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

March 16, 2026 updated by: Frontier Medicines Corporation

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

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

403

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Macquarie Park, New South Wales, Australia, 2109
    • Queensland
      • Southport, Queensland, Australia, 4215
    • South Australia
      • Kurralta Park, South Australia, Australia, 5037
      • North Adelaide, South Australia, Australia, 5006
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Recruiting
        • Eastern Health - Box Hill Hospital
        • Contact:
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Recruiting
        • Linear Clinical Research Ltd
        • Contact:
  • South Korea
    • Jongno-gu
      • Seoul, Jongno-gu, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
    • Seodaemun-gu
      • Seoul, Seodaemun-gu, South Korea, 03722
        • Recruiting
        • Severance Hospital
        • Contact:
          • International Health Care Center
          • Phone Number: +82-2-2228-5800
          • Email: ihcc@yuhs.ac
    • Seongbuk-gu
      • Seoul, Seongbuk-gu, South Korea, 02841
        • Recruiting
        • Korea University Anam Hospital
        • Contact:
    • Seongnam-si
      • Gyeonggi-do, Seongnam-si, South Korea, 13620
        • Recruiting
        • Seoul National University Bundang Hospital
        • Contact:
          • International Healthcare Center
          • Phone Number: +82-31-787-2034
          • Email: ihsi@snubh.org
    • Suwon-si
      • Gyeonggi-do, Suwon-si, South Korea, 16247
        • Recruiting
        • The Catholic University of Korea, St. Vincent's Hospital
        • Contact:
          • International Health Care Center
          • Phone Number: +82-31-249-8016
  • United States
    • California
      • La Jolla, California, United States, 92037
        • Recruiting
        • University of California San Diego (UC San Diego) Health - Jacobs Medical Center - Moores Cancer Center
        • Contact:
      • Orange, California, United States, 92868
        • Completed
        • University of California Irvine (UCI) - Chao Family Comprehensive Cancer Center
      • San Francisco, California, United States, 94158
        • Recruiting
        • University Of California San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center
        • Contact:
    • Florida
      • Lake Mary, Florida, United States, 32746
        • Completed
        • Florida Cancer Specialists and Research Institute
    • Indiana
      • Dyer, Indiana, United States, 46311
    • Kansas
      • Fairway, Kansas, United States, 66205
        • Recruiting
        • The University of Kansas Cancer Center
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Institute
        • Contact:
    • Pennsylvania
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center
        • Contact:
      • Kingwood, Texas, United States, 77339
        • Completed
        • Community Clinical Trials
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • UT Health San Antonio
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • South Texas Accelerated Research Therapeutics, LLC
        • Contact:
    • Utah
      • West Valley City, Utah, United States, 84119
    • Virginia
      • Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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 Daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Limiting Toxicities
Time Frame: Up to 21 Days
Number of participants with Dose Limiting Toxicities (DLTs)
Up to 21 Days
Adverse Events (AEs)
Time Frame: Approximately 24 Months
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
Time Frame: Approximately 24 Months
Cmax
Approximately 24 Months
Time to Reach Maximum Blood Concentration (Tmax) of FMC-376
Time Frame: Approximately 24 Months
Tmax
Approximately 24 Months
Minimum Observed Plasma Concentration (Cmin) of FMC-376
Time Frame: Approximately 24 Months
Cmin
Approximately 24 Months
Elimination Half-life (t1/2) of FMC-376
Time Frame: Approximately 24 Months
t1/2
Approximately 24 Months
Area Under Blood Concentration-Time Curve (AUC) of FMC-376
Time Frame: Approximately 24 Months
AUC
Approximately 24 Months
Volume of Distribution (Vd) of FMC-376
Time Frame: Approximately 24 Months
Vd
Approximately 24 Months
Clearance (CL) of FMC-376 from Blood Plasma
Time Frame: Approximately 24 Months
CL
Approximately 24 Months
Overall Response Rate (ORR)
Time Frame: Approximately 24 Months
Assess per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Approximately 24 Months
Duration of Response (DOR)
Time Frame: Approximately 24 Months
Assess per RECIST v1.1
Approximately 24 Months
Disease Control Rate (DCR)
Time Frame: Approximately 24 Months
Assess per RECIST v1.1
Approximately 24 Months
Progression-Free Survival (PFS)
Time Frame: Approximately 24 Months
Assess per RECIST v1.1
Approximately 24 Months
Overall Survival (OS)
Time Frame: Approximately 24 Months
Approximately 24 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Frontier Medicines Corporation

Investigators

  • Study Director: Medical Lead, Frontier Medicines Corporation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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 18, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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