A Study of an FGFR2/3 Inhibitor (CGT4859) in Patients With Cholangiocarcinoma and Other Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Intrahepatic Cholangiocarcinoma (Icc); Cholangiocarcinoma; Other Solid Tumors, Adult; FGFR2 Gene Fusion/Rearrangement; FGFR2 Gene Amplification; FGFR2 Gene Short Variants; FGFR3 Gene Fusion/Rearrangement; FGFR3 Gene Amplification; FGFR3 Gene Short Variants; FGFR2 Genetic Alterations
• Interventions: Drug: CGT4859

• Registration Number: NCT06777316
• Lead Sponsor: Cogent Biosciences, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-09
• Study First Submitted QC: 2025-01-10
• Study First Posted: 2025-01-15
• Study Start: 2025-01-22
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-02
• Last Update Posted: 2025-05-04
• Primary Completion: 2027-03
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

1. Histologically confirmed locally advanced, metastatic, and/or unresectable iCCA or other solid tumor with documented FGFR2/3 alteration in blood and/or tumor.
2. Previously treated with, not appropriate for, or declined standard-of-care first-line treatment.
3. Have measurable disease per RECIST v1.1.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
5. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits.
6. 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.

Key

Exclusion Criteria

1. Received chemotherapy or anticancer therapies or radiotherapy within certain timeframes before first dose of study drug.
2. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug.
3. Clinically significant corneal or retinal disorders or current evidence of retinal detachment.
4. Received more than 2 prior FGFRi therapies
5. Active, symptomatic, or untreated brain metastases unless the participant is clinically stable and off corticosteroids for ≥2 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1: Dose Escalation	CGT4859	Multiple doses of CGT4859 for oral administration
Phase 2: Signal Seeking	CGT4859	Oral dose of CGT4859 at the RP2D as determined in Phase 1

Primary Outcome Measures

Name	Time	Method
Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - AEs	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	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	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)	Approximately 8 months

Secondary Outcome Measures

Name	Time	Method
Phase 1: Pharmacokinetics	Approximately 28 days	Plasma concentration levels of CGT4859
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	Incidence, severity, and seriousness or treatment-emergent adverse events (AEs) leading to dose modification
Phase 2: Characterize the safety of CGT4859 - Labs, ECG	Approximately 9 months	Changes from baseline in key laboratory results and electrocardiogram (ECG) parameters
Phase 2: Pharmacokinetics at RP2D	Approximately 28 days	Plasma concentration levels of CGT4859

Trial Locations

Locations (10)

Fox Chase cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

Stanford Cancer Institute; 🇺🇸 Palo Alto, California, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

Taussig Cancer Center - Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Huntsman Cancer Institute - University of Utah; 🇺🇸 Salt Lake City, Utah, United States