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

Phase 1

Completed

• Conditions: Cohort 1a and 1b: Glioma (Advanced Gliomas and Glioblastoma Multiforme); Cohort 2a and 2b: Hepatobiliary Tumors (Hepatocellular Carcinoma, Bile Duct Carcinoma, Intrahepatic Cholangiocarcinoma, Other Hepatobiliary Carcinomas); Cohort 3a and 3b: Chondrosarcoma; Cohort 4a and 4b: Intrahepatic Cholangiocarcinoma; Cohort 5a: Other Non-Central Nervous System Solid Tumors With IDH1 Mutations
• Interventions: Drug: FT-2102; Biological: Nivolumab; Drug: Gemcitabine and Cisplatin; Drug: Azacitidine

• Registration Number: NCT03684811
• Lead Sponsor: Forma Therapeutics, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-09-17
• Study First Submitted QC: 2018-09-24
• Study First Posted: 2018-09-26
• Study Start: 2018-11-01
• Primary Completion: 2021-05-24
• Disposition First Submitted: 2022-05-24
• Study Completion: 2022-06-13
• Results First Submitted: 2022-09-27
• Results First Submitted QC: 2023-01-05
• Disposition First Submitted QC: 2023-01-05
• Results First Posted: 2023-01-25
• Disposition First Posted: 2023-01-25
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-16
• Last Update Posted: 2023-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 93

Inclusion Criteria

• Patients must have documented IDH1-R132 gene-mutated disease as evaluated by site
• Glioma: Advanced glioma that has recurred or progressed following standard therapy, or that has not responded to standard therapy.
• Hepatobiliary cancer that is relapsed/refractory or intolerant to approved standard-of-care therapy (including: hepatocellular carcinoma, bile duct carcinoma, intrahepatic cholangiocarcinoma or other hepatobiliary carcinomas)
• Chondrosarcoma that is relapsed or refractory and either locally advanced or metastatic and not amenable to complete surgical excision
• Intrahepatic cholangiocarcinoma that is advanced nonresectable or metastatic cholangiocarcinoma not eligible for curative resection or transplantation. Phase 1b/Safety Lead-in of Phase 2: relapsed or refractory disease. Combination Phase 2 (beyond Safety Lead-in): have received no more than 1 cycle of gemcitabine/cisplatin therapy
• Other solid tumors that have relapsed or refractory to standard-of-care therapy with no other available therapeutic options
• Good performance status
• Good kidney and liver function

Key

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Exclusion Criteria

• Prior solid organ or hematopoietic cell transplant
• Prior treatment with IDH1 inhibitor (single agent cohorts only)
• Congestive heart failure (New York Heart Association Class III or IV) or unstable angina pectoris. Previous history of myocardial infarction within 1 year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmias
• Unstable or severe, uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition, including pneumonitis and/or interstitial lung disease, and uncontrolled diabetes)
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• PD-1 only: active autoimmune disease

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 Cohorts FT-2102 Single Agent (Cohorts 1a-5a)	FT-2102	-
Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b)	FT-2102	-
Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a)	FT-2102	-
Phase 1b and 2 Cohort Combination (Cohort 2b)	FT-2102	-
Phase 1b and 2 Cohort Combination (Cohort 2b)	Nivolumab	-
Phase 1b and 2 Cohort Combination (Cohort 4b)	FT-2102	-
Phase 1b and 2 Cohort Combination (Cohort 4b)	Gemcitabine and Cisplatin	-
Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b)	Azacitidine	-

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	While on 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.
Number of Participants With a Dose Limiting Toxicity (DLT)	Day 1-28	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.

Secondary Outcome Measures

Name	Time	Method
Time for Half of the Drug to be Absent in Blood Stream Following Dose (T 1/2)	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).	Time for half of the drug to be absent in blood stream following dose (T 1/2)
Apparent Clearance (CL/F)	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).	Rate at which drug is removed from the blood stream (CL/F).
Olutasidenib Concentration Within Cerebro-spinal Fluid (CSF)	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.	Olutasidenib concentration within CSF (Glioma Cohorts 1-A and 1-B only). Due to sparse data, analysis was not conducted by timepoint.
Duration of Response (DOR)	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	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
Peak Plasma Concentration (Cmax)	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).	Peak Plasma Concentration (Cmax) was summarized for Cycle 1 and Cycle 2.
Rate of Drug Distribution Within the Blood Stream (Vd/F)	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).	Rate of drug distribution within the blood stream (Vd/F)
Progression-Free Survival (PFS)	From time of entry on study through progression, up to 24 weeks, on average	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
Overall Survival (OS)	From date of first dose until the date of death from any cause, assessed up to 101 weeks	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)	Response may be observed from time of first dose through time of treatment discontinuation, up to 2 years.	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).
Area Under the Plasma Concentration Versus Time Curve (AUC)	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).	Area under the plasma concentration versus time curve (AUC) summarized for Cycle 1 and Cycle 2
Time of Peak Plasma Concentration (Tmax)	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).	Time of peak plasma concentration (Tmax) was summarized for Cycle 1 and Cycle 2.
Time to Progression (TTP)	From first dose of study drug through time of disease progression	Time to progression is defined as the time (in weeks) from start of treatment until disease specified progression.

Trial Locations

Locations (26)

Banner MD Anderson; 🇺🇸 Gilbert, Arizona, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

University of Miami, Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Centre de Lutte Cancre (CLCC) - Lyon; 🇫🇷 Lyon, France

The Royal Marsden Hospital; 🇬🇧 London, United Kingdom

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Australia

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Austin Hospital; 🇦🇺 Heidelberg, Victoria, Australia

Cancer Research Beatson Institute; 🇬🇧 Glasgow, United Kingdom

University of Iowa, Holden Comprehensive Cancer Institute; 🇺🇸 Iowa City, Iowa, United States

Medical College of Wisconsin, Froedtert Hospital; 🇺🇸 Milwaukee, Wisconsin, United States

Vall D'Hebron University Hospital; 🇪🇸 Barcelona, Spain

Centre de Lutte Contre Cancer (CLCC) - Institute Bergonie; 🇫🇷 Bordeaux, France

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Hospital de la Timone; 🇫🇷 Marseille, France

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Institut Gustave Roussy Cancer Campus; 🇫🇷 Villejuif, France

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

Northwestern University, Lurie Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Utah, Huntsman Cancer Hospital; 🇺🇸 Salt Lake City, Utah, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Baylor Scott and White Medical Center; 🇺🇸 Temple, Texas, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States