Phase 2
N=93
A Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
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
Bottom Line
View on ClinicalTrials.gov: NCT03684811 ↗Enrolled (actual)
93
Serious AEs
44.1%
Results posted
Jan 2023
Primary outcome: Primary: Number of Participants With a Dose Limiting Toxicity (DLT) — 0; 2; 0; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- FT-2102 (Drug); Azacitidine (Drug); Nivolumab (Biological); Gemcitabine and Cisplatin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Forma Therapeutics, Inc.
- Primary completion
- May 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With a Dose Limiting Toxicity (DLT) |
0; 2; 0; 1 | — |
| PRIMARY Overall Response Rate (ORR) |
2; 0; 1; 0; 0; 0 | — |
| SECONDARY Area Under the Plasma Concentration Versus Time Curve (AUC) |
6840; 6190; 13140; 12000; 10780; 11030 | — |
| SECONDARY Peak Plasma Concentration (Cmax) |
388.1; 369.5; 879.4; 863.4; 744.1; 815.4 | — |
| SECONDARY Time of Peak Plasma Concentration (Tmax) |
4.18; 3.95; 15.27; 16.37; 7.50; 4.17 | — |
| SECONDARY Time for Half of the Drug to be Absent in Blood Stream Following Dose (T 1/2) |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Apparent Clearance (CL/F) |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Rate of Drug Distribution Within the Blood Stream (Vd/F) |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Olutasidenib Concentration Within Cerebro-spinal Fluid (CSF) |
27.15 | — |
| SECONDARY Progression-Free Survival (PFS) |
8.21; 8.29; NA; 8.57; 8.29; 8.07 | — |
| SECONDARY Time to Progression (TTP) |
8.21; 8.29; NA; 15.00; 13.86; 8.14 | — |
| SECONDARY Duration of Response (DOR) |
43.71; NA | — |
| SECONDARY Overall Survival (OS) |
75.00; NA; NA; NA; 36.43; NA | — |
| SECONDARY Time to Response (TTR) |
38.07; 31.43 | — |
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.
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT03684811). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.