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

Forma Therapeutics, Inc.93 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

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)

Interventions

FT-2102DRUG

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

AzacitidineDRUG

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

NivolumabBIOLOGICAL

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

Gemcitabine and CisplatinDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (26)

Banner MD Anderson

Gilbert, Arizona, United States

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Northwestern University, Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

University of Iowa, Holden Comprehensive Cancer Institute

Iowa City, Iowa, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

...and 16 more locations

Outcomes

Primary Outcomes

Number of Participants With a Dose Limiting Toxicity (DLT)

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

Overall Response Rate (ORR)

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