A Study Evaluating FMC-376 in Participants with KRAS G12C Mutated Solid Tumors

Phase 1

Recruiting

• Conditions: Advanced Solid Tumors with KRAS G12C Mutations; Solid Tumor, Adult; Unresectable Solid Tumor; Metastatic Solid Tumor; Non Small Cell Lung Cancer; Colorectal Cancer; KRAS G12C; Pancreatic Cancer
• Interventions: Drug: FMC-376

• Registration Number: NCT06244771
• Lead Sponsor: Frontier Medicines Corporation

Brief Summary

The goal of this clinical trial is to evaluate FMC-376 in participants with advanced solid tumors with KRAS G12C mutations. This clinical trial will be conducted in 3 parts: Phase 1A (Dose Escalation), Phase 1B (Dose Expansion), and Phase 2 (Cohort Expansion). Multiple dose levels in participants with advanced solid tumors will be evaluated.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-01-19
• Study First Submitted QC: 2024-01-29
• Study First Posted: 2024-02-06
• Study Start: 2024-02-12
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-19
• Last Update Posted: 2025-03-21
• Primary Completion: 2027-10
• Study Completion: 2028-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 403

Inclusion Criteria

• Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors with KRAS G12C mutation
• Received and progressed or been intolerant to prior standard therapy OR standard therapy is considered inappropriate OR an investigational agent is considered standard of care
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate hematological, renal, and hepatic function
• Agrees not to participate in another interventional study while receiving study drug

Exclusion Criteria

• Leptomeningeal disease or carcinomatous meningitis
• Clinically significant toxicity resulting from prior cancer therapies
• Known or suspected hypersensitivity to FMC-376 or any components of the study drug
• Condition that would interfere with study drug absorption
• Any illness or medical history that would impact safety or compliance with study requirements or impact ability to interpret study data

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
FMC-376	FMC-376	Dose Escalation, Dose Expansion, and Cohort Expansion; Administered for 21-day cycle

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicities	Up to 21 Days	Number of participants with Dose Limiting Toxicities (DLTs)
Adverse Events (AEs)	Approximately 24 Months	Number of participants with treatment-emergent adverse events (TEAEs)

Secondary Outcome Measures

Name	Time	Method
Time to Reach Maximum Blood Concentration (Tmax) of FMC-376	Approximately 24 Months	Tmax
Volume of Distribution (Vd) of FMC-376	Approximately 24 Months	Vd
Overall Response Rate (ORR)	Approximately 24 Months	Assess per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Disease Control Rate (DCR)	Approximately 24 Months	Assess per RECIST v1.1
Clearance (CL) of FMC-376 from Blood Plasma	Approximately 24 Months	CL
Duration of Response (DOR)	Approximately 24 Months	Assess per RECIST v1.1
Overall Survival (OS)	Approximately 24 Months
Minimum Observed Plasma Concentration (Cmin) of FMC-376	Approximately 24 Months	Cmin
Area Under Blood Concentration-Time Curve (AUC) of FMC-376	Approximately 24 Months	AUC
Maximum Observed Plasma Concentration (Cmax) of FMC-376	Approximately 24 Months	Cmax
Elimination Half-life (t1/2) of FMC-376	Approximately 24 Months	t1/2
Progression-Free Survival (PFS)	Approximately 24 Months	Assess per RECIST v1.1

Trial Locations

Locations (14)

University of California San Diego (UC San Diego) Health - Jacobs Medical Center - Moores Cancer Center; 🇺🇸 La Jolla, California, United States

University of California Irvine (UCI) - Chao Family Comprehensive Cancer Center; 🇺🇸 Orange, California, United States

University of California San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

Florida Cancer Specialists and Research Institute; 🇺🇸 Lake Mary, Florida, United States

Northwest Cancer Centers; 🇺🇸 Dyer, Indiana, United States

The University of Kansas Cancer Center; 🇺🇸 Fairway, Kansas, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

Community Clinical Trials; 🇺🇸 Kingwood, Texas, United States

South Texas Accelerated Research Therapeutics, LLC; 🇺🇸 San Antonio, Texas, United States

UT Health San Antonio; 🇺🇸 San Antonio, Texas, United States

START Mountain Region; 🇺🇸 West Valley City, Utah, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States