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

NCT03684811 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 2102-ONC-102
• Study Type: interventional
• Target: 93
• Locations: 6 countries
• Sites: 26

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.

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

Keywords

Olutasidenib

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  While on treatment

Secondary Outcomes (12)

• 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).

• 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).

• 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 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).

• 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).

Study Arms (5)

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

EXPERIMENTAL

Drug: FT-2102

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

EXPERIMENTAL

Drug: FT-2102

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

EXPERIMENTAL

Drug: FT-2102; Drug: Azacitidine

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

EXPERIMENTAL

Drug: FT-2102; Biological: Nivolumab

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

EXPERIMENTAL

Drug: FT-2102; Drug: Gemcitabine and Cisplatin

Interventions

FT-2102 DRUG

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

Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a); Phase 1b and 2 Cohort Combination (Cohort 2b); Phase 1b and 2 Cohort Combination (Cohort 4b); Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b); Phase 2 Cohorts FT-2102 Single Agent (Cohorts 1a-5a)

Azacitidine DRUG

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

Also known as: Vidaza

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

Nivolumab BIOLOGICAL

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

Also known as: Opdivo

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

Gemcitabine and Cisplatin DRUG

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

Also known as: Gemzar and Platinol

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Forma Therapeutics, Inc.: lead

Study Sites (26)

Banner MD Anderson

Gilbert, Arizona, 85234, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Northwestern University, Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

University of Iowa, Holden Comprehensive Cancer Institute

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Baylor Scott and White Medical Center

Temple, Texas, 76508, United States

Location

University of Utah, Huntsman Cancer Hospital

Salt Lake City, Utah, 84112, United States

Location

Medical College of Wisconsin, Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, VIC 3000, Australia

Location

Centre de Lutte Contre Cancer (CLCC) - Institute Bergonie

Bordeaux, 33076, France

Location

Centre de Lutte Cancre (CLCC) - Lyon

Lyon, France

Location

Hospital de la Timone

Marseille, 13385, France

Location

Institut Gustave Roussy Cancer Campus

Villejuif, 94800, France

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Vall D'Hebron University Hospital

Barcelona, 08035, Spain

Location

Cancer Research Beatson Institute

Glasgow, G12 OYN, United Kingdom

Location

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• Jones RL, Groisberg R, Blay JY, Colman H, De La Fuente M, Roxburgh P, Chao MM, Tian H, Duffaud F, Bahleda R, Van Tine BA. Olutasidenib in recurrent/relapsed locally advanced or metastatic IDH1-mutated chondrosarcoma: phase 1b/2 trial. Nat Commun. 2026 Jan 29. doi: 10.1038/s41467-026-68716-6. Online ahead of print.

  PMID: 41611702 DERIVED

MeSH Terms

Conditions

Glioblastoma; Carcinoma, Hepatocellular; Bile Duct Neoplasms; Cholangiocarcinoma

Interventions

olutasidenib; Azacitidine; Nivolumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Biliary Tract Neoplasms; Bile Duct Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Medical Affairs
• Organization: Forma Therapeutics, Inc.

medicalinformation@formatherapeutics.com

(617) 679-1970

Study Officials

• Emma Barrett

  Forma Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2018
• First Posted: September 26, 2018
• Study Start: November 1, 2018
• Primary Completion: May 24, 2021
• Study Completion: June 13, 2022
• Last Updated: November 18, 2023
• Results First Posted: January 25, 2023

Record last verified: 2023-11

Locations

KR (3); FR (4); GB (2); ES (1); AU (2); US (14)