Combination of GNS561 and Trametinib in Patients with Advanced KRAS Mutated Cholangiocarcinoma
- Registration Number
- NCT05874414
- Lead Sponsor
- Genfit
- Brief Summary
This is an open-label, multicenter Phase 1b/2a study to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of GNS561 in combination with trametinib in Advanced KRAS Mutated Cholangiocarcinoma after failure of standard-of-care first line therapy
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 74
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description GNS561+Trametinib GNS561 + Trametinib Phase 1b Dose Finding Patients will receive GNS561 (50mg QD; 100mg QD; 150mg; 200mg QD) and trametinib (2mg QD; 1.5mg QD; 1mg QD) in a dose escalation/de-escalation design to determine the maximum tolerated dose (MTD) of the combination. Experimental: Phase 2a Patients will receive GNS561 and trametinib at the recommended dose of the combination determined during Phase 1b
- Primary Outcome Measures
Name Time Method Incidence of dose limiting toxicity (DLT) of GNS561 with trametinib (Phase 1b) At the end of Cycle 1 (each Cycle is 21 days) Defined as Treatment Emergent Adverse Event (TEAE) being at least possibly related to study drug: With Grade ≥ 3 (using NCI CTCAE Version 5.0 or higher as applicable) such as specified in the protocol
Objective response rate (ORR) of the combination of GNS561 with trametinib (Phase 2a) Up to 11 months (estimated) Defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- Secondary Outcome Measures
Name Time Method Time To Progression (TTP) Up to 11 months (estimated) Defined as the time from first dose of study drug to the date of first documented disease progression.
Disease Control Rate (DCR) Up to 11 months (estimated) defined as the proportion of patients with a best overall response of CR or PR or stable disease (SD) using RECIST v1.1
Duration of response (DoR) Up to 11 months (estimated) Defined as the duration between first documentation of CR or PR to first documentation of disease progression or death using RECIST v1.1
Progression-free survival (PFS) Up to 11 months (estimated) Defined as the time from the date of first dose of study drug to the date of first documented disease progression or death
Time To Response (TTR) Up to 11 months (estimated) Defined as the time from first dose of study drug to first documentation of CR or PR using RECIST v1.1
Overall Survival (OS) time Up to approximately 42 months Defined as the time from the date of first dose of study drug to the date of death due to any cause.
Drug concentration in plasma for GNS561 and trametinib Predose to Day 21 of Cycle 1 and predose to Day 21 of Cycle 2 (each Cycle is 21 days) Incidence and severity of treatment emergent adverse event (TEAEs), incidence of serious adverse events (SAEs), incidence of TRAEs, incidence of adverse events of special interest (AESIs), rate of treatment discontinuation or interruption for TRAEs Up to 11 months (estimated) graded according to NCI CTCAE v5.0
Incidence of clinically significant changes or abnormalities from physical examinations, ophthalmologic assessments, vital signs, performance scores, laboratory results, ECGs, echocardiograms or multigated acquisition scans Up to 11 months (estimated)
Trial Locations
- Locations (8)
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University Of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Virginia Comprehensive Cancer Center
🇺🇸Charlottesville, Virginia, United States
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Pan American Center for Oncology Trials, LLC
🇵🇷Rio Piedras, Puerto Rico