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

Purpose

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.

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a)
  • Drug: FT-2102
    FT-2102 will be supplied as a 150 mg capsule and will be administered per the protocol defined frequency and dose level.
Experimental
Phase 2 Cohorts FT-2102 Single Agent (Cohorts 1a-5a)
  • Drug: FT-2102
    FT-2102 will be supplied as a 150 mg capsule and will be administered per the protocol defined frequency and dose level.
Experimental
Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b)
  • Drug: FT-2102
    FT-2102 will be supplied as a 150 mg capsule and will be administered per the protocol defined frequency and dose level.
  • Drug: Azacitidine
    Azacitidine will be administered per the site's standard of care.
    Other names:
    • Vidaza
Experimental
Phase 1b and 2 Cohort Combination (Cohort 2b)
  • Drug: FT-2102
    FT-2102 will be supplied as a 150 mg capsule and will be administered per the protocol defined frequency and dose level.
  • Biological: Nivolumab
    Nivolumab will be administered per the site's standard of care.
    Other names:
    • Opdivo
Experimental
Phase 1b and 2 Cohort Combination (Cohort 4b)
  • Drug: FT-2102
    FT-2102 will be supplied as a 150 mg capsule and will be administered per the protocol defined frequency and dose level.
  • Drug: Gemcitabine and Cisplatin
    Gemcitabine and cisplatin will be administered per the site's standard of care.
    Other names:
    • Gemzar and Platinol

More Details

Status
Completed
Sponsor
Forma Therapeutics, Inc.

Study Contact