Description:
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.
Title
- Brief Title: A Study of FT 2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
- Official Title: A Phase 1b/2 Study of FT 2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
Clinical Trial IDs
- ORG STUDY ID:
2102-ONC-102
- NCT ID:
NCT03684811
Conditions
- Cohort 1a and 1b: Glioma
- Cohort 1a and 1b: 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 Solid Tumors With IDH1 Mutations
Interventions
Drug | Synonyms | Arms |
---|
FT-2102 | | Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a) |
Azacitidine | Vidaza | Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b) |
Nivolumab | Opdivo | Phase 1b and 2 Cohort Combination (Cohort 2b) |
Gemcitabine and Cisplatin | Gemzar and Platinol | Phase 1b and 2 Cohort Combination (Cohort 4b) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a) | Experimental | | |
Phase 2 Cohorts FT-2102 Single Agent (Cohorts 1a-5a) | Experimental | | |
Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b) | Experimental | | |
Phase 1b and 2 Cohort Combination (Cohort 2b) | Experimental | | |
Phase 1b and 2 Cohort Combination (Cohort 4b) | Experimental | | - FT-2102
- Gemcitabine and Cisplatin
|
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 (included: 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,
uncontrolled diabetes)
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy
- PD-1 only: active autoimmune disease
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with a Dose Limiting Toxicity (DLT) [Phase 1] |
Time Frame: | within first 4 weeks of treatment |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Area under the plasma concentration versus time curve (AUC) [Phase 1 and Phase 2] |
Time Frame: | Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days |
Safety Issue: | |
Description: | |
Measure: | Peak Plasma Concentration (Cmax) [Phase 1 and Phase 2] |
Time Frame: | Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days |
Safety Issue: | |
Description: | |
Measure: | Time of peak plasma concentration Tmax [Phase 1 and Phase 2] |
Time Frame: | Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days |
Safety Issue: | |
Description: | |
Measure: | Time for half of the drug to be absent in blood stream following dose (T 1/2) [Phase 1 and Phase 2] |
Time Frame: | Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days |
Safety Issue: | |
Description: | |
Measure: | Rate at which drug is removed from blood stream (CL/F) [Phase 1 and Phase 2] |
Time Frame: | Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days |
Safety Issue: | |
Description: | |
Measure: | Rate of drug distribution within the blood stream (Vd/F) [Phase 1 and Phase 2] |
Time Frame: | Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days |
Safety Issue: | |
Description: | |
Measure: | Drug level within CSF (Glioma only) [Phase 1 and Phase 2] |
Time Frame: | CSF sample for drug concentration collected at day 1 of cycles 1 and 3 (each cycle is 28 days) and through study completion, up to 24 weeks, on average |
Safety Issue: | |
Description: | |
Measure: | Overall response rate of FT-2102 as a single-agent or in combination with azacitidine or nivolumab or gemcitabine/cisplatin [Phase 1] |
Time Frame: | Response Assessment Guidelines for solid tumors or gliomas respectively and based on investigator's assessment within 4 months |
Safety Issue: | |
Description: | |
Measure: | Incidence and severity of adverse events as assessed by CTCAE v4.0 as a single-agent or in combination with azacitidine or nivolumab or gemcitabine/cisplatin [Phase 1and 2] |
Time Frame: | Safety will be assessed from time of first dose through 28 days post last dose |
Safety Issue: | |
Description: | |
Measure: | Progression-Free Survival (PFS) [Phase 1b and 2] |
Time Frame: | From time of entry on study through progression, up to 24 weeks, on average |
Safety Issue: | |
Description: | |
Measure: | Time to Progression (TTP) [Phase 1b and 2] |
Time Frame: | From first dose of study drug through time of first response by blood recovery count, up to 24 weeks, on average |
Safety Issue: | |
Description: | |
Measure: | Duration of Response (DOR) [Phase 1b and 2] |
Time Frame: | From time of first response by blood recovery count through relapse, up to 24 weeks, on average |
Safety Issue: | |
Description: | |
Measure: | Overall Survival (OS) [Phase 1b and 2] |
Time Frame: | From time of entry on study through death or date last known alive at end of follow-up, up to 24 weeks, on average |
Safety Issue: | |
Description: | |
Measure: | Time to Response (TTR) [Phase 1b and 2] |
Time Frame: | From time of entry on study through death or date last known alive at end of follow-up, up to 24 weeks, on average |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Forma Therapeutics, Inc. |
Last Updated
March 29, 2021