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

Forma Therapeutics

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Biological: Nivolumab; Drug: Gemcitabine and Cisplatin; Drug: Azacitidine; Drug: FT-2102

Study type: Interventional

Funder types: Industry

Identifiers

NCT03684811

2102-ONC-102

Details and patient eligibility

About

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.

Enrollment: 93 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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93 participants in 5 patient groups

Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a)

Experimental group

Treatment:

Drug: FT-2102

Phase 2 Cohorts FT-2102 Single Agent (Cohorts 1a-5a)

Experimental group

Treatment:

Drug: FT-2102

Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b)

Experimental group

Treatment:

Drug: Azacitidine

Drug: FT-2102

Phase 1b and 2 Cohort Combination (Cohort 2b)

Experimental group

Treatment:

Drug: FT-2102

Biological: Nivolumab

Phase 1b and 2 Cohort Combination (Cohort 4b)

Experimental group

Treatment:

Drug: Gemcitabine and Cisplatin

Drug: FT-2102