A Study Evaluating FMC-376 in Participants With KRAS G12C Mutated Solid Tumors (PROSPER)

An Open-Label, Phase 1/2 Dose Escalation, Dose Expansion and Cohort Expansion Study Evaluating the Safety, PK and Clinical Activity of FMC-376 in Participants With KRAS G12C Mutated Locally Advanced Unresectable or Metastatic Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Pancreatic Cancer; Non Small Cell Lung Cancer; Metastatic Solid Tumor; Solid Tumor, Adult; Unresectable Solid Tumor; KRAS G12C; Advanced Solid Tumors With KRAS G12C Mutations
• Intervention / Treatment: Drug: FMC-376

• Study Type: Interventional
• Enrollment (Estimated): 403
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Andrew Krivoshik, MD, PhD; Phone Number: +1 (650) 457-1005; Email: andrew.krivoshik@frontiermeds.com

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics, LLC
      • Contact: Physician Referral Coordinator; Phone Number: 210-593-5265; Email: isabel.jimenez@startsa.com
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • START Mountain Region
      • Contact: Director, Clinical Operation; Phone Number: 801-907-4770; Email: marie.asay@startthecure.com
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
      • Contact: Clinical Trials Nurse Navigator; Phone Number: 703-636-1473; Email: carrie.friedman@usoncology.com

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMC-376; Dose Escalation, Dose Expansion, and Cohort Expansion; Administered for 21-day cycle	Drug: FMC-376; Oral Capsule

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Frontier Medicines Corporation
• Investigators: Study Director: Andrew Krivoshik, MD, PhD, Frontier Medicines Corporation

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: January 19, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): February 6, 2024

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: FMC-376-CL101

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