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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03684811
Recruitment Status : Completed
First Posted : September 26, 2018
Results First Posted : January 25, 2023
Last Update Posted : January 25, 2023
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
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 Drug: FT-2102 Drug: Azacitidine Biological: Nivolumab Drug: Gemcitabine and Cisplatin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 93 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
Actual Study Start Date : November 1, 2018
Actual Primary Completion Date : May 24, 2021
Actual Study Completion Date : June 13, 2022


Arm Intervention/treatment
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 Name: 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 Name: 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 Name: Gemzar and Platinol




Primary Outcome Measures :
  1. Number of Participants With a Dose Limiting Toxicity (DLT) [ Time Frame: 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.

  2. Overall Response Rate (ORR) [ Time Frame: 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.


Secondary Outcome Measures :
  1. Area Under the Plasma Concentration Versus Time Curve (AUC) [ Time Frame: 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

  2. Peak Plasma Concentration (Cmax) [ Time Frame: 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.

  3. Time of Peak Plasma Concentration (Tmax) [ Time Frame: 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.

  4. Time for Half of the Drug to be Absent in Blood Stream Following Dose (T 1/2) [ Time Frame: 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)

  5. Apparent Clearance (CL/F) [ Time Frame: 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).

  6. Rate of Drug Distribution Within the Blood Stream (Vd/F) [ Time Frame: 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)

  7. Olutasidenib Concentration Within Cerebro-spinal Fluid (CSF) [ Time Frame: 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.

  8. Progression-Free Survival (PFS) [ Time Frame: 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

  9. Time to Progression (TTP) [ Time Frame: 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.

  10. Duration of Response (DOR) [ Time Frame: 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

  11. Overall Survival (OS) [ Time Frame: 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

  12. Time to Response (TTR) [ Time Frame: 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03684811


Locations
Show Show 26 study locations
Sponsors and Collaborators
Forma Therapeutics, Inc.
Investigators
Layout table for investigator information
Study Director: Emma Barrett Forma Therapeutics
  Study Documents (Full-Text)

Documents provided by Forma Therapeutics, Inc.:
Study Protocol  [PDF] January 28, 2020
Statistical Analysis Plan  [PDF] June 28, 2019

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Responsible Party: Forma Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03684811    
Other Study ID Numbers: 2102-ONC-102
First Posted: September 26, 2018    Key Record Dates
Results First Posted: January 25, 2023
Last Update Posted: January 25, 2023
Last Verified: January 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Forma Therapeutics, Inc.:
Olutasidenib
Additional relevant MeSH terms:
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Neoplasms
Glioblastoma
Glioma
Cholangiocarcinoma
Chondrosarcoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Gemcitabine
Nivolumab
Azacitidine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Enzyme Inhibitors