Clinical trial NCT06777316: A Study of an FGFR2/3 Inhibitor (CGT4859) in Patients With Cholangiocarcinoma and Other Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Cogent Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2025-01-15
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - AEs
timeFrame: Approximately 12 months
measure: Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - Laboratory results
timeFrame: Approximately 12 months
measure: Phase 1: Determine the maximum tolerated dose (MTD) and RP2D of CGT4859 - ECG results
timeFrame: Approximately 12 months
measure: Phase 2: Evaluate antitumor activity of CGT4859 - Objective Response Rate (ORR)
timeFrame: Approximately 8 months
Secondary outcomes:
measure: Phase 1: Pharmacokinetics
timeFrame: Approximately 28 days
measure: Phase 1: Evaluate antitumor activity of CGT4859 - Objective Response Rate (ORR)
timeFrame: Approximately 8 months
measure: Phase 1 and Phase 2: Evaluate antitumor activity of CGT4859 - Disease Control Rate (DCR)
timeFrame: Approximately 8 months
measure: Phase 2: Characterize the safety of CGT4859 - AEs
timeFrame: Approximately 9 months
measure: Phase 2: Characterize the safety of CGT4859 - Labs, ECG
timeFrame: Approximately 9 months
measure: Phase 2: Pharmacokinetics at RP2D
timeFrame: Approximately 28 days
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: Taussig Cancer Center - Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute - University of Utah
state: Utah
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
Study officials:
References: