Open-label Study of FT-2102 With or Without Azacitidine or Cytarabine in Patients With AML or MDS With an IDH1 Mutation

Number of participants with change from baseline in clinically significant abnormal ECG parameter (QTcF) is reported. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate.

Time frame: Phase 1: From Baseline up to 28 days after last dose of study drug (up to 82 months)

Population: SAS. Here, N=Number of participants with available data. Since 150mg BID has been established as MTD, analysis was directed towards emphasizing findings that are most relevant for determining safe and effective treatment strategy. Accordingly, data for other dose levels (100mg QD, 150mg QD, and 300mg QD) were combined as prespecified in SAP.

Number of participants with change from baseline in clinically significant abnormal laboratory values for hematology, chemistry and coagulation with Grade \<1 to 4 is reported. National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 toxicity grade used to determine severity of AE. Grade 1: mild;asymptomatic/mild symptoms; Grade 2: moderate; minimal; Grade 3: severe/medically significant; Grade 4: life-threatening consequences, Grade 5: death.

Time frame: Phase 1: From Baseline up to 28 days after last dose of study drug (up to 82 months)

Population: SAS analyzed. Since 150 mg BID has been established as MTD, the analysis was directed towards emphasizing findings that are most relevant for determining a safe and effective treatment strategy. Accordingly, data for the other dose levels (100 mg QD, 150 mg QD, and 300 mg QD) were combined as prespecified in SAP.

A TEAE was defined as an adverse event (AE) that emerges during treatment, having been absent pre-treatment, or worsens relative to the pre-treatment state. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. Number of participants with TEAEs and SAEs is reported. Safety analysis set (SAS) included all the participants who have received at least one dose of study drug (FT-2102, azacitidine, or cytarabine).

Time frame: Phase 1: From start of drug administration (Day 1) up to 28 days after last dose of study drug (up to 82 months)

Population: SAS analyzed. Since 150 mg BID has been established as MTD, the analysis was directed towards emphasizing findings that are most relevant for determining a safe and effective treatment strategy. Accordingly, data for the other dose levels (100 mg QD, 150 mg QD, and 300 mg QD) were combined as prespecified in statistical analysis plan (SAP).

Percentage of participants with CR plus CRh (CR, Molecular CR \[CRm\], Cytogenetic CR \[CRc\], CRh) is re-ported. CR is defined as bone marrow blasts less than (\<) 5 percent (%) (in aspirate with spicules and 200 nucleated cells), no blasts with auer rods, no extramedullary disease, absolute neutrophil count (ANC) greater than or equal to (\>=) 1000/μL, platelet count \>=100,000/μL and transfusion independ-ence. CRc is defined as CR with no residual cytogenetic abnormalities. CRm is defined as CR with unde-tectable IDH1m minimal residual disease (MRD) and CRh is defined as bone marrow blasts and partial recovery of peripheral blood counts (platelet count \>50 × 10\^9/L and ANC \> 0.5 × 10\^9/L).

Time frame: Phase 2: up to 3 weeks post last dose of study drug or until the introduction of new anticancer therapy, whichever is earlier (up to 82 months)

Population: Efficacy evaluable analysis set included all participants in Phase 2, Cohort 1 with confirmed IDH1-R132 who have received the first dose of FT-2102 180 days or more prior to the analysis cutoff date. This outcome measure is applicable only for Cohort 1.

RFS is defined as the time between the date of first dose until relapse or death from any cause, whichever occurs first. RFS is calculated for all participants in Phase 2 Cohort 2. 4-Month RFS rate is defined as the percentage of participants in Phase 2 Cohort 2 who have not relapsed or died on or before their 4-month response evaluation.

Time frame: Phase 2: From the date of first dose until relapse or death from any cause, whichever occurs first (up to 4 months)

Population: FAS included all the participants who were enrolled in the study and have received at least one dose of FT-2102. This outcome measure is applicable for Cohort 2.

Percentage of participants with CR plus CRh (CR, Molecular CR \[CRm\]), Cytogenetic CR \[CRc\], CRh) is re-ported. CR is defined as bone marrow blasts \<5 % (in aspirate with spicules and 200 nucleated cells), no blasts with auer rods, no extramedullary disease, ANC \>=1000/μL, platelet count \>=100,000/μL and transfusion independ-ence. CRc is defined as CR with no residual cytogenetic abnormalities. CRm is de-fined as CR with undetectable IDH1m MRD and CRh is defined as bone marrow blasts and partial recovery of peripheral blood counts (platelet count \>50 × 10\^9/L and ANC \> 0.5 × 10\^9/L).

Time frame: Phase 2: up to 3 weeks post last dose of study drug or until the introduction of new anticancer therapy, whichever is earlier (up to 82 months)

Population: FAS included all the participants who were enrolled in the study and have received at least one dose of FT-2102. This outcome measure is applicable for Cohort 3, 4, 5, 6, 7 and 8. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Percentage of participants with complete remission (CR) is reported. CR is defined as bone marrow blast ≤ 5% myeloblasts with normal maturation of all cell lines, peripheral blood: Hgb ≥11 grams per deciliter (g/dL), platelets ≥ 100 × 10\^9/L, neutrophils ≥ 1.0 × 10\^9/L and blasts 0%.

Time frame: Phase 2: up to 3 weeks post last dose of study drug or until the introduction of new anticancer therapy, whichever is earlier (up to 82 months)

Population: FAS included all the participants who were enrolled in the study and have received at least one dose of FT-2102. This outcome measure is applicable for Cohort 4 and 5. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Area under the plasma concentration-time curve from zero time until the last measurable concentration is presented.

Time frame: Phase 1: Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle length= 28 days)

Population: The pharmacokinetic (PK) analysis set included those participants for whom it was possible to calculate at least 1 primary PK parameter and who had no major protocol deviations thought to influence the absorption, distribution, metabolism, and excretion of the FT-2102. Here, number anaylzed (n) = participants with available data for specific timepoints.

Duration of response is defined as the time from the date of the first response to the date of the relapse or death. The estimation of median duration of overall response was done by Kaplan-Meier method.

Time frame: Phase 1: From date of the first response to the date of the relapse or death (up to 82 months)

Population: FAS. N=participants with available data for this outcome measure. Since 150mg BID has been established as MTD, analysis was directed towards emphasizing findings that are most relevant for determining safe and effective treatment strategy. Accordingly, data for other dose levels(100mg QD, 150mg QD, and 300mg QD)were combined as prespecified in SAP.

Maximum plasma concentration (Cmax) for FT-2102 is presented.

Time frame: Phase 1: Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle length= 28 days)

Population: The PK analysis set included those participants for whom it was possible to calculate at least 1 primary PK parameter and who had no major protocol deviations thought to influence the absorption, distribution, metabolism, and excretion of the FT-2102. Here, number anaylzed (n) = participants with available data for specific timepoints.

Time to reach the maximum plasma concentration (Tmax) is presented.

Time frame: Phase 1: Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle length= 28 days)

Population: The PK analysis set included those participants for whom it was possible to calculate at least 1 primary PK parameter and who had no major protocol deviations thought to influence the absorption, distribution, metabolism, and excretion of the FT-2102. Here, number anaylzed (n) = participants with available data for specific timepoints.

TTR is the time in months between the first dose of study drug and documentation of the first overall response for participants who achieve a PR or better. This analysis was performed only on participants who have achieved PR or better as a best overall response.

Time frame: Phase 1: Time from first dose of study drug until documentation of the first overall response (up to 82 months)

Population: FAS. N=participants with PR or better as best overall response. Since 150mg BID has been established as MTD, analysis was directed towards emphasizing findings that are most relevant for determining safe and effective treatment strategy. Accordingly, data for other dose levels (100mg QD, 150mg QD, and 300mg QD) were combined as prespecified in SAP.

TTR is the time in months between the first dose of study drug and documentation of the first overall response for participants who achieve a PR or better. This analysis was performed only on participants who have achieved PR or better as a best overall response.

Time frame: Phase 1: Time from first dose of study drug until documentation of the first overall response (up to 82 months)

Population: FAS. N=participants with PR or better as best overall response. Since 150mg BID has been established as MTD, analysis was directed towards emphasizing findings that are most relevant for determining safe and effective treatment strategy. Accordingly, data for other dose levels(100mg QD, 150mg QD, and 300mg QD) were combined as prespecified in SAP.

Area under the plasma concentration-time curve from zero time until the last measurable concentration is presented.

Time frame: Phase 2: Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle length= 28 days)

Population: The PK analysis set included those participants for whom it was possible to calculate at least 1 primary PK parameter and who had no major protocol deviations thought to influence the absorption, distribution, metabolism, and excretion of the FT-2102. Here, Overall Number of Participants Analyzed (N) and number analyzed (n) = participants with available data for specific timepoints.

RFS was calculated for all participants in Phase 2 Cohort 2. RFS is defined as the time (in months) between the date of first dose until relapse or death from any cause, whichever occurs first. Relapse free survival time to event is reported for all participants in Cohort 2.

Time frame: Phase 2: From the date of first dose until relapse or death from any cause, whichever occurs first (up to 82 months)

Population: Full analysis set (FAS) included all the participants who were enrolled in the study and have received at least one dose of FT-2102. This outcome measure is applicable for Cohort 2.

Duration of overall response was calculated similarly to DCR but was assessed the time in months between documentation of the first response of PR or better until the date of relapse, death, whichever is earlier. The estimation of median duration of overall response was done by Kaplan-Meier method. The median duration of overall response is defined as the time at which 50% of the participants in a study have experienced the event of interest (relapse or death). Given the presence of only a single participant in the sample, there is an absence of variability in outcomes, and therefore, it was not possible to ascertain a time point at which half of the participants have experienced the event. Hence, median value could not be calculated.

Time frame: Phase 2: From the documentation of the first response of PR or better until the date of relapse, death, whichever is earlier (up to 82 months)

Population: FAS included all the participants who were enrolled in the study and have received at least one dose of FT-2102. This outcome measure is applicable only for cohort 4 and 5. Here, Overall Number of Participants Analyzed = participants with overall response for this outcome measure.

TTR is the time in months between the first dose of study drug and documentation of the first overall response for participants who achieve a PR or better. This analysis was performed only on participants who have achieved PR or better as a best overall response.

Time frame: Phase 2: Time from first dose of study drug until documentation of the first overall response (up to 82 months)

Population: FAS included all the participants who were enrolled in the study and have received at least one dose of FT-2102. This outcome measure is applicable for Cohort 4 and 5. Here, Overall Number of Participants Analyzed = participants with PR or better as a best overall response.

Duration of overall response is defined as the time from the date of the first response to the date of the relapse or death. The estimation of median duration of overall response was done by Kaplan-Meier method.

Time frame: Phase 2: From the date of the first response to the date of the relapse or death (up to 82 months)

Population: FAS included all the participants who were enrolled in the study and have received at least one dose of FT-2102. Data is reported only for Cohort 1, 4, 5, 6, 7 and 8. No participants achieved an overall response in Phase 2 Cohort 3. Duration of Response is not calculated for Phase 2 Cohort 2. Here, Overall Number of Participants Analyzed = participants with overall response for this outcome measure.

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.

Time frame: Phase 2: From first dose of study drug to disease progression, relapse, death from any cause, treatment failure, or start of other (non-protocol study drug) new antileukemia therapy (up to 82 months)

Population: FAS included all the participants who were enrolled in the study and have received at least one dose of FT-2102

Maximum Plasma Concentartion (Cmax) for FT-2102 is presented.

Time frame: Phase 2: Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle length= 28 days)

Population: The PK analysis set included those participants for whom it was possible to calculate at least 1 primary PK parameter and who had no major protocol deviations thought to influence the absorption, distribution, metabolism, and excretion of the FT-2102. Here, Overall Number of Participants Analyzed (N) and number analyzed (n) = participants with available data for specific timepoints.

Number of participants with change from baseline in clinically significant abnormal ECG parameter (QTcF) is reported. QT interval was the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF was the QT interval corrected for heart rate using Fridericia's formula: QTcF = QT divided by cube root of 60/heart rate.

Time frame: Phase 2: From Baseline up to 28 days after last dose of study drug (up to 82 months)

Population: Safety analysis set included all the participants who have received at least one dose of study drug (FT-2102, azacitidine, or cytarabine). Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Number of participants with change from baseline in clinically significant abnormal laboratory values for hematology, chemistry and coagulation with Grade \<1 to 4 is reported. National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 toxicity grade used to determine severity of AE. Grade 1: mild;asymptomatic/mild symptoms; Grade 2: moderate; minimal; Grade 3: severe/medically significant; Grade 4: life-threatening consequences, Grade 5: death.

Time frame: Phase 2: From Baseline up to 28 days after last dose of study drug (up to 82 months)

Population: Safety analysis set included all the participants who have received at least one dose of study drug (FT-2102, azacitidine, or cytarabine).