REFOCUS: A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors
Phase 1
Active, not recruiting
- Conditions
- FGFR2 Gene TranslocationFGFR2 Gene ActivationCholangiocarcinomaOther Solid Tumors, AdultFGFR2 Gene MutationFGFR2 AmplificationFGFR2 Gene Fusion/RearrangementIntrahepatic Cholangiocarcinoma
- Interventions
- Registration Number
- NCT04526106
- Lead Sponsor
- Elevar Therapeutics
- Brief Summary
This is a Phase 1/2, open-label, FIH study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDy), and antineoplastic activity of RLY-4008, a potent and highly selective FGFR2 inhibitor, in patients with unresectable or metastatic cholangiocarcinoma (CCA) and other solid tumors. The study consists of 3 parts: a dose escalation (Part 1), a dose expansion (Part 2), and an extension (Part 3).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 540
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 4: Rollover RLY-4008 Oral dose of RLY-4008 as determined during Part 1 Dose Escalation. Part 1: Dose Escalation RLY-4008 Multiple doses of RLY-4008 for oral administration. Part 2: Dose Expansion RLY-4008 Oral dose of RLY-4008 as determined during Part 1 Dose Escalation. Part 3: Extension RLY-4008 Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.
- Primary Outcome Measures
Name Time Method Part 1 and Part 4: Number of patients with adverse events and serious adverse events Every cycle (4-week cycles) until study discontinuation, approximately 24 months Part 1: Determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RLY-4008 Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months Part 2 and Part 3: Objective Response Rate (ORR) assessed by Independent Review Committee per RECIST v1.1 Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Part 4: Number of patients with dose interruptions Every 28-day cycle until end of treatment, approximately 24 months. Part 4: Number of patients with dose reductions Every 28-day cycle until end of treatment, approximately 24 months. Part 4: Number of patients with dose discontinuations Every 28-day cycle until end of treatment, approximately 24 months.
- Secondary Outcome Measures
Name Time Method Part 2 and Part 3:Dose intensity Every 28-day cycle until end of treatment, approximately 24 months. Part 2 and Part 3: Correlation between FGFR2 genotype by central tissue assessment and antitumor response, as measured by ORR Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Part 1: Pharmacodynamic parameters including changes in carcinoembryonic antigen (CEA) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months Part 2 and Part 3: Number of patients with dose interruptions Every 28-day cycle until end of treatment, approximately 24 months. Part 2 and Part 3: Number of patients with dose reductions Every 28-day cycle until end of treatment, approximately 24 months. Part 1: Duration of Response (DOR) assessed by Investigator per RECIST v1.1 Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Part 1: Pharmacodynamic parameters including changes in fibroblast growth factor 23 (FGF-23) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months Part 1: Pharmacodynamic parameters including changes in cancer antigen 19-9 (CA 19-9) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every other cycle (4-week cycles) from Cycle 3, approximately 24 months Part 2 and Part 3: Number of patients with dose discontinuations Every 28-day cycle until end of treatment, approximately 24 months. Part 1: FGFR2 gene status in plasma circulating tumor deoxyribonucleic acid (ctDNA) and tumor tissue Every cycle (4-week cycles) through Cycle 3 and every other cycle thereafter until study discontinuation, approximately 24 months Pharmacokinetic parameters including area under the plasma concentration versus time curve (AUC) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles) Pharmacokinetic parameters including half-life (t1/2) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles) Part 2 and Part 3: Duration of response (DOR) assessed by Investigator and Independent Review Committee per RECIST v1.1 Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Part 2 and Part 3: Progression-free survival (PFS) assessed by Investigator and Independent Review Committee per RECIST v1.1 Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Part 1: Disease Control Rate (DCR) as assessed by Investigator per RECIST v1.1 Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Part 1, Part 2, and Part 3: Objective Response Rate (ORR) as assessed by Investigator per RECIST v1.1 Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Pharmacokinetic parameters including maximum plasma drug concentration (Cmax) Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle through Cycle 4 (4-week cycles) Part 2 and Part 3: Disease control rate (DCR) assessed by Investigator and Independent Review Committee per RECIST v1.1 Approximately every 8 weeks during treatment and every 12 weeks after the last dose in the absence of progressive disease, approximately 36 months Part 2 and Part 3:Overall survival (OS) Up to approximately 36 months. Part 2 and Part 3:Change from baseline in quality of life as assessed by EORTC QLQ-C30 Approximately every 4 weeks during treatment, approximately 24 months
Trial Locations
- Locations (46)
The University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Scroll for more (36 remaining)The University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States