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

NCT06777316 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CGT4859-24-101
• Study Type: interventional
• Target: 110
• Locations: 2 countries
• Sites: 13

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.

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; FGFR3 Genetic Alterations; Advanced Solid Tumors

Keywords

Cholangiocarcinoma; Intrahepatic Cholangiocarcinoma; Advanced Solid Tumors; Investigational Drug; Phase 1; Phase 2; FGFR2; FGFR3; FGFR2/3; First in human; FGFR 2 genetic alterations; FGFR3 genetic alterations

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• Phase 1: Pharmacokinetics

  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

  Approximately 9 months

• Phase 2: Characterize the safety of CGT4859 - Labs, ECG

  Approximately 9 months

Study Arms (2)

Phase 1: Dose Escalation

EXPERIMENTAL

Multiple doses of CGT4859 for oral administration

Drug: CGT4859

Phase 2: Signal Seeking

EXPERIMENTAL

Oral dose of CGT4859 at the RP2D as determined in Phase 1

Drug: CGT4859

Interventions

CGT4859 DRUG

CGT4859 is a selective FGFR2/3 inhibitor

Phase 1: Dose Escalation; Phase 2: Signal Seeking

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cogent Biosciences, Inc.: lead

Study Sites (13)

Stanford Cancer Institute

Palo Alto, California, 94305, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Taussig Cancer Center - Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Fox Chase cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute - University of Utah

Salt Lake City, Utah, 84112, United States

Location

Princess Margaret Cancer Centre - UHN

Toronto, Ontario, M5G 2C4, Canada

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 will evaluate multiple ascending doses until the highest safe dose and the recommended phase 2 dose (RP2D) are determined. Phase 2 will evaluate the RP2D in 4 cohorts defined by tumor type and prior therapy based on Phase 1 results.

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: January 15, 2025
• Study Start: January 22, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (12)