Cohort 1a and 1b: Glioma (Advanced Gliomas and Glioblastoma Multiforme) Clinical Trial
Official title:
A Phase 1b/2 Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
| Verified date | November 2023 |
| Source | Novo Nordisk A/S |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 93 |
| Est. completion date | June 13, 2022 |
| Est. primary completion date | May 24, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Austin Hospital | Heidelberg | Victoria |
| Australia | Peter MacCallum Cancer Centre | Melbourne | |
| France | Centre de Lutte Contre Cancer (CLCC) - Institute Bergonie | Bordeaux | |
| France | Centre de Lutte Cancre (CLCC) - Lyon | Lyon | |
| France | Hospital de la Timone | Marseille | |
| France | Institut Gustave Roussy Cancer Campus | Villejuif | |
| Korea, Republic of | Asan Medical Center | Seoul | |
| Korea, Republic of | Samsung Medical Center | Seoul | |
| Korea, Republic of | Seoul National University Hospital | Seoul | |
| Spain | Vall D'Hebron University Hospital | Barcelona | |
| United Kingdom | Cancer Research Beatson Institute | Glasgow | |
| United Kingdom | The Royal Marsden Hospital | London | |
| United States | University of Colorado Anschutz Medical Campus | Aurora | Colorado |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Northwestern University, Lurie Comprehensive Cancer Center | Chicago | Illinois |
| United States | Henry Ford Hospital | Detroit | Michigan |
| United States | Banner MD Anderson | Gilbert | Arizona |
| United States | University of Iowa, Holden Comprehensive Cancer Institute | Iowa City | Iowa |
| United States | University of Miami, Sylvester Comprehensive Cancer Center | Miami | Florida |
| United States | Medical College of Wisconsin, Froedtert Hospital | Milwaukee | Wisconsin |
| United States | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey |
| United States | Columbia University Medical Center | New York | New York |
| United States | Washington University School of Medicine | Saint Louis | Missouri |
| United States | University of Utah, Huntsman Cancer Hospital | Salt Lake City | Utah |
| United States | Baylor Scott and White Medical Center | Temple | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Forma Therapeutics, Inc. |
United States, Australia, France, Korea, Republic of, Spain, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | Area Under the Plasma Concentration Versus Time Curve (AUC) | Area under the plasma concentration versus time curve (AUC) summarized for Cycle 1 and Cycle 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). | |
| Secondary | Peak Plasma Concentration (Cmax) | Peak Plasma Concentration (Cmax) was summarized for Cycle 1 and Cycle 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). | |
| Secondary | Time of Peak Plasma Concentration (Tmax) | Time of peak plasma concentration (Tmax) was summarized for Cycle 1 and Cycle 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). | |
| Secondary | Time for Half of the Drug to be Absent in Blood Stream Following Dose (T 1/2) | 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). | |
| Secondary | Apparent Clearance (CL/F) | Rate at which drug is removed from the blood stream (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). | |
| Secondary | Rate of Drug Distribution Within the Blood Stream (Vd/F) | Rate of drug distribution within the blood stream (Vd/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). | |
| Secondary | Olutasidenib Concentration Within Cerebro-spinal Fluid (CSF) | Olutasidenib concentration within CSF (Glioma Cohorts 1-A and 1-B only). Due to sparse data, analysis was not conducted by timepoint. | 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. | |
| Secondary | Progression-Free Survival (PFS) | 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 | From time of entry on study through progression, up to 24 weeks, on average | |
| Secondary | Time to Progression (TTP) | Time to progression is defined as the time (in weeks) from start of treatment until disease specified progression. | From first dose of study drug through time of disease progression | |
| Secondary | Duration of Response (DOR) | 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 | 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 | |
| Secondary | Overall Survival (OS) | 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 | From date of first dose until the date of death from any cause, assessed up to 101 weeks | |
| Secondary | Time to Response (TTR) | 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). | Response may be observed from time of first dose through time of treatment discontinuation, up to 2 years. |