A Phase 1/2 Study of a Selective FGFR2/3 Inhibitor, CGT4859, in Patients With Cholangiocarcinoma and Other Advanced Solid Tumors Harboring FGFR2 and/or FGFR3 Genetic Alterations
Overview
- Phase
- Phase 1
- Intervention
- CGT4859
- Conditions
- Not specified
- Sponsor
- Cogent Biosciences, Inc.
- Enrollment
- 110
- Locations
- 27
- Primary Endpoint
- Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - AEs
- Status
- Active, not recruiting
- Last Updated
- 15 days ago
Overview
Brief Summary
This is an open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (what the body does to the drug), pharmacodynamic (what the drug does to the body), and antitumor activity of CGT4859 in adult participants with intrahepatic cholangiocarcinoma (iCCA) or other advanced solid tumors with FGFR2 and/or FGFR3 genetic alternations.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed locally advanced, metastatic, and/or unresectable iCCA or other solid tumor with documented FGFR2/3 alteration in blood and/or tumor.
- •Previously treated with, not appropriate for, or declined standard-of-care first-line treatment.
- •Have measurable disease per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits.
- •Resolution of toxicities from prior therapy to ≤Grade 1 (or baseline), including resolution of clinically significant laboratory abnormalities, before the first dose of study drug. Exceptions are alopecia, hypothyroidism, or type 1 diabetes mellitus controlled with medical intervention, and paronychia controlled with local intervention.
Exclusion Criteria
- •Received chemotherapy or anticancer therapies or radiotherapy within certain timeframes before first dose of study drug.
- •Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug.
- •Clinically significant corneal or retinal disorders or current evidence of retinal detachment.
- •Received more than 2 prior FGFRi therapies
- •Active, symptomatic, or untreated brain metastases unless the participant is clinically stable and off corticosteroids for ≥2 months.
Arms & Interventions
Phase 2: Signal Seeking
Oral dose of CGT4859 at the RP2D as determined in Phase 1
Intervention: CGT4859
Phase 1: Dose Escalation
Multiple doses of CGT4859 for oral administration
Intervention: CGT4859
Outcomes
Primary Outcomes
Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - AEs
Time Frame: Approximately 12 months
Incidence, severity, and seriousness or treatment-emergent adverse events (AEs) leading to dose modification
Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - Laboratory results
Time Frame: Approximately 12 months
Clinically significant changes or abnormalities observed from baseline in laboratory results in chemistry, hematology, and coagulation parameters
Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - ECG results
Time Frame: Approximately 12 months
Clinically significant changes or abnormalities observed from baseline in electrocardiogram (ECG) parameters
Phase 2: Evaluate antitumor activity of CGT4859 - Objective Response Rate (ORR)
Time Frame: Approximately 8 months
Secondary Outcomes
- Phase 1: Pharmacokinetics(Approximately 28 days)
- Phase 2: Pharmacokinetics at RP2D(Approximately 28 days)
- Phase 2: Characterize the safety of CGT4859 - Labs, ECG(Approximately 9 months)
- Phase 1: Evaluate antitumor activity of CGT4859 - Objective Response Rate (ORR)(Approximately 8 months)
- Phase 1 and Phase 2: Evaluate antitumor activity of CGT4859 - Disease Control Rate (DCR)(Approximately 8 months)
- Phase 2: Characterize the safety of CGT4859 - AEs(Approximately 9 months)