Advanced Solid Tumors, Cholangiocarcinoma, FGFR2 Gene Amplification, FGFR2 Gene Fusion/Rearrangement, FGFR2 Gene Short Variants, FGFR2 Genetic Alterations, FGFR3 Gene Amplification, FGFR3 Gene Fusion/Rearrangement, FGFR3 Gene Short Variants, FGFR3 Genetic Alterations, Intrahepatic Cholangiocarcinoma (Icc), Other Solid Tumors, Adult
Conditions
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
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.
Interventions
DRUGCGT4859
CGT4859 is a selective FGFR2/3 inhibitor
Sponsors
Cogent Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Canada, United States
Outcome results
None listed