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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumors; Cholangiocarcinoma; FGFR2 Gene Amplification; FGFR2 Gene Fusion/Rearrangement; Other Solid Tumors, Adult; FGFR3 Gene Amplification; Intrahepatic Cholangiocarcinoma (Icc); FGFR2 Gene Short Variants; FGFR3 Gene Fusion/Rearrangement; FGFR3 Gene Short Variants; FGFR2 Genetic Alterations; FGFR3 Genetic Alterations
• Intervention / Treatment: Drug: CGT4859

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Princess Margaret Cancer Centre - UHN
• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford Cancer Institute
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Cleveland, Ohio, United States, 44195
      • Taussig Cancer Center - Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute - University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Dose Escalation; Multiple doses of CGT4859 for oral administration	Drug: CGT4859; CGT4859 is a selective FGFR2/3 inhibitor
Experimental: Phase 2: Signal Seeking; Oral dose of CGT4859 at the RP2D as determined in Phase 1	Drug: CGT4859; CGT4859 is a selective FGFR2/3 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - AEs	Incidence, severity, and seriousness or treatment-emergent adverse events (AEs) leading to dose modification	Approximately 12 months
Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - Laboratory results	Clinically significant changes or abnormalities observed from baseline in laboratory results in chemistry, hematology, and coagulation parameters	Approximately 12 months
Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - ECG results	Clinically significant changes or abnormalities observed from baseline in electrocardiogram (ECG) parameters	Approximately 12 months
Phase 2: Evaluate antitumor activity of CGT4859 - Objective Response Rate (ORR)		Approximately 8 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Cogent Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 10, 2025
• First Posted (Actual): January 15, 2025

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Phase 1; Advanced Solid Tumors; Cholangiocarcinoma; Phase 2; FGFR3; Intrahepatic Cholangiocarcinoma; FGFR2; First in human; Investigational Drug; FGFR2/3; FGFR 2 genetic alterations; FGFR3 genetic alterations
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension
• Other Study ID Numbers: CGT4859-24-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No