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

Primary Purpose

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

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

FT-2102

Azacitidine

Nivolumab

Gemcitabine and Cisplatin

About this trial

This is an interventional treatment trial for Cohort 1a and 1b: Glioma (Advanced Gliomas and Glioblastoma Multiforme) focused on measuring Olutasidenib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

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

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

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

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

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

Arm Description

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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

Peak Plasma Concentration (Cmax)

Peak Plasma Concentration (Cmax) was summarized for Cycle 1 and Cycle 2.

Time of Peak Plasma Concentration (Tmax)

Time of peak plasma concentration (Tmax) was summarized for Cycle 1 and Cycle 2.

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)

Apparent Clearance (CL/F)

Rate at which drug is removed from the blood stream (CL/F).

Rate of Drug Distribution Within the Blood Stream (Vd/F)

Rate of drug distribution within the blood stream (Vd/F)

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.

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

Time to Progression (TTP)

Time to progression is defined as the time (in weeks) from start of treatment until disease specified progression.

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

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

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).

Full Information

NCT ID

NCT03684811

First Posted

September 17, 2018

Last Updated

August 8, 2023

Sponsor

Novo Nordisk A/S

1. Study Identification

Unique Protocol Identification Number

NCT03684811

Brief Title

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

Official Title

A Phase 1b/2 Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

November 1, 2018 (Actual)

Primary Completion Date

May 24, 2021 (Actual)

Study Completion Date

June 13, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novo Nordisk A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

93 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Title

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

Arm Type

Experimental

Arm Title

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

Arm Type

Experimental

Arm Title

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

Arm Type

Experimental

Arm Title

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

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

FT-2102

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Azacitidine

Other Intervention Name(s)

Vidaza

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Nivolumab

Other Intervention Name(s)

Opdivo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Gemcitabine and Cisplatin

Other Intervention Name(s)

Gemzar and Platinol

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants With a Dose Limiting Toxicity (DLT)

Description

Time Frame

Day 1-28

Title

Overall Response Rate (ORR)

Description

Time Frame

While on treatment

Secondary Outcome Measure Information:

Title

Area Under the Plasma Concentration Versus Time Curve (AUC)

Description

Area under the plasma concentration versus time curve (AUC) summarized for Cycle 1 and Cycle 2

Time Frame