the concomitant decrease in 2-HG 
production is expected to restore normal cellular differentiation and provide therapeutic benefit in
IDH1-mutated cancers. Clinical proof-of-concept for this rationale has recently been achieved for 
an IDH1 inhibitor in patients with IDH1-mutated AML (Fan et al. 2015; de Botton et al. 2015). 
1.2 
Toxicokinetics 
The toxicokinetics of FT-2102 were determined in rats and monkeys following repeat oral twice 
daily (BID) dosing for 28 consecutive days and for 3 months. Minimal or no dose accumulation 
was evident in either species. No gender differences were seen in monkeys; however, in rats, 
FT-2102 exposure (as measured by maximum plasma concentration [Cmax] and area under the 
concentration curve [AUC]) was greater in females than in males in both the 1-month and 
3-month study. In both species, exposure increased with increasing dose in a less than
proportional manner across the dose range evaluated.
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1.3 
Enzyme-Mediated Drug-Drug Interaction Potential 
FT-2102 metabolism is mediated primarily by Cytochrome P450 (CYP). Based on a clinical 
drug-drug interaction study (2102-HVS-103) inhibition of CYP3A4 does not impact the PK of 
FT 2102; however, induction of CYP3A4 significantly reduces FT 2102 systemic exposure.  
In vitro, FT-2102 showed non-significant, competitive inhibition of the major drug metabolizing 
CYP enzymes, CYPs 1A2, 2B6, 2C9, 2C19, 2D6, and 3A4 and weak inhibition of CYP2C8. No 
time-dependent inhibition of CYP3A4 was seen. CYP inhibition-mediated clinical DDIs are not 
expected. 
Based on in vitro results, FT-2102 exhibits CYP3A4 induction potential and may impact the PK 
of co-administered sensitive CYP3A4 substrates through increased clearance.   
1.4 
Toxicology 
A series of studies have been conducted to develop a toxicology profile for FT-2102. The 
program was comprised of single- and repeat-dose exploratory toxicology studies and definitive 
1-month and 3-month toxicology studies conducted in two mammalian species (rat and monkey)
using BID dosing of FT-2102 to support the most frequent envisioned dosing schedule in human
clinical trials. In addition, dose-range finding and pivotal embryo-fetal developmental (EFD)
toxicology studies have been completed in rats.
In the definitive 1-month toxicity study conducted in rats, the no-observed-adverse-effect level 
(NOAEL) for FT-2102 was considered to be 450 mg/kg/day (225 mg/kg/dose BID), the highest 
dose administered. Systemic exposure (Cmax and AUC0-12 hr) at the NOAEL on Day 28 was
16,700 ng/mL and 107,000 hr·ng/mL, respectively, in males and 25,000 ng/mL and 
185,000 hr·ng/mL, respectively, in females. Target organs identified histopathologically in the 
rat included the liver (centrilobular hypertrophy) and thyroid gland (follicular-cell hypertrophy). 
The thyroid effects noted in FT-2102-treated rats are considered secondary to the effects noted 
on the liver and represent a rat-specific mechanism that may not be relevant to human risk. In the 
1-month monkey toxicity study, the highest non-severely toxic dose (HNSTD) of FT-2102 was
considered to be 50 mg/kg/day, and the NOAEL was considered to be 30 mg/kg/day
(15 mg/kg/dose BID). Combined-sex systemic exposure (Cmax and area under the concentration
curve to the last time point [AUCTlast]) at the NOAEL on Day 28 was 2,490 ng/mL and
23,600 hr·ng/mL, respectively. Noteworthy histopathological findings in monkeys treated with
FT-2102 included multinucleated cells in the sinusoids of the liver and atrophy of the intestinal
tract. Following the recovery period, intestinal changes were completely reversible, whereas
multinucleated cells in the liver were decreased in severity indicating recovery.
In the pivotal 3-month toxicity study conducted in rat, the NOAEL when dosed BID by oral 
gavage for 3 months was 100 mg/kg/dose (200 mg/kg/day). Systemic exposure (Cmax and 
AUC0-12) at the NOAEL on Day 91 was 16,400 ng/mL and 116,000 ng·h/mL, respectively, for 
males, and 30,200 ng/mL and 236,000 ng·h/mL, respectively, for females. Findings included 
minimal, reversible clinical pathology changes and minimal to slight microscopic findings and 
organ weight changes in the kidney, liver, and thyroid (and higher adrenal weights and lower 
thymus weights with no microscopic findings). In the pivotal 3-month toxicity study in monkey, 
the HNSTD for FT-2102 when dosed BID by oral gavage for 3 months was 50 mg/kg/day 
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(25 mg/kg/dose); and the no-observed-effect-level (NOEL) was 30 mg/kg/day (15 mg/kg/dose). 
At 30 mg/kg/day, this corresponded to combined sex Day 88 Cmax and AUC0-24 values 
of 3,210 ng/mL and 48,400 ng·h/mL, respectively. At doses >30 mg/kg/day, clinical pathology 
findings consistent with hepatobiliary injury and impaired biliary function were observed. 
Microscopic findings in the liver were consistent with the clinical pathology findings. Pathology 
findings were either completely or partially recovered at the end of the 1-month recovery period, 
suggesting signs of reversibility. 
In a neutral red uptake phototoxicity assay conducted in BALB/c 3T3 mouse fibroblasts, 
FT-2102 demonstrated phototoxic potential. FT-2102 was found to be negative in the core 
battery of three pivotal genotoxicity assays that included in vitro bacterial Ames, in vitro 
micronucleus assay in human lymphocytes, and in the in vivo rat micronucleus assay. 
Dose-range finding and pivotal EFD toxicity studies were conducted in the rat. In the pivotal 
EFD study, the NOAELs were considered to be 250 mg/kg BID for maternal toxicity and 
250 mg/kg BID for fetal toxicity (corresponding to an AUC0-24 of 406,000 hr·ng/mL and a 
Cmax(0-24) of 25,300 ng/mL). No FT-2102-related effects on reproductive performance or cesarean 
section parameters were observed. No FT-2102-related fetal external or visceral variations or 
malformations were observed.  
1.5 
Clinical Rationale 
The recent identification of frequent mutations in the IDH1 and isocitrate dehydrogenase 2 
(IDH2) genes in human cancers including AML and MDS has provided novel therapeutic targets 
in these diseases (Mardis et al. 2009; Cairns and Mak 2013). IDH mutation-specific inhibitors 
have been shown to reduce aberrantly elevated levels of the oncometabolite 2-HG, resulting in 
antitumor efficacy in preclinical models (Rohle et al. 2013; Saha et al. 2014). Inhibition of 
mutated IDH1 has recently demonstrated efficacy in AML and initial proof-of-concept in MDS 
(Fan et al. 2015; de Botton et al. 2015; DiNardo et al. 2018). 
 
IDH1 and IDH2 mutations in AML and glioma result in abnormal hypermethylation of histones 
and DNA and suppression of normal cellular differentiation.  
 
Treatment with the hypomethylating agent azacitidine causes tumor growth inhibition in a 
patient-derived IDH1-mutated glioma model by reducing DNA methylation and inducing glial 
differentiation (Borodovsky et al. 2013). Taken together, these data support the combination of 
FT-2102 and azacitidine in the treatment of patients with AML harboring IDH1 mutations. 
Low dose cytarabine (LDAC) is considered a standard of care (SOC) treatment option for AML 
patients ≥ 60 years who are not candidates for intensive therapy. In a xenograft model, the 
combination of an IDH1 inhibitor with short duration low-dose cytarabine decreased the bone 
marrow tumor burden better than either treatment alone (Yen et al. 2013). The combination of 
FT-2102 with LDAC in the subset of those patients harboring IDH1 mutation might result in 
additive clinical benefit. 
 
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1.5.1 
Recommended Phase 2 Dose Selection and Rationale 
Once the maximal tolerated dose (MTD) or maximal evaluated dose (MED) has been identified 
for the single-agent or combination cohorts, selected populations of patients with AML/MDS 
harboring IDH1-R132 mutations will be enrolled to confirm a recommended Phase 2 dose 
(RP2D). Up to 14 additional patients may be enrolled into each dose-expansion cohort to 
confirm and further characterize the safety and clinical activity of FT-2102 as a single agent or in 
combination with azacitidine. Up to five dose-expansion cohorts may be enrolled at the potential 
RP2D; two each for single-agent (SA) FT-2102 and in combination with azacitidine and one 
cohort for FT-2102 in combination with cytarabine.  
From these dose-expansion cohorts, an RP2D of FT-2102 as a single agent or in combination 
will be selected for subsequent evaluation in Phase 2 studies. 
A Sponsor review of available safety data in March 2018 (for single agent), and in June 2018 
(for azacitidine combination), including a review of all AEs reported in patients treated with the 
150 mg BID dose in the expansion cohorts, indicated that the safety profile was consistent with 
that of patients treated in dose escalation; no new safety signals were observed in the expansion 
cohorts. Based on this review and with agreement by participating investigators, FT-2102 
150 mg BID was declared the RP2D for further evaluation both as single agent and in 
combination with azacitidine.  
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2 
STUDY OBJECTIVES 
Primary Objectives 
Phase 1 
• To determine the MTDs, the MEDs, dose-limiting toxicities (DLTs), and the RP2Ds of 
FT-2102 as a single agent, in combination with azacitidine, and in combination with 
cytarabine in patients with AML or MDS harboring an IDH1-R132 mutation 
 
Phase 2 
• To evaluate the antileukemic and antimyelodysplastic activity of FT-2102 as a single agent 
or in combination with azacitidine in patients with AML or MDS, respectively harboring 
an IDH1-R132 mutation 
 
Secondary Objectives 
Phase 1 
• To determine the pharmacokinetics (PK) of FT-2102 as a single agent and in combination 
with azacitidine or cytarabine 
• To observe patients for any evidence of antileukemic or antimyelodysplastic activity of 
FT-2102 as a single agent and in combination with azacitidine or cytarabine 
Phase 2 
• To confirm the safety of FT-2102 as a single agent and in combination with azacitidine in 
select patient populations 
• To evaluate additional measures of the antileukemic or antimyelodysplastic activity of 
FT-2102 as a single agent and in combination with azacitidine  
• To determine the PK of FT-2102 as a single agent and in combination with azacitidine  
 
Exploratory Objectives 
Phase 1 and Phase 2 
• To assess on-target activity of FT-2102, as determined by changes in a pharmacodynamic 
(PD) biomarker in plasma 
• To determine the frequency of cancer-associated mutations and/or genetic alterations in 
responding and nonresponding patients 
• To evaluate PK/PD and clinical response relationships in each cohort 
 
Phase 2 
• To evaluate the health-related quality of life (QOL) of patients receiving FT-2102 as a 
single agent or in combination with azacitidine 
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3 
STUDY ENDPOINTS 
Primary Endpoints 
Phase 1 
•
Incidence and severity of adverse events (AEs), clinical laboratory abnormalities and
changes in electrocardiogram (ECG) parameters
Phase 2 
•
All cohorts except Cohort 2: CR rate (best overall response [BOR] of CR/ CRh) as
determined by the investigator per disease-specific criteria. Refer to Appendix 7 for AML
and Appendix 8 for MDS response criteria
•
Cohort 2: Four-month relapse free survival (RFS) rate.
Secondary Endpoints 
Phase 1 
•
PK parameters derived from FT-2102 concentrations
•
Antileukemic or antimyelodysplastic activity as determined by CR, CRh, CRi, MLFS,
Marrow CR, PR and SD
Phase 2 
• Evidence of clinical benefit (CRi, MLFS, Marrow CR, OR, TI, TTR, DOR, EFS, RFS, OS,
and other definitions of response, including SD)
•
Incidence and severity of adverse events (AEs), clinical laboratory abnormalities and
changes in ECG parameters
•
PK parameters derived from plasma FT-2102 concentrations
Exploratory Endpoints 
Phase 1 and Phase 2 
•
Changes in 2-HG levels (PD biomarker) in plasma
•
Cancer-associated mutations and/or genetic alterations, in bone marrow aspirates and/or
peripheral blood
•
PK/PD in relationship with clinical safety and clinical activity
Phase 2 
•
Health-related QOL of patients as assessed by a patient-reported questionnaire
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4 
STUDY DESIGN 
This Phase 1/2 study will utilize a multicenter, open-label, dose-escalation design to evaluate the 
safety, efficacy, PK, and PD of FT-2102 administered orally to patients with AML or MDS.  
 
Patients will be given FT-2102 daily (QD or BID) in continuous 28-day cycles, alone or in 
combination with azacitidine (administered at the dose of 75 mg/m2 for 7 days IV/SC per every 
28-day cycle) or LDAC (administered at the dose of 20 mg BID SC for 10 days every 28-day 
cycle) until treatment discontinuation. The term “study drug” will refer to either FT-2102, 
azacitidine or cytarabine.  
 
Patients who discontinue for reasons other than disease progression/relapse or withdrawal of 
consent will continue to be followed for response until progression/relapse occurs. 
Patients who achieve an adequate response to study treatment and meet other criteria required to 
undergo hematopoietic stem cell transplantation (HSCT) may proceed to HSCT after 
discontinuation of study treatment and will be followed on study for disease evaluation and any 
new HSCT conditioning or other new antineoplastic therapies received until disease relapse, 
death, withdrawal of consent, lost to follow-up, or end of study. 
If a patient discontinues study drug to undergo HSCT, but is then deemed ineligible for HSCT, 
the patient may restart study drug with Medical Monitor approval. 
Patients who undergo HSCT and then have persistent/recurrent IDH1-mutant (IDH1m) positive 
disease may be eligible to restart treatment with FT-2102 by re-enrolling in the appropriate 
Phase 2 cohort with Medical Monitor approval: 
• Re-enrollment into Cohort 3 if morphologic relapse/progression 
Patients who relapse post-HSCT and elect not to restart FT-2102 treatment will enter the overall 
survival follow-up period. 
Patients participating in Phase 1 may be followed for survival for up to 12 months from C1D1 or 
for 28 days after treatment discontinuation (whichever is longer). 
Patients participating in Phase 2 may be followed for survival for up to 36 months from C1D1 or 
for 28 days after treatment discontinuation (whichever is longer). 
 
As shown in Figure 1, the study is comprised of 3 stages: a Phase 1 dose-escalation stage, a 
Phase 1 dose-expansion stage, and a Phase 2 stage. 
 
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Figure 1 
Study Design 
Phase 1 – Dose Escalation and Dose Expansion 
Phase 2 
AML = acute myeloid leukemia; aza = azacitidine; BID = twice daily; combo = combination; Exp = expansion; IDH = isocitrate 
dehydrogenase; LDAC = low-dose cytarabine; MDS = myelodysplastic syndrome; MED = maximum evaluated dose; 
MTD = maximum tolerated dose; pts = patients; RP2D = recommended Phase 2 dose; R/R = relapsed/refractory; SA = single-
agent. 
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4.1 
Phase 1 Dose-Escalation Stage 
4.1.1 
Single-Agent (SA) Dose Escalation (Complete)  
Dose-escalation will be initiated using SA FT-2102 in patients with AML or MDS harboring an 
IDH1-R132 mutation, as determined by local mutation testing. FT- 2102 will be given orally QD 
(Schedule 1) in continuous 28-day cycles at the dose levels proposed in Table 1. It is planned 
that, at a minimum, doses of 150 mg and 300 mg FT-2102 QD will be tested. Dose increases of 
up to 50% between cohorts is allowed above the 300 mg total daily dose level until the MTD or 
MED is determined. Additional intermediate dose levels may be explored as clinically indicated. 
A BID dose schedule (Schedule 2) may be evaluated as indicated. The starting dose in Schedule 
2 will be calculated from the evaluated dose level on Schedule 1. Actual dose level escalations 
for both schedules will be determined by PK/PD parameters and clinical observations. 
Table 1 
Single-Agent Dose-Escalation Schema 
Single-Agent (FT-2102) Schedule 1 (Complete) 
Dose Level 
% Increments from prior dose level 
Dose (mg) 
1 
— 
150 mg QD 
2 
Up to 100% 
≤ 300 mg QD 
3 
Up to 50% 
≤ 450 mg QD 
4 
Up to 50% 
TBD 
Single-Agent (FT-2102) Schedule 2 (Complete) 
Dose Level 
% Increments from prior dose level 
Dose (mg) 
1 
— 
TBD BIDa 
2 
TBD based on safety experience 
TBD 
3 
TBD based on safety experience 
TBD 
4 
TBD based on safety experience 
TBD 
a 
Due to a 24-hour PK collection on Cycle 1 Day 2 (C1D2), the second dose of FT-2102 should not be administered on 
Cycle 1 Day 1 (C1D1). 
 
In vitro solubility studies of FT-2102 simulating the fed or fasted state indicate that absorption 
may be increased up to 3-fold if FT-2102 is administered with food. If the observed exposure of 
FT-2012 QD and/or BID in dose-escalation indicates absorption in the fasted state may be 
limited, a dose escalation of FT-2102 in the fed state may be evaluated. The starting QD dose of 
FT-2102 in the fed state will be 3-fold lower than a QD dose evaluated in the fasted state found 
to be safe and tolerable. Dose escalation in the fed state will continue until the MTD or MED is 
determined. Intra-patient dose escalation within the first dosing cohort may be allowed in 
Cycle 1, if the FT-2102 concentration at steady state (Css) is below the intended exposure range.  
 
The dose-escalation stage will utilize a 3+3 design whereby three evaluable patients will be 
treated at each dose level. The first cohort of patients will initiate treatment at Dose Level 1.  
 
• A patient will not be enrolled at the next higher dose level until all patients at the current 
dose level have completed the 28-day dose-limiting toxicity (DLT) monitoring period. 
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•
If one of the initial three patients has a DLT before the end of Cycle 1, the cohort will be
expanded to up to six patients. If five of a total of six patients complete the full Cycle without
a DLT, escalation may continue.
•
For a given cohort, once two or more patients have a DLT, further enrollment/treatment for
that cohort will halt, as will dose-escalation. The dose level at which two or more of up to
six patients have a DLT will be considered to be at least one dose level above the MTD.
•
The next lower dose will then be more fully evaluated by treating a total of up to six patients.
If two or more patients have a DLT at this lower dose level, de-escalation will continue until
a dose level is identified at which zero or one of a total of six patients has a DLT. This will
be identified as the MTD.
•
Dose-escalation may also stop before an intolerable dose level is identified when continuous
PD inhibition is demonstrated.
A DLT is defined below in Section 4.1.3. The DLT dose level is defined as the lowest dose level 
at which DLT is experienced in two or more patients within a cohort of ≤ 6 patients. The MTD is 
the highest dose level that does not meet the DLT dose level definition. The MED is the highest 
dose evaluated in the setting when dose escalation is stopped before an MTD is identified.  
Patient entry and dose-escalation will be based upon occurrence of DLTs in all patients at each 
dose level. Adverse events will be reviewed with the Investigators and the Medical Monitor at 
specific timepoints during the conduct of the study. A review will be performed in the 
dose-escalation stage of the protocol prior to the opening of a new dose level and to discontinue 
dose-escalation if the MTD has been reached. 
A minimum of six evaluable patients will be required to confirm the MTD or the MED before 
proceeding to the dose-expansion phase for SA FT-2102. 
Patients will be monitored for safety while on study treatment and for up to 28 days after 
treatment discontinuation (last dose of study drug) to monitor, or until resolution or stabilization 
of AEs, except for patients who withdraw consent.  
Patients participating in the Phase 1 dose-escalation may be followed for survival for up to 12 
months from C1D1 or for 28 days after treatment discontinuation (whichever is longer).  
4.1.2 
FT-2102 + Azacitidine (Combination) Dose-Escalation (Complete) 
During the course of SA dose-escalation, a parallel escalation arm will be initiated for FT-2102 
in combination with azacitidine in patients with AML or MDS harboring an IDH1-R132 
mutation. FT- 2102 will be given orally QD in continuous 28-day cycles as shown in Table 2. 
The starting dose of FT-2102 in the combination arm will be a dose level at which ≤ Grade 2 
toxicities (i.e., no Grade 3 or higher toxicities) were observed when FT-2102 was administered 
as a single agent. A BID dosing schedule and/or dosing in a fed state may be explored, as 
indicated.  
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Table 2 
Combination Dose-Escalation Schema 
Combination Agent (FT-2102 + Azacitidine) Schedule 1a (Complete) 
Dose 
Level 
% Increments from prior dose level 
Dose (mg) 
FT-2102 
Azacitidine 
1 
— 
QD 
75 mg/m2 
2 
TBD based on safety experience 
TBD 
75 mg/m2 
3 
TBD based on safety experience 
TBD 
75 mg/m2 
4 
TBD based on safety experience 
TBD 
75 mg/m2 
Combination Agent (FT-2102 + Azacitidine) Schedule 2b (Complete) 
Dose 
Level 
% Increments from prior dose level 
Dose (mg) 
FT-2102 
Azacitidine 
1 
— 
BID 
75 mg/m2 
2 
TBD based on safety experience 
TBD 
75 mg/m2 
3 
TBD based on safety experience 
TBD 
75 mg/m2 
4 
TBD based on safety experience 
TBD 
75 mg/m2 
BID = twice daily; QD = once daily; TBD = to be determined. 
Note: The starting dose in Schedule 2 will be calculated from the projected dose level on Schedule 1. Actual dose level 
escalations for both schedules will be determined by PK/PD parameters and clinical observations. 
a Schedule 1 is QD dosing of FT-2102 on a 28-day schedule. 
b Schedule 2 is BID dosing of FT-2102 on a 28-day schedule.  
Note: With BID schedule, due to a 24-hour PK collection on Cycle 1 Day 2 (C1D2), the second dose of FT-2102 should not 
be administered on Cycle 1 Day 1 (C1D1). 
With the exception of C1D1 and C2D1, when PK sampling is performed, it is recommended that 
FT-2102 should be administered first on the days when both are given. Azacitidine will be 
administered per SOC. The recommended dosing schedule for azacitidine is daily × 7 days 
consecutively (via subcutaneous injection or intravenous infusion), but a 48-hour dose 
interruption for weekends or holidays is allowed. Azacitidine is to be administered beginning on 
Cycle 1 Day 1 and then Day 1 of each subsequent 28-day treatment cycle. Alternate schedules 
for the start of azacitidine administration (e.g., beginning on Day 8 of each treatment cycle) may 
be evaluated when clinically indicated. 
This escalation will also enroll patients on a 3+3 design, whereby three patients will be treated 
and if one DLT occurs, then the cohort will be expanded to six patients; if more than one DLT 
occurs, escalation will stop at that dose level (or schedule). Patients who are unable or unwilling 
to continue treatment with azacitidine after the first treatment cycle may continue participation in 
the study taking FT-2102 alone, at the discretion of the investigator. 
Patient entry and dose-escalation will be based upon occurrence of DLTs in all patients at each 
dose level. Adverse events will be reviewed with the Investigators and the Medical Monitor at 
specific timepoints during the conduct of the study. A review will be performed in the 
dose-escalation stage of the protocol prior to the opening of a new dose level and to discontinue 
dose-escalation if the MTD has been reached. 
A minimum of six evaluable patients will be required to confirm the MTD or the MED before 
proceeding to the dose-expansion phase for the combination arm. 
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Patients will continue to be monitored for safety while on study treatment and for up to 28 days 
after treatment discontinuation (last dose of study drug) or until resolution or stabilization of 
AEs, except for patients who withdraw consent.  
Patients participating in the Phase 1 dose-expansion may be followed for survival for up to 12 
months from C1D1 or for 28 days after treatment discontinuation (whichever is longer).  
 
4.1.3 
Definition of Dose-Limiting Toxicity 
A dose-limiting toxicity (DLT) is defined as any AE occurring in Cycle 1 that fulfills one or 
more of the following criteria. Toxicities will be graded and documented according to the NCI 
CTCAE, version 4.03 guidelines (see Appendix 4): 
 
• Nonhematological Grade 3 or greater toxicity that is unrelated to underlying disease, 
occurring in Cycle 1 with the following exceptions: 
o Alopecia 
o Grade 3 nausea, vomiting, diarrhea or rash lasting less than 72 hours (with optimal 
medical management) 
o Grade 3 QTcF prolongation that is < 40 msec increase over baseline in a patient with 
a bundle branch block (BBB) 
o Grade 3 or 4 toxicity determined to be a sign or symptom of differentiation syndrome 
that resolves/responds to treatment interventions to < Grade 3 within 7 days (see 
Section 5.5.1) 
• Any Grade 3 non-hematologic laboratory finding, unrelated to underlying disease, 
occurring in Cycle 1 
• Hematologic Grade 4 toxicity as defined by CTCAE on Day 42, in the absence of disease 
• Inability to tolerate a minimum of 75% of FT-2102 scheduled doses during Cycle 1 due to 
an AE. This applies to patients who have their dose held due to AEs per Section 6.8.1. 
 
All patients will be monitored for bone marrow function throughout the study, but these findings 
may not be considered a DLT unless they fulfill the above criteria. 
A DLT is defined within the 28 days of Cycle 1. However, the sponsor will evaluate all safety 
data, on an ongoing basis, beyond Cycle 1 for determination of an appropriate dose for Phase 2 
or later trials. 
 
4.1.4 
Phase 1 Dose-Expansion Stage 
The following expansion cohorts are proposed: 
1. SA FT-2102 at the MTD or MED in patients with relapsed or refractory (R/R) AML or MDS 
 
2. SA FT-2102 at a dose less than the MTD or MED (only if MTD or MED > 150 mg QD) in 
patients with R/R AML or MDS 
 
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3. Combination FT-2102 (MTD or MED) + azacitidine in patients with AML or MDS with no
prior anti-AML/MDS therapy
4. Combination FT-2102 (MTD or MED) + azacitidine in patients with AML or MDS that is
R/R to prior anti-AML/MDS therapy (including hypomethylating therapies)
Patients will continue to be monitored for safety while on study treatment and for up to 28 days 
after treatment discontinuation (last dose of study drug) or until resolution or stabilization of 
AEs, except for patients who withdraw consent. Patients will also be monitored for evidence of 
antileukemic or antimyelodysplastic activity (Section 4.3). 
Patients participating in the dose-expansion cohorts may be followed for survival for up to 12 
months from C1D1 or for 28 days after treatment discontinuation (whichever is longer).  
FT-2102 in combination with cytarabine: 
After dose-expansion is complete for FT-2102 as a single agent and FT-2102 in combination 
with azacitidine, a cohort of 6 patients with AML harboring IDH1 mutation will be treated with 
FT-2102 in combination with cytarabine 20 mg BID for 10 days, and then cytarabine will be 
stopped for 18 days. FT-2102 will be given in accordance with dosing schedule × 28 days out of 
28 days. The starting dose of FT-2102 will be 150 mg BID. Further dose-escalation of FT-2102 
in combination with cytarabine will not occur beyond 150 mg BID.  
If ≥ 1 DLTs are observed at the 150 mg BID dose in combination with cytarabine, a lower dose 
level of FT-2102 may be explored. 
4.2 
Phase 2 Stage 
Specific populations of patients with AML/MDS harboring IDH1-R132 mutations will be 
enrolled to further characterize the safety and efficacy of FT-2102 at the RP2D in Phase 2 
cohorts. Only 1 dose level of FT-2102 as SA and 1 dose level of FT-2102 in combination with 
azacitidine will be evaluated in the proposed Phase 2 cohorts. 
FT-2102 150 mg BID is the RP2D (see Section 1.5.1). This RP2D has been confirmed for SA 
and azacitidine combination treatment. 
Phase 2 cohorts may include the following: 
Single-Agent Cohorts: 
Cohort 1 (SA FT-2102): approximately 173 evaluable patients with R/R AML. To account for 
discordance between local and central mutation testing, approximately 190 patients may be 
enrolled into this cohort to obtain 173 evaluable patients. 
Cohort 2 (SA FT-2102): approximately 53 patients with AML in morphologic CR/CRi after 
prior therapy (+/- HSCT) with residual IDH1-R132 mutation (≥ 0.01%) detected in the bone 
marrow. 
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Cohort 3 (SA FT-2102): approximately 20 patients with R/R AML/MDS that have been 
previously treated with FT-2102. Patients who undergo HSCT on-study then relapse post-HSCT 
are allowed in this cohort. 
 
Azacitidine Combination Cohorts: 
Cohort 4 (FT-2102 in combination with azacitidine): approximately 20 patients with R/R 
AML/MDS that is naïve to prior hypomethylating therapy and IDH1 inhibitor therapy. 
Cohort 5 (FT-2102 in combination with azacitidine): approximately 20 patients with R/R 
AML/MDS that have inadequately responded to or have progressed on prior hypomethylating 
therapy. 
Cohort 6 (FT-2102 in combination with azacitidine): approximately 44 patients with R/R 
AML/MDS that have been previously treated with SA FT-2102 as their last therapy prior to 
study enrollment. The actual number of patients in this cohort may be larger, since patients from 
the FT-2102 SA cohorts of this study are allowed to be enrolled in Cohort 6 after their disease 
progression. 
 
Treatment Naïve Cohorts: 
Cohort 7 (SA FT-2102): Approximately 54 treatment naïve AML patients for whom standard 
treatments are contraindicated. 
Cohort 8 (FT-2102 in combination with azacitidine): Approximately 28 treatment naïve AML 
patients who are candidates for azacitidine as a first line treatment. 
 
Note for Phase 2 Cohort 7 and Phase 2 Cohort 8: Treatment naïve is defined as no prior 
treatment for AML. Patients may have received a prior treatment for another hematologic 
malignancy.  
 
Patients will be monitored for safety while on study treatment and for up to 28 days after 
treatment discontinuation (last dose of study drug) or until resolution or stabilization of AEs, 
except for patients who withdraw consent.  
 
4.3 
Response Assessment  
All patients participating in this study will undergo response assessments through evaluation of 
clinical findings and bone marrow/peripheral blood cell counts and morphology. Criteria to 
guide the investigator’s assessment of response are defined in Table 3 below and Appendix 7 and 
Appendix 8.  
Bone marrow for response assessment is required at: 
• C2D1 if no peripheral blasts; otherwise, at C3D1, regardless of peripheral blast count 
o Not applicable for patients enrolled after Protocol Version 7/ Amendment 6  
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•
For patients with AML, every 6 cycles thereafter unless there is a suspicion of
relapse/progression
•
For patients with MDS, to be performed as clinically indicated
•
When progressive disease is suspected
•
The same assessment frequency should carry on post-HSCT
•
For Phase 2 Cohort 2 only: bone marrow assessment should be done at C2D1, C4D1,
C6D1, and only if relapse is suspected thereafter
Response criteria are derived from the International Working Group (IWG) response criteria for 
AML (2003) and MDS (2006) where applicable; refer also to Stein et al. 2017. 
In general, HSCT is not considered an event in time to event analyses. Patients who stop 
treatment with FT-2102 to have HSCT will continue to be monitored for duration of response. 
HSCT is not considered an anti-leukemia therapy for purposes of analyses described herein. 
Table 3 
Response Assessment Criteria 
Per Protocol Response Criteriona,b 
Corresponding IWG Response/ 
Modified Response Criteria 
AML (2003) 
MDS (2006) 
Morphologic Complete Remission 
CRc 
CR 
CR with partial hematologic recovery 
CRh 
Not applicable 
CR with incomplete blood count recovery 
CRi 
Marrow CR 
Morphologic leukemia-free state 
MLFS 
Not applicable 
Partial Response 
PR 
PR 
Stable Diseased 
Stable Diseased 
Stable Disease 
Treatment Failure 
Progressive disease (PD) e
/Relapse 
Relapse /PD 
AML = acute myelogenous leukemia; CR = complete remission; CRh = complete response with partial hematologic recovery; 
CRi = complete remission with incomplete blood count recovery; MLFS = morphologic leukemia-free state; PD = progressive 
disease; PR = partial response.  
Source: Cheson et al. 2003; Cheson et al. 2006 ; Stein et al. 2017 
a
Additional response criteria per IWG (e.g., cytogenetic or molecular complete remission) may be collected when available 
or provided. However, investigators will be asked to provide response assessment corresponding to the per protocol 
response criteria outlined. 
b
For MDS, responses must last at least 4 weeks (i.e., confirmation required at 4 weeks) and hematologic improvements (HI) 
must last at least 8 weeks. For AML, no minimum duration of response required to qualify for a given response.  
c
The assessment frequency for CR should also be applied to patients in CRm and CRc. Please refer to Appendix 7 for 
definitions. 
d
Stable Disease (SD) is defined as failure to achieve a partial response but not meeting criteria for progressive disease. SD 
lasting for a period of more than 8 weeks is considered clinical benefit  
e
Progressive disease (PD) in AML is defined as previously having demonstrated partial remission or stable disease. For those 
with 5% to 66% bone marrow blasts at nadir, a > 50% increase in bone marrow blast count percentage from the nadir and 
percentage is ≥ 20%; and for patients with ≥ 67% bone marrow blasts at nadir, a doubling of the nadir absolute peripheral 
blood blast count with a final absolute peripheral blood blast count > 10 × 109/L  
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4.4 
Eligibility Criteria 
4.4.1 
Inclusion Criteria 
To be considered eligible to participate in this study, a patient must meet ALL inclusion criteria 
listed below: 
1. 
Pathologically proven AML (except acute promyelocytic leukemia with the t(15;17) 
translocation) or intermediate risk, high risk or very high risk MDS as defined by the 
World Health Organization (WHO) criteria or Revised International Prognostic Scoring 
System (IPSS-R) harboring IDH1-R132 mutations, and one of the following based 
on enrollment stage or treatment cohort: 
 
a. Single Agent Phase 1 Cohorts including Dose-Escalation/ Dose-Expansion: 
AML/MDS either R/R to standard therapy, or for whom standard treatments are 
contraindicated 
 
b. Combination (FT-2102 + azacitidine) Phase 1 Dose-Escalation/ Dose-
Expansion (patients must meet one of the following): 
i. Patients with AML that is either R/R to standard therapy, or for whom 
standard treatments are contraindicated 
ii. Patients with MDS that is either R/R to standard therapy, or are treatment-
naïve, who are eligible for azacitidine therapy 
 
c. Combination (FT-2102 + cytarabine) Phase 1 Dose-Escalation/Dose-Expansion 
Cohort: Patients ≥ 60 years with treatment-naïve AML for whom standard 
treatments are contraindicated 
 
d. Phase 2 Cohort 1 (Single Agent) only: AML R/R to standard therapy 
  
e. Phase 2 Cohort 2 (Single Agent) only: AML in morphologic CR/CRi after prior 
therapy (+/- HSCT) with residual IDH1-R132 mutation (≥ 0.01%) detected in the 
bone marrow 
 
f. Phase 2 Cohort 3 (Single Agent) only: R/R AML/MDS that have been previously 
treated with FT-2102 AND for whom standard treatments are contraindicated 
 
g. Phase 2 Cohort 4 (FT-2102 + Azacitidine) only: Patients < 60 years old with R/R 
AML/MDS with no prior hypomethylating agent therapy AND no prior IDH1 
inhibitor therapy 
 
h. Phase 2 Cohort 5 (FT-2102 + Azacitidine) only: R/R AML/MDS that have 
inadequately responded to or have progressed on prior treatment with a 
hypomethylating agent  
 
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i.
Phase 2 Cohort 6 (FT-2102 + Azacitidine) only: R/R AML/MDS that have been
previously treated with single agent FT-2102 as their last therapy prior to study
enrollment
j.
Phase 2 Cohort 7 (Single Agent) only: Treatment naïve AML patients for whom
standard treatments are contraindicated
k. Phase 2 Cohort 8 (FT-2102 + Azacitidine) only: Treatment naïve AML patients
who are candidates for azacitidine as a first line treatment
•
Note for Phase 2 Cohort 7 and Phase 2 Cohort 8: Treatment naïve is defined
as no prior treatment for AML. Patients may have received a prior treatment
for another hematologic malignancy.
2.
Patients must have documented IDH1-R132 gene-mutated disease as evaluated by the
site
3.
Patients ≥ 18 years old
4.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
(see Appendix 3)
5.
Signed informed consent prior to beginning study and undergoing procedures
6.
No prior solid organ allograft
7.
Acceptable liver function:
a.
Bilirubin ≤ 2 times upper limit of normal (ULN) (≤ 3 times ULN in patients with
Gilbert Syndrome)
b. Aspartate transaminase (AST, also referred to as SGOT), alanine transaminase
(ALT, also referred to as SGPT) and alkaline phosphatase (ALP) ≤ 3 times ULN
8.
Acceptable renal function:
a.
Serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance ≥ 50 mL/min
(Cockcroft and Gault 1976)
9.
Recovery from the non-hematologic toxic effects of prior treatment to Grade ≤ 1, or
baseline value according to NCI CTCAE classification (excluding infertility, alopecia,
or Grade 1 neuropathy)
10.
Baseline QTcF ≤ 450 msec (average of the QTcF values of screening triplicate ECGs)
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Note: This criterion does not apply to patients with a bundle branch block (BBB); for 
patients with BBB, a cardiology consult is recommended to ensure that QTcF is not 
prolonged.  
11.
Negative serum pregnancy test if female of childbearing potential
12.
For fertile men and women, agreement to use highly effective contraceptive methods
for the duration of study participation and 90 days after the last dose of study
medication (Section 5.6.1)
13.
Agreement for male patients not to donate sperm and for female patients of
childbearing potential not to donate ova during the study and for 90 days after the final
dose of study drug (see Section 5.6.2)
14.
Phase 2 Cohorts 1 - 8 (SA and combination) only: Pre-treatment peripheral blood
and bone marrow aspirate available for retrospective central confirmation of IDH1-
R132 mutation is required.
Note: Central confirmation of IDH1-R132 mutation is not required for study
enrollment.
4.4.2 
Exclusion Criteria 
To be eligible for entry into the study, the patient must NOT meet any of the exclusion criteria 
listed below: 
1.
Phase 1 Single Agent Dose-escalation/Dose-expansion Cohorts and Phase 2
Cohorts 1, 4, 5, 7 and 8 only: Patients who have been treated with an IDH1 targeted
therapy are excluded
2.
Phase 2 Single Agent Cohorts 1-3 and 7 only: Patients with IDH2 mutation
detection at baseline or history of IDH2m inhibitor treatment are excluded
3.
History of prior malignancy unless disease-free for ≥ 12 months or considered
surgically cured; patients with nonmelanoma skin cancers or with carcinomas in situ
are eligible regardless of the time from diagnosis (including concomitant diagnoses)
4.
Patients with symptomatic central nervous system (CNS) metastases or other tumor
location (such as spinal cord compression, other compressive mass, uncontrolled
painful lesion, bone fracture, etc.) necessitating an urgent therapeutic intervention,
palliative care, surgery or radiation therapy
5.
Patients with previous allogeneic HSCT, if they meet any of the following criteria:
< 100 days from time of HSCT; active acute or chronic graft vs. host disease
(GvHD); or receiving immunosuppressive therapy as treatment or prophylaxis against
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GvHD 
Note: Doses < 20 mg methylprednisolone (or its equivalent) daily are not an 
exclusion criterion. 
 
6. 
Treatment with radiation therapy, major surgery (requiring general anesthesia) within 
one month prior to study drug dosing 
 
7. 
Treatment with chemotherapy or small molecule anticancer therapeutic within five 
half-lives of the agent or within 21 days if the half-life is unknown. Patients re-
enrolling in Cohort 6 after relapse/progression on Cohort 1 are exempt from this 
washout requirement (i.e. can continue FT-2102 treatment until re-enrollment)  
 
8. 
Treatment with an anticancer therapeutic antibody less than four weeks before first 
dose of study drug 
 
9. 
Treatment with other experimental therapies or participation in another clinical trial 
within a period of time that is less than the cycle length or within 21 days prior to 
starting study drug, whichever is shorter 
 
10. 
Patients unable to swallow oral medications, or patients with gastrointestinal 
conditions (e.g., malabsorption, resection, etc.) deemed by the Investigator to 
jeopardize intestinal absorption 
 
11. 
Congestive heart failure (New York Heart Association Class III or IV) or unstable 
angina pectoris; previous history of myocardial infarction within one year prior to 
study entry, uncontrolled hypertension, or uncontrolled arrhythmias (see Appendix 5) 
 
12. 
Patients with a family history of QT prolongation 
 
13. 
Concomitant medication(s) known to cause Torsades de Pointes (TdP) initiated less 
than the duration required to reach steady-state plasma concentration (approximately 
five half-lives )before first dose of study drug (see Appendix 6) (medications used as 
needed [PRN] (e.g. Zofran) are exempt) 
 
14. 
Concurrent treatment with chronic corticosteroids except if chronic treatment with 
< 20 mg of methylprednisolone daily or equivalent (pulse steroids for treatment or 
prophylaxis are allowed [e.g., for transfusion or medication reactions]) 
 
15. 
Known HIV positivity 
 
16. 
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy 
(prophylactic systemic antimicrobials permitted) 
 
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17.
Uncontrolled disease-related metabolic disorder (e.g., hypercalcemia)
18.
Pregnant or nursing women or women of childbearing potential not using highly
effective contraception; male patients not using highly effective contraception
Note: Women of childbearing potential (see Section 5.6) and men must agree to use
highly effective contraception (see Section 5.6.1) prior to study entry and for the
duration of study participation and 90 days after.
Should a woman become pregnant or suspect she is pregnant while participating in
this study, she should inform her treating physician immediately.
19.
Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions)
that could compromise protocol objectives in the opinion of the Investigator and/or
the Sponsor
20.
Unwillingness or inability to comply with procedures either required in this protocol
or considered standard of care
21.
Medical, uncontrolled disease-related metabolic disorder, psychiatric, cognitive, or
other conditions that may compromise the patient’s ability to understand the patient
information, give informed consent, comply with the study protocol, or complete the
study
22.
History of severe allergic reaction to azacitidine (if patient enrolling into azacitidine
combination cohort) or low-dose cytarabine (if patient enrolling into cytarabine
combination cohort)
23.
Prisoners or patients who are involuntarily incarcerated or are compulsorily detained
for treatment of either a psychiatric or physical (e.g. infectious disease) illness
Note: Under certain specific circumstances, a person who has been imprisoned may
be included or permitted to continue as a patient, if local regulations permit. Strict
conditions apply and Forma’s approval is required.
Note: Eligibility criteria waivers will not be granted. 
4.5 
Study Assessments 
The assessments for this study are listed in Section 6.1. 
4.6 
Replacement of Dropouts in Phase 1 Dose-Escalation Cohorts 
Patients participating in Phase 1 dose-escalation cohorts who discontinue early before 
completing Cycle 1 for any reason other than an AE may not be evaluable and therefore may be 
replaced at the discretion of the Sponsor. To be considered evaluable, patients must have 
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completed a minimum of 75% of FT-2102 scheduled doses during Cycle 1, except those 
experiencing a DLT. All patients who come off study should complete both an end-of-study and 
a 28-day follow-up evaluation. 
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5 
STUDY DRUG INFORMATION AND DOSAGE 
5.1 
Identification and Description of Test Articles 
5.1.1 
FT-2102 
FT-2102 capsules incorporate FT-2102 active pharmaceutical ingredient (API) powder blended 
with compendial grade excipients to impart suitable flow and dissolution properties, and are 
subsequently filled in a Coni-Snap® hard gelatin capsule. FT-2102 Capsules are initially 
presented as two unit strengths for oral administration. The capsules contain 50 or 150 mg 
FT-2102 fill weight per capsule. Each dose strength is filled in white capsules that have a 
distinctive size. 
•
Size 2 White/White opaque capsules are filled with formulated bulk that contains 50 mg
FT-2102.
•
Size 00 White/White opaque capsules are filled with formulated bulk that contains
150 mg FT-2102.
5.1.2 
Azacitidine 
Azacitidine is supplied as a lyophilized powder in 100 mg single-use vials containing no 
preservative and is packaged in cartons of one vial.  
5.1.3 
Cytarabine 
Cytarabine Injection is supplied as 20 mg/mL clear, colorless sterile isotonic solution, which 
contains no preservative, and is packaged in cartons of one vial.  
5.2 
Administration, Storage and Handling of Test Articles 
5.2.1 
FT-2102 
FT-2102 capsules shall be stored according to storage conditions provided on the drug product 
label. 
FT-2102 will be administered as a fixed dose. Patients should make all attempts to take FT-2102 
capsules at the same time on scheduled dose days. Capsules may be taken with 240 mL of water. 
Capsules should be ingested at least 2 hours after a meal or at least 30 minutes prior to their next 
meal. Guidance on the timing of FT-2102 capsule ingestion relative to meals may be modified by 
the Sponsor based on the clinical experience with FT-2102. 
In case of BID dosing, FT-2102 should be taken every 12 hours with a minimum of 8 hours 
between doses. 
If a patient vomits at any time after dosing, the dose of FT-2102 should not be re-administered. 
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Doses of FT-2102 that are omitted for AEs or for any other reason should not be replaced or 
made up at the end of the dosing period. 
When administered in combination with azacitidine, with the exception of C1D1 and C2D1 
(when PK sampling is performed), it is recommended that FT-2102 should be administered first 
on the days when both FT-2102 and azacitidine are given. 
The site personnel will train the patients and their caregivers on procedures for drug 
administration. The pharmacist or study nurse will provide the patients with the correct amount 
of drug for the subsequent dosing period. Patients will be supplied with the correct amount of 
capsules for the number of doses to be taken prior to the next scheduled visit. 
5.2.2 
Azacitidine 
Unreconstituted vials of azacitidine must be stored according to storage conditions provided in 
the VIDAZA® package insert. 
Please see pharmacy manual for reconstitution guidelines. 
 Azacitidine will be administered per SOC at a starting dose of 75 mg/m2. The recommended 
dosing schedule for azacitidine is daily × 7 days consecutively (via subcutaneous injection or 
intravenous infusion), but a 48-hour dose interruption for weekends or holidays is allowed. 
Azacitidine is to be administered beginning on C1D1 and then Day 1 of each subsequent 28-day 
treatment cycle. Alternate schedules for the start of azacitidine administration (e.g., beginning on 
Day 8 of each treatment cycle) may be accepted when clinically indicated. 
5.2.3 
Cytarabine 
Vials of Cytarabine 20 mg/mL Injection must be stored according to the storage condition 
provided in the package insert. Patients enrolled in the Phase 1 combination cohort of cytarabine 
+ FT-2102 will be treated at a flat dose of 20 mg BID of cytarabine given SC for 10 days every
28-day cycle.
5.3 
Drug Accountability and Return of Study Supplies 
The Investigator will keep a record of the dates and amounts of study drug received, the amount 
dispensed to study patients, and the amount unused.  
Additionally, patients will be asked to record their dosing in a patient diary.  
Drug accountability may be recorded on the appropriate electronic case report form (eCRF) page 
and on a separate Drug Disposition Record. Returned and/or unused drug should be maintained 
per institutional policy in a secure location until the Sponsor orders it to be destroyed. 
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5.4 
Concomitant Medications 
5.4.1 
Allowed Medications 
Concomitant medications can be administered at the Investigator’s discretion according to 
standard practice during the treatment period. Necessary supportive measures for optimal 
medical care will be given throughout the study.  
 
Patients who enroll in the study with leukocytosis at baseline or develop leukocytosis after 
initiation of therapy may receive hydroxyurea. Suggested guidelines for administering 
hydroxyurea are as follows: 
 
• For a WBC 10 – 50 x 109/L consider administering hydroxyurea 500 mg four times a day 
• For a WBC > 50 x 109/L consider administering hydroxyurea 1000 mg four times a day 
• Hydroxyurea should be tapered/discontinued when WBC count is < 10 x109/L 
 
Patients who enroll in the study requiring CNS prophylaxis due to prior CNS involvement and 
remain asymptomatic may receive intrathecal chemotherapy at the discretion of the investigator. 
Patients may receive premedication for nausea and/or vomiting at the discretion of the 
investigator. 
 
Patients may receive antimicrobial treatment or prophylaxis at the discretion of the investigator. 
 
All concomitant medications and supportive therapy administered, starting the first day prior to 
the first dose and until 28 days after the last dose of FT-2102, must be recorded on the 
appropriate eCRF page. 
 
5.4.1.1 Concomitant Medications to Use with Caution 
Co-administration of FT-2102 with strong CYP3A4 inducers significantly reduces FT-2102 
systemic exposure, therefore co-administration is not recommended and investigators should 
consider alternative medications. 
FT-2102 exhibits CYP3A4 induction potential in vitro and may impact the PK of co-
administered sensitive CYP3A4 substrates through increased clearance. Medications that are 
sensitive substrates of CYP3A4 should not be used while taking FT-2102. 
If the patient’s clinical condition requires a medication of concern, please discuss with the 
Medical Monitor. Refer to Appendix 9 for a list of strong CYP3A4 inducers and sensitive 
CYP3A4 substrates. 
Additional information can be found at: 
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteracti
onsLabeling/ucm093664.htm#table3-1 
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5.4.2 
Prohibited Medications 
No other investigational medicinal products will be allowed during this study. 
5.4.3 
Anticancer Therapy 
No concomitant anticancer therapy with the exceptions (hydroxyurea or CNS prophylaxis) noted 
above, will be allowed during this study. 
5.5 
Precautions 
5.5.1 
Differentiation Syndrome 
Differentiation syndrome has been observed in patients participating in this ongoing study and 
has also been reported in patients with AML/MDS receiving other therapies targeting IDH1/2 
mutations (Birendra et al. 2016; Fathi et al. 2018) or receiving azacitidine (Laufer and Roberts 
2015). 
Differentiation syndrome can be defined by the presence of any of the following symptoms: 
unexplained fever, cough, fast weight gain of more than 10 pounds (5 kg) within a week, bone 
pain, dizziness or feeling lightheaded, respiratory distress or shortness of breath, interstitial 
pulmonary infiltrates, pleural or pericardial effusion, swelling of arms & legs and swelling 
around the neck, groin or underarm with or without hyperleukocytosis (Frankel et al. 1992; 
Montesinos et al. 2009). No single sign or symptom may be considered per se as diagnostic of 
the syndrome. However, given the life-threatening character of a full-blown (overt) syndrome, it 
is recommended that the prophylactic and therapeutic measures indicated below are undertaken 
at the earliest manifestations of suspected differentiation syndrome (e.g., unexplained respiratory 
distress). 
•
Temporary discontinuation of FT-2102 (and azacitidine where indicated) for a minimum of
three days;
•
Prompt initiation of dexamethasone, 10 mg/12 hrs IV until disappearance of symptoms and
signs, and for a minimum of three days;
•
Furosemide, supportive measures and hemodynamic monitoring when clinically required.
As soon as the symptoms and the patient’s clinical condition improve, and after a minimum of 
three days, treatment with FT-2102 may be resumed. In case of reappearance of symptoms, 
FT-2102 should again be held. Resumption of FT-2102, if indicated, should be reduced one dose 
level for a minimum of the first 7 days after the disappearance of the differentiation syndrome. 
Thereafter, in absence of worsening of the previous toxicity, FT-2102 can be resumed at full 
dosage. 
Where indicated, as soon as the symptoms and the patient’s clinical condition improve, and after 
a minimum of 3 days, treatment with azacitidine may be reinstituted at ≤ standard dosing and/or 
delayed further at the investigator’s discretion. No dose modifications are required for LDAC. 
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5.5.2 
Leukocytosis 
Rapid myeloid proliferation, presenting as leukocytosis has been observed with other IDH 
inhibitors in the absence of clinical manifestations of differentiation syndrome. In the absence of 
differentiation syndrome, and unless clinically indicated, leukocytosis does not require dose 
interruption and should be managed by hydroxyurea as per Section 5.4.1. 
 
5.5.3 
Hepatic Injury 
Adverse events potentially associated with hepatic dysfunction have been reported in 
approximately 20% of patients receiving FT-2102 to date. As such, adverse events potentially 
associated with liver injury have been identified as Adverse Events of Special Interest (AESI). 
AESI, as defined in Section 7.2.4, regardless if serious or non-serious, must be reported to Forma 
Therapeutics Pharmacovigilance within 24 hours of knowledge of event as described in 
Section 7.2.4. 
Patients should be monitored for any new or unusual symptoms suggestive of liver injury 
unrelated to the patient’s primary malignancy. Symptoms may include anorexia, nausea, fatigue, 
right upper abdominal discomfort or vomiting, dark urine or jaundice. In the event of the 
development of any new clinical signs or symptoms of hepatic dysfunction, the following 
clinical investigation is recommended with additional action based upon the patient’s clinical 
presentation and at the treating investigator’s discretion.  
a. Evaluation of international normalized ratio/prothrombin time (INR/PT), albumin, total 
bilirubin, direct and indirect bilirubin, amylase, lipase, AST, ALT, gamma glutamyl 
transpeptidase, complete blood count with differential and alkaline phosphatase 
If there is evidence of new liver injury, the following actions should occur: 
a. Report the AE per Section 7.2.4 
b. Consider obtaining FT-2102 serum levels if aberrant dosing is suspected 
c. Obtain tests for viral and other infectious etiologies of hepatitis (including hepatitis A, B, 
C, D and E) and tests for autoimmune hepatitis 
d. Consider diagnostic imaging (hepatic ultrasound or MRI) and hepatic biopsy if the 
patient’s clinical status permits 
e. Obtain detailed history of symptoms and concurrent or prior disease, concomitant 
medications including herbal and dietary supplements, alcohol use, recreational drugs 
(e.g., cannabidiol or tetrahydrocannabinol) and special diets 
f. Review medical history to include non-alcoholic steatohepatitis (fatty liver), 
cardiovascular disease, diabetes, alcoholism or autoimmune disease 
g. Evaluate and discontinue if feasible, all hepatic injury-inducing concomitant medications 
(prescription and over-the-counter) and other hepatic injury-inducing agents (e.g., 
ethanol) 
h. Consider gastrointestinal or hepatology consult 
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i.
Frequent monitoring of AST, ALT, alkaline phosphatase, albumin, INR/PT, and total
bilirubin should be initiated. Frequency would be, at minimum, twice per week until
asymptomatic and the patient has returned to baseline or Grade 1 toxicity.
Restarting FT-2102 after suspected liver injury: 
a.
Once the AE returns to Grade 0-1 or baseline, resume treatment with FT-2102 at 150 mg
once daily (see Table 8).
b. For the next 28 days, while reduced dosing at 150 mg once daily, AST, ALT and total
bilirubin should be monitored at minimum twice per week for the first 2 weeks and then
weekly if no recurrence of elevations are observed.
c.
If the AE recurs at 150 mg once daily, the patient will be discontinued from study
treatment (see Section 6.8.2).
d. If after a minimum of 28 days of 150 mg once daily, the AST, ALT and total bilirubin
have not elevated to Grade 2 or greater and no other symptoms, then FT-2102 may be re-
escalated to the dose level prior to event.
e.
Frequent monitoring (at least twice per week) is required upon re-escalation, and may be
decreased after patient has been on the escalated dose for at least 28 days without an
increase in the AST, ALT and total bilirubin.
Patients on active treatment with FT-2102 should be informed to promptly notify study staff if 
they develop any clinical symptoms of jaundice and to avoid personal habits (excessive ethanol 
consumption, over-the-counter hepatic injurious medications, herbal medications [e.g., 
cannabidiol or comparable products]) that may cause additional risk of hepatic injury. 
5.5.4 
Phototoxicity 
A phototoxic potential was demonstrated for FT-2102 in a standard in vitro assay system. Until 
the photosafety of FT-2102 has been adequately demonstrated in vivo, phototoxicity risks in the 
clinical setting will be managed by the use of light-protective measures. Patients should be 
instructed to avoid extensive sun exposure, phototherapy, or use of a tanning salon within a 
prudent amount of time prior to and following trial participation. 
5.6 
Childbearing Potential 
For all patients of childbearing potential, all methods of contraception, including abstinence, 
must be in use from the time of consent through the final study visit, and for 90 days after the 
last dose of study drug. Patients who are not sexually active during the Screening Period must 
agree to the contraceptive requirements if they become sexually active with a partner of the 
opposite sex during the study and for 90 days after the last dose of study drug. Unique situations 
that may not fall within these specifications may be discussed with the Forma Therapeutics 
Medical Monitor on an individual basis.  
Female patients will be considered of childbearing potential after the onset of their first 
menstrual period. Female patients who are documented as being of nonchildbearing potential 
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(postmenopausal or having undergone surgical sterilization) are exempt from this requirement. 
Female patients will be considered postmenopausal if they have had 12 months of consecutive 
spontaneous amenorrhea or less than 12 months of consecutive spontaneous amenorrhea and a 
serum FSH level > 40 mIU/mL at Screening. Female patients will be considered surgically 
sterile if they are post-hysterectomy, 6 months post-surgical bilateral oophorectomy, or 6 months  
post-tubal ligation. 
 
5.6.1 
Contraception Guidelines 
Acceptable methods of contraception under this protocol are listed below. Periodic abstinence 
(calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhoea method are not acceptable methods of contraception. 
Male patients who can father a child must agree to use one highly effective method of 
contraception, which includes: 
• Abstinence: abstinence can be used, when in line with the preferred and usual lifestyle of 
the patient.  
• 
If a male patient confirms that his female partner(s) is not of childbearing potential (i.e., 
postmenopausal or post-surgical sterilization, as defined above) or is using a highly 
effective method of contraception, this is acceptable as the only means of contraception.  
 
Examples of highly effective methods of contraception for male patients’ female 
partner(s) include: 
o  Hormonal contraceptives 
o  Intrauterine device (IUD) 
 
Male patients with documented infertility or surgical sterilization (performed at least six months 
before the first dose of study drug) are exempt from the contraception requirement. Infertility 
may be documented through examination of a semen specimen or by demonstration of the 
absence of the vas deferens on ultrasound before the first dose of study drug (Day 1). 
 
Female patients who are considered of childbearing potential must agree to use a highly 
effective method of contraception, which may include: 
• IUD 
• Abstinence: abstinence can be used, when in line with the preferred and usual lifestyle of 
the patient. 
• If a female patient confirms that her male partner(s) has been confirmed to be clinically 
sterile, this method is acceptable as the only means of contraception. 
 
Hormonal contraceptives are not considered an effective method of birth control for female 
patients participating in this study. Male condoms with female condoms should not be used 
together.  
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5.6.2 
Guidance Against Donating Sperm or Ova 
Male patients are prohibited from donating sperm and female patients of childbearing potential 
are prohibited from donating ova during the study and for 90 days after the final dose of study 
drug. 
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6 
STUDY PROCEDURES 
6.1 
Measurements and Evaluations 
See Appendix 1 and Appendix 2 for a detailed study Schedule of Events, including 
measurements and evaluations for the entire study period (Screening to Follow-up) presented in 
tabular form. 
 
For Protocol Version 7/ Amendment 6, a reduced Schedule of Events has been introduced for all 
ongoing patients receiving treatment at the time of the amendment (see Appendix 1) and a new 
Schedule of Events has been added for patients enrolled after Protocol Version 7/ Amendment 6 
(eg, patients that transfer from Cohort 1 to Cohort 3 or Cohort 6) (see Appendix 2). 
 
6.1.1 
Pre-screening 
Sites that do not perform IDH1 mutation testing as part of their SOC may have the option to send 
pre-screening patients’ samples for central laboratory IDH1 mutation detection before study 
enrollment.  
 
6.1.2 
Informed Consent 
Prior to the initiation of any study-specific procedures or assessments, the Investigator or 
designee must provide to each patient a complete explanation of the purpose and methods 
(procedures and assessments) of the study. Subsequently, the patient must receive and sign a 
copy of both the Informed Consent Form (ICF) and the Authorization of Use and Disclosure of 
Protected Health Information (PHI) approved by the study site Institutional Review Board (IRB)/ 
ethics committee (EC). Once informed consent has been obtained, the eligibility of the patient 
will be determined, and Screening Period assessments can then be performed. 
 
6.1.3 
Screening Period (Within 14 Days Prior to Day 1) 
The following evaluations will be performed to assess the patient's eligibility for the study per 
schedule of events: 
• Complete medical history (including surgical and cardiac history) 
• Leukemia and/or MDS medical history with treatment history 
• Physical examination  
• Height and weight 
• Concomitant medication assessment 
• Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) 
• ECOG performance status 
• Serum pregnancy test (for nonsterile women of childbearing potential) 
• 12-lead ECG in triplicate (should be conducted within a 10-minute period) 
o Performed as clinically indicated for patients enrolled after Protocol Version 7/ 
Amendment 6 
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•
Clinical serum chemistries
•
CBC with differential and platelet count
•
Bone marrow aspirate and peripheral blood (for clinical purposes), refer to the laboratory
manual for details of sample collection and timing
o
Not applicable for patients enrolled after Protocol Version 7/ Amendment 6 if
collected at End of Treatment visit prior to roll-over
•
Local IDH1m confirmation (this may have occurred > 28 days prior)
•
Coagulation parameters (PT and PTT)
•
Blood sample collection for PD analysis (See Section 6.5 for PD sampling times)
•
Urinalysis
o
Not applicable for patients enrolled after Protocol Version 7/ Amendment 6
•
AE monitoring
•
EQ-5D-5L QOL (any time prior to first dose) (Phase 2 only)
o
Not applicable for patients enrolled after Protocol Version 7/ Amendment 6
6.1.4 
Cycle 1, Day 1 
All procedures to be performed predose, with the exception of postdose PK/PD sample collection 
and ECG. Following completion of predose procedures, patients will receive their first dose of 
FT-2102.  
Note: Patients will receive only a single dose of study drug (single-agent arm and combination 
arm) on Cycle 1 Day 1: 
•
Concomitant medication assessment
•
Weight
•
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate)
•
ECOG performance status
•
Physical examination
•
Serum or urine pregnancy test (for nonsterile women of childbearing potential)
•
12-lead ECG (predose [Phase 1 and 2], and 2 hr, 4 hr, 8 hr postdose [Phase 1 only]) in
triplicate should be conducted within a 10-minute period
o
As clinically indicated for patients enrolled after Protocol Version 7/
Amendment 6
•
Clinical serum chemistries
•
CBC with differential and platelet count
•
Urinalysis
o
Not applicable for patients enrolled after Protocol Version 7/ Amendment 6
•
AE monitoring
•
Blood sample collection for PK analysis (see Section 6.4 for PK sampling times)
o
Not applicable for patients enrolled after Protocol Version 7/ Amendment 6
•
Blood sample collection for PD analysis (see Section 6.5 for PD sampling times)
o
Not applicable for patients enrolled after Protocol Version 7/ Amendment 6
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• 24-hour Holter monitoring (see manual for details) at all centers in the United States (US) 
and select centers outside of the US (ex-US) 
o Not applicable for patients enrolled after Protocol Version 7/ Amendment 6 
 
Day 1 testing, with the exception of PK/ PD collections and ECG (including Holter) assessments, 
may be done within 72 hours prior to the Day 1 visit and do not need to be repeated if performed 
during Screening within the allotted window. 
 
Note: Patients taking BID dose will be instructed to not administer their 2nd dose of FT-2102 on 
C1D1. 
 
6.1.5 
Cycle 1, Day 2 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
The following procedures will be performed at this visit: 
• Concomitant medication assessment 
• AE monitoring  
• Blood sample collection for PK analysis (see Section 6.4 for PK sampling times); to 
occur prior to dosing and at or near the same time as collection at the previous study visit 
(i.e., approximately 24 hours after the first dose of study drug was administered) 
• Blood sample collection for PD analysis (see Section 6.5 for PD sampling times); to 
occur prior to dosing and at or near the same time as collection at the previous study visit 
(i.e., approximately 24 hours after the first dose of study drug was administered) 
• Completion of 24-hour Holter monitoring (pre-dose) at all centers in the US and select 
centers ex-US 
 
Note: Patients receiving FT-2102 on a BID schedule should be instructed to take a second dose 
of study drug later in the day. 
 
6.1.6 
Cycle 1, Day 5 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
The following procedures should be performed (local laboratory testing allowed): 
• CBC with differential and platelet count 
• Clinical serum chemistries  
 
6.1.7 
Cycle 1, Day 8 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
All procedures to be performed predose: 
• Concomitant medication assessment 
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•
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate)
•
Symptom-directed physical examination
•
12-lead ECG in triplicate should be conducted within a 10-minute period
•
Clinical serum chemistries
•
CBC with differential and platelet count
•
AE monitoring
•
Blood sample collection for PK analysis (see Section 6.4 for PK sampling times)
•
Blood sample collection for PD analysis (see Section 6.5 for PD sampling times)
Day 8 testing, with the exception of PK/PD and ECG collections, may be done within 24 hours 
prior to the Day 8 visit.  
6.1.8 
Cycle 1, Day 12 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
The following procedures should be performed (local laboratory testing allowed): 
•
Clinical serum chemistries
•
CBC with differential and platelet count
6.1.9 
Cycle 1, Day 15 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
All procedures to be performed predose: 
•
Concomitant medication assessment
•
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate)
•
Symptom-directed physical examination
•
12-lead ECG in triplicate should be conducted within a 10-minute period
•
Clinical serum chemistries
•
CBC with differential and platelet count
•
AE monitoring
•
Blood sample collection for PK analysis (see Section 6.4 for PK sampling times)
•
Blood sample collection for PD analysis (see Section 6.5 for PD sampling times)
Day 15 testing, with the exception of PK/PD and ECG collections, may be done within 48 hours 
prior to the Day 15 visit.  
6.1.10 Cycle 1, Day 19 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
The following procedures should be performed (local laboratory testing allowed): 
•
Clinical serum chemistries
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•
CBC with differential and platelet count
6.1.11 Cycle 1, Day 22 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
All procedures to be performed predose: 
•
Concomitant medication assessment
•
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate)
•
Symptom-directed physical examination
•
12-lead ECG in triplicate should be conducted within a 10-minute period
•
Clinical serum chemistries
•
CBC with differential and platelet count
•
AE monitoring
•
Blood sample collection for PK analysis (see Section 6.4 for PK sampling times)
•
Blood sample collection for PD analysis (see Section 6.5 for PD sampling times)
Day 22 testing, with the exception of PK/PD and ECG collections, may be done within 48 hours 
prior to the Day 22 visit.  
6.1.12 Cycle 1, Day 26 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
The following procedures should be performed (local laboratory testing allowed): 
•
Clinical serum chemistries
•
CBC with differential and platelet count
6.1.13 Cycle 2, Day 1 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
All procedures to be performed predose, with the exception of postdose PK/PD sample collection 
and ECG: 
•
Concomitant medication assessment
•
Weight
•
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate)
•
ECOG performance status
•
Symptom-directed physical examination
•
Serum or urine pregnancy test for female patients of childbearing potential
•
12-lead ECG (predose [Phase 1 and 2], and 2 hr, 4 hr, 8 hr postdose [Phase 1 only]) all
timepoints in triplicate should be conducted within a 10-minute period
•
Clinical serum chemistries
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• CBC with differential and platelet count 
• Coagulation parameters (PT and PTT) 
• Urinalysis 
• AE monitoring 
• Blood sample collection for PD analysis (see Section 6.5 for PD sampling times) 
• Blood sample collection for PK analysis (see Section 6.4 for PK sampling times) 
• Note: A 72-hour wash-out post C2D1 dosing will be requested from all patients 
participating in the dose-expansion stage. After the C2D1 FT-2102 AM dose, patients 
will be asked to refrain from taking FT-2102 until the AM of C2D4. 
• Bone marrow aspirate or biopsy for disease assessment/ cancer-associated mutation 
analysis (for an early disease assessment in patients with resolution of peripheral blasts) 
• 24-hour Holter monitoring (see manual for details) at all centers in the US and select 
centers ex-US. 
• EQ-5D-5L QOL (Phase 2 only) 
Cycle 2 Day 1 testing, with the exception of PK/PD and ECG (including Holter), collections may 
be done within 48 hours prior to the Day 1 visit.  
 
6.1.14 Cycle 2, Day 2 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
Applicable for all patients participating in the Phase 1 dose-expansion stage and the subset of 
patients participating in 24-hour Holter monitoring (see manual for details): 
• Concomitant medication assessment 
• AE monitoring 
• Blood sample collection for PD analysis (see Section 6.5 for PD sampling times) 
• Blood sample collection for PK analysis (see Section 6.4 for PK sampling times) 
• Completion of 24-hour Holter monitoring (pre-dose) at all centers in the US and select 
centers ex-US 
 
6.1.15 Cycle 2, Day 4 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
Applicable for all patients participating in the Phase 1 dose-expansion stage: 
• Concomitant medication assessment 
• AE monitoring 
• Blood sample collection for PD analysis (see Section 6.5 for PD sampling times) 
• Blood sample collection for PK analysis (see Section 6.4 for PK sampling times) 
Note: Collect prior to re-starting FT-2102 
 
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6.1.16 Cycle 2, Day 8 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
The following procedure should be performed (local laboratory testing allowed): 
•
Clinical serum chemistries
•
CBC with differential and platelet count
6.1.17 Cycle 2, Day 15 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
All procedures to be performed predose: 
•
Concomitant medication assessment
•
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate)
•
Symptom-directed physical examination
•
12-lead ECG in triplicate should be conducted within a 10-minute period
•
Clinical serum chemistries
•
CBC with differential and platelet count
•
AE monitoring
•
Blood sample collection for PK analysis (see Section 6.4 for PK sampling times)
•
Blood sample collection for PD analysis (see Section 6.5 for PD sampling times)
Cycle 2 Day 15 testing, excluding PK and PD collections, may be done within 48 hours prior to 
the Day 15 visit.  
6.1.18 Cycle 2, Day 22 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
The following procedures should be performed (local laboratory testing allowed): 
•
CBC with differential and platelet count
•
Clinical serum chemistries
6.1.19 Cycle 3, Day 1 
All procedures to be performed predose: 
•
Concomitant medication assessment
•
Weight
•
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate)
•
ECOG performance status
•
Symptom-directed physical examination
•
Serum or urine pregnancy test for female patients of childbearing potential
•
12-lead ECG in triplicate should be conducted within a 10-minute period
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o As clinically indicated for patients enrolled after Protocol Version 7/ 
Amendment 6 
• Clinical serum chemistries 
• CBC with differential and platelet count  
• Bone marrow aspirate or biopsy for disease assessment and cancer-associated mutation 
analysis: 
o Required on Cycle 3 Day 1 in any patient who did not undergo a Cycle 2 Day 1 
bone marrow aspirate (BMA) or biopsy (Bx) assessment 
o Not applicable for patients enrolled after Protocol Version 7/ Amendment 6 
• Urinalysis (if medically indicated) 
• AE monitoring 
• Blood sample collection for PK analysis (see Section 6.4 for PK sampling times) 
o Not applicable for patients enrolled after Protocol Version 7/ Amendment 6 
• Blood sample collection for PD analysis (see Section 6.5 for PD sampling times) 
o Not applicable for patients enrolled after Protocol Version 7/ Amendment 6 
• EQ-5D-5L QOL (Phase 2 only) 
o Not applicable for patients enrolled after Protocol Version 7/ Amendment 6  
 
Cycle 3, Day 1 testing, with the exception of PK/PD, may be done within 72 hours prior to the 
Day 1 visit. 
 
6.1.20 Cycle 3, Day 15 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
The following procedures should be performed (local laboratory testing allowed): 
• Clinical serum chemistries  
• CBC with differential and platelet count 
 
6.1.21 Cycle 4, Day 1 (Not Applicable for Patients Enrolled after Protocol 
Version 7/ Amendment 6) 
All procedures to be performed predose: 
• Concomitant medication assessment 
• Weight  
• Vital signs (temperature, blood pressure, pulse rate, and respiratory rate)  
• ECOG performance status 
• Symptom-directed physical examination 
• Serum or urine pregnancy test for female patients of childbearing potential 
• 12-lead ECG in triplicate should be conducted within a 10-minute period 
• Clinical serum chemistries 
• CBC with differential and platelet count  
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•
Bone marrow aspirate or biopsy for disease assessment and cancer-associated mutation
analysis:
o
Day 1 on any cycle where response assessment is indicated per Response
assessment guidelines (see Section 4.3)
•
Urinalysis (if medically indicated)
•
AE monitoring
•
Blood sample collection for PK analysis Day 1 of every cycle (see Section 6.4 for PK
sampling times)
•
Blood sample collection for PD analysis Day 1 of every cycle (see Section 6.5 for PD
sampling times)
•
EQ-5D-5L QOL (Phase 2 only)
Cycle 4: Day 1 testing, with the exception of PK/PD, may be done within 72 hours prior to the 
Day 1 visit. 
6.1.22 Cycle 5 and Beyond, Day 1 (Every Other Cycle) 
Beginning with Cycle 5, patients will return to the clinic every other cycle. 
All procedures to be performed predose: 
•
Concomitant medication assessment
•
Weight
•
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate)
•
12-lead ECG as clinically indicated
•
ECOG performance status
•
Symptom-directed physical examination
•
Serum or urine pregnancy test for female patients of childbearing potential
•
Clinical serum chemistries
•
CBC with differential and platelet count
•
Bone marrow aspirate or biopsy for response assessment
o
For patients with AML: Every 6 cycles unless there is an indication of
relapse/progression
o
For patients with MDS: As clinically indicated
o
For patients enrolled in Phase 2 Cohort 2: Only if there is a suspicion of relapse
•
AE monitoring
Cycle 5 and beyond (every other cycle): Day 1 testing may be done within 72 hours prior to the 
Day 1 visit. 
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6.1.23 End of Treatment Assessments 
The following assessments should be performed within 7 days from decision to discontinue 
treatment with FT-2102 (vs. discontinuation from the entire study, as detailed in Section 8.2): 
•
Concomitant medication assessment
•
Weight
•
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate)
•
ECOG performance status
•
Physical examination
•
Serum or urine pregnancy test for female patients of childbearing potential
•
12-lead ECG as clinically indicated
•
Clinical serum chemistries
•
CBC with differential with platelet count
•
Bone marrow aspirate or biopsy (for disease assessment) as clinically indicated
•
Urinalysis if medically indicated
•
AE monitoring
If the patient had any of these assessments within the previous 2 weeks (4 weeks for bone 
marrow aspirate or biopsy), then these assessments need not be repeated. 
6.1.24 Safety Follow-up Visit/Interview 
All AEs will be followed for 28 days after administration of last dose of study drug or until 
resolution or stabilization as documented by physical examination or appropriate laboratory 
results. If subsequent anticancer therapy is initiated earlier, this visit or contact should occur 
before the initiation of subsequent anticancer therapy. The data should be documented on the 
appropriate eCRF page. 
6.1.25 Disease Response Follow-up 
Patients who discontinue study treatment for reasons other than treatment failure and have not 
withdrawn consent from overall study participation, should continue to be followed for disease 
response assessments until the time of disease progression/relapse or the initiation of a new 
treatment regimen. Patients who have stopped FT-2102 treatment for HSCT should continue to 
be followed until disease progression/ relapse. This information should be documented on the 
appropriate eCRF page. 
6.1.26 Survival Follow-up 
After a patient discontinues or completes study treatment, the study site may be requested to 
contact the patient approximately every 3 months to collect survival status and data pertaining to 
any other alternative anti-neoplastic therapy. Patients enrolled in the Phase 1 dose-escalation/ 
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dose-expansion stages may have survival follow-up performed for up to 12 months from C1D1 
or 28 days after administration of last dose of drug (whichever is longer). Patients enrolled in the 
Phase 2 cohorts may have survival follow-up for up to 36 months from C1D1 or 28 days after 
administration of last study drug (whichever is longer). 
 
6.2 
Safety 
Safety variables to be assessed include: AEs, clinical laboratory tests, vital signs measurements, 
physical examination findings, and ECG readings (see manual for details of Holter monitoring 
procedures). 
6.2.1 
Data Monitoring Committee 
Close monitoring of serious safety events as they are reported is conducted by the medical 
monitor. Serious and non-serious adverse event review is conducted regularly by the medical 
monitor through monthly listing review. Safety events are also reviewed during regular study 
conduct meetings between the medical monitor, the clinical team, pharmacovigilance, and the 
participating investigators.  
These study-conduct meetings during the Phase 1 component of this trial include bi-weekly 
internal review meetings to monitor study progress/safety events and bi-weekly teleconferences 
with investigators. For the Phase 2 component of the trial monthly meetings with investigators 
are held.  
Periodic safety reviews by Forma’s internal DMC, consisting of the clinical study team, 
pharmacovigilance, and medical monitors not directly involved in the conduct of Study 2102-
HEM-101, also occur.  
This internal DMC meets at least bi-annually to review safety listings and on an ad hoc basis in 
response to new safety signals to rapidly assess overall risk to participants. The outcome of these 
internal DMC meetings, when relevant, is quickly communicated to study investigators so they 
may share current risk information with their patients and collect updated informed consent 
forms, if appropriate. 
6.3 
Bone Marrow Aspirate and/or Biopsy 
A bone marrow aspirate for clinical purposes should be obtained from each patient prior to 
initiating study treatment (baseline) and while on treatment at the time of response assessment 
(as per Section 4.3).  
 
Bone marrow materials prepared according to the guidelines in the laboratory manual will meet 
specifications to enable central testing (where indicated) for mutational analysis (including 
confirmation of presence of IDH1-R132 mutation). Bone marrow biopsy may be used for on-
study disease assessment when bone marrow aspirate is a dry tap. 
 
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Refer to the laboratory manual for additional instructions on collecting and processing bone 
marrow aspirates and biopsies. 
6.4 
Pharmacokinetics 
Note: As of Protocol Version 7/ Amendment 6, PK samples are no longer being collected. 
The plasma PK collections will be performed as detailed in Table 4. Blood samples will be 
collected. The actual time of blood collection must be documented in the respective form, and 
any deviations outside of the time limits must be commented upon. The scheduled blood 
sampling times will be used for the PK analysis; however, any deviations outside the limits (real 
times) are relevant and the data sets will be adjusted for the PK evaluations and the real times 
will be used.  
A laboratory manual will be provided with instructions for collecting and processing of the 
samples. 
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Table 4 
Pharmacokinetic Sampling Times: FT-2102 
Cycle 
Day 
Sample 
Collection Timesa 
Phase 1 
Patients 
Phase 2 Patients 
(24 hr Holter 
Monitoring) 
Phase 2 Patients 
(No 24 hr Holter 
Monitoring) 
1 
1  
1 
Predose 
X 
X 
X 
2 
30 minutes after dosing  
(+/- 5 minutes) 
X 
X 
 
3 
1 hr after dosing (+/- 5 minutes) 
X 
X 
 
4 
2 hr after dosing (+/- 15 minutes) 
X 
X 
 
5 
4 hr after dosing  
(+/- 15 minutes or 2 hoursb) 
X 
X 
X 
6 
8 hr after dosing (+/- 30 minutes) 
X 
X 
 
2  
1 
Predose 
X 
X 
 
8, 15, 
and 22 
1 
Predose 
X 
 
 
2 
1 
1 
Predose 
X 
X 
X 
2 
30 minutes after dosing  
(+/- 5 minutes) 
X 
X 
 
3 
1 hr after dosing (+/- 5 minutes) 
X 
X 
 
4 
2 hr after dosing (+/- 15 minutes) 
X 
X 
 
5 
4 hr after dosing (+/- 15 minutes) 
X 
X 
 
6 
8 hr after dosing (+/- 30 minutes) 
X 
X 
 
2 
1  
24 hrs after C2D1 dosing (+/- 2 hrs) 
X 
X 
 
4 
1 
Predose  
[72 hrs after C2D1 dosing (+/- 4 hrs)] 
Xc 
 
 
15 
1 
Predose 
X 
 
 
3 and 4 
1 
1 
Predose 
X 
X 
X 
Random 
TBD 
1 
Collected in the setting of potential 
treatment-related AE 
X 
X 
X 
a 
PK sampling times are specific for FT-2102.  
b 
+/- 15 minutes for Phase 1/ Phase 2 Holter Monitor and +/- 2 hours for Phase 2. 
c 
Performed in patients participating in the dose-expansion stage only. 
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Plasma concentration data will be used to determine the following PK parameters: 
•
AUC Area under the concentration curve
•
Cmax 
Maximum plasma concentration
•
Tmax  Time to maximum plasma concentration
•
t1/2 
Terminal elimination half life
•
CL/F Total body clearance
•
Vd/F 
Apparent volume of distribution
6.5 
Pharmacodynamics 
Note: As of Protocol Version 7/ Amendment 6, PD samples are no longer being collected. 
Peripheral blood samples for exploratory PD assessments will be collected at the specified times 
detailed in Table 5. Blood samples will be collected. The actual time of blood collection must be 
documented in the respective form and any deviations outside of the time limits must be 
commented upon.  
The scheduled blood sampling times will be used for the PD biomarker analysis; however, any 
deviations outside the limits (actual times) are relevant and the data sets will be adjusted for the 
PD evaluations and the actual times will be used.  
A laboratory manual will be provided with instructions for collecting and processing of the 
samples. 
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Table 5 
Pharmacodynamic Sampling Times: FT-2102 (Single Agent) and FT-2102 
plus Azacitidine or Low-Dose Cytarabine (Combination) 
Cycle 
Days 
Sample 
Collection Times 
Phase 1 
Patients 
Phase 2 Patients 
(24 hr Holter 
Monitoring) 
Phase 2 Patients 
(No 24 hr Holter 
Monitoring) 
Screening 
NA 
1 
Predose 
X 
 
 
1 
1  
1 
Predose 
X 
X 
X 
2 
1 
Predose 
X 
 
 
8 
1 
Predose 
X 
 
 
15 
1 
Predose 
X 
 
 
22 
1 
Predose 
X 
 
 
2 
1 
1 
Predose 
X 
X 
X 
2a 
1b 
-- 
X 
 
 
4a 
1b 
Predose 
X 
 
 
15 
1b 
Predose 
X 
 
 
3 and 4 
1 
1 
Predose 
X 
X 
X 
a 
Collected in dose-expansion patients during C2D2 and at the end of 72 hr FT-2102 washout (C2D4) (see Schedule of Events 
in Appendix 1). 
b 
Not required in Phase 2. 
 
6.6 
Mutational Analysis 
Note: As of Protocol Version 7/ Amendment 6, samples for mutational analysis are no longer 
being collected. 
 
Bone marrow aspirate and peripheral blood samples for exploratory assessments of 
cancer-associated mutations and/or genetic alterations will be collected as follows: 
 
A bone marrow aspirate sample will be collected during the Screening period, prior to Cycle 1 
Day 1. If the patient had a bone marrow aspirate performed within 28 days of Cycle 1 Day 1 and 
there is sufficient sample available for analysis, it does not need to be repeated. 
At any time while on treatment, if a patient undergoes a bone marrow aspirate or biopsy sample 
collection for response assessment, material will be requested for cancer-associated mutations 
analysis (refer to Section 4.3 and Section 6.3 for timepoint details). 
 
Peripheral blood samples will be collected at Screening and at each timepoint that a bone 
marrow aspirate or biopsy is obtained.  
 
See the laboratory manual provided for details of the specific analyses and instructions on 
collecting and processing of these samples. 
 
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Note: Pretreatment bone marrow aspirate and peripheral blood samples for retrospective 
confirmation of IDH1m by the central assay is mandatory for efficacy evaluable (EE) population 
definition, and not an exploratory assessment.   
6.7 
Outcome Research Assessment 
Note: As of Protocol Version 7/ Amendment 6, quality of life assessments are no longer being 
performed. 
Throughout the clinical trial period, patients will be asked about their quality of life via the 
Quality of Life questionnaires EQ-5D-5L.  
The EQ-5D-5L is a standardized instrument developed by the EuroQol Group to describe and 
value health related quality of life. The instrument comprises the following five dimensions: 
mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is 
rated by the patients on a 5 point scale as having ‘no problems’ (a score of 1), ‘slight problems (a 
score of 2), ‘moderate problems’, (a score of 3), ‘severe problems’, (a score of 4) and ‘extreme 
problems’, (a score of 5) based on descriptive examples: the scores are not intended to be 
summed. Present overall state of health is also to be rated on a vertical visual analogue scale 
(approximately 20cm in length) from 0 to 100 (the higher the number the better quality of life. 
The EQ-5D-5L will be performed at screening (any time prior to first dose) and then monthly on 
Day 1 of Cycles 1 to 4 (completed prior to all other D1 procedures) for all Phase 2 patients. 
Patients should self-complete the EQ-5D-5L and return to the site. Data will then be entered into 
the patient’s eCRF. 
6.8 
Dose Modifications  
6.8.1 
FT-2102 Dose Modifications 
Patients participating in the dose-escalation stage who are receiving a dose of FT-2102 that is 
one level below an established safe dose may be considered for intrapatient dose escalation if 
they have not experienced a protocol-defined dose limiting toxicity at the lower dose level, and 
pending a consultation between the Investigators and Medical Monitor. 
If a patient has an AE that is judged by the Investigator as related to study drug (i.e., assessed as 
unrelated to the underlying disease, intercurrent illness, or concomitant medications), then dose 
modifications can be made according to the guidelines in Table 6. Dose modification guidelines 
for liver function test (LFT) abnormalities are presented in Table 7. Dose reduction guidelines 
are presented in Table 8. 
Deviations from these guidelines (e.g., drug interruption for a Grade 2 pleural effusion) may 
occur if agreed upon by the Principal Investigator and Medical Monitor. There should be no 
attempt to make up doses omitted due to toxicity.  
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Table 6 
FT-2102 Recommended Dose Modifications for Adverse Events Unrelated to 
Liver Function Abnormalities 
Severity of Adverse 
Events 
Dose Modifications for FT-2102 c 
Non-Hematologic  
Hematologic 
Grade 1 
Continue treatment at the same dose 
Continue treatment at the same dose 
Grade 2 
Continue treatment at the same dose. If 
dose interruption is clinically indicated, 
resume dosing at same dose level after 
recovery to ≤ G1 
Continue treatment at the same dose 
Grade 3 
Hold treatment until recovery to ≤ G1 or 
baseline, whichever is worse a, then 
resume at the next lower dose level. 
Contact Medical Monitor if resumption of 
FT-2102 at full dose is clinically 
indicated. 
Continue treatment at the same dose. If dose 
interruption is clinically indicated, resume 
dosing at same dose level after recovery to 
≤ G2 
Grade 4 
Permanently discontinue treatment b 
Hold treatment until recovery to ≤ G2 or 
baseline, whichever is worse, then resume at 
the next lower dose level. 
Contact Medical Monitor if resumption of 
FT-2102 at full dose is clinically indicated. 
AE = adverse event. 
a 
In the event of Grade 3 nausea, vomiting, diarrhea, or rash, the patient can continue at the same dose if the 
patient is responsive to treatment measures within 72 hr. 
b 
A patient with a Grade 4 AE may resume treatment at the next lower dose level if the AE recovers to Grade 0-1 
or baseline and if in the opinion of the Investigator and Sponsor, the patient can be monitored for recurrence of 
AE. 
c 
Dose modification may be more or less conservative at the Investigator’s discretion and after consultation with 
the medical monitor. 
 
Table 7 
FT-2102 Recommended Dose Modifications for Liver Function Test 
Abnormalities 
Laboratory Abnormality 
Action to be Taken with FT-2102 
AST or ALT or total bilirubin is Grade 3 
Hold FT-2102   
AST or ALT is > 3 times the ULN and patient has signs and 
symptoms of a hypersensitivity reaction not related to underlying 
disease [e.g., fatigue, nausea, vomiting, RUQ pain or tenderness, 
fever, rash and/or eosinophilia (>5%)]  
Hold FT-2102  
For patient with elevated AST or ALT or total bilirubin at baseline: 
AST or ALT > 2 times baseline AND > 3.0 times ULN OR AST or 
ALT > 8.0 times ULN- whichever is lower- combined with total 
bilirubin > 2 times baseline AND > 2 times ULN  
Hold FT-2102  
AST or ALT is > 3 times the ULN and the total bilirubin is > 2 times 
ULN and Alkaline phosphatase < 2 times ULN in the absence of a 
clear alternative explanation  
Permanently discontinue FT-2102  
AST or ALT or total bilirubin is Grade 4  
Permanently discontinue FT-2102  
ALT = alanine aminotransferase; AST = aspartate aminotransferase; RUQ = right upper quadrant; ULN = upper 
limit of normal. 
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6.8.2 
FT-2102 Recommended Dose Reductions 
A dose may be withheld up to 28 days (up to 14 days for Cycle 1 only) for toxicity. Doses 
withheld for > 28 days (> 14 days for Cycle 1 only) may result in discontinuation from the study, 
unless approved by the medical monitor.  
In the Phase 1 dose escalation part of the study: Dose reductions in Cycle 1 are allowed only 
after a DLT and not below the 150 mg QD.  
Recommended dose reductions for all AEs including those associated with LFT abnormalities 
are outlined in Table 8.  
Table 8 
Recommended FT-2102 Dose Reduction Levels 
Starting Dose 
Reduction Level -1 
150 mg BIDa 
150 mg QD 
a.
Patients currently treated with 100 mg BID can further reduce to 150 mg QD if clinically indicated.
Patients who have a dose reduction due to toxicity may be eligible for a dose increase back to the 
initial dose if the following criteria are met: 
1. Patient has recovered to baseline levels from the toxicity which caused the dose reduction
2. Patient has tolerated the lower treatment dose for > 1 week (or at least 28 days for liver
function test abnormality AEs)
Any patient who requires a dose reduction > 1 level below starting dose will be discontinued 
from the study. Patients who discontinue treatment must be monitored per study procedure and 
assessment schedule, unless they withdraw consent.  
6.8.3 
Azacitidine Dose Modifications 
Patients enrolled in the combination arm of azacitidine + FT-2102 will be treated at a stable 
azacitidine dose of 75 mg/m2/day for 7 days consecutively (via subcutaneous injection or 
intravenous infusion), but a 48-hour dose interruption for weekends or holidays is allowed. 
Azacitidine is to be administered beginning on Cycle 1 Day 1 and then Day 1 of each subsequent 
28-day treatment cycle. Alternate schedules for the start of azacitidine administration (e.g.,
beginning on Day 8 of each treatment cycle) is accepted when clinically indicated at the
investigator’s discretion.
Patients who are unable or unwilling to continue treatment with azacitidine after the first 
treatment cycle may continue participation in the study taking FT-2102 alone, at the discretion of 
the investigator. During Cycle 1, in dose escalation cohorts only, patients who do not receive at 
least 75% of their scheduled dose due to drug toxicity (dose hold) will have that counted towards 
the criteria for a DLT. 
Azacitidine dose adjustment may be more or less conservative per investigator’s discretion 
according to the local institutional guidelines. 
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6.8.3.2 Dose Adjustment of Azacitidine Based on Serum Electrolytes and 
Renal Toxicity 
If unexplained reductions in serum bicarbonate levels to < 20 mEq/L occur, the dosage should be 
reduced by 50% on the next course. Similarly, if unexplained elevations of BUN or serum 
creatinine occur, the next cycle should be delayed until values return to normal or baseline and 
the dose should be reduced by 50% on the next treatment course. In addition, the laboratory 
parameters that resulted in the dose delay or reduction should be rechecked twice weekly until 
they return to baseline or grade 1 level, whichever is worse. 
6.8.4 
Cytarabine 
Patients enrolled in the Phase 1 combination cohort of cytarabine + FT-2102 will be treated at a 
flat dose of 20 mg BID of cytarabine given subcutaneously (SC) for 10 days every 28-day cycle. 
Cytarabine dosing delays and interruptions for adverse events are allowed at the Investigator’s 
discretion. 
Patients who are unable or unwilling to continue treatment with LDAC after the first treatment 
cycle may continue participation in the study taking FT-2102 alone, at the discretion of the 
investigator. During Cycle 1, patients who do not receive their scheduled dose due to drug 
toxicity (resulting in dose hold) will have that counted towards the criteria for a DLT.  
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7 
PROCEDURES FOR REPORTING ADVERSE EVENTS 
7.1 
Adverse Events Definitions 
The Investigator will monitor the occurrence of AEs during the course of the study and for 
28 days after the administration of the last dose of study drug. 
The following definitions of terms are guided by the International Council on Harmonisation and 
the United States Code of Federal Regulations and are included here verbatim. 
Adverse event is any untoward medical occurrence in a patient or clinical investigation patient 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. 
Serious Adverse Event is any adverse event that results in any of the following outcomes: Death, 
a life-threatening event, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant disability/incapacity, or a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse event when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
Life-threatening refers to any adverse event that places the patient or subject, in the view of the 
Investigator, at immediate risk of death from the reaction as it occurred (i.e., it does not include a 
reaction that, had it occurred in a more severe form, might have caused death). 
Associated with the use of the drug means that there is a reasonable possibility that the 
experience (event) may have been caused by the drug. 
Unexpected adverse event means any adverse event, the specificity or severity of which is not 
consistent with those listed in the current Investigator's Brochure (IB). 
7.2 
Reporting of Adverse Events 
7.2.1 
Adverse Events 
Refer to Section 6.2.1 for a summary of ongoing safety review during the study, including 
review of any new Suspected Unexpected Serious Adverse Reactions (SUSARs). 
Serious AEs (SAEs) will be collected from the time the patient signs the informed consent form 
until 28 days after the last dose of study drug, or until the initiation of an investigational agent or 
cytotoxic chemotherapy, whichever comes first, and as per Section 7.2.3. Serious AEs will be 
collected on the Adverse Event eCRF from the time of first dose of study drug until 28 days after 
the last dose of study drug, or until the initiation of an investigational agent or cytotoxic 
chemotherapy, whichever comes first. 
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Adverse Events of Special Interest (AESI), as defined in Section 7.2.4, should be collected on 
the AESI Form from the time of first dose of study drug until 28 days after the last dose of study 
drug and reported to Forma Therapeutics Pharmacovigilance within 24 hours of knowledge of 
event. 
Non-serious adverse events will be collected and reported on the Adverse Event eCRF from the 
time of the first dose of study drug until 28 days after the last dose of study drug, or until the 
initiation of an investigational agent or cytotoxic chemotherapy, whichever comes first. 
Patients withdrawn from the study because of AEs will be followed by the Investigator until the 
outcome is determined. When appropriate, additional written reports and documentation will be 
provided. 
All AEs beginning after the last exposure of study drug must be reported to the Sponsor or its 
designee if the onset of the AE was within 28 days of the last exposure to study drug. All AEs, 
whether serious or nonserious, that are judged by the Investigator to be at least possibly related 
to study drug administration must be reported to the Sponsor or its designee regardless of how 
much time has elapsed since the last exposure to study drug (i.e., beyond 28 days of the last 
exposure to study drug). 
7.2.2 
Laboratory Abnormalities 
To the extent possible, all new or worsening laboratory abnormalities observed during the course 
of the study will be included under a reported AE describing a clinical syndrome (e.g., elevated 
blood urea nitrogen and creatinine in the setting of an AE of “renal failure” or elevated 
ALT/AST in the setting of an AE of “hepatitis”). In these cases (e.g., an AE of renal failure), the 
laboratory abnormality itself (e.g., elevated creatinine) does not need to be recorded as an AE. 
An abnormal laboratory value that is not already associated with an AE (e.g., symptoms or 
diagnosis) is to be recorded as an AE only if an action on the study drug or concomitant 
medication is made as a result of the abnormality, if intervention or management of the 
abnormality is required, or at the discretion of the Investigator.  
Patients experiencing laboratory abnormalities will be assessed and appropriate evaluations 
performed until all parameters have returned to baseline levels, or are consistent with the 
patient’s then-current physical condition. 
7.2.3 
Serious Adverse Events 
Instructions for reporting Serious Adverse Events are found on Page 4.  
A written report of all SAEs and deaths that occur between the signing of the ICF and 28 days 
after administration of the last dose must be submitted to the IRB/EC and Forma Therapeutics 
Pharmacovigilance. All SAEs must be reported to Forma Therapeutics Pharmacovigilance within 
24 hours for a determination of expedited reporting to the relevant regulatory health authority, as 
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described in Section 7.5. In all SAE reports, the Investigator will advise whether or not the SAE 
is judged to be related to study drug administration.  
Serious AEs and deaths that occur more than 28 days after administration of the last dose and are 
not reasonably associated with study drug do not require reporting per the instructions given 
below. All SAEs that are judged by the Investigator to be at least possibly related to study drug 
administration must be reported to the Sponsor or its designee regardless of how much time has 
elapsed since the last exposure to study drug. All nonserious AEs must be communicated to the 
appropriate IRB/EC and/or reported in accordance with local laws and regulations. 
7.2.4 
Adverse Events of Special Interest 
As described in Section 5.5.3, adverse events potentially associated with liver injury have been 
identified as AESI. These AESI (regardless if serious or non-serious) include the following: 
a.
All events of Grade 2 or higher elevations in ALT, AST, or total bilirubin in patients with
normal LFTs at baseline; in patients with elevated LFTs at baseline, one Grade shift or
higher in ALT, AST, or total bilirubin;
b. Any hepatic adverse event, e.g., acute hepatitis, cholestatic hepatitis, cholestasis, or
hepatic insufficiency
AESI occurring from time of first dose through 28 days after last dose must be reported as 
outlined below: 
a.
Report to Forma Therapeutics Pharmacovigilance within 24 hours of knowledge of event
b. If the event meets both AESI and SAE criteria, complete both the SAE and AESI form
c.
If the event is non-serious, complete the AESI form alone
Relevant forms (AESI, SAE, or both) should be submitted via fax (+1-617-321-4111) or email 
(safety@formatherapeutics.com) to Forma Therapeutics Pharmacovigilance. 
7.2.5 
Reporting of Pregnancies 
If a patient, or the female partner(s) of a male study patient, becomes pregnant during the course 
of the study, the Investigator or site personnel must notify Forma Therapeutics 
Pharmacovigilance (see Page 4 for contact details) within 24 hours of the Investigator or site 
personnel becoming aware of the pregnancy. If an SAE occurs in conjunction with the 
pregnancy, then the reporting time frame for an SAE (within 24 hours) must be met.  
The Sponsor’s representative will provide instructions on how to collect pregnancy information 
as per the pregnancy reporting guidelines. The pregnancy reporting period begins upon 
administration of the first dose of FT-2102, and pregnancies will be reported until 90 days after 
the last dose of FT-2102. A final Pregnancy Report Form should be completed when outcome of 
the pregnancy is known. Any follow-up information on the outcome of the pregnancy should be 
forwarded to the Sponsor. 
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7.2.6 
Disease Progression 
If progression of the underlying disease (i.e., the condition being treated with study drug) might 
be reasonably anticipated given the nature and severity of the underlying disease, then 
progression of the underlying disease per se will not constitute an AE. However, if the 
progression of the underlying disease meets the criterion for “serious” categorization of AEs 
(e.g., the underlying disease results in death or hospitalization), then the progression of 
underlying disease should be reported as an SAE (See Section 7.2.3). 
 
7.2.7 
Overdoses 
Overdoses during the course of the study (whether symptomatic or not) should be reported by the 
Investigator or qualified designee as a protocol violation within 24 hours of the Investigator or 
qualified designee first becoming aware of the overdose. If an overdose results in an AE, the 
eCRF AE page should be completed, and source documents included. If the overdose results in 
an SAE, then SAE reporting should be followed using the specific eCRF pages with overdose 
information entered in the narrative section. All available clinical information relevant to 
overdose, including signs and symptoms, laboratory findings, and therapeutic measures or 
treatments administered, should be summarized and discussed. The overdose should also be 
captured on the appropriate FT-2102 exposure eCRF. 
 
7.3 
Classification of Adverse Events by Severity 
The severity refers to the intensity of the AE. The Investigator must categorize the severity of 
each AE according to the NCI CTCAE version 4.03 (see Appendix 4). CTCAE guidelines can be 
referenced at the following website: http://ctep.cancer.gov/reporting/ctc.html. 
 
For any term that is not specifically listed in the CTCAE scale, intensity will be assigned a grade 
of one through five using the following CTCAE guidelines: 
 
Grade 1: Mild; asymptomatic or mild symptoms, clinical or diagnostic observations only; 
intervention not indicated 
 
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living 
 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living 
 
Grade 4: Life-threatening consequences; urgent intervention indicated 
 
Grade 5: Death related to AE 
 
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7.4 
Classification of Adverse Events by Relationship to Study 
Drug Administration 
The relationship of each AE to the study drug administration will be assessed by the Investigator; 
after careful consideration of all relevant factors such as (but not limited to) the underlying study 
indication, coexisting disease, concomitant medication, relevant history, pattern of the AE, 
temporal relationship to the study medication and dechallenge or rechallenge according to the 
following guidelines: 
YES (possible, probably, or definitely related): there is a reasonable possibility that the study 
drug caused the event; one or more of the following criteria apply: 
•
The event follows a reasonable temporal sequence from administration of study drug
•
The event could not be reasonably attributed to the known characteristics of the patient’s
clinical state, environment, or toxic factors or other modes of therapy, administered to the
patient
•
The event follows a known pattern of response to study drug
•
The event disappears or decreases on cessation or reduction in dose of the study drug. In
some situations, an AE will not disappear or decrease in intensity upon discontinuation of
the study drug despite other clear indications of relatedness
NO (unlikely, probably not related, or definitely not related): There is no reasonable possibility 
that the study drug caused the event; one or more of the following criteria apply: 
•
The event does not follow a reasonable temporal sequence from administration of study
drug
•
The event could be reasonably attributed to the known characteristics of the patient’s
clinical state, concurrent illness, environment, or toxic factor or other modes of therapy
administered to the patient
•
The event does not follow a known pattern of response to study drug
•
The event does not disappear or decrease on cessation or reduction in dose of the study
drug, and it does not reappear or worsen when the study drug is re-administered
7.5 
Adverse Events Qualifying for Reporting to Regulatory Authorities 
The AEs that are serious and unexpected, and assessed as related to study drug, will be reported 
to the regulatory authorities by Forma Therapeutics, Inc. in accordance with local regulations. 
Serious, unexpected, and study drug-related events are to be reported to the regulatory authorities 
within 15 calendar days of initial notification to Forma Therapeutics, Inc. or its designee. If the 
AE is serious, unexpected, and related to study drug and is fatal or life threatening, the event will 
also be reported to the regulatory authorities within seven calendar days. 
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8 
STUDY OR STUDY SITE TERMINATION AND PATIENT 
DISCONTINUATION 
8.1 
Study or Study Site Termination 
If the Investigator, the Sponsor or Sponsor’s Study Director or appropriate regulatory officials 
discover conditions arising during the study that indicate that the study should be halted or that 
the study center should be terminated, this action may be taken after appropriate consultation 
among the Sponsor, Investigator, and Study Monitor. Criteria that may be considered when 
determining a potential termination of the study would be unacceptable toxicity and/or an 
unfavorable risk-benefit profile.  
Study termination and follow-up will be performed in compliance with the conditions set forth in 
the International Council on Harmonisation (ICH) sixth efficacy publication (E6) on Good 
Clinical Practice, Section 4.12, ICH E6 4.13, ICH E6 5.20, and ICH E6 5.21, with appropriate 
notification of the FDA and all IRB’s/EC’s having approved the study protocol and ICF. 
8.2 
Treatment and Study Discontinuation 
8.2.1 
Treatment Discontinuation 
Study treatment discontinuation occurs when a patient is no longer receiving any study drug (FT-
2102, azacitidine, or cytarabine, as applicable). Treatment discontinuation is not necessarily 
accompanied by discontinuation from the study, as discussed in Section 8.2.2. 
A patient should be discontinued from study treatment if, in the opinion of the Investigator, 
doing so is medically necessary, or if it is the wish of the patient. Reasons for discontinuation 
from study treatment may include any of the following: 
• Unacceptable AE or failure to tolerate study therapy
• Delay in dosing of > 28 days, without approval of Sponsor
• Treatment failure (i.e., progression or relapse) (see Section 4.3, Table 3 for definition)
• Hematopoietic stem cell transplant (HSCT)
• Withdrawal of consent (no further study participation)
• Patient decision to discontinue study treatment
• Discretion of the Investigator
• Major protocol violation
• Pregnancy
• Lost to follow-up
• Death
• Termination of the study by Sponsor
All AEs leading to the discontinuation of study drug will be followed for 28 days after 
administration of last dose of study drug or until resolution or stabilization as documented by 
physical examination or appropriate laboratory results. 
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All patients who discontinue study treatment should undergo the End-of-Treatment assessments 
(see Section 6.1.23) and undergo Safety Follow-up (Section 6.1.24)/ enter Survival Follow-up 
(Section 6.1.26).  
Patients who discontinue study treatment for reasons other than disease progression/relapse, 
including those who discontinue for HSCT, will continue to be followed for response duration 
until progression/relapse occurs (see Section 6.1.25). 
Patients who discontinue treatment for HSCT should continue to be assessed for response as per 
the protocol-defined schedule. 
8.2.2 
Study Discontinuation 
Patients may voluntarily withdraw from the study at any time for any reason without prejudice. 
Patients will be withdrawn from the study in the case of any of the following reasons: 
•
Death
•
Lost to follow-up
•
Completion of follow-up period
•
Termination of the study by Sponsor
•
Withdrawal of consent
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9 
DATA RECORDING, CRF PROCESSING, AND STATISTICAL 
ANALYSIS 
9.1 
Data Recording and CRF Processing 
In place of recording patient data on paper CRFs, which will not be used in this study, site 
personnel are responsible for entering such data into the Electronic Data Capture (EDC) system. 
This system has been validated and is compliant with FDA, ICH, and European Union (EU) 
regulations and guidelines and with Department of Health and Human Services 21 CFR Part 11 
rules for electronic records and electronic signatures. No data will be requested other than what 
is routinely written on paper CRFs. 
An audit may be performed at any time during or after completion of the clinical study by 
Sponsor personnel or their designee. All study-related documentation must be made available to 
the designated auditor. 
9.2 
Statistical Analysis 
9.2.1 
General Considerations 
Unless otherwise specified, continuous endpoints will be summarized with n, mean, standard 
deviation (SD), median, minimum (min), and maximum (max). If the measurements in the 
source (raw) data are integers, then the corresponding mean and median will be presented to 1 
decimal place and the SD to 2 decimal places; if the measurements are obtained to 1 decimal 
place, then the mean and median will be presented to 2 decimal places and the SD to 3 decimal 
places; and so forth. Minimum and maximum will be displayed as reported in the source (raw) 
data. In addition, change from baseline values will be calculated at each timepoint and 
summarized descriptively. For categorical endpoints, descriptive summaries will include counts 
and percentages. Percentages will be presented to 1 decimal place unless otherwise specified.  
All analyses and summary outputs will be generated using SAS® version 9.3 (or higher). 
All patient data, including those derived, will be presented in the patient data listings; listings 
will display for all patients, regardless of whether or not they received study drug. In general, the 
patient data listings will be sorted by treatment (dose levels), patient number and assessment visit 
and date (and time, if applicable). The summary tables will be presented descriptively overall 
and by treatment group.  
For the purpose of all safety and efficacy analyses where applicable, baseline is defined as the 
last non-missing measurement prior to the start of study drug administration. 
9.2.2 
Sample Size 
Sample size calculations are based on the primary objectives for each study cohort. 
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9.2.2.1  Phase 1 
The primary objective for Phase 1 in this study is to evaluate DLT or identify MTD/MED and 
recommend a dose for Phase 2. Within the Phase 1 portion of the study, the Dose-Escalation 
Stage is based on a traditional 3+3 design to avoid selection of a dose going forward in 
development that causes a treatment-limiting toxicity in more than 17% of patients. At each dose 
level, 3 patients will be enrolled; if < 1/3 DLTs are identified, the dose will be escalated to the 
next dose level. If 1 DLT is identified, 3 additional patients will be added to the same dose level. 
If 1/6 DLT is identified, the study will be escalated to the next dose level. Otherwise, the MTD 
will be identified as the dose lower than the dose with > 1/6 DLTs.  
 
The total number of patients who will be enrolled in the dose-escalation stage will depend on the 
number of DLTs observed within each dose cohort. It is anticipated that, at a minimum, doses of 
150 mg and 300 mg FT-2102 QD will be tested as a single agent and in combination with 
azacitidine. If 6 patients are treated at each dose level, approximately 24 patients will be treated 
in the dose-escalation stage. 
 
During the Phase 1 Dose-Expansion Stage, each of the non-LDAC cohorts would have 
14 patients. With 20 patients treated (at least 6 from the dose-escalation stage, 14 from  
dose-expansion) at the determined MTD/MED, the probability of observing at least 1 incidence 
is > 87% for adverse events of true incidence rate of ≥17%. For the LDAC cohort, the selection 
of 6 patients is a minor variation of the traditional 3+3 design in order to identify the risk of 
LDAC for toxicities in more than 17% of patients. 
 
9.2.2.2 Phase 2 
The primary objective of Phase 2 is to evaluate the clinical activities of FT-2102 alone or in 
combination in patients with R/R AML or MDS and confirmed IDH1 mutation. 
 
Cohort 1 (patients with R/R AML harboring IDH1-R132 mutations): A group sequential design 
is planned for this cohort with two interim analyses and a final test. One hundred seventy three 
(173) patients provide 90% power to test the null hypothesis that the true complete response rate 
(CR + CRh) is 15% or less versus the one-sided alternative hypothesis that the true complete 
response rate is greater than 15%, with a 2.5% significance level using a one-sided exact test for 
a binomial proportion, assuming the true response rate is 25%.  
 
Two interim analyses are planned, at approximately 33% and 67% of the information. O’Brien-
Fleming stopping boundaries will be used for both alpha and beta adjustments. At the first 
interim, if ≤ 6/58 responses are observed (or crude p-value ≥ 0.88), the trial may be stopped early 
for futility. The first interim analysis will be conducted on the Full Analysis Set (FAS) within 
Phase 2 Cohort 1. At the first interim analysis, the study is not intended to stop for efficacy. At 
the second interim analysis, if ≥ 28/115 responses are observed (or crude p-value is ≤ 0.0057), 
the trial may stop enrollment for efficacy and if there are 20 or fewer responses (or crude p-value 
is > 0.2718) the trial may be stopped for futility. The second interim analysis will be conducted 
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in the Efficacy Evaluable (EE) Set within Phase 2 Cohort 1. In the event of an early stop for 
efficacy, all enrolled patients would remain on treatment and their long-term efficacy data, such 
as EFS and OS, will continue to be observed. 
If the study is not stopped early for efficacy or futility, at least 173 evaluable patients are planned 
to be enrolled. A one-sided exact test will be performed. If the one-sided p-value is ≤ 0.0245, the 
null hypothesis (the response rate is ≤ 15%) will be rejected, and the alternative hypothesis that 
the response rate is > 15% will be accepted. If exactly 173 patients are evaluable, this is 
equivalent to 36 or more responses observed. 
To account for potential discordance between central and local testing of the IDH1-R132 
mutation, approximately 190 patients are planned to be enrolled into this cohort. 
Cohort 2 (patients with AML with persistent IDH1-R132 mutation + bone marrow 
demonstrating morphologic CR/CRi after prior therapy +/- HSCT): A Simon optimal two-stage 
design will be used. The null hypothesis that the true 4-month RFS rate is 80% will be tested 
against a one-sided alternative. In the first stage, 11 patients will be evaluated. If 9 or fewer of 
the first 11 patients are relapse-free at 4 months, the study will be stopped. Otherwise, 42 
additional patients will be accrued, for a total of 53 patients. The null hypothesis will be rejected 
if 48 or more of these 53 patients are event-free at 4 months. This design yields a 1-sided type I 
error rate of 0.025 and power of 80% when the true 4-month RFS rate is 94%.  
Cohorts 3-5 (patients with AML/MDS harboring IDH1-R132 mutations that are R/R to prior 
IDH1 inhibitor therapy; or naïve to hypomethylating and IDH1m inhibitor treatments; or R/R to 
prior hypomethylating therapy): A single-stage design with 20 patients will be used. If 4 or more 
complete responses are observed in these 20 patients, the lower bound of a one-sided 85% 
confidence interval based on an exact binomial distribution will be greater than 10%, thus 
supporting the hypothesis that the true complete response rate is greater than 10%. 
Cohort 6 (patients with AML/MDS harboring IDH1-R132 mutations that are R/R to immediately 
prior SA IDH1 inhibitor therapy): A Simon’s optimal two-stage design will be used. The null 
hypothesis that the true complete response rate is 15% will be tested against a one-sided 
alternative. In the first stage, 14 patients will be evaluated. If there are 2 or fewer complete 
responses in the first 14 patients, the study will be stopped. Otherwise, 30 additional patients will 
be accrued for a total of 44 patients. The null hypothesis will be rejected if 11 or more complete 
responses are observed in these 44 patients. This design yields a 1-sided type I error rate of 0.05 
and power of 80% when the true complete response rate is 32%. The probability that the trial 
will be stopped at the end of the first stage if the true complete response rate is 10% is 0.65. 
Cohort 7 (treatment naïve AML patients for whom standard treatments are contraindicated): A 
Simon’s optimal two-stage design will be used. The null hypothesis that the true complete 
response rate is 25% will be tested against a one-sided alternative. In the first stage, 17 patients 
will be evaluated. If there are 5 or fewer complete responses in the first 17 patients, the study 
will be stopped. Otherwise, 37 additional patients will be accrued for a total of 54 patients. The 
null hypothesis will be rejected if 20 or more complete responses are observed in these 54 
patients. This design yields a 1-sided type I error rate of 0.025 and power of 80% when the true 
complete response rate is 45%. 
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Cohort 8 (treatment naïve AML patients who are candidates for azacitidine first line treatment): 
A Simon’s optimal two-stage design will be used. The null hypothesis that the true complete 
response rate is 25% will be tested against a one-sided alternative. In the first stage, 7 patients 
will be evaluated. If there are 2 or fewer complete responses in the first 7 patients, the study will 
be stopped. Otherwise, 21 additional patients will be accrued for a total of 28 patients. The null 
hypothesis will be rejected if 12 or more complete responses are observed in these 28 patients. 
This design yields a 1-sided type I error rate of 0.025 and power of 80% when the true complete 
response rate is 55%. 
 
9.2.3 
Analysis Sets 
DLT-Evaluable Set will include all patients in dose escalation who have received at least one 
dose of FT-2102 and completed at least 75% of doses in the first cycle during the DLT 
evaluation period, or have discontinued due to adverse events meeting the DLT evaluation 
criteria. This set will be used for DLT analyses only, unless otherwise specified. 
Safety Analysis Set will include all patients who have received at least one dose of study drug 
(FT-2102, azacitidine, or cytarabine). All safety analyses will be based on the Safety Set unless 
otherwise specified. Patients will be analyzed under the first dose level received by the patient. 
Full Analysis Set (FAS) will include all patients who were enrolled in the study and received at 
least one dose of FT-2102. This analysis set will be used for efficacy analyses. Patients will be 
analyzed under the assigned dose. 
Efficacy Evaluable (EE) Set will include all patients in Phase 2 Cohort 1 with confirmed IDH1-
R132 (by central lab) who have received the first dose of FT-2102 at least 6 months prior to the 
analysis cutoff date or who have died, progressed, or discontinued study participation. This 
analysis set is the primary set for the Phase 2, Cohort 1 efficacy evaluation. Patients will be 
analyzed by assigned dose. 
Per Protocol (PP) Analysis Set is a subset of patients in the EE set, excluding patients who have 
protocol violations that could impact the evaluation of the efficacy of FT-2102. Some violations 
that would result in exclusion from the PP Analysis Set are: not meeting all inclusion/ exclusion 
criteria for a particular cohort, having received chemotherapy not per protocol, received starting 
dose of FT-2102 other than 150 mg BID, not having at least one post-baseline response 
assessment. The full list of protocol violations will be reviewed on a de-identified basis by the 
medical, data management, and statistical leads prior to locking the database, and membership in 
the PP Analysis Set will be documented and determined based on that review. 
PK Analysis Set consists of patients for whom it is possible to calculate at least one primary PK 
parameter (e.g. Cmax, AUClast and AUCinf) and who do not have any major protocol deviations 
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PD Analysis Set consists of all patients who have received at least one dose of FT-2102 and have 
completed at least one PD assessment. The PD Analysis Set will be used for PK/PD-related 
analyses unless otherwise specified. 
9.2.4 
Analysis of Clinical Data 
9.2.4.1 Demographic and Tumor Characteristics 
Baseline demographic and tumor characteristics will be summarized using descriptive statistics 
(n, mean, median, minimum, maximum, standard deviation [SD], standard error [SE] for 
continuous variables; n, percent for categorical variables) for each cohort using the cohort to 
which they were initially assigned, and all patients will be accounted for. 
9.2.4.2  Safety Analysis 
For DLT-evaluable patients, the summary of DLTs will be provided by dose/dosing schedule for 
patients in the Phase 1 dose-escalation stage. All other safety analyses will be based on the 
Safety Set. 
For each stage, the safety and tolerability of FT-2102 will be assessed, as evaluated by adverse 
events, concomitant medication usage, changes from baseline in physical examination, vital 
signs, clinical laboratory evaluations, and ECG. Safety data will be listed by patient and 
summarized descriptively.  
A treatment-emergent adverse event (TEAE) is defined as an adverse event with onset on or after 
the start of study drug, or any worsening of a pre-existing medical condition/adverse event with 
onset on or after the start of study drug and until 28 days after the last dose. For each stage, all 
adverse events will be coded using MedDRA version 19.1 or higher and summarized by SOC 
and PT, for each treatment group. Multiple occurrences of an AE are counted only once per 
patient per SOC and PT for summary tables. Causality of TEAEs (not related, related) and 
severity (NCI CTCAE version 4.03 or higher) will be summarized by treatment for each stage.  
Relationship will be presented by study drug when applicable. All adverse events and serious 
adverse events (including those with onset or worsening before the start of study drug) will be 
listed.  
Safety laboratory, vital sign, ECG and physical examinations will be summarized by visit. The 
change from baseline will be presented along with the by-visit summaries. Shifts in laboratory 
grades, as well as QTcF shifts, will be tabulated. Assessment of changes in liver function tests 
will be conducted. Abnormal safety assessments will be flagged and separately presented. All 
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Assessment of differentiation syndrome will be conducted as per Montesinos et al. 2009, 
searching for candidate cases of differentiation syndrome based on AE reports of dyspnea, 
pulmonary infiltrates, edema, weight gain, pleural effusion, renal failure, hypotension, 
pericardial effusion, and unexplained fever. Specific methods of identifying candidate cases will 
be fully described in the Statistical Analysis Plan (SAP). 
9.2.4.3 Antileukemic and Antimyelodysplastic Activity 
All analysis in the section will be based on patients in the EE Set as the primary analysis, with 
additional analyses on the FAS, and in some cases the PP Set as supportive. 
Primary Efficacy Endpoints and Hypotheses 
CR/ CRh Rate 
The primary efficacy endpoint for all Phase 2 cohorts, with the exception of Cohort 2, is the 
CR/CRh rate (defined as bone marrow blasts < 5% with complete (CR) or partial (CRh) 
hematologic recovery; see Appendix 7 and Appendix 8 for complete definition). The 
CR/CRh rate will be calculated and presented together with the Clopper-Pearson 95% 
confidence interval for each cohort.  
For Phase 2, Cohort 1, to test the hypothesis that the complete response rate is greater than 
15%, a 1-sided exact test for a binomial proportion will be performed. If the exact 1-sided p-
value is less than 0.023, the alternative hypothesis will be accepted. This is equivalent to at 
least 36 CR/CRh responses of 173 EE patients. 
For Phase 2, Cohorts 3, 4, and 5 test the hypothesis that the 85% confidence interval for the 
complete response rate does not include 10%. If there are 5 or more complete responses of 
the 20 patients in these cohorts, the 85% confidence interval will be greater than 10%, and 
the alternative hypothesis that the response rate is greater than 10% will be accepted. 
Phase 2 Cohorts 6, 7, and 8 are Simon 2-Stage designs and the primary efficacy endpoint 
will be evaluated via the number of CR/CRh responses stipulated in the design criteria 
described in Section 9.2.2. 
4-Month RFS
The primary endpoint for Phase 2 Cohort 2 is the 4-Month RFS. This will be evaluated by a 
Simon 2-Stage design described in Section 9.2.2, testing the null hypothesis that the 
4-month RFS is < 80%. It is defined as the proportion of patients who have not relapsed or
died on or before their 4-month response evaluation. If a patient does not receive a disease
response assessment at their 4-month visit but has a subsequent disease response assessment
on or after study day 120 that shows non-progression/ non-relapse, they will be evaluated as
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Secondary Efficacy Endpoints 
CRi, MLFS, Marrow CR, and PR definitions will be derived from the IWG response criteria (see 
Section 4.3, Appendix 7 and Appendix 8) for AML (2003) and MDS (2006) based on 
investigator’s assessment.  
Transfusion independence, defined as the proportion of patients who have received a packed red 
blood cell or platelet transfusion in the eight weeks prior to first dose of FT-2102 who have a 
28-day period during any point on study with no transfusion required. Additionally, the number
of patients who are transfusion independent for at least 56 consecutive days will also be
summarized. Percent of transfusion independence will be calculated based on the number of
patients who were transfusion dependent prior to first dose of FT-2102.
For each cohort, the number and percentage of the best overall response will be presented by 
response category and by treatment group. Other binomial endpoints including overall response 
rate (CR + CRh + CRi + MLFS + PR) and rate of responses in the individual response category, 
will also be analyzed. Number and percentage of patients within each response category will be 
presented by dose/dosing schedule and visit. Clopper-Pearson 95% confidence intervals will be 
provided along with the responses. 
Overall survival for all cohorts at landmark timepoints will be analyzed. 
Time to event data will be analyzed using Kaplan-Meier (KM) methods for each cohort. The 
median time will be tabulated along with the 95% Brookmeyer Crowley confidence intervals. 
The estimated probability of survival over time will be plotted as KM curves for each cohort (or 
by disease type and by treatment). 
Detailed considerations for all time to event variables are provided in the SAP. 
Additional efficacy analyses will be specified in the SAP. 
9.2.5 
Pharmacokinetic Analysis 
Pharmacokinetic analysis will be performed in patients in the PK Analysis Set. 
Concentration-time profiles will be constructed from the plasma samples obtained. Estimates of 
the AUC and slope of the terminal decay phase will be used to calculate values of the following 
PK parameters: t1/2, CL/F, Tmax, and Vd/F. The plasma profiles will also be fitted by nonlinear 
regression analysis whenever possible. An analysis of variance or corresponding nonparametric 
statistical tests will be applied:  
•
To compare mean values of PK variables and parameters determined at different doses
and
•
To identify the existence of trends in Cmax and/or metabolite concentrations within
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9.2.6 
Pharmacodynamic Analysis 
Pharmacodynamic analysis will be performed in patients in the PK Analysis Set.  
 
All PD data will be presented in tabular and/or graphical format and summarized descriptively. 
Absolute change from baseline and/or percentage change from baseline will be summarized by 
dose level. Patients in the dose expansion portion of this study will be considered a separate 
cohort for the purposes of these presentations. 
 
9.2.7 
Genotypic Analysis  
All genotypic data will be presented in tabular and/or graphical format and summarized 
descriptively. Cancer-associated mutations and/or genetic alterations will be correlated with 
responding and nonresponding patients. Patients in the dose expansion portion of this study will 
be considered a separate cohort for the purposes of these presentations. 
 
9.2.8 
Quality of Life Analysis 
Quality of life, as assessed by the EQ-5D-5L, will be analyzed for patients in the EE and FAS. 
EQ-5D-5L data will be summarized from the screening visit through cycle 4 for the FAS and EE 
Analysis sets (Phase 2). The number and percentage of patients reporting each score per 
dimension will be summarized, as well as the number reporting some problems on that 
dimension (score > 1). Also the change from baseline in the number reporting some problems in 
each dimension will be reported (raw and percent change). Additional analyses and techniques 
for handling missing data will be described in the SAP. 
 
9.2.9 
Interim Analysis 
Interim analyses will be performed for the Phase 2 Cohort 1 and in other applicable Phase 2 
cohorts that use two-stage designs, at defined timepoints. These are described in Section 9.2.2.2. 
As a result of these analyses, enrollment in a given cohort may be stopped early either for 
efficacy or futility. 
 


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10 
ADMINISTRATIVE ASPECTS 
10.1 
Institutional Review Board/Ethics Committee 
This protocol and the proposed informed consent form must be reviewed and approved by the 
appropriate IRB/EC, prior to the start of the study. The proposed informed consent form must 
also be agreed to by Forma Therapeutics, Inc. or their designee. A copy of the IRB/EC approval 
letter of the protocol, any amendments, and the ICF must be supplied to Forma Therapeutics, 
Inc. or their designee prior to starting the study.  
 
During the course of the study, the Investigator shall make timely and accurate reports to the 
IRB/EC on the progress of the trial, at intervals not exceeding one year, as well as satisfying any 
other local IRB/EC regulations regarding reporting. Copies of all reports to and correspondence 
with and from the IRB/EC must be provided to Forma Therapeutics, Inc. or their designee. 
 
Any significant changes or revisions in the study protocol or any changes that may alter patient 
risk must be approved by Forma Therapeutics, Inc. (and may require other review and/or 
approval) and must be approved in writing by the IRB/EC prior to implementation. A protocol 
change intended to eliminate an apparent immediate hazard may be implemented immediately 
provided that Forma Therapeutics, Inc. is immediately notified and an amendment is 
subsequently provided by Forma Therapeutics, Inc. and approved by the IRB/EC. 
 
It is the Investigator's obligation to maintain an IRB/EC correspondence file and to make this 
available for review by Forma Therapeutics, Inc. representatives or their designee as part of the 
study monitoring process. 
 
10.2 
Informed Consent and Authorization for Use and Disclosure of 
Protected Health Information 
Written informed consent and authorization of use and disclosure of PHI must be obtained from 
each patient (or the patient's legal representative) prior to performing any study-specific 
Screening Period evaluations. The authorization for use and disclosure of PHI must contain the 
elements required by 45 CFR 164.508(b) for valid authorizations. The proposed informed 
consent form must be in compliance with regulatory regulations and must have been reviewed 
and approved by Forma Therapeutics, Inc. and the Investigator’s IRB/EC prior to initiation of the 
study. The proposed informed consent form should contain the 20 elements of informed consent 
described in ICH E6 4.8, including a full explanation of the purpose and nature of the study, a 
description of the procedures, the possible advantages, risks, alternate treatment options, and a 
statement of confidentiality of patient study records, a statement regarding voluntary 
compensation and availability of treatment in the case of injury, an explanation of whom to 
contact about the research, the patient’s rights, and notification that participation is voluntary and 
refusal will involve no penalty or loss of medical benefits.  
 
These requirements are in accordance with the Code of Federal Regulations as detailed in the 21 
CFR 50.25 and the Declaration of Helsinki. It should also indicate by signature that the patient, 
or where appropriate, legal guardian/representative, permits access to relevant medical records 


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by Forma Therapeutics, Inc. staff, Forma’s duly appointed representatives, and by 
representatives of the United States (US) Food and Drug Administration (FDA) or other 
applicable regulatory agency. Additionally, Investigators in states with specific regulations 
regarding patients’ rights have a responsibility to follow and document their fulfillment of those 
regulations. 
The Investigator will be responsible for obtaining written informed consent from potential 
patients or the patient’s legally authorized representative prior to any study specific screening 
and entry into the study, and also additional consent for future research provisions (see ICF).  
A copy of the signed document will be provided to the patient, and a copy will be maintained 
with the patient's eCRFs, or in the study documentation notebook. The original will be retained 
by the Investigator along with the eCRFs. The source documents for each individual shall 
document that informed consent was obtained prior to participation in the study. 
10.3 
Delegation of Investigator Responsibilities 
The Investigator should ensure that all persons involved in the conduct of the study are informed 
about the protocol, protocol amendments, study procedures, and study-related duties. 
10.4 
Study Documentation  
10.4.1 Investigator Information 
Investigator information is included in the Study Procedures Manual, which is updated regularly. 
10.4.2 Laboratory Accreditation 
Any laboratory facility to be used for analysis of routine clinical laboratory samples required by 
this protocol must provide evidence of adequate licensure or accreditation. Licensure/accreditations 
and reference values and/or normal ranges for the test results must be provided to Forma 
Therapeutics, Inc. 
Forma Therapeutics, Inc. must be notified immediately in writing of any changes occurring in 
reference values during the course of the study. 
10.4.3 Study Files 
Documentation concerning Investigator data and IRB/EC data is required prior to shipment of 
study drug to the study site. Copies of these documents as well as supplemental information, 
such as the IB and Responsibilities and Obligations of Investigators and Sponsors, will be kept 
on-site in an Investigator study file binder. This file also will contain drug accountability 
(receipt/dispensing) records, Sponsor/Investigator correspondence, IRB/EC correspondence, 
changes to the protocol, information regarding monitoring activities, patient exclusion records, 


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biological sample records, and eCRFs. 
 
10.4.4 Source Documentation 
The Investigator must make study data accessible to the Sponsor, to other authorized 
representatives of the Sponsor, and to the appropriate regulatory authority inspectors. The eCRF 
for each patient will be checked against source documents at the study site by the Study Monitor. 
 
10.4.5 Retention of Study Documents 
According to ICH E6 4.9, all eCRFs, as well as supporting documentation and administrative 
records, must be retained by the Investigator for a minimum of two years following notification 
that the appropriate regulatory authority has approved the product for the indication under study, 
notification that the entire clinical investigation will not be used in support of a marketing 
application, or notification that the marketing application was not approved. No study documents 
will be destroyed or moved to a new location without prior written approval from the Sponsor. If 
the Investigator relocates, retires, or withdraws from the clinical study for any reason, all records 
required to be maintained for the study should be transferred to an agreed-upon designee, such as 
the Study Monitor, another Investigator, or the institution where the study was conducted. 
 
10.5 
Confidentiality 
10.5.1 Data 
All information regarding the nature of the proposed investigation provided by the Sponsor or 
Study Monitor to the Investigator (with the exception of information required by law or 
regulations to be disclosed to the IRB/EC, the patient, or the appropriate regulatory authority) 
must be kept in confidence by the Investigator. 
10.5.2 Patient Anonymity 
The anonymity of participating patients must be maintained. Patients will be identified by an 
assigned patient number on eCRFs and other documents submitted to the Study Monitor. 
Documents that will not be submitted to the Study Monitor and that identify the patient (eg, the 
signed ICF) must be maintained in strict confidence by the Investigator, except to the extent 
necessary to allow auditing by the appropriate regulatory authority, the Study Monitor, or 
Sponsor representatives. 
 
10.6 
Protocol Compliance 
Substantive changes in the protocol include changes that affect the safety of patients or changes 
that alter the scope of the investigation, the scientific quality of the study, the experimental 
design, dosages, assessment variable(s), the number of patients treated, or the patient selection 
criteria. Such changes must be prepared as a protocol amendment by the Study Monitor only 
upon joint approval of the Sponsor, Investigator, and the Study Monitor. A protocol amendment 


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August 20, 2020 
must receive IRB/EC approval prior to implementation. In parallel with the IRB/EC approval 
process, the protocol amendment will be submitted to the appropriate regulatory authority as an 
amendment to the regulatory submission under which the study is being conducted. If a protocol 
amendment requires changes to the ICF, the revised ICF prepared by the Investigator must be 
reviewed by the Sponsor and the Study Monitor and approved by the IRB/EC. 
Emergency departures from the protocol that eliminate an apparent immediate hazard to a 
particular patient and that are deemed crucial for the safety and well-being of that patient may be 
instituted for that patient only.  
The Investigator or other attending physician also will contact the Sponsor as soon as possible in 
the case of such a departure. These departures do not require pre-approval by the IRB/EC; 
however, the IRB/EC and Sponsor must be notified in writing as soon as possible after the 
departure has been made. In addition, the Investigator will document in the patient's eCRF the 
reasons for the protocol deviation and the ensuing events. 
10.7 
Monitoring Functions and Responsibility 
Throughout the course of the study, the Forma Therapeutics, Inc. representatives, or monitors 
designated by Forma Therapeutics, Inc., may make frequent contacts with the Investigator. This 
may include telephone and/or on-site visits at appropriate and necessary intervals. 
The Investigator or appointed delegate will be available to the Forma Therapeutics, Inc. 
representative(s) during on-site visits and will provide necessary study documents for inspection 
and will respond to all inquiries that may arise as part of this review. On completion of the study, 
the Forma Therapeutics, Inc. monitor(s) may arrange for a final review of the study files after 
which the files should be secured for the appropriate time period as specified in Section 10.4.5 
(or Section 10.9). The Investigator will also permit inspection of the study files by authorized 
representatives of the FDA or other applicable regulatory agency. 
The progress of the study will be monitored by using the following methods: 
•
Periodic on-site visits
•
Frequent telephone and written communications between the Investigator, Sponsor, and
the Study Monitors
•
Review of eCRFs and clinical records
10.8 
Drug Accountability 
The investigational drug is to be prescribed only by the Principal Investigator or physician 
subinvestigators named on Form FDA 1572 and submitted to the IND for FT-2102. Under no 
circumstances will the Investigator(s) allow the investigational drug to be used other than as 
directed by this protocol. 
The Investigator must maintain accurate records that account for the receipt of the investigational 
drug supplies using the Sponsor’s Investigational Materials Shipping Order and for the 


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August 20, 2020 
disposition of the drug using dispensing records, which identify the person to whom the drug is 
dispensed, the quantity and the date of dispensing, and any unused drug returned. This record is 
in addition to any drug accountability information recorded on the case report forms. At the 
termination of the study or at the request of the Sponsor, the Investigator will destroy or return 
unused study medication and all partially dispensed or empty containers. 
 
10.9 
Record Retention 
Records of drug receipt and disposition, eCRF, and reports of this investigation must be 
maintained by the Investigators for a period of at least two years following the date on which the 
investigational drug is approved by the FDA or other applicable regulatory agency for marketing, 
for the purposes that were the patient of the clinical investigations. If no application is to be filed, 
records must be retained until two years following the date that the study is discontinued and the 
FDA or other applicable regulatory agency is notified. If the application is not approved by the 
FDA or other applicable regulatory agency for such indication, records must be retained for two 
years after notification by Forma Therapeutics, Inc. of the FDA or other applicable regulatory 
agency decision. Forma Therapeutics, Inc. should be notified in writing at least 30 days prior to 
the disposal of any study records related to this protocol. 
 
10.10 Financial Disclosure 
The Investigator and subinvestigators, as noted on the Form FDA 1572, shall provide Forma 
Therapeutics, Inc. with sufficient accurate financial disclosure information to allow Forma 
Therapeutics, Inc. to submit complete and accurate certification or disclosure statements as 
required under 21 CFR 312.54. 
 
The Investigator shall promptly update this information if any relevant changes occur during the 
course of the investigation and for one year following the completion of the study. 
 
10.11 Patient Confidentiality 
Every effort will be made to maintain the anonymity and confidentiality of patients during this 
study. However, because of the experimental nature of this treatment, the Investigator agrees to 
allow representatives of the Sponsor as well as authorized representatives of regulatory 
authorities to inspect, for purposes of verification, the hospital or clinic records of all patients in 
this study. 
 
10.12 Disclosure of Data 
All information obtained as a result of this study or during the conduct of this study will be 
regarded as confidential. The conditions regulating dissemination of the information derived 
from this clinical trial are described in the Clinical Trial Agreement. 
 


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10.13 Publication Agreement 
The conditions regulating publications derived from this clinical trial are described in the 
Clinical Trial Agreement. 
10.14 General Information 
The Investigator should refer to the associated IB, the Study Procedures Manual, information 
provided during the study initiation visit, information provided by the Study Monitor, and the 
appendices of this clinical study protocol for further information regarding this investigational 
new product or details of the procedures to be followed during the course of this study. 


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11 REFERENCES 
Birendra KC, DiNardo CD. Evidence for clinical differentiation and differentiation syndrome in 
patients with acute myeloid leukemia and IDH1 mutations treated with the targeted mutant IDH1 
inhibitor, AG-120. Clin Lymphoma Myeloma Leuk. 2016;16(8):460-5. 
 
Borodovsky A, Salmasi V, Turcan S, et al. 5-azacytidine reduces methylation, promotes 
differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft. 
Oncotarget. 2013; 1-11. 
 
Cairns RA, Mak TW. Oncogenic isocitrate dehydrogenase mutations: Mechanisms, models, and 
clinical opportunities. Cancer Discov. 2013; 3:730-741. 
 
Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International 
Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and 
Reporting Standards of Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003; 
21:4642-4649. 
 
Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification 
of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006; 
108(2): 419-25. 
 
Cockcroft DW and Gault MH. Prediction of creatinine clearance from serum creatinine. 
Nephron. 1976; 16(1):31-41. 
 
de Botton S, Pollyea DA, Stein EM, et al. Clinical safety and activity of AG-120, a first-in-class 
potent inhibitor of the IDH1 mutant protein, in a Phase 1 study of patients with advanced, IDH1-
mutant hematological malignancies. 20th Congress of the European Hematology Association 
2015, Abstract P563. 
 
DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated 
relapsed or refractory AML. N Engl J Med. 2018 Jun 21;378(25):2386-2398. 
 
Fan, B, Chen Y, Wang F, et al. Pharmacokinetic/pharmacodynamics evaluation of AG-120, a 
potent inhibitor of the IDH1 mutant protein, in a Phase 1 study of IDH-1 mutant advanced 
hematologic malignancies. 20th Congress of the European Hematology Association 2015, 
Abstract P572. 
 
Fathi AT, DiNardo CD, Kline I, et al. Differentiation syndrome associated with enasidenib, a 
selective inhibitor of mutant isocitrate dehydrogenase 2. Analysis of a Phase 1/2 study. JAMA 
Oncol. 2018;4(8):1106-1110. 
 
Frankel SR, Eardley A, Lauwers G, Weiss M, Warrell RP Jr. The "retinoic acid syndrome" in 
acute promyelocytic leukemia. Ann Intern Med. 1992 Aug 15;117(4):292-6. 
 


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August 20, 2020 
Gross S, Cairns RA, Minden MD, et al. Cancer-associated metabolite 2-hydroxyglutarate 
accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. 
J Exp Med. 2010; 207(2):339-44. 
Laufer CB, Roberts O. Differentiation syndrome in acute myeloid leukemia after treatment with 
azacitidine. Eur J Haematol. 2015; 95(5):484-5. 
Lee SH, Erber WN, Porwit A, Tomonaga M, Peterson LC; International Council for 
Standardization In Hematology. ICSH guidelines for the standardization of bone marrow 
specimens and reports. Int J Lab Hematol. 2008 Oct;30(5):349-64. doi: 10.1111/j.1751-
553X.2008.01100.x. 
Losman JA, Looper RE, Koivunen P, et al. (R)-2-hydroxyglutarate is sufficient to promote 
leukemogenesis and its effects are reversible. Science. 2013; 339(6127):1621-1625. 
Mardis, E, Ding L, Dooling D, et.al. Recurring mutations found by sequencing an acute myeloid 
leukemia genome. N Engl J Med. 2009; 361:1058-1066. 
Montesinos P, Bergua JM, Vellenga E, Differentiation syndrome in patients with acute 
promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: 
characteristics, outcome, and prognostic factors. Blood. 2009 Jan 22;113(4):775-83. 
Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am. J. Clin Oncol. 1982; 5:649-655. 
Rohle D, Popovici-Muller J, Palaskas N, et al. An inhibitor of mutant IDH1 delays growth and 
promotes differentiation of glioma cells. Science. 2013; 340 (6132):626-630. 
Saha SK, Parachoniak CA, Ghanta KS, et al. Mutant IDH inhibits HNF-4α to block hepatocyte 
differentiation and promote biliary cancer. Nature. 2014; 513:110-114. 
Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, et al. Enasidenib in 
mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017 Aug 10;130(6):722-
731. doi: 10.1182/blood-2017-04-779405.
UNC Lineberger Comprehensive Cancer Center. Simon’s Two Stage Design. Available 
at http://cancer.unc.edu/biostatistics/program/ivanova/SimonsTwoStageDesign.aspx.  
Yen K, Lemieux R, Popovici-Muller J, et al. IDH1 mutant inhibitor induces cellular 
differentiation and offers a combination benefit with Ara-C in a primary human IDH1 mutant 
AML xenograft model. Blood. 2013, 122:3946. 


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Appendix 1 
Schedule of Events (Ongoing Patients) 
Study 
Procedures 
Pre-
screening 
(Optional) 
Screening 
(D -14 to 
D1) 
Cycle 1
Cycle 2
Cycle 3 
Cycle 
4 
Cycle 5 
and 
beyond 
End of 
Txb
28-day
Follow-
upc 
Survival 
Follow-
up 
Days
D1
D2
D5 
± 
1D
D8 
± 
1D
D12 
± 
2D
D15 
± 
2D
D19 
± 
2D
D22 
± 
2D
D26 
± 
2D
D1 
± 
2D
D2 
± 
2D
D4 
± 
2D
D8 
± 
2D
D15 
± 
2D
D22 
± 
2D
D1 
± 
3D
D15 
± 
2D 
D1 
± 
3D 
D1 ± 3D 
Every 
other 
cyclea 
± 7D
+ 7D
q 3 mo
Signed 
Informed 
Consentd 
Xd
Complete 
Medical 
Historye 
X
Concomitant 
Medications 
X
X
Xf
X
X
X
X
X
X
X 
X 
X
X
Height and 
Weightg 
X
X
X
X
X 
X 
X
Vital Signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG PS 
X 
X 
X 
X 
X 
X 
X 
Physical 
Examination 
X
X
Xi
Xi
Xi
Xi
Xi
Xi
Xi 
Xi 
X
Serum or Urine 
Pregnancy 
Testj 
X
X
X
X
X 
X 
X
12-lead ECGk
X 
Xk 
Xk 
Xk 
Xk 
Xk 
Xk 
X 
X 
Xl 
Xl 
Holter 
Monitoring 
(Phase 2 only)m 
X 
X 
X 
X 
Clinical Serum 
Chemistriesn,o 
X
X
Xp
X
Xp
X
Xp
X
Xp
X
Xp
X
Xp
X
Xp 
X 
X 
X
CBC with 
Differential 
and Platelet 
Counto,q 
X
X
Xp
X
Xp
X
Xp
X
Xp
X
Xp
X
Xp
X
Xp 
X 
X 
X
Coagulation 
Parametersr 
X
X
Bone Marrow 
Aspirates 
X
X
X
X 
X 
X
Urinalysiso,t 
X 
X 
X 
X 
X 
X 
CONFIDENTIAL


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Protocol No. 2102-HEM-101 (Amendment 6) 
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Study 
Procedures 
Pre-
screening 
(Optional) 
Screening 
(D -14 to 
D1) 
Cycle 1
Cycle 2
Cycle 3 
Cycle 
4 
Cycle 5 
and 
beyond 
End of 
Txb
28-day
Follow-
upc 
Survival 
Follow-
up 
Days
D1
D2
D5 
± 
1D
D8 
± 
1D
D12 
± 
2D
D15 
± 
2D
D19 
± 
2D
D22 
± 
2D
D26 
± 
2D
D1 
± 
2D
D2 
± 
2D
D4 
± 
2D
D8 
± 
2D
D15 
± 
2D
D22 
± 
2D
D1 
± 
3D
D15 
± 
2D 
D1 
± 
3D 
D1 ± 3D 
Every 
other 
cyclea 
± 7D
+ 7D
q 3 mo
AE Monitoring
Continuous
X 
PK (Peripheral 
Blood)u
X 
X 
X 
X
X
Xv
X
X
X
X
X
PD (Peripheral 
Blood)w
Xx 
X 
X 
X 
X 
X
X
X
X
X
X
X
X
EQ-5D-5L 
(Phase 2 only) 
Xy 
X 
X 
X 
Study Drug 
Diaryz 
X 
X 
X 
X 
X 
Study Drug 
Adminaa,bb,cc 
Drug will be given in accordance with the dosing schedules for FT-2102, azacitidine and LDAC
Survivaldd 
X 
Admin = administration; AE = adverse event; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; C1D1 = Cycle 
1 Day 1; C2D1 = Cycle 2 Day 1; Ca = calcium; CBC = complete blood count; Cl = chloride; ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance 
status; FSH = follicle‑stimulating hormone; K = potassium; LDAC = low dose cytarabine; LDH = lactate dehydrogenase; LH = luteinizing hormone; MDS = myelodysplastic syndrome; 
Mg = magnesium; Na = sodium; PD = pharmacodynamic; PK = pharmacokinetic; PT = prothrombin time; PTT = partial thromboplastin time; Tx = treatment. 
NOTE: All assessments will be conducted predose unless specified otherwise. 
a
Beginning with Cycle 5, scheduled assessments will be performed every 2 cycles. 
b
End of Treatment visit to be conducted within 7 days of the decision to discontinue treatment. End of Treatment assessments need not be repeated if they were completed 
within the previous 2 weeks (4 weeks for bone marrow assessments). 
c
28-day Follow-up visit to be conducted within 28 days (+ 7 days) of last dose for adverse event follow-up and to capture initiation of new therapies (con-medications).
d
Informed consent must be completed prior to the initiation of any study-specific procedures or assessments. The informed consent process may be completed prior to the 
Screening Period (i.e., before Day -14) (see Section 6.1.2). 
e
Includes complete surgical and cardiac history and complete leukemia or MDS medical history. Complete leukemia or MDS medical history will include applicable 
treatment history as well as cytogenetic risk categorization at diagnosis by NCCN or ELN guidelines. 
f
Only required in patients enrolled in Phase 1 and patients in Phase 2 participating in Holter monitoring. 
g
Height at Screening only. 
h
Includes temperature, blood pressure, pulse rate, and respiratory rate. Prior to dosing on Days 1, 8, 15, and 22 (Cycle 1); Cycle 2 predose on Days 1 and 15 and Cycle 3 
and beyond predose on Day 1. 
i
Symptom-directed physical examination due to specific findings or abnormalities. 
CONFIDENTIAL


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Protocol No. 2102-HEM-101 (Amendment 6) 
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j
To be performed on all female patients of childbearing potential and within 72 hr of dosing (Day 1 only of every cycle). At Screening, women aged 55 and under, are not 
surgically sterile, and who are amenorrheic must have LH, FSH, and estradiol measurements within the postmenopausal range for the institution, to be considered of 
nonchildbearing potential. A serum pregnancy test is required at Screening; serum or urine pregnancy tests are allowed for post-Screening visits. 
k
Phase 1: Electrocardiograms will be performed in triplicate (within a 10-minute period) predose and at 2 (± 15 minutes), 4 (± 15 minutes), and 8 hr postdose (± 30 
minutes) on Cycle 1 Day 1 and Cycle 2 Day 1, and predose at all study visits where indicated. Phase 2: Electrocardiograms will be performed in triplicate (within a 
10-minute period) predose on Cycle 1 Day 1 and Cycle 2 Day 1, and at all study visits where indicated. All electrocardiograms will be performed in a supine position.
l
Electrocardiograms performed as clinically indicated for Cycle 5 and beyond.
m
24-hour 12-lead continuous Holters will be collected on C1D1 and C2D1 for patients at all centers in the US and select centers ex-US. The Holters should run from
approximately 1 hour before dosing until 24 hours (the next day). Patients should remain supine for 10-15 minutes before and 5 minutes after ECG collection. See 
manual for further guidance on Holter monitoring. 
n
Clinical serum chemistries to include Na, K, Cl, bicarbonate, Mg, Ca, BUN, creatinine, AST, ALT, ALP, albumin, total bilirubin, direct bilirubin (collected only if total 
bilirubin is abnormal), LDH, glucose, amylase, lipase, uric acid, and thyroid function test (TFT) panel, which includes thyroid-stimulating hormone, free T3, and T4. In 
addition to the other chemistry panels, TFT panel is to be completed at Screening, C1D1, C2D1, and C3D1, then as clinically indicated. 
o
May be performed from 48 hr (Cycle 2) or 72 hr (Cycle 3 and 4) prior to Day 1 of a cycle (see Section 6.1).
p
Clinical serum chemistries and CBC with differential and platelet count only at these study visits. May be performed through local laboratory testing. 
q
Includes hemoglobin, hematocrit, platelets, and white blood cell count with differential. 
r
Includes PT and PTT. 
s
Bone marrow aspirate for response assessment as described in Section 4.3. Refer to the laboratory manual for details of sample collection timing. 
•
Local IDH confirmation may have occurred > 28 days prior.
•
C3D1 to be done on any patient who did not undergo a C2D1 bone marrow aspirate or biopsy.
•
Patients who discontinue study treatment for reasons other than treatment failure and have not withdrawn consent from overall study participation, should
continue to be followed for disease response assessments until the time of disease progression/relapse or the initiation of a new treatment regimen. Patients who
have stopped FT-2102 treatment for HSCT should continue to be followed until disease progression/ relapse. This information should be documented on the
appropriate eCRF page
t
Urinalysis parameters include specific gravity, pH, total protein, protein, glucose, ketones, and blood. Microscopic examinations are to be performed as clinically 
indicated. For Cycle 3 & beyond and End of Study visit, urinalysis to be performed if clinically indicated.  
u
Blood samples will be collected for measurement of plasma concentrations of FT-2102 (single agent) or FT-2102 + azacitidine (combination agent). Blood will be
collected relative to FT-2102 administration as described in Section 6.4 and Table 4.
v
A 72-hour wash-out post C2D1 dosing will be requested from all patients participating in the dose-expansion stage. After the C2D1 FT-2102 AM dose, patients will be 
asked to refrain from taking FT-2102 until the AM of C2D4. PK samples will be collected on C2D2 and C2D4*. 
w
Blood samples will be collected for PD biomarker analysis for single agent FT-2102 and FT-2102/azacitidine combination. Blood will be collected relative to FT-2102 
administration as described in Section 6.5 and Table 5. 
x
Optional pre-screening blood sample for 2-HG level detection and IDH1 mutation testing (in 2-HG abnormal). 
y
EQ-5D-5L survey can be completed anytime during screening prior to C1D1 dose. 
z
Study drug diary should be distributed by the site to the subject at each clinic visit and collected at the next clinic visit. 
aa
Single agent (FT-2102): FT-2102 will be given in accordance with dosing schedule × 28 days out of 28 days. On C1D1 only a single dose of FT-2102 is taken. 
bb
Combination agent (FT-2102 + azacitidine): azacitidine will be administered via subcutaneous injection or intravenous infusion in combination with oral FT-2102 for 
7 days, and then azacitidine will be stopped for 21 days; a 48-hr dose interruption of the azacitidine for weekends or holidays is allowed. On C1D1 and C2D1, 
azacitidine is to be administered immediately prior to FT-2102 (to enable consistent PK assessments). On all other days and cycles when FT-2102 and azacitidine are 
co-administered, it is recommended to dose FT-2102 prior to azacitidine. 
CONFIDENTIAL


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cc 
Combination FT-2102 + cytarabine: cytarabine will be administered at a dose of 20 mg BID subcutaneously (SC) for 10 days every 28-day cycle 
dd 
After a patient discontinues study treatment and has completed their last study treatment visit, the study site may contact the patient approximately every 3 months to 
collect survival data and data pertaining to any other alternative anti-neoplastic therapy the patients begins for up to 12 months from the time of their 1st dose of study 
drug for the Phase 1 part of the study and up to 36 months for the Phase 2 part of the study. Patients who discontinue for reasons other than disease progression or who 
withdraw consent will continue to be followed for response until progression occurs. 
*
Not required in Phase 2.
CONFIDENTIAL


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Protocol No. 2102-HEM-101 (Amendment 6) 
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Appendix 2 
Schedule of Events (Patients Enrolled After Protocol Version 7/ Amendment 6) 
Study Procedures 
Screening 
(D -14 to D1) 
Cycle 1 and beyond 
End of Txb
28-day
Follow-
upc 
Survival 
Follow-up
Days
D1 ± 3D 
Every other cyclea 
± 7D
+ 7D
q 3 mo
Signed Informed Consentd 
Xd 
Complete Medical Historye 
X 
Concomitant Medications 
X 
X 
X 
X 
Height and Weightf 
X 
X 
X 
Vital Signsg 
X 
X 
X 
ECOG PS 
X 
X 
X 
Physical Examination 
X 
Xh 
X 
Serum or Urine Pregnancy Testi 
X 
X 
X 
12-lead ECG
X 
As clinically indicated 
Xj 
Clinical Serum Chemistriesk,l 
X 
X 
X 
CBC with Differential and Platelet Countm 
X 
X 
X 
Coagulation Parametersn 
X 
As clinically indicated 
Bone Marrow Aspirateo 
X 
X 
X 
AE Monitoring 
Continuous 
X 
Study Drug Diaryp 
X 
Study Drug Adminq,r
Drug will be given in accordance with the dosing schedules 
for FT-2102 and azacitidine 
Survivals 
X 
Admin = administration; AE = adverse event; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase; BUN = blood 
urea nitrogen; C1D1 = Cycle 1 Day 1; C2D1 = Cycle 2 Day 1; Ca = calcium; CBC = complete blood count; Cl = chloride; ECG = electrocardiogram;  
ECOG PS = Eastern Cooperative Oncology Group performance status; FSH = follicle‑stimulating hormone; K = potassium; LDH = lactate dehydrogenase;  
LH = luteinizing hormone; Mg = magnesium; Na = sodium; PT = prothrombin time; PTT = partial thromboplastin time; Tx = treatment. 
NOTE: All assessments will be conducted predose unless specified otherwise. 
a
Scheduled assessments will be performed every 2 cycles. 
b
End of Treatment visit to be conducted within 7 days of the decision to discontinue treatment. End of Treatment assessments need not be repeated if they 
were completed within the previous 2 weeks (4 weeks for bone marrow assessments). 
c
28-day Follow-up visit to be conducted within 28 days (+ 7 days) of last dose for adverse event follow-up and to capture initiation of new therapies
(con-medications). 
d
Informed consent must be completed prior to the initiation of any study-specific procedures or assessments. The informed consent process may be 
completed prior to the Screening Period (i.e., before Day -14) (see Section 6.1.2). 
CONFIDENTIAL


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Protocol No. 2102-HEM-101 (Amendment 6) 
Page 104 of 114 
Forma Therapeutics, Inc. 
 
August 20, 2020 
e
Includes complete surgical and cardiac history and complete leukemia medical history. Complete leukemia medical history will include applicable 
treatment history as well as cytogenetic risk categorization at diagnosis by NCCN or ELN guidelines. 
f
Height at Screening only. 
g
Includes predose temperature, blood pressure, pulse rate, and respiratory rate. 
h
Symptom-directed physical examination due to specific findings or abnormalities. 
i
To be performed on all female patients of childbearing potential and within 72 hr of dosing (Day 1 only of every cycle). At Screening, women aged 55 and 
under, are not surgically sterile, and who are amenorrheic must have LH, FSH, and estradiol measurements within the postmenopausal range for the 
institution, to be considered of nonchildbearing potential. A serum pregnancy test is required at Screening; serum or urine pregnancy tests are allowed for 
post-Screening visits. 
j
Electrocardiograms performed as clinically indicated. 
k
Clinical serum chemistries to include Na, K, Cl, bicarbonate, Mg, Ca, BUN, creatinine, AST, ALT, ALP, albumin, total bilirubin, direct bilirubin 
(collected only if total bilirubin is abnormal) conducted as indicated. 
l
Clinical serum chemistries also include LDH, glucose, amylase, lipase, uric acid, and thyroid function test (TFT) panel (including thyroid-stimulating
hormone, free T3, and T4) conducted at Screening then as clinically indicated.
m
Includes hemoglobin, hematocrit, platelets, and white blood cell count with differential. 
n
Includes PT and PTT. 
o
Bone marrow aspirate for response assessment to be done at Screening (if not taken at End of Treatment prior to roll-over) and then every 6 cycles unless
there is suspicion of relapse/progression (see Section 4.3). Refer to the laboratory manual for details of sample collection timing.
•
Local IDH confirmation may have occurred > 28 days prior.
•
Patients who discontinue study treatment for reasons other than treatment failure and have not withdrawn consent from overall study participation,
should continue to be followed for disease response assessments until the time of disease progression/relapse or the initiation of a new treatment
regimen. Patients who have stopped FT-2102 treatment for HSCT should continue to be followed until disease progression/ relapse. This information
should be documented on the appropriate eCRF page
p
Study drug diary should be distributed by the site to the subject at each clinic visit and collected at the next clinic visit. 
q
Single agent (FT-2102): FT-2102 will be given in accordance with dosing schedule × 28 days out of 28 days. On C1D1 only a single dose of FT-2102 is 
taken. 
r
Combination agent (FT-2102 + azacitidine): azacitidine will be administered via subcutaneous injection or intravenous infusion in combination with oral 
FT-2102 for 7 days, and then azacitidine will be stopped for 21 days; a 48-hr dose interruption of the azacitidine for weekends or holidays is allowed. On 
all days and cycles when FT-2102 and azacitidine are co-administered, it is recommended to dose FT-2102 prior to azacitidine. 
s
After a patient discontinues study treatment and has completed their last study treatment visit, the study site may contact the patient approximately every 
3 months to collect survival data and data pertaining to any other alternative anti-neoplastic therapy the patients begins for up to 12 months from the time 
of their 1st dose of study drug for the Phase 1 part of the study and up to 36 months for the Phase 2 part of the study. Patients who discontinue for reasons 
other than disease progression or who withdraw consent will continue to be followed for response until progression occurs.  
CONFIDENTIAL


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
Page 105 of 114 
Forma Therapeutics, Inc. 
 
August 20, 2020 
Appendix 3 
ECOG Performance Status 
Grade 
ECOG Performance Status 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, eg, light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities; up and about 
more than 50% of waking hours 
3 
Capable of only limited self-care; confined to bed or chair more than 50% of waking hours 
4 
Completely disabled; cannot carry on any self-care; totally confined to bed or chair 
5 
Dead 
Source: Oken et al. 1982. 


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
Page 106 of 114 
Forma Therapeutics, Inc. 
 
August 20, 2020 
Appendix 4 
National Cancer Institute Common Terminology Criteria for Adverse Events 
(NCI CTCAE) Version 4.03 
The NCI CTCAE version 4.03 can be found by going to the following web site: 
http://ctep.cancer.gov/reporting/ctc.html 
Copies of the spiral-bound book of the NCI CTCAE Version 4.03 have been obtained from 
CTEP/DCT/NCI and are on file for AE classification by site clinical trial, nursing and medical 
staffs and in the Sponsor’s clinical and data management offices. 
Inquiries specifically regarding the Common Toxicity Criteria (CTC) should be addressed to: 
ncictephelp@ctep.nci.nih.gov 


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
 
Page 107 of 114 
 
Forma Therapeutics, Inc. 
 
 
August 20, 2020 
Appendix 5 
NYHA Classification 
Class 
Patient Symptoms 
Class I (Mild) 
No limitation of physical activity. Ordinary physical activity does not 
cause undue fatigue, palpitation, or dyspnea (shortness of breath). 
Class II (Mild) 
Slight limitation of physical activity. Comfortable at rest, but ordinary 
physical activity results in fatigue, palpitation, or dyspnea. 
Class III 
(Moderate) 
Marked limitation of physical activity. Comfortable at rest, but less than 
ordinary activity causes fatigue, palpitation, or dyspnea. 
Class IV (Severe) 
Unable to carry out any physical activity without discomfort. Symptoms 
of cardiac insufficiency at rest. If any physical activity is undertaken, 
discomfort is increased. 
 
 
 


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
 
Page 108 of 114 
 
Forma Therapeutics, Inc. 
 
 
August 20, 2020 
Appendix 6 
Drugs that are Generally Accepted by Authorities to have a Risk of Causing 
Torsades de Pointes 
It has been recognized for a number of years that certain prescription medications can prolong 
the QT/QTc interval. Medications that prolong the QT interval and/or have a risk of inducing 
Torsade de Pointes (TdP) are listed below. Additional information can be found at: 
https://crediblemeds.org/index.php 
 
Drugs 
Amiodarone 
Anagrelide 
Arsenic trioxide 
Astemizole (Removed from Market) 
Azithromycin 
Bepridil (Removed from Market) 
Chloroquine 
Chlorpromazine 
Cilostazol 
Ciprofloxacin 
Cisapride (Removed from Market) 
Citalopram 
Clarithromycin 
Cocaine 
Disopyramide 
Dofetilide 
Domperidone (Only on Non US Market) 
Donepezil 
Dronedarone 
Droperidol 
Erythromycin 
Escitalopram 
Flecainide 
Fluconazole 
Gatifloxacin (Removed from Market) 
Grepafloxacin 
Halofantrine 
Haloperidol 
Ibogaine (Only on Non US Market) 
 
Ibutilide 
Levofloxacin 
Levomepromazine (Only on Non US 
Market) 
Levomethadyl acetate (Removed from 
Market) 
Levosulpride (Only on Non US Market) 
Mesoridazine (Removed from Market) 
Methadone 
Moxifloxacin 
Ondansetron 
Oxaliplatin 
Papaverine HCl 
Pentamidine 
Pimozide 
Probucol (Removed from Market) 
Procainamide 
Propofol 
Quinidine 
Roxithromycin (Only on Non US Market) 
Sevoflurane 
Sotalol 
Sparfloxacin (Removed from Market) 
Sulpiride (Only on Non US Market) 
Sultopride (Only on Non US Market) 
Terfenadine (Removed from Market) 
Terlipressin (Only on Non US Market) 
Terodiline (Only on Non US Market) 
Thioridazine 
Vandetanib 
Source: www.AZCert.org accessed 13 March 2017 
 


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
 
Page 109 of 114 
 
Forma Therapeutics, Inc. 
 
 
August 20, 2020 
Appendix 7 
Response Criteria for AML 
Adapted from IWG Response Criteria (Cheson et al. 2003); see also Stein et al. 2017. 
Response Category 
Response criteria (no minimum duration required unless 
indicated) 
Morphologic 
leukemia free state 
(MLFS) 
• BM blasts < 5% (in aspirate with spicules and 200 nucleated 
cells) 
• No blasts with Auer rods 
• No extramedullary disease 
Morphologic 
complete remission 
(CR) 
Same as MLFS, and: 
• ANC ≥ 1000/µL 
• Platelets ≥ 100,000/µL 
• Transfusion Independence 
Cytogenetic Complete 
Remission (CRc) 
CR with no residual cytogenetic abnormalitiesa 
Molecular Complete 
Remission (CRm) 
CR with undetectable IDH1m minimal residual disease (MRD) 
CR with incomplete 
hematologic recovery 
(CRi) 
CR but with ANC < 1000/µL, or platelets < 100,000/µL 
CR with partial 
hematologic recovery 
(CRh) 
< 5% BM blasts and partial recovery of peripheral blood counts 
(platelets > 50 x 109/L and ANC > 0.5 x 109/L) 
Partial remission (PR) Reduction of BM blasts: 
• to a value between 5 % – 25%, if baseline was ≥ 50% 
• by 50% to a value >5%, if baseline was between 5% - 49% 
Persistence of Auer rods, even if BM blasts ≤ 5% 
Hematologic values consistent with a CR: 
• ANC ≥ 1000/µL and 
• Platelets ≥ 100,000/µL 
Stable Disease (SD)  
Failure to achieve at least a PR but not meeting criteria for 
progressive disease (PD). SD for a period of 8 weeks or more 
indicates clinical benefit  


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
 
Page 110 of 114 
 
Forma Therapeutics, Inc. 
 
 
August 20, 2020 
Response Category 
Response criteria (no minimum duration required unless 
indicated) 
Recurrence, 
Morphologic Relapse 
In patients who achieved CR, CRh, CRi, MLFS: 
• Reappearance of peripheral blasts, or 
• ≥ 5% BM blasts (if no peripheral blasts, may repeat BM 
assessment to distinguish relapse from BM regeneration) 
• Development of extramedullary disease 
Disease Progression 
In patients with PR or SD: 
• For patients with 5% to 66% BM blasts at nadir, a >50% 
increase in BM blast count percentage from the nadir and 
percentage is ≥ 20%; and  
• For patients with ≥ 67% BM blasts at nadir, a doubling of the 
nadir absolute peripheral blood blast count with a final 
absolute peripheral blood blast count >10 x 109/L 
• New extramedullary disease 
BM = bone marrow 
a Analysis by either conventional banded karyotyping or FISH is accepted 


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
 
Page 111 of 114 
 
Forma Therapeutics, Inc. 
 
 
August 20, 2020 
Appendix 8 
Response Criteria for MDS  
Adapted from IWG Response Criteria for MDS (Cheson et al. 2006)  
Response Category 
Response criteria (responses must last at least 4 wks) 
Complete remission 
(CR) 
• Bone marrow: ≤ 5% myeloblasts with normal maturation of all 
cell lines* Persistent dysplasia will be noted* 
• Peripheral blood‡: 
o Hgb ≥ 11 g/dL 
o Platelets ≥ 100 × 109/L  
o Neutrophils ≥ 1.0 × 109/L  
o 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 CR 
Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over 
pretreatment 
Peripheral blood: if HI responses, they will be noted in addition to 
marrow CR 
Stable disease (SD) 
Failure to achieve at least PR, but no evidence of progression for 
> 8 wks 
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 in Hgb concentration by ≥ 1.5 g/dL or transfusion 
dependence 


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
 
Page 112 of 114 
 
Forma Therapeutics, Inc. 
 
 
August 20, 2020 
Response Category 
Response criteria (responses must last at least 4 wks) 
Disease progression 
(PD) 
For patients with: 
• Less than 5% blasts: ≥ 50% increase in blasts to > 5% blasts  
• 5%-10% blasts: ≥ 50% increase to > 10% blasts 
• 10%-20% blasts: ≥ 50% increase to > 20% blasts 
• 20%-30% blasts: ≥ 50% increase to > 30% blasts 
Any of the following: 
• At least 50% decrement from maximum remission/response in 
granulocytes or platelets  
• Reduction in Hgb by ≥ 2 g/dL 
• Transfusion dependence 
HI: hematologic improvement 
*Dysplastic changes should consider the normal range of dysplastic changes. 
‡ 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. 
 
 
 
 
 
 
 
 
CONFIDENTIAL


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
 
Page 113 of 114 
 
Forma Therapeutics, Inc. 
 
 
August 20, 2020 
Modiﬁed International Working Group Response Criteria for Hematologic Improvement 
Hematologic 
improvement* 
Response criteria (responses must last at least 8 wks) 
Erythroid response 
(pretreatment, 
< 11 g/dL) 
Hgb increase by ≥ 1.5 g/dL 
Relevant reduction of units of RBC transfusions by an absolute 
number of at least 4 RBC transfusions/8 wks compared with the 
pretreatment transfusion number in the previous 8 wks. Only RBC 
transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment will count in 
the RBC transfusion response evaluation 
Platelet response 
(pretreatment, 
< 100 X 109/L) 
Absolute increase of ≥ 30 × 109/L for patients starting with 
≥ 20 × 109/L platelets 
Increase from < 20 × 109/L to > 20 × 109/L and by at least 100% 
Neutrophil response 
(pretreatment, 
< 1.0 × 109/L) 
At least 100% increase and an absolute increase > 0.5 × 109/L 
Progression or 
relapse after HI‡ 
At least 1 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 
*Pretreatment counts averages of at least 2 measurements (not inﬂuenced by transfusions) ≥ 1 week apart. 
‡In the absence of another explanation, such as acute infection, repeated courses of chemotherapy, gastrointestinal 
bleeding, hemolysis, and so forth. It is recommended that the 2 kinds of erythroid and platelet responses be reported 
overall as well as by the individual response pattern. 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL


FT-2102 
Protocol No. 2102-HEM-101 (Amendment 6) 
 
Page 114 of 114 
 
Forma Therapeutics, Inc. 
 
 
August 20, 2020 
Appendix 9 Drugs that are Strong Inducers or Sensitive Substrates of CYP3A4 
 
Strong Inducers: Carbamazepine, rifampin, ritonavir, enzulatamide, mitotane, phenytoin, 
phenobarbital and St. John’s wort 
 
Sensitive Substrates: Alfentanil, avanafil, buspirone, conivaptan, darifenacin, darunavir, 
ebastine, everolimus, ibrutinib, lomitapide, lovastatin, midazolam, naloxegol, nisoldipine, 
saquinavir, simvastatin, sirolimus, tacrolimus, tipranavir, triazolam, vardenafil, budesonide, 
dasatinib, dronedarone, eletriptan, eplerenone, felodipine, indinavir, lurasidone, maraviroc, 
quetiapine, sildenafil, ticagrelor, tolvaptan    
 
Additional information can be found at: 
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteracti
onsLabeling/ucm093664.htm#table3-1 
 
CONFIDENTIAL

SAP_001.pdf: 
Cover Page for Statistical Analysis Plan 
Sponsor name: 
FORMA Therapeutics, Inc 
NCT number 
NCT02719574 
Sponsor trial ID: 
2102-HEM-101 
Official title of study: 
A Phase 1/2, Multicenter, Open-label Study of FT-2102 as a 
Single Agent and in Combination with Azacitidine or 
Cytarabine in Patients with Acute Myeloid Leukemia 
or Myelodysplastic Syndrome with an IDH1 Mutation 
Document date* 
13-Apr-2015
*Document date refers to the date on which the document was most recently updated.
Note: The date in the Page 2 is the document saved date and not of an update to content.




Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan  
Page 2 of 58  
 
 
Prepared by: 
 
                                          
 
 
 
 
 
 
, 
 
FORMA Therapeutics, Inc 
 
 
Signature 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Approved by: 
 
                                      
 
 
 
  
 
 
 
 
FORMA Therapeutics, 
Inc. 
 
Signature 
Date 
 
 
 
 
 


FORMA / Protocol: 2102-HEM-101 
 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan  
Page 3 of 58  
 
 
 


FORMA / Protocol: 2102-HEM-101 
 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan  
Page 4 of 58  
Summary of Changes 
 
Version 1.0 
N/A; first version 
Version 2.0 
Numerous revisions based on regulatory agency interactions.  Clarify 
language, describe imputation of missing data, clarify exposure 
calculations, edit algorithm for AESI differentiation syndrome, edit 
transfusion independence analysis, edit censoring rules for time to event 
endpoints 
Version 3.0 
Add detail on alpha and beta spend for Phase 2 cohort 1 interim analyses, 
add sensitivity analysis for the effect of COVID-19 on time to event 
endpoints. Revise description of AESI analysis. 
Version 4.0 
Add detail about missing data imputation for QOL assessment.  Update 
definition of BOR. Updates to DS analysis details. Add sensitivity analysis 
for efficacy. 
Version 5.0 
Time from diagnosis and time to event end points units changed from 
weeks to months. Total number of prior regimens received categorical 
presentation updated. Duration of response definition has been updated to 
exclude introduction of new anticancer therapy from the events list as per 
the FDA guidance. Added sensitivity analyses for time to event efficacy 
end points. Updated analyses for adverse events of special interest: hepatic 
adverse drug reactions.  Clarified that some analyses performed for pivotal 
IA2 will not be performed for final analysis. 
 
 


FORMA / Protocol: 2102-HEM-101 
 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan  
Page 5 of 58  
CONTENTS 
 
Abbreviations ............................................................................................................................ 7 
I.Introduction ............................................................................................................................ 9 
II.Protocol Objectives ............................................................................................................... 9 
A. Primary .................................................................................................................... 9 
B. Secondary ................................................................................................................ 9 
C. Exploratory ........................................................................................................... 10 
III.Study Endpoints ................................................................................................................. 10 
A. Primary .................................................................................................................. 10 
B. Secondary .............................................................................................................. 10 
IV.Study Design ...................................................................................................................... 11 
A. Design Overview .................................................................................................. 11 
B. Study Population ................................................................................................... 14 
C. Sample Size ........................................................................................................... 14 
D. Treatment Randomization ..................................................................................... 16 
E. Assessment Schedule ............................................................................................ 16 
V.Interventions........................................................................................................................ 16 
A. Clinical Trial Material........................................................................................... 16 
VI.General Analytical Considerations .................................................................................... 17 
A. Definition of Baseline ........................................................................................... 17 
B. Methods of Pooling Data ...................................................................................... 17 
C. Missing Data/ Data Imputation ............................................................................. 18 
D. Multiple Study Centers ......................................................................................... 21 
E. Covariate Adjustment in Primary Analysis .......................................................... 21 
F. Sample Size Reassessment ................................................................................... 21 
G. Interim Analyses ................................................................................................... 21 
H. Multiple Comparisons ........................................................................................... 22 
I. Analysis Sets ......................................................................................................... 22 
J. Subgroup Analyses ............................................................................................... 24 
K. Data Display Characteristics ................................................................................. 25 
L. Blinded Review of Data ........................................................................................ 25 
VII.Baseline Patient Characteristics and Disposition ............................................................. 25 
A. Disposition ............................................................................................................ 25 
B. Demographics ....................................................................................................... 25 
C. Disease History ..................................................................................................... 26 
D. Cytogenetics and Molecular Genetics .................................................................. 27 
E. Baseline Disease Characteristics ........................................................................... 27 
F. Medical and Surgical History ............................................................................... 28 
G. Prior Anti-Cancer Therapies ................................................................................. 28 


FORMA / Protocol: 2102-HEM-101 
 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan  
Page 6 of 58  
H. Protocol Deviations ............................................................................................... 28 
VIII.Safety Analyses ............................................................................................................... 28 
A. Exposure ............................................................................................................... 28 
B. Adverse Events ..................................................................................................... 29 
C. Clinical Laboratory Results .................................................................................. 35 
D. Vital Signs ............................................................................................................. 36 
E. Electrocardiogram (ECG) ..................................................................................... 36 
F. Physical Examination and Pregnancy Test ........................................................... 37 
G. Concomitant Medications ..................................................................................... 37 
H. ECOG Performance Status ................................................................................... 38 
IX.Pharmacokinetic Analyses ................................................................................................. 38 
X.Pharmacodynamic Analyses ............................................................................................... 39 
XI.Efficacy Analyses .............................................................................................................. 39 
A. Efficacy Endpoints ................................................................................................ 39 
B. Efficacy Analysis .................................................................................................. 43 
C. Quality of Life Analysis........................................................................................ 47 
XII.References ........................................................................................................................ 49 
Appendix 1   Schedule of Events ............................................................................................ 51 
Appendix 2   SAS code for Efficacy Analyses ....................................................................... 55 
A. CR/CRh Rate ........................................................................................................ 55 
B. EFS, DOR and OS ................................................................................................ 55 
Appendix 3   Column Headings for Analysis Tables ............................................................. 56 
 


FORMA / Protocol: 2102-HEM-101 
 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan  
Page 7 of 58  
ABBREVIATIONS 
Abbreviation 
Definition 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT (SGPT) 
alanine transaminase 
AML 
acute myeloid leukemia 
AST (SGOT) 
aspartate transaminase 
ATC 
anatomical therapeutic chemical  
AUC 
area under the concentration curve 
AUClast 
AUC up to the last measurable concentration 
AUCinf 
AUC to infinite time 
AUCtau 
AUC over the dosing interval 
BID 
twice daily 
CBC 
complete blood count 
CL/F 
total body clearance 
Cmax 
maximum plasma concentration 
CTCAE 
common terminology criteria for adverse events 
CR 
complete remission 
CRh  
complete remission with partial hematological recovery  
CRi  
complete remission with incomplete blood count recovery  
DLT 
dose-limiting toxicity 
DS 
differentiation syndrome 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
2-HG 
(R)-2-hydroxyglutarate 
HSCT 
hematopoietic stem cell transplantation 
IDH1 
isocitrate dehydrogenase 1 
IDH2 
isocitrate dehydrogenase 2 
IPSS-R 
Revised International Prognostic Scoring System 
LDAC 
low-dose cytarabine 
MDS 
myelodysplastic syndrome 
MED 
maximum evaluated dose 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
PT 
prothrombin time 


FORMA / Protocol: 2102-HEM-101 
 
Document Number: FORM 694.01 
Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan 
Page 8 of 58
PT 
preferred term 
PTT 
partial thromboplastin time 
QD 
once daily 
RFS 
relapse free survival 
SAP 
statistical analysis plan 
SA 
single agent 
SCT 
stem cell transplant 
SD 
stable disease 
SMQ 
Standardised MedDRA Query 
SOC 
system organ class 
TEAE 
treatment emergent adverse event 
t1/2 
terminal elimination half life 
Tmax 
time to maximum plasma concentration 
VAS 
visual analogue scale 
Vd/F 
volume of distribution 
WHO 
World Health Organization 


 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan 
Page 9 of 58  
I. 
Introduction 
 
This is a phase 1/2, multicenter, open-label study of FT-2102 as a single agent (SA) and in 
combination with azacitidine or cytarabine in patients with acute myeloid leukemia (AML) 
or myelodysplastic syndrome (MDS) with an IDH1 mutation. 
This Statistical Analysis Plan (SAP) is based on version 5 of Protocol 2102-HEM-101.   
This SAP will govern the analysis of data from this study.  The plan may be modified until 
the time of database lock.  Any deviations from the analysis plan, including any after the time 
of database lock, will be documented as such in the study report.   
Any protocol-specified statistical analyses for pharmacokinetics (PK), or PK/PD in 
relationship with clinical safety and clinical activity will be prepared by related function in a 
separate document. 
 
II. 
Protocol Objectives 
 
A. Primary 
 
The primary objectives are:  
 
Phase 1  
 To determine the maximum tolerated doses (MTDs), the maximum evaluated doses 
(MEDs), dose-limiting toxicities (DLTs), and the Recommended Phase 2 doses 
(RP2Ds) of FT-2102 as a single agent in combination with azacitidine, and in 
combination with cytarabine in patients with AML or MDS harboring an IDH1-R132 
mutation.  
 
Phase 2 
 To evaluate the antileukemic and antimyelodysplastic activity of FT-2102 as a single 
agent or in combination with azacitidine in patients with AML or MDS, respectively 
harboring an IDH1-R132 mutation 
 
B. Secondary 
 
The secondary objectives are: 
 
Phase 1 
 To determine the pharmacokinetics (PK) of FT-2102 as a single agent and in 
combination with azacitidine or cytarabine 
 To observe patients for any evidence of antileukemic or antimyelodysplastic activity 
of FT-2102 as a single agent and in combination with azacitidine or cytarabine  
 
Phase 2 


 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
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 To confirm the safety of FT-2102 as a single agent and in combination with 
azacitidine in select patient populations 
 To evaluate additional measures of the antileukemic or antimyelodysplastic activity 
of FT-2102 as a single agent and in combination with azacitidine  
 To determine the PK of FT-2102 as a single agent and in combination with 
azacitidine 
 
C. Exploratory 
 
The exploratory objectives are: 
 
Phase 1 and Phase 2 
 
 To assess on-target activity of FT-2102, as determined by changes in a PD biomarker 
in plasma 
 To determine the frequency of cancer-associated mutations and/or genetic alterations 
in responding and nonresponding patients 
 To evaluate PK/PD and clinical response relationships in each cohort 
 
Phase 2 
 To evaluate the health-related quality of life (QOL) of patients receiving FT-2102 as 
a single agent or in combination with azacitidine 
 
III. 
Study Endpoints 
 
A. Primary 
 
The primary endpoints are: 
 
Phase 1 
 
 Incidence and severity of adverse events (AEs), clinical laboratory abnormalities, and 
changes in electrocardiogram (ECG) parameters 
 
Phase 2 
 All cohorts except Cohort 2: Complete Response rate (best overall response [BOR] of 
complete remission (CR)/complete remission with partial hematological recovery 
(CRh)) as determined by the investigator per disease-specific criteria. Refer to 
Appendix 6 for AML and Appendix 7 for MDS response criteria in the protocol. 
 Cohort 2: Four-month relapse free survival (RFS) rate 
 
B. Secondary 
 
The secondary endpoints are: 
 


 
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Phase 1 
 PK parameters derived from FT-2102 concentrations 
 Antileukemic or antimyelodysplastic activity as determined by CR, CRh, complete 
remission with incomplete blood count recovery (CRi), morphologic leukemia-free 
state (MLFS), Marrow CR, partial remission (PR) and stable disease (SD)  
 
Phase 2 
 Evidence of clinical benefit (CRi, MLFS, Marrow CR, Overall Response (OR), 
Transfusion Independence (TI), Time to Response (TTR), Duration of Response 
(DOR), event free survival [EFS], RFS, Overall Survival (OS), and other definitions 
of response, including SD)  
 Incidence and severity of adverse events (AEs), clinical laboratory abnormalities and 
changes in electrocardiogram (ECG) parameters 
 PK parameters derived from plasma FT-2102 concentrations 
 
IV. 
Study Design 
 
A. Design Overview  
  
This Phase 1/2 study will utilize a multicenter, open-label, dose-escalation design, to evaluate 
the safety, efficacy, PK, and PD of FT-2102 administered orally to patients with AML or 
MDS.  Patients will be given FT-2102 daily (QD or BID) in continuous 28-day cycles, alone 
or in combination with azacitidine (administered at the dose of 75 mg/m2 for 7 days IV/SQ 
per every 28-day cycle) or low-dose cytarabine (LDAC) (administered at the dose of 20 mg 
BID SC for 10 days every 28-day cycle) until treatment discontinuation.  
The study is comprised of 3 stages: a Phase 1 dose-escalation stage, a Phase 1 dose-
expansion stage, and a Phase 2 stage. See protocol sections 4.1 and 4.2 for details. 
 
Phase 1 Dose-Escalation Stage 
Dose escalation will be initiated using FT-2102 as a single agent in patients with AML or 
MDS harboring an IDH1-R132 mutation, as determined by local mutation testing.  It is 
planned that doses of 150 and 300 mg FT-2102 QD (Schedule 1) will be tested.  Twice-daily 
(BID) dosing (Schedule 2) and/or dosing with food to improve on bioavailability may be 
explored when indicated.  
The dose-escalation stage will utilize a 3+3 design, whereby three evaluable patients will be 
treated at each dose level and if a DLT occurs, then the cohort will be expanded to six 
patients to determine a non-tolerated dose and MTD.  For a given cohort, once two or more 
patients have a DLT, further enrollment/treatment for that cohort will halt, as will dose 
escalation.  The dose level at which two or more of up to six patients have a DLT will be 
considered to be at least one dose level above the MTD. 
The DLT dose level is defined as the lowest dose level at which DLT is experienced in two 
or more patients within a cohort of six or less patients.  The MTD is the highest dose level 


 
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that does not meet the DLT dose level definition.  The MED is defined as the highest dose 
level evaluated in the setting when dose escalation is stopped before an MTD is identified.  
A dose-limiting toxicity is defined as any AE occurring in Cycle 1 that fulfills one or more of 
the following criteria. Toxicities will be graded and documented according to the NCI 
CTCAE, version 4.03 guidelines (see Appendix 3 of protocol): 
 
 Nonhematological Grade 3 or greater toxicity that is unrelated to underlying disease, 
occurring in Cycle 1 with the following exceptions: 
o Alopecia 
o Grade 3 nausea, vomiting, diarrhea or rash lasting less than 72 hours (with 
optimal medical management) 
o Grade 3 QTcF prolongation that is < 40 msec increase over baseline in a 
patient with a bundle branch block (BBB) 
o Grade 3 or 4 toxicity determined to be a sign or symptom of differentiation 
syndrome that resolves/responds to treatment interventions to < Grade 3 
within 7 days 
 Any Grade 3 non-hematologic laboratory finding, unrelated to underlying disease, 
occurring in Cycle 1 
 Hematologic Grade 4 toxicity as defined by CTCAE on Day 42, in the absence of 
disease 
 Inability to tolerate a minimum of 75% of FT-2102 scheduled doses during Cycle 1 
due to an AE. This applies to patients who have their dose held due to AEs per 
Section 6.8.1 of protocol. 
 
All patients will be monitored for bone marrow function throughout the study, but these 
findings may not be considered a DLT unless they fulfill the above criteria. 
A DLT is defined within the 28 days of Cycle 1. However, the sponsor will evaluate all 
safety data, on an ongoing basis, beyond Cycle 1 for determination of an appropriate dose for 
Phase 2 or later trials. 
The dose-escalation portion of the study will allow dose increases of up to 50% between 
cohorts above the 300 mg total daily dose level until the MTD or an MED is determined.  
Initiation of Schedule 2 will occur following analysis of PK/PD parameters and clinical 
observations, and may be independent of an MTD in Schedule 1.  
 
FT-2102 + Azacitidine (Combination) Dose-Escalation 
During the course of dose escalation, a parallel escalation arm will be initiated for FT-2102 
in combination with azacitidine in patients with AML or MDS harboring an IDH1-R132 
mutation.  The starting dose of FT-2102 in the combination agent is a dose level at which ≤ 
Grade 2 toxicities (i.e., no Grade 3 or higher toxicities) were observed when FT-2102 was 
administered as a single agent. This escalation will also enroll patients on a 3+3 design, 
whereby three patients will be treated and if one DLT occurs, then the cohort will be 
expanded to six patients; if more than one DLT occurs, escalation will stop at that dose level 
(or schedule). FT-2102 will be given orally QD (or BID) in continuous 28-day cycles.  
 


 
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Phase 1 Dose-Expansion Stage 
Once the MTD or MED has been identified for the SA or azacitidine combination cohort, up 
to 14 additional patients will be enrolled in up to 2 expansion cohorts each of SA FT-2102 or 
in combination with azacitidine to confirm and to further characterize the safety and clinical 
activity of FT-2102 as a single agent or in combination with azacitidine.  From these dose 
expansion cohorts, a recommended Phase 2 dose (RP2D) of FT-2102 as a single agent or in 
combination with azacitidine will be selected for subsequent evaluation in Phase 2.  
 
 
FT-2102 in combination with cytarabine 
After dose-expansion is complete for FT-2102 as a single agent and FT-2102 in combination 
with azacitidine, a cohort of 6 patients with AML harboring IDH1 mutation will be treated 
with FT-2102 in combination with cytarabine 20 mg BID for 10 days, and then cytarabine 
will be stopped for 18 days.  Starting dose of 150 mg FT-2102 will be given twice daily in 
accordance with dosing schedule × 28 days out of 28 days.  Further dose-escalation of FT-
2102 in combination with cytarabine will not occur beyond 150 mg BID. 
If > 1 DLTs are observed at the 150 mg BID dose in combination with cytarabine, a lower 
dose level may be explored. 
 
Recommended Phase 2 Dose 
 FT-2102 150 mg BID is the RP2D confirmed for single-agent and azacitidine combination 
treatment. 
 
Phase 2 
The Phase 2 portion of the study is comprised of 4 patient cohorts receiving single agent 
therapy, and 4 patient cohorts receiving combination therapy, defined as follows. 
 
Single-Agent Cohorts: 
- 
Cohort 1 (SA FT-2102): approximately 173 evaluable patients with R/R AML. To 
account for potential discordance between local and central mutation testing, 
approximately 190 patients may be enrolled into this cohort. 
- 
Cohort 2 (SA FT-2102): approximately 53 patients with AML in morphologic 
CR/CRi after prior therapy (+/-hematopoietic stem cell transplantation [HSCT]) 
with residual IDH1-R132 mutation (> 0.01%) detected in the bone marrow.  
- Cohort 3 (SA FT-2102): approximately 20 patients with R/R AML/MDS that have 
been previously treated with IDH1 inhibitor therapy. Patients who undergo HSCT 
on-study then relapse post-HSCT are allowed in this cohort. 
- 
Cohort 7 (SA FT-2102): approximately 54 treatment naïve AML patients for 
whom standard treatments are contraindicated. 
 
Azacitidine Combination Cohorts: 
- 
Cohort 4 (FT-2102 in combination with azacitidine): approximately 20 patients 
with R/R AML/MDS that are naïve to prior hypomethylating therapy and IDH1 
inhibitor therapy. 


 
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- 
Cohort 5 (FT-2102 in combination with azacitidine): approximately 20 patients 
with R/R AML/MDS that have inadequately responded to or have progressed on 
prior hypomethylating therapy. 
- 
Cohort 6 (FT-2102 in combination with azacitidine): approximately 44 patients 
with R/R AML/MDS that have been previously treated with SA IDH1 inhibitor 
therapy as their last therapy prior to study enrollment. The actual number of 
patients in this cohort may be larger, since patients from FT-2102 SA cohorts are 
allowed to enroll in Cohort 6 after their disease progression. 
- 
Cohort 8 (FT-2102 in combination with azacitidine): approximately 28 treatment 
naïve AML patients who are candidates for azacitidine first line treatment. 
 
Note that for Cohorts 7 and 8, treatment naïve is defined as no prior treatment for 
AML.  Patients may have received a prior treatment for another hematologic 
malignancy. 
The primary analysis will occur when approximately 190 patients in Phase 2 Cohort 1 
have completed 6 months of treatment or discontinued study drug. 
 
B. Study Population 
 
The study will include patients with pathologically proven AML or intermediate risk, high 
risk or very high risk MDS as defined by the World Health Organization (WHO) criteria or 
Revised International Prognostic Scoring System (IPSS-R) harboring IDH1-R132 mutations, 
that is either relapsed or refractory to standard therapy, or for whom standard treatments are 
contraindicated.  Patients must have documented IDH1-R132 gene-mutated disease and must 
be ≥ 18 years of age.  See protocol section 4.4 Eligibility Criteria for details.  
 
C. Sample Size 
 
Phase 1 
The number of patients who will be enrolled in the dose escalation stage will depend on the 
number of DLTs observed within each dose cohort.  It is anticipated that, at a minimum, 
doses of 150 mg and 300 mg FT-2102 QD will be tested as a single agent and in combination 
with azacitidine.  If 6 patients are treated at each dose level, approximately 24 patients will 
be treated in the dose-escalation stage.  
During the Phase 1 Dose-Expansion Stage, each of the non-LDAC cohorts would have 14 
patients. With 20 patients treated (at least 6 from the dose-escalation stage, 14 from dose-
expansion) at the determined MTD/MED there is 90% power of observing adverse events 
whose true incidence rate is 11% or higher.  For the LDAC cohort, the selection of 6 patients 
is a minor variation of the traditional 3+3 design in order to identify the risk of LDAC for 
toxicities in more than 17% of patients. 
 
Phase 2 
Cohort 1 (patients with R/R AML harboring IDH1-R132 mutations): A group sequential 
design is planned for this cohort with two interim analyses and a final test.  One hundred 


 
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seventy-three (173) patients provide 90% power to test the null hypothesis that the true 
complete response rate (CR + CRh) is 15% or less versus the one-sided alternative 
hypothesis that the true complete response rate is greater than 15%, assuming a true response 
rate of 25%, with a 2.5% significance level using a one-sided exact test for a binomial 
proportion. 
Two interim analyses are planned, at approximately 33% and 67% of the information, 
respectively.  O’Brien-Fleming stopping boundaries will be used for both alpha and beta 
adjustments.  At the first interim, if  6/58 responses are observed (or crude p-value , 
the trial may be stopped early for futility.  Interim analysis 1 spends 0 alpha and 0.004 beta.  
The first interim analysis will be conducted on the full analysis set (FAS) within Phase 2 
Cohort 1.   At the first interim analysis the study is not intended to stop for efficacy. At the 
second interim analysis, if  28/115 responses are observed (or crude p-value is  0.0057), 
the trial may stop enrollment for efficacy and if there are 20 or fewer responses (or crude p-
value is > 0.2718) the trial will be stopped for futility.  Interim analysis 2 spends 0.006 alpha 
and 0.044 beta.  The second interim analysis will be conducted in the efficacy evaluable (EE) 
analysis set within Phase 2 Cohort 1.   
In the event of an early stop for efficacy, all enrolled patients would remain on treatment and 
their long-term efficacy data, such as, EFS and OS, will continue to be observed. 
If the study is not stopped early for efficacy or futility, at least 173 evaluable patients are 
planned to be enrolled. A one-sided exact test will be performed. If the one-sided p-value is ≤ 
0.0245, the null hypothesis (the response rate is ≤ 15%) will be rejected, and the alternative 
hypothesis that the response rate is > 15% will be accepted. If exactly 173 patients are 
evaluable, this is equivalent to 36 or more responses observed. 
To account for discordance between central and local testing of the IDH1-132 mutation, 
approximately 190 patients are planned to be enrolled into this cohort. 
  
Cohort 2 (patients with AML with persistent IDH1-R132 mutation + bone marrow 
demonstrating morphologic CR/CRi after prior therapy +/- HSCT): A Simon optimal two-
stage design will be used. The null hypothesis that the true 4-month RFS rate is 80% will be 
tested against a one-sided alternative. In the first stage, 11 patients will be evaluated. If 9 or 
fewer of the first 11 patients are relapse-free at 4 months, the study will be stopped. 
Otherwise, 42 additional patients will be accrued, for a total of 53 patients.  The null 
hypothesis will be rejected if 48 or more of these 53 patients are relapse-free at 4 months.  
This design yields a 1-sided type I error rate of 0.025 and power of 80% when the true 4-
month RFS rate is 94%.  
 
Cohorts 3-5 (patients with AML/MDS harboring IDH1-R132 mutations that are R/R to prior 
IDH1 inhibitor therapy; or naïve to hypomethylating and IDH1m inhibitor treatments; or R/R 
to prior hypomethylating therapy): A single-stage design with 20 patients will be used. If 4 or 
more complete responses are observed in these 20 patients, the lower bound of a one-sided 
85% confidence interval based on an exact binomial distribution will be greater than 10%, 
thus supporting the hypothesis that the true complete response rate is greater than 10%. 
 


 
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Cohort 6 (patients with AML/MDS harboring IDH1-R132 mutations that are R/R to 
immediately prior SA IDH1 inhibitor therapy): A Simon’s optimal two-stage design will be 
used.  The null hypothesis that the true complete response rate is 15% will be tested against a 
one-sided alternative.  In the first stage, 14 patients will be evaluated. If there are 2 or fewer 
complete responses in the first 14 patients, the study will be stopped. Otherwise, 30 
additional patients will be accrued for a total of 44 patients.  The null hypothesis will be 
rejected if 11 or more complete responses are observed in these 44 patients. This design 
yields a 1-sided type I error rate of 0.05 and power of 80% when the true complete response 
rate is 32%.  The probability that the trial will be stopped at the end of the first stage if the 
true complete response rate is 10% is 0.65. 
 
Cohort 7 (treatment naïve AML patients for whom standard treatments are contraindicated): 
A Simon’s optimal two-stage design will be used. The null hypothesis that the true complete 
response rate is 25% will be tested against a one-sided alternative. In the first stage, 17 
patients will be evaluated. If there are 5 or fewer complete responses in the first 17 patients, 
the study will be stopped. Otherwise, 37 additional patients will be accrued for a total of 54 
patients. The null hypothesis will be rejected if 20 or more complete responses are observed 
in these 54 patients. This design yields a 1-sided type I error rate of 0.025 and power of 80% 
when the true complete response rate is 45%. 
 
Cohort 8 (treatment naïve AML patients who are candidates for azacitidine first line 
treatment): A Simon’s optimal two-stage design will be used. The null hypothesis that the 
true complete response rate is 25% will be tested against a one-sided alternative. In the first 
stage, 7 patients will be evaluated. If there are 2 or fewer complete responses in the first 7 
patients, the study will be stopped. Otherwise, 21 additional patients will be accrued for a 
total of 28 patients. The null hypothesis will be rejected if 12 or more complete responses are 
observed in these 28 patients. This design yields a 1-sided type I error rate of 0.025 and 
power of 80% when the true complete response rate is 55%. 
 
D. Treatment Randomization 
 
No randomization is planned.  
 
E. Assessment Schedule 
 
See Appendix 1 for a detailed study Schedule of Events, including measurements and 
evaluations for the entire study period.  All planned assessments will be performed predose 
with the exception of postdose PK/PD sample collection and ECG. 
 
V. 
Interventions 
 
A. Clinical Trial Material 
 
FT-2102 
FT-2102 Capsules are initially presented as two unit strengths, 50 or 150 mg, for oral 
administration.  FT-2102 will be administered as a fixed dose. In case of BID dosing, FT-


 
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2102 should be taken every 12 hours with a minimum of 8 hours between doses. When 
administered in combination with azacitidine, with the exception of C1D1 and C2D1 (when 
PK sampling is performed), it is recommended that FT-2102 should be administered first on 
the days when both FT-2102 and azacitidine are given.  The protocol provides additional 
product details in Section 5. 
 
Following provide dose-escalation schema. 
 
 Single-Agent Dose-Escalation Schema 
1. 150 mg QD 
2. 300 mg QD 
3. 150 mg BID 
 
 Food Effect Cohort 
1. 100 mg QD 
 
 Combination Dose with Azacitidine 
1. FT-2102 150 mg QD and Azacitidine 75 mg/m2 I.V. or S.C. for 7 days per cycle 
2. FT-2102 150 mg BID and Azacitidine 75 mg/m2 I.V. or S.C. for 7 days per cycle 
 
 Combination Dose with Cytarabine 
1. FT-2102 150 mg BID and Cytarabine 20 mg BID S.C. for 10 days per cycle 
 
As of Protocol Amendment 3, FT-2102 150 mg BID as SA and in combination with 
azacitidine will be evaluated in the proposed Phase 2 cohorts.  As of Protocol Amendment 5, 
one patient was enrolled to receive Combination Dose with Cytarabine, after which the 
cohort was closed. This patient will not be summarized in tables; his data will be contained in 
listings only. 
 
VI. 
General Analytical Considerations 
 
A. Definition of Baseline 
 
Unless otherwise specified, the baseline value for each quantity being analyzed is defined as 
the last non-missing value prior to first dose of study drug.  Baseline for ECG parameter is 
defined as the average of the last three ECG measurements taken prior to first dose of study 
treatment. 
For laboratory data, if a sample was taken on C1D1 that will serve as baseline, even if time 
of sample draw or time of dosing does not allow for a definitive determination of whether it 
was drawn prior to first dose. 
 
B. Methods of Pooling Data 
 
Data from all sites will be pooled for tabular summaries.  Study center or treatment-by-center 
interactions will not be included in any statistical analysis.  For patients enrolled in Phase 1 


 
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of the study, data from multiple dose levels from the dose escalation phase will be pooled 
together.  Dose escalation and dose expansion phase data will be pooled together.  See 
Appendix 3 for the table shell headers. 
 
Phase 2 is comprised of 8 separate cohorts representing different patient populations and so 
patients enrolled in Phase 2 will be summarized by the cohort in which they are enrolled, and 
any statistical hypothesis testing will be performed within a cohort. 
 
A single patient enrolled in the Phase 1 treatment arm of FT-2102 + low-dose cytarabine 
(LDAC) before that arm was closed (removed in the most recent protocol amendment).  That 
patient’s data will not be summarized; it will be listed. 
 
C. Missing Data/ Data Imputation 
 
Unless stated otherwise, missing data will not be imputed. However, if there are dates 
missing for AEs or medications, some intermediate steps may be taken for the determination 
of being treatment emergent or not. Sections below address such procedures for the handling 
of those dates in the relevant analyses:  
 
Missing or Partial AE or Medication start or stop date: 
For missing or partial start-dates: 
1. If the onset date is unknown, then the date will not be imputed and will be 
assigned a missing value.  
2. If the month and day are unknown, then: 
a. If the year matches the year of the first dose date, then impute the month 
and day of the first dose date. 
b. Otherwise, assign as missing. 
3. If the day of the month is unknown, then: 
a. If the month and year match the month and year of the first dose date, then 
impute the day of the first dose date. 
b. Otherwise, assign as missing. 
For partial end-dates: 
1. If the year is unknown, then the date will not be imputed and will be assigned a 
missing value. 
2. If the month is unknown, then assign as missing. 
3. If the day is unknown, then assign the last day of the month. 
 
Missing Pharmacokinetic (PK) Data: 
 
Missing FT-2102 concentration data in a given profile will not be imputed. Missing 
samples will be reported as no sample ("NS") and excluded from analysis.  The affected 


 
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profile(s) will be evaluated whether sufficient FT-2102 concentrations are available to 
calculate any of the planned PK parameters. 
 
FT-2102 concentrations below the lower limit of quantitation (LLOQ) will be indicated 
by BLQ in the listings and will be treated as follows: 
 
 For predose samples prior to the FT-2102 administration: Concentrations that are 
BLQ or missing will be assigned a numerical value of zero for the calculation of 
AUC. Any anomalous concentration values observed at predose will be included in 
the computation of AUC. If the predose concentration is greater than 5% of Cmax, 
the data will be evaluated on a case-by-case basis to determine if exclusion of the 
affected profile is warranted.   
 
For all other BLQ concentrations: Any other BLQ concentrations will be assigned a 
value of zero if they precede quantifiable samples in the initial portion of the 
concentration-time profile. A BLQ value that occurs between quantifiable data 
points, especially prior to Cmax, will be evaluated to determine if an assigned 
concentration of zero makes sense, or if exclusion of the data is warranted. 
Following Cmax, BLQ values embedded between 2 quantifiable data points will be 
treated as missing when calculating AUC. If BLQ values occur at the end of the 
collection interval (after the last quantifiable concentration), these will be set to 
zero. If consecutive BLQ concentrations are followed by quantifiable 
concentrations in the terminal portion of the concentration curve, these quantified 
values will be excluded from the PK analysis by setting them to missing, unless 
otherwise warranted by the concentration-time profile. 
 
Missing Pharmacodynamic (PD) Data: 
 
Missing 2-HG concentration data will not be imputed. Missing samples will be reported 
as no sample ("NS") and excluded from analysis. 
 
Blast in Hematology and Bone Marrow Blast %: 
 
The CRF captures hematologic blast % data in 2 fields: a numeric percentage and a text 
field, as some pathology reports note absent or infrequent blasts, but do not quantify the 
result.  If the numerical blast % is missing but the text field says “absent,” or inferior to 
1%, 0 will be imputed for blast %.  If the blast % is missing but the text field contains any 
of the following words: isolated, scattered, few, rare, occasional, not enumerated, no 
value, no total, present, less than 1%, some, then 1% blasts will be imputed.  Bone 
marrow results of “less than 5%” will be imputed as 4.9%.   
 


 
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Hematology Differentials: 
 
If the absolute values for the hematology differentials are missing but results are present 
in percentages, the absolute value result may be imputed as follows: 
Absolute basophils = White blood cells* basophils % 
This approach will be taken for all hematology differential parameters. 
 
Missing Quality of Life (QOL) Data: 
 
The imputation will be done according to methodology proposed by Diehr et al. (2007). 
Data will be imputed for missing assessments of Phase 2 patients and will be performed 
separately for each of five dimensions and VAS score of the EQ-5D-5L. VAS and each 
of the dimensions is represented by QOL in the imputation algorithm below. The five 
domains of EQ-5D-5L responses are ordered categories ranging from “no problems” to 
“extreme problems.”  Answers will be converted to a 5-point scale in which 1=no 
problems and 5= extreme problems. The VAS score of EQ-5D-5L ranges from 0 (worst 
health) to 100 (best health). 
 
 Compute QOL-transformed (QOLt): 
QOL score will be transformed to the probability that a person will have good QOL 
next cycle (have domain QOL ≤ 3 next cycle; or have VAS QOL ≥ 80), estimated 
from his QOL this cycle. All transition pairs (two values of QOL for the same person 
1 cycle apart) will be used in the longitudinal data, and the transformation parameters 
will be estimated from a logistic regression of a binary variable “Good QOL 1 cycle 
later” on “QOL now.” In the longitudinal data for each patient a column with one 
space for every cycle of that patient's potential follow-up will be created. 
The regression model will be as follows: 
 
logit (Good QOL 1 cycle later) = a + b*QOL now. 
 
The estimated probability of having good QOL 1 cycle later as a function of current QOL 
is then: 
QOLt = Prob(Good QOL 1 cycle later | QOL) = exp(a+b*QOL)/(1+exp(a+b*QOL)). 
 
 Compute QOL transformed with deaths added (QOLtd): 
Set the values of QOLt for the cycles after a patient died to zero. For cycles after death, 
patients should receive a zero because they have no probability of having good QOL one 
cycle later. 
 
 Compute QOLtd imputed (QOLtdi): 
QOL for cycles when patients were alive but had no QOL data will be imputed from the 
regression of QOLtd on the logarithm of time from death (or time from the analysis date 
if still alive). 
 
1) Calculation of time variable Cycle before death/end of follow-up (CBD):  
CBD = Cycle before death = cycle minus the integer part of (#days survived/28) + 1. 


 
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or 
CBD = Cycle before end of follow-up = cycle minus the integer part of (#days on 
study/28) + 1 
 
Unobserved cycles (e.g. due to missed visit, or time between last observed cycle and 
death when subject was alive but did not provide data) before deaths or end of follow-
up will be imputed. 
 
2) Time variable CBD will be transformed to log form (LCBD) as below: 
 
LCBD=log( absolute value of CBD + 1) 
 
3) A mixed model will be used to predict QOLtdi. The dependent variable is QOLtd; 
the mixed model will contain random intercept and slope subject effect, and fixed 
time effect (LCBD). QOLtdi will be predicted at imputed cycles.  
 
 Compute QOLtdi re-transformed to the original scale (QOLback): 
This should be done by inverting the logistic regression equation. 
 
QOLback = (logit(QOLt) - a)/b = [ln ((QOLt)/(1-QOLt)) - a]/b. 
 
 Round imputed values up to the nearest whole number.  
 
Note that no numerical values will be given after death, but “999” flags will be included 
to indicate cycles when patient was dead. 
 
D. Multiple Study Centers 
 
No stratification by the study centers will be utilized for analyses of efficacy or safety data. 
 
E. Covariate Adjustment in Primary Analysis 
 
Not planned for the primary analysis. 
 
F. Sample Size Reassessment 
 
No sample size reassessment is planned. 
 
G. Interim Analyses  
 
Interim analyses will be performed for the Phase 2 Cohort 1 and in other applicable Phase 2 
cohorts that use two-stage designs, at defined timepoints, as outlined in section IV.C. 
 Phase 2 Cohort 1: two interim analyses with 33% and 67% of patients’ information 
respectively  
 Phase 2 Cohort 2: with first 11 patients evaluable for response  
 Phase 2 Cohort 6: with first 14 patients evaluable for response 
 Phase 2 Cohort 7: with first 17 patients evaluable for response 


 
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 Phase 2 Cohort 8: with first 7 patients evaluable for response 
As a result of these analyses, enrollment in a given cohort may be stopped early for futility, 
or in Cohort 1 for efficacy as well.  Interim analyses that meet stopping criteria for futility are 
binding. 
 
H. Multiple Comparisons 
 
Alpha is controlled for the primary analysis within each Phase 2 cohorts.  Corrections for 
multiple comparisons are not applied for the secondary or exploratory endpoints, as they are 
descriptive analyses. 
 
I. Analysis Sets  
 
Seven analysis sets are defined for use in various analyses.  The following table illustrates the 
relationship between each analysis set and the analyses. Within an analysis set, the summary 
table will summarize data within cohorts, as described in Appendix 3.  Due to the large 
number of cohorts in this study (there are eight Phase 2 cohorts), individual cohorts do not 
have their own analysis set; the result for a hypothesis being tested on a single cohort is 
found in the summary table for the applicable analysis set, within the table column that 
describes patients in the applicable cohort.   
 
 Analysis Set 
Analysis 
Patient 
Characteristics 
Patient 
Disposition 
Efficacy 
Safety 
PK 
PD 
DLT 
Evaluation 
DLT Evaluable Set 
 
 
 
 
 
 
X 
Safety Analysis Set 
 
X 
 
X 
 
 
 
Efficacy Evaluable 
Analysis Set 
X 
 
X 
 
 
 
 
Full Analysis Set 
X 
X 
X 
 
 
 
 
Per Protocol 
Analysis Set 
 
 
X 
 
 
 
 
PK Analysis Set 
 
 
 
 
X 
 
 
PD Analysis Set 
 
 
 
 
 
X 
  
 
1. DLT Evaluable Set 
 
All Phase 1 patients who enrolled in the dose escalation cohorts and who have received at 
least one dose of FT-2102 and completed at least 75% of doses in the first cycle during the 
DLT evaluation period or have discontinued / interrupted due to adverse events meeting the 
DLT evaluation criteria.  This set will be used for DLT analyses only, unless otherwise 
specified. 
 
2. Safety Analysis Set 
 
All patients who have received at least one dose of study drug (FT-2102, azacitidine, or 
cytarabine).  All safety analyses will be based on the Safety analysis set unless otherwise 
specified.  Patients will be analyzed under the first dose level received by the patient. 
 


 
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3. Full Analysis Set (FAS)  
 
All patients who were enrolled in the study and have received at least one dose of FT-2102. 
This analysis set will be used for efficacy analyses and baseline characteristics. Patients will 
be analyzed under the assigned dose. 
 
4. Efficacy Evaluable (EE) Analysis Set  
 
All patients in Phase 2, Cohort 1 with confirmed IDH1-R132 (by central lab) who have 
received the first dose of FT-2102 180 days or more prior to the analysis cutoff date. These 
patients will be included in the analysis set regardless of duration of treatment. This analysis 
set is the primary analysis set for Phase 2, Cohort 1 efficacy evaluation and early stopping 
decisions. Patients will be analyzed by assigned dose.  Patients who received first dose of 
FT-2102 less than 180 days prior to the analysis cut off date will not be included in the EE 
Set, even if they have response assessments recorded.  Patients who do not have any response 
data will be considered to be non-responders if they received the first dose of FT-2102 180 
days or more before the analysis cut off date.  Analyses based on the EE analysis set will not 
be produced for the final CSR. 
 
5. Per Protocol (PP) Analysis Set 
A subset of patients in the EE analysis set, excluding patients who have protocol violations 
that could impact the evaluation of the efficacy of FT-2102.  Some violations that would 
result in exclusion from the PP analysis set are: not meeting all inclusion/ exclusion criteria 
for a particular cohort, having received chemotherapy not per protocol, received starting dose 
of FT-2102 other than 150 mg BID, not having at least one post-baseline response 
assessment.  The full list of protocol violations will be reviewed on a de-identified basis by 
the medical, data management, and statistical leads prior to locking the database, and 
membership in the PP analysis set will be documented and determined based on that review.  
Analyses based on the PP analysis set will not be produced for the final CSR. 
 
6. PK Analysis Set 
 
All patients for whom it is possible to calculate at least one primary PK parameter (e.g. Cmax, 
AUClast and AUCinf) and who do not have any major protocol deviations thought to influence 
the absorption, distribution, metabolism and excretion of the FT-2102.  
PK parameters for patients who discontinue after a single dose of study drug may be presented 
in the listings but will not be used for summary statistics or any statistical analysis. Data may 
be excluded from PK analysis (concentrations listed only) if any of the following criteria are 
fulfilled: 
 concomitant medication which could render the plasma concentration-time profile 
unreliable  
 Patient vomits within 2 x the reported median Tmax for the study drug. 
Any data excluded will be discussed in the CSR.  
 


 
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7. PD Analysis Set 
 
All patients who have received at least one dose of FT-2102 and have completed at least one 
PD assessment. The PD analysis set will be used for PK/PD-related analyses unless 
otherwise specified. 
 
J. Subgroup Analyses 
 
Data from subgroups of patients in the defined analysis sets will be summarized. The 
subgroups that may be analyzed include but are not limited to the following:   
 
Subgroup Name 
Levels 
Additional Details, if applicable 
Diagnosis 
AML or MDS 
 
AML Type 
Primary AML vs. Secondary AML 
Applies only to AML patients 
Disease State 
Relapsed/Refractory vs.  treatment 
naïve 
 
AML Cytogenetic Risk 
Classification 
intermediate risk, poor, favorable 
risk, unknown/missing risk 
Applies only to AML patients.  Exclude patients 
with unknown or missing risk classification 
IDH1 Mutation Type 
R132C, R132H, and  
[R132L, G, or S] 
If central lab result is available, that should be used.  
Otherwise, mutation type may be taken from CRF. 
IDH1 Mutation 
Confirmed by Central Lab 
yes, no 
 
Age Group 
< 65, 65 - < 75, ≥ 75 years 
 
Sex 
male, female 
 
Region 
North America, EU, Asia Pacific 
 
Race 
White vs. other 
 
Baseline ECOG 
Performance Score 
Grade 0/1, 2 
 
Number of Prior 
Regimens 
1, 2, ≥ 3 
Prior number of regimens 
Prior HSCT for AML 
yes, no 
 
Prior Hypomethylating 
Agents 
yes, no 
Prior treatment with hypomethylating agents.   This 
will be defined by whether the patient has 
azacitidine, decitabine, or guandecitabine listed on 
their prior therapies list. 
Prior IDH1 Therapy 
yes, no 
This includes prior treatment with FT-2102 (if 
enrolling from one cohort to another), or treatment 
with ivosidenib.  The subgroup is applicable for 
Phase 2 Cohort 3 patients; and for phase 2 Cohort 6 
patients who will be allowed to roll over from 
Cohort 1 after progressive disease. 
Prior FT-2102 Treatment 
yes, no 
This subgroup is applicable for Phase 2 Cohort 3 
patients, whose prior IDH1 inhibitor therapy may 
have included FT-2102; and for Phase 2 Cohort 6 
patients, who will be allowed to roll over from 
Cohort 1 after progressive disease. 
Renal Function 
normal, mildly impaired, moderately 
impaired, severely impaired 
Categories of renal function are determined based 
on baseline creatinine clearance as follows: normal 
(≥ 90 mL/min), mildly impaired (60 to 89 mL/min), 
moderately impaired (30 to 59 mL/min), and 
severely impaired (15 to 29 mL/min). 
 
Baseline creatinine clearance is calculated as: 


 
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Subgroup Name 
Levels 
Additional Details, if applicable 
(140 − age) * baseline weight (kg) * (0.85 if 
female) /  
(72 * baseline serum creatinine [mg/dL]) 
  
K. Data Display Characteristics 
 
Data displays produced for this study will include three types—summary tables, data listings, 
and figures.  Unless stated otherwise, data listings will be produced for all recorded data as 
well as derived variables.  Summary tables will be produced as specified in following 
sections.  Figures will be produced when specified in sections to follow. 
Listings will be ordered by phase, treatment (dose and schedule), cohort, patient number, and 
nominal visit.  When expedient, additional levels of ordering hierarchy may reflect subsets of 
assessments within patient. Data listings will not display patient initials. 
Tables will be organized differently based on the purpose of the data analysis being 
performed: interim safety analyses or formal interim analysis or final analysis.  Data 
snapshots taken for the purpose of safety analysis (regulatory reporting, IB update, etc.) will 
be organized as outlined in Appendix 3. Table generation for interim futility and efficacy 
analyses as well as final analyses will be organized as specified in Appendix 3. 
The summary statistics displayed will be a function of the type of data associated with the 
summarized assessment.  Unless stated otherwise in relevant sections to follow, continuous 
data will be summarized with the number of non-missing values, mean, standard deviation, 
minimum, median, and maximum.  Categorical data will be summarized with the number of 
non-missing values and the numbers of values equal to each of the possible values.  
Percentages of patients with each of the possible values will be calculated from the number 
of patients in the corresponding analysis set, unless stated otherwise.  Some continuous 
variables may also be grouped into categorical levels and evaluated in frequency tables. 
 
L. Blinded Review of Data 
 
Not applicable for this study, as it is open label. 
 
VII. Baseline Patient Characteristics and Disposition 
 
A. Disposition 
 
The number of patients enrolled will be summarized, as will the number and percentage of 
patients in each analysis set.  The reason for discontinuation of treatment will be 
summarized, as will treatment status (ongoing or off-study treatment).  The number and 
percentage of patients who have discontinued from study participation will also be 
summarized.  Percentages of patients who discontinued for each of these reasons will be 
calculated using the Safety analysis set in the relevant cohort group for the denominator. 
Disposition will be listed for all subjects in the Safety analysis set. 
 
B. Demographics   
 


 
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Data collected about the following patient characteristics will be summarized in tables for the 
FAS, EE analysis set, and PP analysis set, and listed for all patients in the FAS: 
 Age at time of consent 
 Age category (18 -< 40, 40 -< 65, 65 -< 75, 75 -< 85, ≥85 years) 
 Sex at Birth (Male, Female) 
 Race (American Indian or Alaskan Native, Asian, Black or African American, Native 
Hawaiian or Other Pacific Islander, White, Other, Not Reported) 
 Ethnicity: Hispanic or Latino origin (Yes, No, Not Reported) 
 Height (cm) at baseline 
 Weight (kg) at baseline 
 BMI at baseline 
BMI will be calculated as:  
BMI (kg/m2) = weight / (height/100)2 
 
C. Disease History 
Data collected about the following patient characteristics will be summarized in tables for 
both the FAS (both phases) and the EE analysis set.   
Data will be listed for all patients in the FAS. 
 
AML disease histories (including time from diagnosis to study participation in weeks, 
AML Type (primary de novo, secondary, transformed MDS, therapy-related, and 
other), AML disease state (treatment naive, relapsed, refractory), time since relapse 
(≤12 months or >12 months), and AML WHO Classification). 
 
MDS disease histories (including time from diagnosis to study participation in weeks, 
MDS risk category, MDS WHO Classification, disease state (treatment naive, relapsed/ 
refractory)). 
 
A manual review by Sponsor clinical staff will classify AML patients who are not treatment 
naïve into the following categories based on their prior therapies: primary refractory, 
untreated relapse, refractory relapse. 
 Primary refractory: patients that enter the study who are refractory to the initial 
induction treatment. 
 Untreated relapse: patients that enter the study who have relapsed after the most 
recent prior line of therapy 
 Refractory relapse: patients that enter the study who have relapsed to a prior line of 
therapy and then became refractory to an attempt of salvage therapy. 
 
Disease history will be summarized separately for AML and MDS patients.  The 
denominator for percentages will be the number of patients with that disease (AML or MDS).   


 
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Time from diagnosis in months will be calculated by subtracting the diagnosis date from the 
informed consent date, and dividing the number of days by 30.4375, and rounding to one 
decimal place. 
The total number of prior regimens received (based on the prior therapies CRF) will be 
summarized both by descriptive statistics (mean, standard deviation, median, minimum, 
maximum) and categorically (number of regimens received: 1, 2, 3, or 4 or more).  The site 
enters regimen number into the CRF (i.e., a single regimen may be comprised of one or more 
drugs).  The maximum regimen number for each patient will be used for tabular 
summarization of total number of prior regimens. 
The number of patients who have received various types of treatment regimens (induction, 
re-induction, consolidation, salvage, maintenance, autologous HSCT, allogenic HSCT, 
transplant-DLI, and conditioning) will be tabulated.  This information is taken from the prior 
therapies CRF. 
 
D. Cytogenetics and Molecular Genetics 
The following information collected about genetic mutations will be summarized for the FAS 
(both phases) and for the EE analysis set.  The cytogenetics summary will also be produced 
by subgroup for the following subgroups: disease state (relapsed/refractory vs. treatment 
naive) for Phase 1 patients only. 
Data will be listed for all patients in the FAS.   The following data will be summarized 
separately for AML and MDS patients.  The denominator for percentages of patients having 
a certain mutation will be the number of patients with that disease (AML or MDS). 
 
 Cytogenetic risk classification per CRF 
 Cytogenetics per CRF 
 Result of central test of IDH1 mutation 
 IDH1 mutation type at baseline per CRF 
 IDH1 mutation type at baseline per companion diagnostic 
 Total number of co-mutations at baseline per CRF 
 Incidence of co-mutations at baseline per CRF 
 
E. Baseline Disease Characteristics 
The following baseline disease characteristics will be summarized for the FAS for Phase 1 
and 2, and for the EE analysis set.  Baseline disease characteristics summaries will also be 
produced by subgroup for the following subgroups for FAS: diagnosis (AML vs. MDS) for 
all patients; and disease state (relapsed/refractory vs. treatment naive) for Phase 1 patients 
only. 
 ECOG performance status at baseline 
 Baseline bone marrow blasts (%): bone marrow aspirate will be used as the primary 
source. If no aspirate assessment is available, biopsy assessment will be used as default  
 Baseline peripheral blood blasts (%) 


 
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 Categorical description of baseline values of the following laboratory parameters, as well 
as descriptive statistics summarizing WBC, ANC, hemoglobin, and platelets:  
 
- 
white blood cells (WBC) (< 15 × 109/L, 15 to < 30 × 109/L, ≥ 30 × 109/L),  
- 
absolute neutrophil count (ANC) (< 0.5 × 109/L, 0.5 to < 1 × 109/L, ≥ 1.0 × 109/L), 
- 
hemoglobin (< 80 g/L, ≥ 80 g/L),  
- 
platelet count (<50 × 109/L, ≥ 50 × 109/L),  
- 
creatinine clearance (< 15 mL/min, 15 to 29 mL/min, 30 to 59 mL/min, 60 to 89 
mL/min, ≥ 90 mL/min) 
 
F. Medical and Surgical History 
Medical and surgical history will be summarized on the FAS for Phase 1 and 2. 
Medical histories will be coded via MedDRA version 19.1 and summarized by SOC and PT.  
Medical history will be summarized in a separate table from surgical history.  Surgical 
history will be summarized by surgical category, as indicated by the investigator. Data will 
also be presented in a listing for the FAS. 
 
G. Prior Anti-Cancer Therapies 
Prior anti-cancer therapies will be summarized on the FAS for Phase 1 and 2, and for the EE 
analysis set for Phase 2.  Prior anti-cancer therapy summaries will also be produced by 
subgroup for the following subgroup for FAS: diagnosis (AML vs. MDS). 
Prior anti-cancer therapies will be summarized by ATC class and medication name, which 
will be coded via WHODrug (September 2016 version).  Prior anti-AML/MDS therapies will 
also be presented in a listing for the FAS. 
 
H. Protocol Deviations 
Protocol deviations will be summarized as major or minor deviations and by deviation 
criteria for the Safety analysis set.  Protocol deviations will be listed for the FAS, including 
description and date of deviation. No CRF will be utilized to collect the protocol deviations. 
They will be provided by clinical operations team prior to database lock.  Protocol deviations 
which have occurred due to COVID-19 will be summarized. 
 
 
VIII. Safety Analyses 
 
Safety data will be summarized and listed for the Safety analysis set, unless otherwise 
specified.   
 
A. Exposure 
 
Exposure to the study drug FT-2102 will be characterized via the following parameters: 


 
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• 
Treatment duration in days calculated as (date of last dose of study drug – date of first 
dose of study drug + 1)   
• 
Total dose taken (mg).  Total dose taken will only be calculated for Phase 2 patients, as 
data in phase 1 were not collected in a manner that allows calculation of total dose.  
• 
The number of cycles of treatment patients received will also be summarized. For phase 
1 patients, a patient will be considered to have had a cycle of treatment if they have had 
one or more doses in a given cycle. For phase 2 patients, the number of cycles of 
treatment received will be calculated as treatment duration in days divided by 28.  This 
number will then be rounded up to a whole number. 
• 
Number and percentage of patients experiencing dose increases, dose reductions, dose 
interruptions, drug withdrawals, and reasons for dose modifications or dose 
interruptions. 
• 
Treatment compliance will be calculated as a percentage (total dose taken divided by 
total dose prescribed x 100) for Phase 2 patients only 
 
Drug administration data will be presented in data listings including dose modifications and 
dose interruptions as well as reasons for modifications and interruptions. 
Exposure to azacitidine will be summarized as the number of cycles having received 
azacitidine and the duration of azacitidine dosing.  Exposure to cytarabine will be presented 
in data listing only.  
 
B. Adverse Events 
 
Adverse Events (AEs) will be summarized and recorded from the time of first dose through 
28 days after the last dose of study drug, and serious adverse events from the time of 
informed consent to 28 days after the last dose of study drug.  AEs will be coded using the 
MedDRA dictionary version 19.1, with verbatim terms coded by System Organ Class (SOC) 
and Preferred Term (PT) and graded via the CTCAE version 4.03.  Sponsor coding 
conventions will be applied during the creation of analysis datasets.  Therefore, the raw 
dataset may reflect a different preferred term than the ADAE data set. 
A treatment-emergent AE (TEAE) is an AE that emerges after the first dose of study drug 
through 28 days post last dose, having been absent pretreatment, that occurred on or after the 
first dose of study treatment or within 28 days after the last dose, or occurred prior to the first 
dose and increased in grade during study treatment. If an AE has partial onset date, the 
imputed onset date as specified in Section VI.C will be used to define TEAE. 
The causality of an AE includes related or unrelated. A treatment-related AE is defined as an 
AE considered “Possibly Related”, “Probably Related”, or “Definitely Related” to the study 
drug by the investigator. Missing relationship will be treated as unknown and excluded from 
summary of treatment-related AEs considered to be related; events reported as “Definitely 
Not Related”, “Probably Not Related”, or “Unlikely” will be considered not related. 
If the AE start or stop date is still missing after implementing the rules specified in Section 
VI.C, the following strategy will be used to determine whether AEs with missing start or stop 
dates are pre-treatment or treatment-emergent: 


 
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1. If the start date and stop date are both missing, the most conservative approach is 
taken, and the AE is considered to be treatment-emergent. 
2. If the start date is missing but the stop date is not missing and is after the day of study 
dose administration, then the most conservative approach is taken, and the AE is 
considered to be treatment-emergent. 
3. If the start date is missing but the stop date is not missing and is on or before the day 
of study dose and after the date of signed informed consent, then the AE is considered 
to be pre-treatment (not TEAE). 
 
The following AE summaries will be produced for both Phase 1 and 2: 
 Overall Summary of AEs. This will include the total number of AEs, the total number of 
TEAEs, the total number of treatment-related TEAEs, and the number of patients with: at 
least one TEAE, at least one treatment-related TEAE, at least one Grade 3 or higher 
TEAE, at least one Grade 4 or higher TEAE, at least one treatment-related Grade 3 or 
higher TEAE, at least one treatment-related Grade 4 or higher TEAE, at least one 
treatment emergent serious adverse event (TESAE), at least one related TESAE,  at least 
one TEAE that led to study drug discontinuation, at least one TEAE that led to dose 
modification, and TEAE leading to death. 
 Summary of TEAEs by system organ class and preferred term, or by preferred term. For 
each event term, the numbers and percentages of patients experiencing an AE with that 
term will be summarized. If a patient reports the occurrence of a particular adverse event 
more than once, the event is only counted once.   
 Summary of TEAEs by system organ class, preferred term, and grade: if a patient has 
multiple AEs the most severe/ related one will be utilized for the summary.  This 
summary will be presented for a limited subset of patients – total Phase 1 single agent 
FT-2102 patients; total Phase 1 combination therapy patients; total Phase 2 single agent 
Cohort 1 patients; total Phase 2 single agent patients overall; and total Phase 2 
combination therapy patients.  A similar summary of TEAEs will be produced by 
preferred term and grade. 
Summaries by system organ class and preferred term will be sorted alphabetically by system 
organ class, and alphabetically by preferred term within system organ class.  Summaries by 
preferred term will be sorted in descending frequency per the Overall column for the table. 
 
The table below indicates the types of summaries that will be provided for various sets of 
TEAEs: 
TEAE Set 
By SOC and 
PT 
By SOC, PT, and 
Grade 
By PT 
By PT and Grade 
TEAEs 
X 
X 
X 
X 
Treatment-related TEAEs 
X 
 
X 
 
TEAEs of G3 or G4 
X 
 
X 
 
Treatment-related TEAEs of G3 
or G4 
X 
 
X 
 


 
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TEAE Set 
By SOC and 
PT 
By SOC, PT, and 
Grade 
By PT 
By PT and Grade 
TESAEs 
X 
 
 
 
Treatment-related TESAEs 
X 
 
 
 
TEAEs leading to withdrawal 
from study drug 
X 
 
 
 
Treatment-related TEAEs leading 
to withdrawal from study drug 
X 
 
 
 
TEAEs leading to dose 
modification 
X 
 
 
 
Treatment-related TEAEs leading 
to dose modification 
X 
 
 
 
TEAEs leading to death 
X 
 
 
 
Treatment-related TEAEs leading 
to death 
X 
 
 
 
TEAE of Special Interest  
X 
 
 
 
 
All AEs occurring on study (treatment emergent or not) will be provided in patient data 
listings.  The following additional by-patient listings of AEs (treatment emergent or not) will 
be provided: all SAEs, all AEs leading to withdrawal of study drug, all AEs leading to dose 
modification, and all AEs leading to death. 
In addition, a listing of all deaths with related information regarding the death will be 
provided, including AEs leading to death, as well as deaths that are not reported as due to an 
adverse event.   
A summary of DLTs by system organ class and preferred term, and a listing of all AEs that 
caused a DLT, will be provided for the DLT evaluable set.  
Adverse Events of Special Interest (AESI): Hepatotoxic and Gallbladder disorder 
Some patients taking FT-2102 have experienced transaminase elevations.  As such,  
summary tables of AEs for hepatotoxicand gallbladder disorders will be created, with 
tabulations of the number of patients experiencing such events by SOC and PT.  Under each 
PT within each grouping, the time to onset will be summarized descriptively, and time to 
resolution will be summarized using Kaplan-Meier (KM) methods. 
In addition, overall summary table for TEAEs for each AESI group will be created. It will 
include the number of patients with TEAEs, treatment-related TEAEs, grade 3 or 4 TEAEs, 
treatment related grade 3 or 4 TEAEs, serious TEAEs, treatment related serious, TEAEs 
resulting in FT-2102 discontinuation, treatment related TEAEs resulting in FT-2102 
discontinuation; TEAEs leading to dose reduction, TEAEs leading to dose hold, treatment 
related TEAEs leading to dose hold, TEAEs resulting in on-treatment death, treatment related 
TEAEs resulting in death. 
All TEAEs in each group occurring on study will be provided in corresponding patient data 
listings. 


 
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The table below presents preferred terms in each subgroup: 
 
Hepatotoxicity Grouping  
Gallbladder disorder Grouping 
Alanine aminotransferase increased 
Aspartate aminotransferase increased 
Hepatic enzyme increased 
Hypertransaminasemia  
Liver function test abnormal  
Liver function test increased  
Transaminases increased 
Hepatitis acute 
Blood alkaline phosphatase increased 
Hyperbilirubinemia 
Blood bilirubin increased 
Biliary tract disorder 
Biliary colic  
Cholangitis 
Cholestasis 
 
 
AESI: Differentiation Syndrome 
Differentiation syndrome (DS) is a risk of drugs in this class.  While many of the symptoms 
of differentiation syndrome are non-specific and best judged by the treating clinician, in the 
spirit of the article by Montesinos et al. (2009), and using methodology outlined by 
Norsworthy et al. (2020), candidate cases of DS will be summarized.  This analysis will be 
conducted for IA2 only, and not for the final study reporting. 
The number of patients with an investigator reported AE of DS will be summarized.   
In addition, candidate cases of DS will be summarized based on AE data and also leukocyte 
count results from the laboratory data set.  AE preferred terms will be summarized into 
categories representing possible symptoms of DS as per the table below, and tabulated by the 
number of patients experiencing an AE in the category in the first 90 days and 180 days post 
first dose. 
Candidate DS AESI 
Symptom Category 
AE Preferred Terms 
Dyspnoea 
Acute respiratory distress syndrome 
Acute respiratory failure 
Cardiopulmonary failure 
Cardio-respiratory distress 
Cough 
Dyspnoea 
Dyspnoea exertional 
Dyspnoea at rest 
Orthopnea  
Productive cough 
Respiratory distress 


 
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Pulmonary infiltrates or 
Pleuropericardial effusion 
 
Acute interstitial pneumonitis 
Acute lung injury 
Acute pulmonary oedema 
Acute respiratory distress syndrome 
Atypical pneumonia 
Bilateral pulmonary infiltrates 
Generalized oedema 
Interstitial pneumonitis 
Localized oedema 
Lower respiratory tract infection 
Lower respiratory tract inflammation 
Lung disorder 
Lung infection 
Lung infiltration 
Non-cardiogenic pulmonary oedema 
Pericardial effusion 
Pleural effusion 
Pneumonia 
Pneumonitis 
Pneumonitis NOS 
Pulmonary infiltration NOS 
Pulmonary congestion 
Pulmonary oedema 
Pulmonary toxicity 
 
 
Kidney injury 
 
Acute kidney injury 
Anuria 
Blood creatinine abnormal 
Blood creatinine increased 
Cardiorenal syndrome 
Hepatorenal failure 
Prerenal failure 
Renal failure 
Renal failure acute 
Renal function test abnormal 
Renal impairment 
Renal injury 
Creatinine value >26.52 µmol/L or >1.5x baseline value in the lab dataset 
Hypotension 
Hypotension 
Orthostatic hypotension 
Blood pressure decreased 
Blood pressure systolic low 
Blood pressure diastolic decreased 
Any systolic blood pressure in vital signs data set < 90 mmHg 
Fever 
Pyrexia 
Febrile bone marrow aplasia 
Febrile neutropenia 
Temperature in vital signs data set ≥ 38.3˚ C 
Weight gain 
Capillary leak syndrome 
Fluid overload 


 
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Fluid retention 
Generalized oedema 
Hydraemia 
Hypervolaemia 
Oedema 
Oedema peripheral 
Weight increased 
Weight (any value > 5 kg from baseline from vital signs data) 
 
 
 
Candidate cases of DS will be identified based on patients having: any 2 or more AESI 
categories from the table above occurring concomitantly.  Concomitant is defined for AESIs 
as AE start dates within 7 days of each other.  Two or more AESI can comprise a DS 
episode.  Repeat DS episodes are separated by > 14 days between the start dates of the 
AESIs.   
The number of patients with candidate cases who have concomitant leukocytosis will be 
summarized.  Concomitant leukocytosis is defined as having AE PT of “Leukocytosis,” 
“Hyperleukocytosis,” or “White blood cell count increased,” or having laboratory results 
showing leukocyte count > 10 G/L within 7 days before or after AESI. 
Candidate cases will be reviewed by an adjudication committee (details are contained within 
a separate DS Adjudication Committee charter).  Committee members will review the patient 
cases and adjudicate which cases are DS, and the number of episodes of DS that each patient 
experienced.  The number and percentage of patients who have a committee-adjudicated case 
of DS will be tabulated. 
Of the cases adjudicated as having DS, the following summaries will be presented: 
 The number of patients with multiple episodes of DS will be tabulated.   
 The number of patients with concomitant leukocytosis will be tabulated. 
 The number of patients experiencing severe and moderate DS will be tabulated.  If a 
patient has a reported AE of differentiation syndrome, the severity will be assessed 
via CTCAE grade, with severe being grade 3/4/5, and moderate being grade 2.  If 
they did not have an investigator-reported AE of differentiation syndrome, then 
severe is defined as experiencing more than 3 DS AESI categories concomitantly, and 
moderate is defined as experiencing 2 or 3 DS AESI concomitantly as per Montesinos 
(2009).  These will be tabulated within the first 90 days post first dose, and the first 
180 days post first dose. 
 The number and percentage of patients reporting at least one DS AESI will be 
summarized by those occurring during the first 90 and 180 and days post first dose.   
 The median time to onset of the DS episode (the first DS AESI for adjudicated cases) 
will be calculated, along with the 1st and 3rd quartiles of time to onset and the range.   
 The number and percentage of patients who also had a best overall response of CR or 
CRh will be tabulated 
 


 
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A listing will be created to identify patients with DS AESI, presenting all criteria that 
qualified them for candidate DS. 
 
C. Clinical Laboratory Results 
 
Laboratory test results (including hematology, coagulation, serum chemistry, and urinalysis) 
and abnormal laboratory values will be presented in data listings.  The test results will be 
presented in SI units.  Patients enrolled in Phase 1 of the study use standard laboratory 
reference ranges to determine normal ranges for CTCAE grades.  The standard ranges used 
are: 
- 
New England Journal of Medicine October 2004 
- 
Oxford Handbook of Clinical Haematology 
- 
Mercy North Hospital Laboratory 
Patients enrolled in the Phase 2 portion of the study will have local laboratory normal ranges 
used for CTCAE grading.  If local ranges cannot be obtained, then the standard ranges will 
be applied.   
Hematology differentials will be summarized in absolute values, not percent.  If missing, 
absolute values of hematology differentials will be imputed using percentages as described in 
Section VI.C.  Listings will present percent differentials if reported, and will also present 
derived absolute values, which will be identified as derived. 
Summaries of actual values and changes from baseline will be presented by cohort for each 
assessment time point, beginning with the screening visit.   
Shift tables summarizing the counts and percentages of patients’ baseline CTCAE grade vs. 
their highest CTCAE grade on study will also be displayed for hematology and, serum 
chemistry, and coagulation.   
Summaries of laboratory data by nominal visit will not present unscheduled visits.  However, 
shift tables will include data from unscheduled visits in consideration of the worst value on 
study. No summaries will be presented when fewer than five patients’ data are available at an 
assessment time point. 
Evaluation of liver function tests 
A shift table for liver function tests will be produced as described above, presenting shift 
from baseline to worst post-baseline and shift from baseline to each planned visit. Parameters 
included in this shift table will be ALT, AST, alkaline phosphatase, total bilirubin, and direct 
bilirubin. 
Scatter plots presenting the maximum ALT by the concomitant total bilirubin, and the 
maximum AST by the concomitant total bilirubin for each patient on study (i.e., eDISH 
plots) will be produced.  Results without concomitant bilirubin cannot be presented in eDISH 
plots, so the maximum value of visits which have both ALT and bilirubin (or AST and 
bilirubin) should be presented. 
A separate summary of liver function test abnormalities will be produced, based on the 
FDA’s guidance for industry on drug induced liver injury (June 2009), in addition to the 


 
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summaries described above.  The number and percentage of patients experiencing the 
following abnormalities will be summarized. 
 
Flag # 
Clinical Laboratory 
Parameter 
Category  
1 
ALT 
>3 × ULN; >5 × ULN; >10 × ULN; >20 × ULN; 
2 
AST 
>3 × ULN; >5 × ULN; >10 × ULN; >20 × ULN 
3 
AST or ALT 
>3 × ULN; >5 × ULN; >10 × ULN; >20 × ULN 
4 
Total Bilirubin (TBL) 
>1.5 × ULN; ≥2 × ULN 
5 
ALP  
>2.5 × ULN; >5 x ULN 
6 
Concurrent AST, ALT and Total 
Bilirubin  
(ALT or AST >3 x ULN) and (TBL >1.5 x ULN);  
(ALT or AST >3 x ULN) and (TBL >2 x ULN); 
7 
Concurrent AST, ALT, Total 
Bilirubin, without ALP 
abnormality 
(AST or ALT >3 × ULN) and (TBL >1.5 × ULN) and ALP <2 x ULN;  
(AST or ALT >3 × ULN) and (TBL >2 × ULN) and ALP <2 x ULN; 
8 
ALT>3x ULN or AST>3x ULN 
with concurrent report of 
selected TEAEs during study* 
(ALT >3x ULN) or (AST >3x ULN) and with TEAEs* starting +/- 7 
days of the lab sample 
*Selected TEAEs include nausea, vomiting, anorexia, abdominal pain, abdominal discomfort, fatigue, jaundice, 
pruritus, chromaturia, and faeces discoloured.  
The flags in the table above are only applied for post-baseline values.  For flag #6, if ALT or 
AST is elevated > 3x ULN, all total bilirubin results within 7 days of the result should be 
considered.  If Flag #6 is applied and ALP is <2x ULN for all samples drawn within +/- 7 
days of the AST, ALT, bilirubin sample, then Flag #7 will be applied.  Flag #8 requires the 
adverse event start date to occur within +/- 7 days of an AST/ ALT value exceeding 3x ULN. 
 
D.  Vital Signs 
 
Descriptive statistics of actual value and change from baseline value in vital signs (including 
temperature, pulse, respiration rate, systolic blood pressure, diastolic blood pressure, and 
weight) will be presented by cohort group for each nominal visit and time point.  However, 
no summaries will be presented when fewer than five patients’ data are available at an 
assessment time point. Summaries by nominal visit will not present unscheduled visits. A 
vital signs listing will also be provided.  
 
E. Electrocardiogram (ECG) 
 
QTcF and QTcB are calculated automatically in the EDC system using the following 
formulae: 
QTcF = 
𝑄𝑇
𝑅𝑅1/3 
QTcB = 
𝑄𝑇
𝑅𝑅1/2 
Descriptive statistics of actual value and change from baseline value in ECG parameters 
(including PR, RR, QRS, QT, QTcB, and QTcF) will be listed by cohort group and time 


 
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point.  In addition, the summary will include descriptive statistics for the maximum post-
baseline value and the minimum post-baseline value.  Summaries of data for nominal time 
points will not include unscheduled visits; summaries of maximum and minimum post-
baseline value will include unscheduled visits. The average of the triplicate ECGs at a 
nominal time point will be used for analysis; values will be rounded to the nearest whole 
number before assigning to reporting categories. If the triplicate ECGs are not available, the 
average of ECGs will be calculated using one or two ECGs measured at the same visit. No 
summaries will be presented when fewer than five patients’ data are available at an 
assessment time point. 
In addition, the number and percentage of patient experiencing the following parameters will 
be tabulated and summarized:  
 Change (increase) from baseline in QTcF at any time during study 
o >30 to ≤60 msec 
o  >60 msec 
 Reaching a value in QTcF at any time during study 
o    ≤450 msec 
o    >450 to ≤480 msec 
o    >480 to ≤500 msec 
o    >500 msec 
A shift table summarizing the counts and percentages of patients’ baseline QTcF events vs. 
their maximum post-baseline event will also be presented. 
A subset of approximately 30 patients will be consented to 24-hour Holter ECG monitoring 
for the purposes of the exposure-response modeling the effect of drug exposure on QTcF 
interval.  This model-based analysis will be described in a separate, stand-alone SAP. 
A data listing of all ECG values will also be provided, which will list the triplicate values 
obtained for each timepoint, as well as the derived mean value for each nominal time point. 
 
F. Physical Examination and Pregnancy Test 
 
Physical examination findings and data for pregnancy test will be listed in a patient data 
listing, but not summarized. The records of abnormal findings prior to or after the first dose 
of study drug from physical exam will be captured in the medical history CRF and adverse 
events CRF, respectively.  
 
G. Concomitant Medications 
 
Medications will be coded using the WHO Drug Dictionary version of September 2016, with 
verbatim terms coded by Anatomical Therapeutic Chemical (ATC) classification and 
Preferred Term (PT). 


 
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To determine whether a medication is a prior or concomitant medication, the imputed non-
missing stop date of the medication is used. If this date is on or after the start of first dosing 
date of study drug, the medication will be defined as concomitant medication; otherwise it 
will be classified as prior medication. 
If the medication stop date is missing, imputation rules specified for AE stop date will be 
applied. If the medication date is still missing after implementing the rules, the most 
conservative approach is taken, and the medication is considered to be concomitant. 
The concomitant medications will be summarized by ATC classification and PT. For each 
medication term, the numbers and percentages of patients experiencing a medication with 
that term. If a patient reports the occurrence of a particular medication more than once, the 
medication is only counted once.  These will be summarized for the Safety analysis set. 
Concomitant medication is defined as any medication with a start date prior to the date of the 
first dose of study treatment and continuing after the first dose of study treatment or with a 
start date between the dates of the first and last dose of study treatment.  Any medication 
with a start date after the date of the last dose of study treatment will not be considered a 
concomitant medication. 
A data listing of prior and concomitant medications will be provided. 
 
H. ECOG Performance Status 
  
ECOG Performance Status by visit will be summarized in a shift table for the Safety analysis 
set.  The summary will also include shift to worst post-baseline value.  Shifts to nominal time 
points will not include unscheduled visits; the shift to worst post-baseline value will include 
unscheduled visits. All ECOG scores will be presented in a data listing. 
 
IX. 
Pharmacokinetic Analyses 
 
Pharmacokinetic analysis will be performed in patients in the PK analysis set, and data will 
be listed for all patients in the Safety analysis set. Protocol Section 6.4 provides the PK 
sample collection time points. 
 
Pharmacokinetic concentration data will be listed by patient including actual sampling times 
relative to dosing. Plasma concentrations will be summarized by phase, treatment (dose, 
schedule, single agent or combination therapy), cohort, and nominal visit. The following 
descriptive statistics will be presented at each nominal time point: n, arithmetic mean, standard 
deviation, coefficient of variation (CV%), geometric mean, geometric standard deviation, 
geometric CV%, median, minimum and maximum values.   
 
 


 
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X. 
Pharmacodynamic Analyses 
 
Pharmacodynamic analysis will be performed in Phase 1 patients in the PD analysis set, and 
listed for patients in the Safety analysis set. See Protocol Section 6.5 for the PD assessment 
time points.  
 
Concentration of 2-HG (including absolute change from baseline and/or percentage change 
from baseline) will be listed by patient and will be summarized by phase, treatment (dose, 
schedule, single agent or combination therapy), cohort, and nominal visit. The following 
descriptive statistics will be presented at each nominal time point: n, arithmetic mean, standard 
deviation, coefficient of variation (CV%), geometric mean, geometric standard deviation, 
geometric CV%, median, minimum and maximum values.   
Geometric mean 2-HG concentration versus time profiles and/or geometric mean change from 
baseline versus time for each cohort will be presented graphically on a linear-linear and/or log-
linear scale (as appropriate).  
 
XI. 
Efficacy Analyses  
 
Efficacy endpoints will be listed for all patients in the FAS, unless otherwise specified. 
Hematologic parameters evaluated for efficacy will be included in the laboratory listings, and 
listed for the Safety analysis set.  
 
A. Efficacy Endpoints 
 
Response assessments will be performed through evaluation of clinical findings and bone 
marrow/peripheral blood cell counts and morphology. Response criteria are derived from the 
International Working Group (IWG) response criteria for AML (Cheson et al. 2003) and 
MDS (Cheson et al. 2006) where applicable, and Stein et al. 2017, as outlined in the protocol 
section 4.3, Appendix 6 and Appendix 7.  
 
Bone marrow for response assessment is required: 
 at C2D1 if no peripheral blasts; otherwise, at C3D1, regardless of peripheral blast 
count;  
 at least every 2 cycles (4 to 8 weeks) until morphologic complete remission (CR) is 
achieved, then up to every 3 cycles (for duration of response assessment) for 12 
months after CR achievement, then up to every 6 cycles thereafter; 
 when progressive disease is suspected; 
 for Phase 2 Cohort 2 only: at C2D1, C4D1, C6D1 and every 6 cycles thereafter. 
Response assessment requirements and frequency are the same for all subjects, including 
those that discontinue treatment due to hematopoietic stem cell transplant (HSCT). 
 
In general, HSCT is not considered an event in time to event analyses.  Patients who stop 
treatment with FT-2102 to have HSCT will continue to be monitored for duration of 


 
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response.  HSCT is not considered an anti-leukemia therapy for purposes of analyses 
described herein. 
 
In general, for the purposes of statistical analyses, relapse, progressive disease (PD), or 
disease progression will be treated interchangeably as being indicative of disease worsening.   
 
AML Response: Following responses for AML will be evaluated by investigator based on 
the modified Cheson criteria (Cheson et al. 2003).  Best overall response for each patient is 
selected based on the highest category achieved on study from the ordered list in the table 
below: 
Investigator Assessment of AML Response 
CR/CRh 
Complete 
Response 
Overall 
Response 
Molecular CR (CRm) 
√ 
√ 
√ 
Cytogenetic CR (CRc) 
√ 
√ 
√ 
Complete Remission (CR) 
√ 
√ 
√ 
CR with Partial Hematologic Recovery (CRh) 
√ 
 
√ 
CR with incomplete recovery (CRi) 
 
 
√ 
Morphologic leukemia-free state (MLFS) 
 
 
√ 
Partial Remission (PR) 
 
 
√ 
Clinical Benefit 
 
 
 
Stable Disease 
 
 
 
Resistant Disease 
 
 
 
Relapse 
 
 
 
Progressive Disease (PD) 
 
 
 
Not Evaluable 
 
 
 
Not Done 
 
 
 
 
MDS Response:  Response for MDS will be evaluated by investigator based on the response 
criteria adapted from IWG Response Criteria for MDS (Cheson et al. 2006).  Appendix 7 of 
the protocol provides details. 
Investigator Assessment of MDS Response 
Complete 
Response 
Overall 
Response 
Complete Remission (CR) 
√ 
√ 
Marrow CR 
 
√ 
Partial Remission (PR)  
 
√ 
Clinical Benefit 
 
 
Stable Disease 
 
 
Disease Progression (PD) 
 
 
Not Evaluable 
 
 
Not Done 
 
 
 
CR/CRh rate: The primary efficacy endpoint for AML patients is the CR/CRh rate.  It is 
defined as the proportion of patients who achieve CRm, CRc, CR or CRh, as outlined in the 


 
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table for investigator assessment of AML response above.  This rate is not calculated for 
MDS patients.  
Complete response rate (CRR): For AML patients, CRR is defined as the proportion of 
patients who achieve CRm, CRc, or CR at any time while on study.  For MDS patients it is 
defined as the proportion of patients who achieve CR.  
Overall response rate (ORR):  For AML patients, ORR is defined as the proportion of 
patients who achieve Molecular CR (CRm), Cytogenetic CR (CRc), Complete Remission 
(CR), CR with Partial Hematologic Recovery (CRh), CR with incomplete recovery (CRi), 
Morphologic leukemia-free state (MLFS), or Partial Remission (PR).  For MDS patients it is 
defined as the proportion of patients who achieve Complete Remission (CR), Marrow CR, or 
Partial Remission (PR). 
 
Best overall response (BOR): BOR is the best response achieved by the patient up to 3 weeks 
post last dose of study drug or until the introduction of new anticancer therapy, whichever is 
earlier.  
 
Time to CR/CRh (TTCR/CRh):  TTCR/CRh is the time in months between the first dose of 
study drug and documentation of the CR/CRh for patients who achieve a CR/CRh.  This 
analysis will be performed only on patients who have achieved CR/CRh as a best overall 
response.  Kaplan Meier analyses will not be performed; summary will be descriptive.   
 
Time to complete response (TTCR):  TTCR is the time in months between the first dose of 
study drug and documentation of the CR for patients who achieve a CR.  This analysis will 
be performed only on patients who have achieved CR as a best overall response.  Kaplan 
Meier analyses will not be performed; summary will be descriptive.   
 
Time to response (TTR):  TTR is the time in months between the first dose of study drug and 
documentation of the first overall response for patients who achieve a PR or better.  This 
analysis will be performed only on patients who have achieved PR or better as a best overall 
response.  Kaplan Meier analyses will not be performed; summary will be descriptive.  This 
analysis will not be performed on Phase 2 Cohort 2, as it is not applicable since patients enter 
the study already in response. 
 
Duration of CR/CRh (DCR/CRh): DCR/CRh is the time in months between documentation 
of the first CR or CRh until the date of relapse or death, whichever is earlier. Patients will be 
censored as per Table 1.  DCR/CRh will only be calculated for patients who achieve a CR or 
CRh as the best response.       
 
Duration of complete remission (DCR): DCR is the time in months between documentation 
of the first CR until the date of relapse or death, whichever is earlier. Patients will be 
censored as per Table 1.  DCR will only be calculated for patients who achieve a CR as the 
best response.   
 
Duration of overall response (DOR): Duration of overall response will be calculated 
similarly to DCR but will assess the time in months between documentation of the first 
response of PR or better until the date of relapse, death, whichever is earlier. Patients will be 


 
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censored as per Table 1.  This analysis will not be performed on Phase 2 Cohort 2, as it is not 
applicable since patients enter the study already in response. 
 
Patients who respond and stop FT-2102 to undergo HSCT will continue to be followed until 
relapse. Duration of response endpoints (DRC/CRh, DCR, DOR) for these patients will 
encompass time between HSCT and relapse ordeath. For patients with no report of relapse by 
the end of the follow-up data collection, duration of response (DCR/CRh, DCR, DOR) will 
be censored as per Table 1.  
 
A separate sensitivity analysis will be conducted for duration of response of Phase 2, Cohort 
1 patients, which analyzes duration of response as described above, but for those patients 
who have enrolled under Phase 2 Cohort 2 due to MRD positivity, the duration of response 
will be the total duration of response experienced in Cohort 1 and Cohort 2 together. 
 
An additional sensitivity analysis will be performed on DCR/CRh, DCR, and DOR in which 
HSCT will be handled as the end of response. 
 
Since this study was ongoing during the COVID-19 pandemic, a sensitivity analysis will be 
performed on OS, DCR, DCR/CRh, and DOR in which patients who have died due to 
COVID-19 will be censored to assess the effect that COVID-19 had on time to event 
endpoints. 
 
4-Month Relapse-Free Survival (RFS) Rate: The primary endpoint for Phase 2 Cohort 2 
AML patients is the 4-Month RFS rate. This will be evaluated by a Simon 2-Stage design 
described in Section IV.C, testing the null hypothesis that the 4-month RFS rate is < 80%. It 
is defined as the proportion of patients in Phase 2 Cohort 2 who have not relapsed or died on 
or before their 4-month response evaluation. If a patient does not receive a disease response 
assessment at their 4-month visit but has a subsequent disease response assessment on or 
after study day 120 that shows non-progression/ non-relapse, they will be evaluated as 
having achieved 4-month RFS.  This rate is not calculated for MDS patients, or for AML 
patients in any other cohort. 
 
Relapse-Free Survival (RFS): RFS will be calculated for all patients in Phase 2 Cohort 2, 
who are patients who have achieved a response of CRi or better. It is the time in months 
between the date of first dose until relapse, start of other (non-protocol study drug) new 
antileukemia therapy, or death from any cause, whichever occurs first. Hematopoietic stem 
cell transplant (HSCT) is not considered an event for RFS. For a patient who is responding 
and experiences none of these events before the end of study follow up, RFS will be 
censored as per Table 1. The percentage of patients with RFS will be estimated at landmark 
timepoints. 
 
Event-free survival (EFS): EFS is defined as the time in months between first dose of study 
drug and disease progression, relapse, death from any cause, treatment failure, or start of 
other (non-protocol study drug) new antileukemia therapy, whichever occurs first.  HSCT is 
not an event for EFS, and patients experiencing HSCT will continue to be followed until an 
event occurs.  For EFS, treatment failure will be operationally defined as not achieving a best 


 
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overall response of CR, CRh, or CRi on study.  The date of treatment failure for patients with 
this event will be the date of the last response assessment while on study. 
 
For a patient with none of these events before the end of study follow-up, EFS will be 
censored as per Table 1. For patients lost to follow-up prior to any evidence of event, the 
EFS data will be censored at their last completed assessment date that is SD or better prior to 
the initiation of anti-cancer therapy. 
 
Overall survival (OS): OS is defined as the time in months from the first dose of study drug 
until death from any cause. For patients who are not known to have died by the end of study 
follow-up, OS will be censored on the date the patient was last known to be alive.  
  
Transfusion independence (TI): Patients will be classified as “dependent” or “independent” 
at baseline within each category of platelets, pRBC, any (i.e., receiving either platelets or 
pRBC or both) and both (i.e., receiving both platelets and pRBC) if they received a 
transfusion within 8 weeks prior to the first dose of FT-2102.  TI will be defined as patients 
who experience at least a 28-day or 56-day period during any point on treatment with no 
transfusion of that type required.  For the “both” category, patients who are classified as 
dependent must have received both a platelet and pRBC transfusion within the 8 weeks prior 
to baseline, and to be classified post baseline as independent, they must experience a 28 or 56 
day minimum duration on study where they did not require a transfusion of either platelets or 
pRBC.   
 
 
B. Efficacy Analysis 
 
Any response assessment occurring after the start of alternate anti-cancer therapy will not be 
included in the analyses using response assessments.   
 
Note that some patients who were assigned to single agent therapy in Phase 1 requested to 
start combination therapy with azacitidine when a response was not observed on single agent 
treatment.  In such cases, upon beginning dosing with azacitidine (if the patient was assigned 
to single agent therapy), then response assessments occurring after the first dose of 
azacitidine will not be included in efficacy analyses.  Time to event analyses for such 
instances will be treated as if the patient has experienced disease progression when 
azacitidine is initiated. 
 
The overall survival and event-free survival analyses will be based on patients in the FAS.  
All other efficacy analyses will be based on patients in the EE analysis set as the primary 
analysis, with selected analyses on the FAS and PP analysis set as supportive.  The following 
table indicates the analysis sets to be analyzed for each endpoint. 
 
 


 
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Endpoint 
Patients Analyzed 
Analysis Set 
EE* 
FAS 
PP* 
CR/CRh Rate, 
DCR/CRh, TTCR/CRh AML only 
x 
x 
x 
CRR, DCR, TTCR 
Each disease group separately 
x 
x 
x 
ORR, DOR, TTR 
Each disease group separately 
x 
x 
x 
Best overall Response 
Each disease group separately 
x 
x 
x 
4-month RFS Rate 
Phase 2 Cohort 2 only 
x 
RFS 
Phase 2 Cohort 2 only 
x 
EFS, OS 
All patients combined 
x 
TI 
All patients combined 
x 
x 
*EE and PP analyses will only be performed for IA2. 
 
CR/CRh rate will be analyzed for all cohorts except Phase 2 Cohort 2.  For Phase 2 Cohort 1, 
to test the hypothesis that the CR/CRh rate is greater than 15%, a 1-sided exact test for a 
binomial proportion will be performed.  If the exact one-sided p-value is less than 0.0245, the 
alternative hypothesis will be accepted.  This is equivalent to at least 36 CR/CRh responses 
of 173 EE patients. 
For Phase 2, Cohorts 3, 4, and 5 test the hypothesis that the 85% confidence interval for the 
CR/CRh rate does not include 10%. If there are 5 or more CR/CRh responses of the 20 
patients in these cohorts, the 85% confidence interval will be greater than 10%, and the 
alternative hypothesis that the response rate is greater than 10% will be accepted. 
Phase 2 Cohorts 6, 7, and 8 are Simon 2-Stage designs and the primary efficacy endpoint will 
be evaluated via the number of CR/CRh responses stipulated in the design criteria described 
in Section IV.C.  
The number and proportion of patients achieving CR/CRh response will be reported by 
cohort from the binomial proportion, along with Clopper-Pearson 95% confidence interval 
for AML and MDS patients respectively.  Appendix 2 provides the SAS code.  
For Phase 2 Cohort 1, a sensitivity analysis will be performed on the CR/CRh rate in which 
Atkinson and Brown confidence intervals will be calculated. 
4-Month RFS, BOR, ORR, TI: The proportional endpoints listed here will be summarized as 
the number and percentage of patients within each category, and will be presented by cohort 
along with Clopper-Pearson 95% confidence intervals. The 4-month RFS endpoint will be 
analyzed for Phase 2 Cohort 2 only. 
 
RFS, EFS, OS, TTCR/CRh, TTCR, TTR, DCR/CRh, DCR, DOR: Time to event endpoints 
listed here will be expressed as the number of months from first dose to the event and will be 
analyzed using Kaplan-Meier (KM) methods for each cohort, with the exception of TTCR/ 
CRh, TTCR, and TTR, since these analyses are performed only on the subset of responders 
and censoring is unnecessary. The analysis will include median, 1st and 3rd quartiles for time 
calculated using Kaplan-Meier methods, and the 95% confidence interval for the median 


 
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calculated using the Brookmeyer-Crowley method. The estimated probability of survival 
over time for RFS, EFS, OS, DCR/CRh, DCR, and DOR will be plotted as KM curves for 
Phase 2 Cohort 1, with the exception of RFS, which will be performed for Phase 2 Cohort 2 
only. Appendix 2 provides the SAS code.   
 
The survival probability and 95% confidence interval will be estimated at selected landmark 
timepoints of: 3 months, 6 months, 12 months, and 24 months based on Kaplan-Meier 
product-limit method and Greenwood’s formula. A month will be calculated as time in days 
divided by 30.4375.  
 
Table 1. Censoring Rules 
Case 
Censoring Rule 
Patient has no post baseline assessments 
and no date of death recorded 
Censor at date of first dose 
Patient did not die or experience PD or 
relapse* 
Censor at date of last adequate response 
assessment (any response assessment that is 
not "Not Evaluable" or "Not Done") 
Patient in Phase 1 started on single agent 
therapy, but switched to combination 
therapy 
Censor at date of last adequate response 
assessment prior to the combination therapy 
*For patients who discontinue FT-2102 treatment to receive HSCT and remain on study to be followed until 
documented disease relapse, confirmation of relapse is not required in this situation, and a single occurrence of 
relapse will be considered as documented “confirmed” relapse in analyses of response. 
 
The following sensitivity analyses of DCR/CRh will be performed with censoring rule 
variations in EE patients: 
1. Patients who undergo HSCT will be censored at the last adequate assessment prior to 
HSCT 
2. Patients who discontinued study treatment due to undocumented progression will be 
considered as events at the date of last dose 
3. Patients with subsequent anti-cancer therapies prior to an event date will be 
considered to be censored the day before the start of the anti-cancer therapy.   
4. Patients with subsequent anti-cancer therapies prior to an event date will be 
considered as having an event as the start of the anti-cancer therapy.   
5. Patients who didn’t have an event and are still on treatment will be censored at the 
last treatment date, otherwise will be censored at the last response assessment. 
 
For DOR and DCR HSCT sensitivity analysis will be performed, where patients who 
undergo HSCT will be censored at the last adequate assessment prior to HSCT. 
The following subgroup analyses will be performed: 
 CR/CRh rate, ORR, DCR/CRh – For AML patients in the EE analysis set: AML type 
(primary or secondary), disease state (relapsed/refractory or treatment naive), AML 
cytogenetic risk classification, IDH1 mutation type, IDH1 mutation confirmed by 


 
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Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan 
Page 46 of 58  
central lab, age group, sex, region, race, baseline ECOG PS, prior HSCT for AML, 
prior HMA, prior IDH1 therapy, and prior FT-2102 therapy.   
 OS, EFS – For AML patients in the FAS analysis set: AML type (primary or 
secondary), disease state (relapsed/refractory or treatment naive), AML cytogenetic 
risk classification, IDH1 mutation type, IDH1 mutation confirmed by central lab, age 
group, sex, region, race, baseline ECOG PS, prior HSCT for AML, prior HMA, prior 
IDH1 therapy, and prior FT-2102 therapy. 
Kaplan Meier plots will not be produced for subgroup analyses. 
 
Transfusion Independence 
Transfusion independence will be analyzed as part of the clinical benefit expected from FT-
2102.  The percentage of patients who are transfusion dependent at baseline will be 
summarized (overall and by type of blood product of RBC and/or platelets).  The proportion 
of patients who became transfusion independent during any 28-day and 56-day period during 
treatment will be summarized by best overall response on study.  Percentages will be based 
on the number of patients within the best overall response category.   
 
Swim Lane Plot of Time on Treatment and Duration of Response 
A swim lane plot will be created for patients in the FAS population to visualize the time on 
treatment with FT-2102.  Time of first response and time of HSCT will be annotated on the 
plot.  The length of the bar will represent the time (in weeks) on study, including both time 
on active treatment of FT-2102 and time in follow-up.  The bar will be one color during 
active treatment, and then patients who stop treatment but are still being followed for 
continuing response will have the bar turn a different color.  Patients who are still ongoing 
(either on treatment with or without response, or off treatment but being actively followed for 
response) will be indicated with arrows at the end of the bar.  Best overall response will be 
annotated at the end of the bar. 
A repeat of the swim lane plot will be done where there is no color coding by on/off 
treatment status.  Rather, the bar will change color if/ when 28 days of transfusion 
independence is achieved.  The length of the bar will represent the time (in weeks) on 
treatment.  Best overall response will be annotated at the end of the bar. 
 
Forest Plot 
At IA2, A forest plot will be created for Phase 2 cohort 1 patients in the EE analysis set to 
present the CR/CRh rate compared across all of the relevant subgroups specified in the 
section VI.J; the subgroups not applicable to this cohort and excluded from the forest plot are 
diagnosis, disease state, prior IDH-1 therapy, prior FT-2102 treatment, and renal function. 
The plot will show the point estimate of each rate with 95% CI.   
 
A similar plot will be created to present ORR for Phase 2 cohort 1 patients in the EE analysis 
set. 
 
Hematologic Efficacy Analyses  
Hematologic efficacy analyses will be performed for IA2 only. 


 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
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Document Title: Statistical Analysis Plan 
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The absolute and percent change in marrow blasts from baseline will be tabulated by visit 
and maximum post baseline decrease. This table summarizes blasts from either the bone 
marrow biopsy or bone marrow aspirate form together.  At each nominal visit, if there is both 
a bone marrow biopsy result and a bone marrow aspirate result reported, the aspirate result 
will be used.  Blast results of “less than 5%” will be imputed as 4.9%.  No summaries will be 
presented when fewer than five patients’ data are available at an assessment time point. 
A waterfall plot will be created for Phase 2 cohort 1 patients in the EE analysis set to present 
the maximum % decrease in blast % experienced on study.   
Line plots showing the mean (+/- SE) bone marrow blasts, ANC count, hematocrit, platelet 
count will be presented over time on Day 1 for cycles 1-15 for patients in the Phase 2 Cohort 
1 FAS and EE analysis set by best response (CR/CRh, non-CR/CRh responders, and non-
responders).   
 
Efficacy Profiles  
For IA2, For those patients who have a best overall response of PR or better, patient plots of 
ANC, platelet count, hemoglobin, and bone marrow blasts (analyzed as described above) will 
be produced for all patients in the Phase 2 Cohort 1 FAS and for patients in the Phase 1 FAS 
whose starting dose of FT-2102 was 150 mg BID. 
 
C. Quality of Life Analysis 
The EQ-5D-5L consists of five dimensions: mobility, self-care, usual activities, pain/ 
discomfort, and anxiety/depression.  Each dimension has 5 levels of health state: no 
problems, slight problems, moderate problems, severe problems and extreme problems.  The 
patient indicates his/her health state by selecting the most appropriate statement in each of 
the five dimensions. This decision results in a 1-digit number that expresses the level selected 
for that dimension.  The digits for the five dimensions can be combined into a 5-digit number 
that describes the patient’s health state.  Present overall state of health is also to be rated on a 
vertical visual analogue scale (VAS) from 0 (worst health) to 100 (best health). This 
assessment was only performed on Phase 2 patients. EQ-5D-5L data will be summarized 
from the screening visit through cycle 8 for the FAS (Phase 2) and EE analysis sets (Phase 
2).   
Five domains of EQ-5D-5L  
The number and percentage of patients reporting each score per dimension will be 
summarized, as well as the number reporting some problems on that dimension (score >1).  
Also, the change from baseline in the number reporting some problems in each dimension 
will be reported (raw and percent change).  An additional summary table will be produced 
that summarizes the EQ-5D-5L data by best response (3 groups: CR/ CRh, Other 
Responders, Non-Responders).   Missing data will be imputed as described in Section VI.C. 
A stacked bar chart will be produced to illustrate the domain values.  In the chart, the x axis 
will represent nominal visit (screening, cycle 2, cycle 3, etc.) and the y axis will represent 
percentage.  Each bar will add to 100% and be color coded to represent the percent of 
patients reporting each level (1-5) of problems within the dimension for that visit.  A separate 
chart will be created for each of the dimensions.  This figure will only be created for the 


 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan 
Page 48 of 58  
Phase 2, Cohort 1, EE analysis set.  The figure will also be produced by best overall 
response, as described above for the summary table. 
VAS score of EQ-5D-5L 
The VAS score of overall state of health will be summarized by descriptive statistics (mean, 
standard deviation, median, Q1, Q3, minimum, maximum) by visit, as well as the number 
and percentage of patients reporting bad overall state of health (score < 80). An additional 
summary table will be produced to summarize change from baseline to first response for CR/ 
CRh and Other Responders, or change from baseline to best score for non-responders, by 
descriptive statistics by best response (3 groups: CR/ CRh, Other Responders, Non-
Responders). Missing data will be imputed as described in Section VI.C. 
All EQ-5D-5L data will be listed.  In the listing, imputed data will be flagged. 
 
 


 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
DCN # 1372 
Document Title: Statistical Analysis Plan 
Page 49 of 58  
 
XII. References 
Atkinson EN and Brown BW. Confidence limits for probability of response in 
multistage phase II clinical trials. Biometrics 1985; 41 (3): 741-744. 
 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. 
Biometrics 1982; 38:29-41. 
 
Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the 
International Working Group for Diagnosis, Standardization of Response Criteria, 
Treatment Outcomes, and Reporting Standards of Therapeutic Trials in Acute 
Myeloid Leukemia. J Clin Oncol. 2003; 21:4642-4649. 
 
Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for 
modification of the International Working Group (IWG) response criteria in 
myelodysplasia.  Blood 2006; 108: 419-425. 
 
Diehr, P., Lafferty, W.E., Patrick, D.L. et al. Quality of life at the end of life. Health 
Qual Life Outcomes 2007; 5, 51. https://doi.org/10.1186/1477-7525-5-51  
 
Fan, B, Chen Y, Wang F, et al. Pharmacokinetic/pharmacodynamics evaluation of 
AG-120, a potent inhibitor of the IDH1 mutant protein, in a phase 1 study of IDH-
1mutant advanced hematologic malignancies. 20th Congress of the European 
Hematology Association 2015, Abstract P572. 
 
Food and Drug Administration. Guidance for Industry Drug-Induced Liver Injury: 
Premarketing Clinical Evaluation. July 2009. Available at 
https://www.fda.gov/downloads/guidances/UCM174090.pdf 
 
ICH-E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic 
Potential for Non-Antiarrhythmic Drugs, October 2005. 
 
Mardis, E, Ding L, Dooling D, et.al. Recurring mutations found by sequencing an 
acute myeloid leukemia genome. N Engl J Med. 2009; 361:1058-1066. 
 
Montesinos P, Bergua JM, Vellenga E, et al. Differentiation syndrome in patients 
with acute promyelocytic leukemia treated with all-trans retinoic acid and 
anthracycline chemotherapy: characteristics, outcome, and prognostic factors.  Blood 
2008; 113 (4): 775-783. 
 
Norsworthy KJ, Mulkey F, Scott EC, Ward AF, Przepiorka D, Charlab R, Dorff S, 
Deisseroth AB, Kazandjian D, Sridhara R, Beaver JA, Farrell AT, De Claro RA, 
Pazdur R.  Differentiation syndrome with ivosidenib and enasidenib treatment in 
patients with relapsed or refractory IDH-mutated AML: a U.S. Food and Drug 
Administration systematic analysis. Clin Cancer Res. 2020; 26 (16): 4280-4288.  
 


 
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Rohle D, Popovici-Muller J, Palaskas N, et al. An inhibitor of mutant IDH1 delays 
growth and promotes differentiation of glioma cells. Science. 2013; 340 (6132):626-
630. 
 
Savona MR, Malcovati L, Komrokji R, et al. An international consortium proposal of 
uniform response criteria for myelodysplastic/myeloproliferative neoplasms 
(MDS/MPN) in adults. Blood. 2015; 125(12):1857-1865. 
 
Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant-IDH2 relapsed or 
refractory acute myeloid leukemia. Blood. 2017 130:722-731.   
 
 
 


 
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Appendix 1   Schedule of Events 
Study Procedures 
Pre-
screening 
(Optional) 
Screening 
(D -14 to 
D1) 
Cycle 1 
Cycle 2 
Cycle 3 
and 
Beyond 
End of 
Treatmenta 
28-day 
Follow-
upb 
Survival 
Follow-
up 
Days 
D1 
D2 
D5 
± 
1D 
D8 
± 
1D 
D12 
± 
2D 
D15 
± 
2D 
D19 
± 
2D 
D22 
± 
2D 
D26 
± 
2D 
D1 
± 
2D 
D2 
± 
2D 
D4 
± 
2D 
D8 
± 
2D 
D15 
± 
2D 
D22 
± 
2D 
D1 
± 
3D 
± 7D 
+ 7D 
q 3 mo 
Signed Informed 
Consentc 
 
Xc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete Medical 
Historyd 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
Medications 
 
X 
X 
Xe 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
 
Height and Weightf 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
 
 
Vital Signsg 
 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
X 
X 
 
 
ECOG PS 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
 
 
Physical 
Examination 
 
X 
X 
 
 
Xh 
 
Xh 
 
Xh 
 
Xh 
 
 
 
Xh 
 
Xh 
X 
 
 
Serum or Urine 
Pregnancy Testi 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
 
 
12-lead 
Electrocardiogramj 
 
X 
Xj 
 
 
Xj 
 
Xj 
 
Xj 
 
X 
 
 
 
Xj 
 
X 
X 
 
 
Holter Monitoring 
(Phase 2 only) k 
 
 
X 
X 
 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
Clinical Serum 
Chemistriesl, m 
 
X 
X 
 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
 
 
Xn 
X 
Xn 
X 
X 
 
 
CBC with 
Differential and 
Platelet Countm, o 
 
X 
X 
 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
 
 
Xn 
X 
Xn 
X 
X 
 
 
Coagulation 
Parametersp 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Bone Marrow 
Aspirateq 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
 
 
Urinalysism, r 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
 
 
Adverse Event 
Monitoring 
 
Continuous 
X 
 
Pharmacokinetics 
(Peripheral Blood)s 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Xt 
X 
X 
 
X 
 
X 
 
 
 


 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
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Document Title: Statistical Analysis Plan 
Page 52 of 58 
Study Procedures 
Pre-
screening 
(Optional) 
Screening 
(D -14 to 
D1) 
Cycle 1 
Cycle 2 
Cycle 3 
and 
Beyond 
End of 
Treatmenta 
28-day 
Follow-
upb 
Survival 
Follow-
up 
Days 
D1 
D2 
D5 
± 
1D 
D8 
± 
1D 
D12 
± 
2D 
D15 
± 
2D 
D19 
± 
2D 
D22 
± 
2D 
D26 
± 
2D 
D1 
± 
2D 
D2 
± 
2D 
D4 
± 
2D 
D8 
± 
2D 
D15 
± 
2D 
D22 
± 
2D 
D1 
± 
3D 
± 7D 
+ 7D 
q 3 mo 
Pharmacodynamics 
(Peripheral Blood)u 
Xv 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
 
X 
 
 
 
EQ-5D-5L (Phase 2 
only) 
 
Xw 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
 
 
Study Drug Diaryx 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
Study Drug 
Administrationy,z,aa 
 
 
Drug will be given in accordance with the dosing schedules for FT-2102, azacitidine and LDAC 
 
 
 
Survivalbb 
 
 
 
 
 
X 
 
ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; C1D1 = Cycle 1 Day 1; 
C2D1 = Cycle 2 Day 1; Ca = calcium; CBC = complete blood count; Cl = chloride; ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group 
performance status; FSH = follicle‑stimulating hormone; K = potassium; LDAC = low dose cytarabine; LDH = lactate dehydrogenase; LH = luteinizing hormone; MDS = 
myelodysplastic syndrome; Mg = magnesium; Na = sodium; PD = pharmacodynamic; PK = pharmacokinetic; PT = prothrombin time; PTT = partial thromboplastin time. 
NOTE: All assessments will be conducted predose unless specified otherwise.  
a 
End of Treatment visit to be conducted within 7 days of the decision to discontinue treatment. End of Treatment assessments need not be repeated if they 
were completed within the previous 2 weeks (4 weeks for bone marrow assessments). 
b 
28-day Follow-up visit to be conducted within 28 days (+ 7 days) of last dose for adverse event follow-up and to capture initiation of new therapies (con-
medications). 
c 
Informed consent must be completed prior to the initiation of any study-specific procedures or assessments. The informed consent process may be completed 
prior to the Screening Period (i.e., before Day -14) (see Section 6.1.2 of protocol). 
d 
Includes complete surgical and cardiac history and complete leukemia or MDS medical history. Complete leukemia or  MDS medical history will include 
applicable treatment history as well as cytogenetic risk categorization at diagnosis by NCCN or ELN guideline. 
e 
Only required in patients enrolled in Phase 1 and patients in Phase 2 participating in Holter monitoring. 
f 
Height at Screening only. 
g 
Includes temperature, blood pressure, pulse rate, and respiratory rate. Prior to dosing on Days 1, 8, 15, and 22 (Cycle 1); Cycle 2 predose on Days 1 and 15 
and Cycle 3 and beyond predose on Day 1. 
h 
Symptom-directed physical examination due to specific findings or abnormalities. 
i 
To be performed on all female patients of childbearing potential and within 72 hr of dosing (Day 1 only of every cycle). At Screening, women aged 55 and 
under, are not surgically sterile, and who are amenorrheic must have LH, FSH, and estradiol measurements within the postmenopausal range for the 


 
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Effective Date:  13-Apr-2015 
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Document Title: Statistical Analysis Plan 
Page 53 of 58 
institution, to be considered of nonchildbearing potential. A serum pregnancy test is required at Screening; serum or urine pregnancy tests are allowed for 
post-Screening visits. 
j 
Phase 1: Electrocardiograms will be performed in a supine position in triplicate (within a 10-minute period) predose and at 2 (± 15 minutes), 4 (± 15 
minutes), and 8 hr postdose (± 30 minutes) on Cycle 1 Day 1 and Cycle 2 Day 1, and predose at all study visits where indicated. Phase 2: Electrocardiograms 
will be performed in triplicate (within a 10-minute period) predose on Cycle 1 Day 1 and Cycle 2 Day 1, and at all study visits where indicated. All 
electrocardiograms will be performed in a supine position. 
k 
24-hour 12-lead continuous Holters will be collected on C1D1 and C2D1 for patients at all centers in the US and select centers ex-US. The Holters should 
run from approximately 1 hour before dosing until 24 hours (the next day). Patients should remain supine for 10-15 minutes before and 5 minutes after ECG 
collection. See manual for further guidance on Holter monitoring. 
l 
Clinical serum chemistries to include Na, K, Cl, bicarbonate, Mg, Ca, BUN, creatinine, AST, ALT, ALP, albumin, total bilirubin, direct bilirubin (collected 
only if total bilirubin is abnormal), LDH, glucose, amylase, lipase, uric acid, and thyroid function test (TFT) panel, which includes thyroid-stimulating 
hormone, free T3, and T4. In addition to the other chemistry panels, TFT panel is to be completed at Screening, C1D1, C2D1, and C3D1, then as clinically 
indicated. 
m 
May be performed from 48 hr (Cycle 2) or 72 hr (Cycle 3 and beyond) prior to Day 1 of a cycle (see Section 6.1 of protocol). 
n 
Clinical serum chemistries and CBC with differential and platelet count only at these study visits. May be performed through local laboratory testing. 
o 
Includes hemoglobin, hematocrit, platelets, and white blood cell count with differential. 
p 
Includes PT and PTT. 
q 
Bone marrow aspirate for clinical purposes and research to be done at screening, C2D1 (if no peripheral blasts), C3D1 (if not taken at C2D1), every one to 
two cycles until CR (not CRi or CRh) and then every two to three cycles until12 months after CR achievement, then at least every 6 cycles afterwards, End 
of Treatment, and at time of progression/relapse, per Response assessment guidelines (see Section 4.3 of protocol),  For Phase 2 Cohort 2, bone marrow 
should be done at C2D1, C4D1, C6D1 and C12D1 then every 6 cycles thereafter.  Refer to the laboratory manual for details of sample collection timing. 
 
Local IDH confirmation may have occurred  > 28 days prior.  
 
C3D1 to be done on any patient who did not undergo a C2D1 bone marrow aspirate or biopsy. 
 
Patients who discontinue study treatment for reasons other than treatment failure and have not withdrawn consent from overall study participation, 
should continue to be followed for disease response assessments until the time of disease progression/relapse or the initiation of a new treatment 
regimen. Patients who have stopped FT-2102 treatment for HSCT should continue to be followed until disease progression/ relapse. This information 
should be documented on the appropriate eCRF page 
r 
Urinalysis parameters include specific gravity, pH, total protein, protein, glucose, ketones, and blood. Microscopic examinations are to be performed as 
clinically indicated. For Cycle 3 & beyond and End of Study visit, urinalysis to be performed if clinically indicated.  
s 
Blood samples will be collected for measurement of plasma concentrations of FT-2102 (single agent) or FT-2102 + azacitidine (combination agent)  Blood 
will be collected relative to FT-2102 administration as described in Section 6.4 and Table 4 of protocol  
t 
A 72-hour wash-out post C2D1 dosing will be requested from all patients participating in the dose-expansion stage. After the C2D1 FT-2102 AM dose, 
patients will be asked to refrain from taking FT-2102 until the AM of C2D4. PK samples will be collected on C2D2 and C2D4**. 
u 
Blood samples will be collected for PD biomarker analysis for single agent FT-2102 and FT-2102/azacitidine combination. Blood will be collected  relative 
to FT-2102 administration as described in Section 6.5 and Table 5 of protocol. 
v 
Optional pre-screening blood sample for 2-HG level detection and IDH1 mutation testing (in 2-HG abnormal). 
w 
EQ-5D-5L survey can be completed anytime during screening prior to C1D1 dose. 
x 
Study drug diary should be distributed by the site to the patient on each cycle day 1, and collected at the next cycle day 1 visit 


 
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y 
Single agent (FT-2102): FT-2102 will be given in accordance with dosing schedule × 28 days out of 28 days. On C1D1 only a single dose of FT-2102 is 
taken. 
z 
Combination agent (FT-2102 + azacitidine): azacitidine will be administered via subcutaneous injection or intravenous infusion in combination with oral FT
‑2102 for 7 days, and then azacitidine will be stopped for 21 days; a 48-hr dose interruption of the azacitidine for weekends or holidays is allowed. On C1D1 
and C2D1, azacitidine is to be administered immediately prior to FT-2102 (to enable consistent PK assessments). On all other days and cycles when FT-
2102 and azacitidine are co-administered, it is recommended to dose FT-2102 prior to azacitidine. 
aa 
Combination FT2102 + cytarabine: cytarabine will be administered at a dose of 20 mg BID subcutaneously (SC) for 10 days every 28-day cycle 
bb 
After a patient discontinues study treatment and has completed their last study treatment visit, the study site will contact the patient approximately every 3 
months to collect survival data and data pertaining to any other alternative anti-neoplastic therapy the patient begins for up to 12 months from the time of 
their 1st dose of study drug. Patients who discontinue for reasons other than disease progression or who withdraw consent will continue to be followed for 
response until progression occurs. 
*  Not required in Phase 2 unless patient is participating in 24-hour Holter monitoring. 
**   Not required in Phase 


 
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Document Title: Statistical Analysis Plan 
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Appendix 2   SAS code for Efficacy Analyses 
 
A. 
CR/CRh Rate 
 
The SAS® code (SAS Version 9.3 or more current) of the following form will be used for the CR/CRh rate estimate along with 
confidence interval.  
proc freq data=DATA_NAME ; 
by COHORT; 
tables OUTCOME / exact binomial (p=0.15); 
weight count; 
exact binomial; 
run; 
Where DATA_NAME is the name of the dataset, COHORT is a vector containing treatment group assignment; OUTCOME is 
a vector containing the investigator response for each patient. 
 
B. 
EFS, DOR and OS  
 
The following SAS® code (SAS Version 9.3 or more current) will be used:  
 
proc lifetest data=DATA_NAME; 
time OSTIME*CENSOR(1);  
id COHORT;        
run;  
Where DATA_NAME is the name of the dataset, OSTIME is a vector containing the OS measurement for each patient, 
CENSOR is its respective censoring vector (1=censored, 0=non-censored event), COHORT is a vector containing cohort 
assignment.  
 
The following SAS® code (SAS Version 9.3 or more current) will be used for OS:  
proc lifetest data=DATA_NAME plots=(s, ls, lls) intervals=3, 6, 12, 24; 
time OSTIME*CENSOR(1);  
id COHORT;        
run; 
 
 


 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
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Document Title: Statistical Analysis Plan 
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Appendix 3   Column Headings for Analysis Tables 
 
1. Data snapshots taken for the purpose of safety analysis (regulatory reporting, IB update, etc.) 
will be organized as follows: 
Single Agent 
Combination 
Parameter 
FT-2102 
150 mg 
BID 
Phase 1 FT-2012 
Single Agent  
Total FT-
2102 
Single 
Agent 
FT-2102 150 mg 
BID+ Azacitidine 
75 mg/m2 
Phase 1 
FT-2102 + 
Azacitidine 
75 mg/m2 
Total FT-2102 + 
Azacitidine 75 
mg/m2 
 
Overall 
 
Note: to be performed on data from both phase 1 and phase 2 patients, regardless of cohort # 
 
 
 
 
 
2. Table generation for interim futility and efficacy analyses as well as final analyses will be 
organized as follows: 
Phase 1:  
Table xxx: Title 
xxx Analysis Set, Phase 1 
 
Single Agent 
Combination: Azacitidine 75 mg/m2   
  
Parameter 
FT-2102  
150 mg BID 
Total  
FT-2102  
  
FT-2102 
150 mg BID 
Total 
FT-2102 
  
Phase 1 
Overall 
 
 
 


 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
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Document Title: Statistical Analysis Plan 
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For Safety Tables: 
Phase 2 Single Agent Therapy: 
Table xxx: Title 
xxx Analysis Set, Phase 2 Single Agent 
 
 
FT-2102 150 mg BID 
Parameter 
Cohort 1  
Cohort 2  
Cohort 3  
Cohort 7 
Phase 2 
Single Agent  
Overall 
 
Ph.1 AML R/R  
& Ph.2 Cohort 1 
 
Phase 2 Combination Therapy: 
Table xxx: Title 
xxx Analysis Set, Phase 2 Combination Therapy 
 
 
FT-2102 150 mg BID + Azacitidine 75 mg/m2 
Parameter 
Cohort 4  
Cohort 5  
Cohort 6  
Cohort 8 
Phase 2 
Combination 
Therapy 
Overall 
 
 
For Efficacy Tables: 
Phase 2 Single Agent: 
Table xxx: Title 
xxx Analysis Set, Phase 2 Single Agent 
 
 
FT-2102 150 mg BID 
Parameter 
Cohort 1  
Cohort 2  
Cohort 3  
Cohort 7 
 
Ph.1 AML R/R & 
Ph.2 Cohort 1 


 
Document Number: FORM 694.01 
 
Effective Date:  13-Apr-2015 
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Document Title: Statistical Analysis Plan 
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Phase 2 Combination Therapy: 
Table xxx: Title 
xxx Analysis Set, Phase 2 Combination Therapy 
 
 
FT-2102 150 mg BID + Azacitidine 75 mg/m2 
Parameter 
Cohort 4  
Cohort 5  
Cohort 6  
Cohort 8 
 
 




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