A Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation

DLTs are AEs unrelated to the underlying disease and considered related to FT-2102. For non-hematologic AEs: Grade 3 or higher per CTCAE v 4.03 criteria except Grade 3 nausea, vomiting, diarrhea, or rash: lasting \<72 hours (with optimal medical management) or clinically relevant Grade 3 or higher non-hematologic laboratory finding. For hematologic AEs: Grade 3 or higher thrombocytopenia or febrile neutropenia or Grade 4 or higher neutropenia lasting for \>7 days.

Time frame: Day 1-28

Population: All patients in the Safety Lead-in Period who either experienced a DLT during Cycle 1 or completed at least 75% of the prescribed Cycle 1 dose. The Safety-Lead-in Period will employ a traditional 3+3 design, whereby 3 patients with any of the solid tumors (Cohorts 2a-5) and 3 patients with gliomas (Cohort 1a) are treated with FT-2102 150 mg BID and monitored for DLTs during the first cycle of study treatment.

ORR is defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) as per RANO (2010) criteria for patients with high grade glioma (Cohorts 1a and 1b). For patients with low grade glioma, ORR is defined as CR+PR+minor response (MR) as per LGG RANO criteria (2011). For Cohorts 2-5, ORR is defined as CR+PR as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

Time frame: While on treatment

Population: The Response-Evaluable Analysis Set is defined as all patients with measurable disease at baseline are included in the Safety Analysis Set and had at least 1 post-baseline response assessment or discontinued the treatment phase due to disease progression (including death caused by disease progression) within 8 weeks (+2-week window) of the first dose of study treatment.

Rate at which drug is removed from the blood stream (CL/F).

Time frame: Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).

Population: The PK analysis set is defined as patients who have received at least one dose of FT-2102 and for whom it is possible to calculate at least one primary PK parameter (e.g. Cmax, AUC). Results were not estimable for this outcome measure because of the limited sampling interval post Day 1.

Area under the plasma concentration versus time curve (AUC) summarized for Cycle 1 and Cycle 2

Time frame: Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).

Population: The PK analysis set is defined as patients from Stage 1 who have received at least one dose of FT-2102 and for whom it is possible to calculate at least one primary PK parameter (e.g. Cmax, AUC).

Duration of response (DOR), defined as the time from the first response to documented disease progression as determined by applicable disease criteria. First response is defined as first observation of overall response of CR+PR+MR (glioma) or CR+PR (Cohort 2-5). Disease progression as measured by the appropriate response criteria, unless deemed by the Investigator to be receiving clinical benefit

Time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 44 weeks

Population: Response-Evaluable Analysis Set defined as all patients with measurable disease at baseline are included in the Safety Analysis Set and had at least 1 post-baseline response assessment or discontinued the treatment phase due to disease progression (including death caused by disease progression) within 8 weeks (+2-week window) of the first dose of study treatment. Duration of response was calculated on the subset of patients in the Response Evaluable Set who experienced an Overall Response.

Olutasidenib concentration within CSF (Glioma Cohorts 1-A and 1-B only). Due to sparse data, analysis was not conducted by timepoint.

Time frame: CSF sample for drug concentration was collected at Day 1 of Cycles 1 and 3 (each cycle is 28 days) and through study completion, up to 24 weeks, on average.

Population: Glioma patients who had a CSF sample obtained while on study treatment were analyzed. CSF samples were not collected for cohorts 2-5, per protocol.

Overall survival (OS), defined as the time in weeks from the first dose to death due to any cause or date last known alive at end of follow-up

Time frame: From date of first dose until the date of death from any cause, assessed up to 101 weeks

Population: Safety Analysis Set - Patients who have received at least one dose of study medication.

Peak Plasma Concentration (Cmax) was summarized for Cycle 1 and Cycle 2.

Time frame: Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).

Population: The PK analysis set is defined as patients from Stage 1 who have received at least one dose of FT-2102 and for whom it is possible to calculate at least one primary PK parameter (e.g. Cmax, AUC).

Progression-Free Survival from time of entry on study. Progression-free survival (PFS) is defined as the time from the first dose to disease progression as determined by applicable disease criteria or death due to any cause, whichever was sooner. Disease progression as measured by the appropriate response criteria, unless deemed by the Investigator to be receiving clinical benefit

Time frame: From time of entry on study through progression, up to 24 weeks, on average

Population: The Response-Evaluable Analysis Set is defined as all patients with measurable disease at baseline are included in the Safety Analysis Set and had at least 1 post-baseline response assessment or discontinued the treatment phase due to disease progression (including death caused by disease progression) within 8 weeks (+2-week window) of the first dose of study treatment.

Rate of drug distribution within the blood stream (Vd/F)

Time frame: Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).

Population: The PK analysis set is defined as patients who have received at least one dose of FT-2102 and for whom it is possible to calculate at least one primary PK parameter (e.g. Cmax, AUC). Results were not estimable for this outcome measure because of the limited sampling interval post Day 1.

Time for half of the drug to be absent in blood stream following dose (T 1/2)

Time frame: Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).

Population: The PK analysis set is defined as patients who have received at least one dose of FT-2102 and for whom it is possible to calculate at least one primary PK parameter (e.g. Cmax, AUC). Results were not estimable for this outcome measure because of the limited sampling interval post Day 1.

Time of peak plasma concentration (Tmax) was summarized for Cycle 1 and Cycle 2.

Time frame: Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).

Population: The PK analysis set is defined as patients who have received at least one dose of FT-2102 and for whom it is possible to calculate at least one primary PK parameter (e.g. Cmax, AUC).

Time to progression is defined as the time (in weeks) from start of treatment until disease specified progression.

Time frame: From first dose of study drug through time of disease progression

Population: The Response-Evaluable Analysis Set is defined as all patients with measurable disease at baseline are included in the Safety Analysis Set and had at least 1 post-baseline response assessment or discontinued the treatment phase due to disease progression (including death caused by disease progression) within 8 weeks (+2-week window) of the first dose of study treatment.

Time to response (TTR) in weeks. TTR is defined as the time from first dose to first response. First response is defined as first observation of overall response of CR+PR+MR (glioma) or CR+PR (Cohort 2-5).

Time frame: Response may be observed from time of first dose through time of treatment discontinuation, up to 2 years.

Population: The Response-Evaluable Analysis Set is defined as all patients with measurable disease at baseline are included in the Safety Analysis Set and had at least 1 post-baseline response assessment or discontinued the treatment phase due to disease progression (including death caused by disease progression) within 8 weeks (+2-week window) of the first dose of study treatment.