Neoplasms

All Conditions

Digestive System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Cholangiocarcinoma

Glioma

Glioblastoma

Carcinoma, Hepatocellular

Carcinoma, Ductal

Chondrosarcoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Neuroepithelioma

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Nivolumab

Azacitidine

Cisplatin

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enzyme Inhibitors

FT-2102 will be supplied as a 150 mg capsule and will be administered per the protocol defined frequency and dose level.

FT-2102

Azacitidine will be administered per the site's standard of care.

Nivolumab will be administered per the site's standard of care.

Gemcitabine and cisplatin will be administered per the site's standard of care.

Gemcitabine and Cisplatin

Emma Barrett

This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 as a single agent and in combination with other anti-cancer drugs in patients with advanced solid tumors and gliomas.

The study is divided into two parts: single agent FT-2102 followed by combination therapy.

Part 1: A single agent, open-label study in up to five cohorts (glioma, hepatobiliary tumors, chondrosarcoma, intrahepatic cholangiocarcinoma, and other IDH1 mutant solid tumors) that will include a Phase 1 dose confirmation followed by a Phase 2 investigation of clinical activity in up to 4 cohorts. During the dose confirmation, additional doses or altered dose schedules may be explored.

Part 2: An open-label study of FT-2102 in combination with other anti-cancer agents. Patients will be enrolled across 4 different disease cohorts, examining the effect of FT-2102 + azacitidine (glioma and chondrosarcoma), FT-2102 + nivolumab (hepatobiliary tumors), and FT-2102 + gemcitabine/cisplatin (intrahepatic cholangiocarcinoma). There will be a safety lead-in followed by a Phase 2 evaluation in up to four cohorts of patients.

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

A Phase 1b/2 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.

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.

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

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

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

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

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

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

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

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

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

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 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).

Forma Therapeutics, Inc.

Glioma

Olutasidenib (150 mg BID) was administered orally in continuous 28 day cycles until criteria for treatment discontinuation were met.

Cohort 1A

Glioma

Olutasidenib (150 QD or 150 mg BID) was administered orally in continuous 28 day cycles until criteria for treatment discontinuation were met.

Azacitidine (75 mg/m2/day × 7 days every 28 days) was administered intravenously (or subcutaneously) daily for 7 days in combination with olutasidenib.

Cohort 1B

Hepatobiliary Tumors (Hepatocellular Carcinoma, Bile Duct Carcinoma, Intrahepatic Cholangiocarcinoma, Other Hepatobiliary Carcinomas)

Olutasidenib (150 mg BID) was administered orally in continuous 28 day cycles until criteria for treatment discontinuation were met.

Cohort 2A

Chondrosarcoma

Olutasidenib (150 mg BID) was administered orally in continuous 28 day cycles until criteria for treatment discontinuation were met.

Cohort 3A

Intrahepatic Cholangiocarcinoma

Olutasidenib (150 mg BID) was administered orally in continuous 28 day cycles until criteria for treatment discontinuation were met.

Cohort 4A

Other Non-Central Nervous System Solid Tumors With IDH1 Mutations

Olutasidenib (150 mg BID) was administered orally in continuous 28 day cycles until criteria for treatment discontinuation were met.

Cohort 5A

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

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

Medical Affairs

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.

Number of Participants With a Dose Limiting Toxicity (DLT)

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.

Overall Response Rate (ORR)

Cycle 1

Cycle 2

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).

Area Under the Plasma Concentration Versus Time Curve (AUC)

Peak Plasma Concentration (Cmax)

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 of Peak Plasma Concentration (Tmax)

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)

Apparent Clearance (CL/F)

Rate of Drug Distribution Within the Blood Stream (Vd/F)

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.

Olutasidenib Concentration Within Cerebro-spinal Fluid (CSF)

Progression-Free Survival (PFS)

Time to Progression (TTP)

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.

Duration of Response (DOR)

Overall Survival (OS)

Time to Response (TTR)

Hepatobiliary Tumors (Hepatocellular Carcinoma, Bile Duct Carcinoma, Intrahepatic Cholangiocarcinoma, Other Hepatobiliary Carcinomas)

Olutasidenib (150 mg BID) was administered orally in continuous 28 day cycles until criteria for treatment discontinuation were met.

Nivolumab (240 mg intravenously every 2 weeks) was to be administered in combination with olutasidenib.

No patients were enrolled into Cohort 2b.

Cohort 2B

Chondrosarcoma

Olutasidenib (150 mg BID) was administered orally in continuous 28 day cycles until criteria for treatment discontinuation were met.

Azacitidine (75 mg/m2/day × 7 days every 28 days) was to be administered intravenously (or subcutaneously) daily for 7 days in combination with olutasidenib.

No patients were enrolled in Cohort 3b.

Cohort 3B

Intrahepatic Cholangiocarcinoma

Olutasidenib (150 mg BID) was administered orally in continuous 28 day cycles until criteria for treatment discontinuation were met.

GemCis (cisplatin \[25 mg/m2\] followed by gemcitabine \[1000 mg/m2\], each administered on Days 1 and 8, every 3 weeks, for 8 cycles of up to 24 weeks) was to be administered in combination with olutasidenib.

No patients were enrolled in Cohort 4b.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation	NCT03684811	Cohort 1a and 1... Cohort 2a and 2... Cohort 3a and 3... Cohort 4a and 4... Cohort 5a: Othe...	FT-2102 Azacitidine Nivolumab Gemcitabine and...	18 Years -	Novo Nordisk A/S
A Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation	NCT03684811	Cohort 1a and 1... Cohort 2a and 2... Cohort 3a and 3... Cohort 4a and 4... Cohort 5a: Othe...	FT-2102 Azacitidine Nivolumab Gemcitabine and...	18 Years -	Novo Nordisk A/S

Spots Global Cancer Trial Database for cohort 2a and 2b: hepatobiliary tumors (hepatocellular carcinoma, bile duct carcinoma, intrahepatic cholangiocarcinoma, other hepatobiliary carcinomas)