Advanced Solid Tumors With KRAS G12C MutationsPhase 1/2PROSPERNCT06244771

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

A Phase 1/2 study testing FMC-376 in people with Advanced Solid Tumors With KRAS G12C Mutations and Solid Tumor, Adult, run by Frontier Medicines Corporation at 26 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

Search all trials

Trial summary

The goal of this clinical trial is to evaluate FMC-376 monotherapy and in combination with pembrolizumab 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Solid Tumors With KRAS G12C Mutations, Solid Tumor, Adult, Unresectable Solid Tumor
What is being tested?: FMC-376
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 293 participants
Where: 26 sitesin 3 countries
Study dates: 12 Feb 2024to Apr 2028
Phase: Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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
NSCLC Participants (in the first-line advanced or metastatic setting who refused standard therapy or standard therapy was considered inappropriate)
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
For patients receiving FMC-376 in combination with pembrolizumab: No history of autoimmune disease, and no history of immune-related adverse events or hepatitis

Who cannot join

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
For patients receiving FMC-376 in combination with pembrolizumab: Has severe hypersensitivity (≥ Grade 3) to pembrolizumab, history of radiation-related toxicities, or history of non-infectious pneumonitis.

Trial locations and contacts

26 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Medical Lead contact

+1 (650) 457-1005

clinicaltrials@frontiermeds.com

Country

City, postcode or hospital

Sites recruiting now only

26 sites in 3 countries

United States15 sites, 11 recruiting

Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Study Coordinator, 877-338-7425, matthew_olszewski@dfci.harvard.edu
Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201
Study Coordinator, 313-576-9816, galiciv@karmanos.org
Recruiting
Northwest Cancer Centers
Dyer, Indiana, 46311
Study Coordinator, 219-924-8178, karyn.burnworth@usoncology.com
Recruiting
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Clinical Trials Nurse Navigator, 703-636-1473, carrie.friedman@usoncology.com
Recruiting
The University of Kansas Cancer Center
Fairway, Kansas, 66205
Study Coordinator, 913-945-7552, CTNurseNav@kumc.edu
Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Study Coordinator, 1-888-513-6613, adeshmukh1@mdanderson.org
Recruiting
Community Clinical Trials
Kingwood, Texas, 77339
Completed
University of California San Diego (UC San Diego) Health - Jacobs Medical Center - Moores Cancer Center
La Jolla, California, 92037
Study Coordinator, 858-822-5354, rrpatel@health.ucsd.edu
Recruiting
Florida Cancer Specialists and Research Institute
Lake Mary, Florida, 32746
Completed
University of California Irvine (UCI) - Chao Family Comprehensive Cancer Center
Orange, California, 92868
Completed
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Program Manager, 267-414-6179, jennifer.louie2@pennmedicine.upenn.edu
Recruiting
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229
Physician Referral Coordinator, 210-593-5265, isabel.jimenez@startsa.com
Recruiting
UT Health San Antonio
San Antonio, Texas, 78229
Clinical Trials Specialist, 210-450-5798, goodwine@uthscsa.edu
Recruiting
University of California San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Project Manager, 415-344-8642, Lauren.Helwig@ucsf.edu
Recruiting
START Mountain Region
West Valley City, Utah, 84119
Completed

Other trials in United States

Australia6 sites, 4 recruiting

Eastern Health - Box Hill Hospital
Box Hill, Victoria, 3128
Completed
Icon Cancer Centre Kurralta Park
Kurralta Park, South Australia, 5037
Sue Yeend, +61 8 84740240, adelaideresearch@icon.team
Recruiting
Macquarie University
Macquarie Park, New South Wales, 2109
Study Contact, +61 2 9812 2956, clinicaltrials@mq.edu.au
Recruiting
Linear Clinical Research Ltd
Nedlands, Western Australia, 6009
Head of Project Operations, 61 (08) 6382 5100, actcmanagement@linear.org.au
Recruiting
GenesisCare North Adelaide
North Adelaide, South Australia, 5006
Completed
Tasman Health Care
Southport, Queensland, 4215
Study Contact, (07) 5613 2480, research@tasmanhealthcare.com.au
Recruiting

Other trials in Australia

South Korea5 sites, 5 recruiting

Seoul National University Bundang Hospital
Gyeonggi-do, Seongnam-si, 13620
International Healthcare Center, +82-31-787-2034, ihsi@snubh.org
Recruiting
The Catholic University of Korea, St. Vincent's Hospital
Gyeonggi-do, Suwon-si, 16247
International Health Care Center, +82-31-249-8016
Recruiting
Seoul National University Hospital
Seoul, Jongno-gu, 03080
Medical Service, +82-2-2072-2890, international@snuh.org
Recruiting
Severance Hospital
Seoul, Seodaemun-gu, 03722
International Health Care Center, +82-2-2228-5800, ihcc@yuhs.ac
Recruiting
Korea University Anam Hospital
Seoul, Seongbuk-gu, 02841
International Healthcare Center, +82-2-920-5677, kumcihc@kumc.or.kr
Recruiting

Other trials in South Korea

About this study

Official title: An Open-Label, Phase 1/2 Dose Escalation, Dose Expansion and Cohort Expansion Study Evaluating the Safety, PK and Clinical Activity of FMC-376 Monotherapy and in Combination With Pembrolizumab in Participants With KRAS G12C Mutated Advanced Solid Tumors

Conditions: Advanced Solid Tumors With KRAS G12C Mutations, Solid Tumor, Adult, Unresectable Solid Tumor, Metastatic Solid Tumor, Non Small Cell Lung Cancer, KRAS G12C
Being tested: FMC-376
Keywords: Lung Cancer, KRAS, G12C
Medical subject headings: Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FMC-376Drug
Oral Daily

Study groups in NCT06244771
Study group	Role	What they receive
FMC-376	Experimental	Dose Escalation, Dose Expansion, and Cohort Expansion; Administered for 21-day cycle Receives: Drug: FMC-376

What is being measured

The primary outcome is the main question the study is designed to answer.

Ph 1a: Dose Limiting Toxicities
Number of participants with Dose Limiting Toxicities (DLTs)
Measured: Up to 21 Days
Ph 1a: Adverse Events (AEs)
Number of participants with treatment-emergent adverse events (TEAEs)
Measured: Approximately 24 Months
Ph 1b/Ph2: Overall Response Rate (ORR)
Assess per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Measured: Approximately 24 Months

Secondary outcomes (12)

Ph1a/Ph1b/Ph2: Maximum Observed Plasma Concentration (Cmax) of FMC-376
Cmax
Measured: Approximately 24 Months
Ph1a/Ph1b/Ph2: Time to Reach Maximum Blood Concentration (Tmax) of FMC-376
Tmax
Measured: Approximately 24 Months
Ph1a/Ph1b/Ph2: Minimum Observed Plasma Concentration (Cmin) of FMC-376
Cmin
Measured: Approximately 24 Months
Ph1a/Ph1b/Ph2: Elimination Half-life (t1/2) of FMC-376
t1/2
Measured: Approximately 24 Months
Ph1a/Ph1b/Ph2: Area Under Blood Concentration-Time Curve (AUC) of FMC-376
AUC
Measured: Approximately 24 Months
Ph1a/Ph1b/Ph2: Volume of Distribution (Vd) of FMC-376
Vd
Measured: Approximately 24 Months
Ph1a/Ph1b/Ph2: Clearance (CL) of FMC-376 from Blood Plasma
CL
Measured: Approximately 24 Months
Ph1a: Overall Response Rate (ORR)
Assess per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Measured: Approximately 24 Months
Ph1a/Ph1b/Ph2: Duration of Response (DOR)
Assess per RECIST v1.1
Measured: Approximately 24 Months
Ph1a/Ph1b/Ph2: Disease Control Rate (DCR)
Assess per RECIST v1.1
Measured: Approximately 24 Months
Ph1a/Ph1b/Ph2: Progression-Free Survival (PFS)
Assess per RECIST v1.1
Measured: Approximately 24 Months
Ph1a/Ph1b/Ph2: Overall Survival (OS)
Measured: Approximately 24 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Feb 2024Apr 2028

First posted6 Feb 2024
Study start12 Feb 2024
Primary completionOct 2027 (estimated)
Study completionApr 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Advanced Solid Tumors With KRAS G12C MutationsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Model description: Phase 1A: sequential; Phase 1B and Phase 2: parallel
Masking: None (open label)
Enrolment: 293 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06244771
Sponsor's protocol ID: FMC-376-CL101
Acronym: PROSPER
Status last verified: Oct 2026
First submitted: 19 Jan 2024
Last updated: 19 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Interested in taking part?

Medical Lead

+1 (650) 457-1005

clinicaltrials@frontiermeds.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

Active, not recruitingPhase 1/2
Rollover Study for Participants Who Have Been Treated With and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other Study Treatments
Locally Advanced or Metastatic KRAS G12C-mutated Non-small Cell Lung Cancer, Advanced Solid Tumors Harboring the KRAS G12C Mutation
RecruitingPhase 1
A Phase I Study of BAY3498264 Given Together With Sotorasib in Participants Who Have Advanced Solid Cancers With Specific Genetic Changes Called KRASG12C Mutation
Advanced Solid Tumors Harboring KRAS G12C Mutation
Not yet recruitingPhase 1
Phase 1 Study of HS-10541 as Monotherapy or in Combination With Other Anti-cancer Therapies in Patients With KRAS G12C Mutation Advanced Solid Tumors.
KRAS G12C Mutation Advanced Solid Tumor
Not yet recruitingPhase 1
A Study to Investigate the Safety and Efficacy of KQB368 as Monotherapy in Participants With Advanced Solid Malignancies
Advanced Solid Tumors, Colorectal Cancer (CRC)
Not yet recruitingPhase 1/2
GH21 Combined With D-1553 in KRAS G12C Mutant Advanced Solid Tumors
Locally Advanced or Metastatic Solid Tumors Harboring KRAS G12C Mutation

All Advanced Solid Tumors With KRAS G12C Mutations trials