RecruitingPhase 1Phase 2NCT07020221

A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors

A Phase 1/2, Open-label Study of VS-7375, a KRAS G12D (ON/OFF) Inhibitor, as Monotherapy and in Combination, in Patients With Advanced KRAS G12D-Mutated Solid Tumors


Sponsor

Verastem, Inc.

Enrollment

295 participants

Start Date

Jun 24, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

This study will assess the safety and efficacy of VS-7375 alone and in combination in patients with advanced solid tumors harboring a KRAS G12D-mutation.


Eligibility

Min Age: 18 Years

Inclusion Criteria9

  • Individuals ≥18 years of age.
  • Agreement to sign and date an informed consent form (ICF) approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
  • Histologic or cytologic evidence of locally advanced unresectable or metastatic solid tumor harboring a KRAS G12D mutation.
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate organ function
  • Adequate cardiac function
  • Recovered from all AEs due to previous therapies to Grade ≤1 or baseline.
  • Agreement to use highly effective contraception

Exclusion Criteria8

  • Underwent major surgical procedure as defined by the Investigator, other than for diagnosis, within 4 weeks prior to Cycle 1 Day 1,
  • Receipt of chemotherapy, targeted therapy, or radiotherapy (excluding palliative radiation) within 4 weeks or 5 half-lives, whichever is shorter, or immunotherapy within 4 weeks prior to Cycle 1 Day 1
  • Treatment with any investigational drug at least 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1.
  • History of treatment with direct and specific KRAS G12D inhibitors.
  • Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
  • Inability to swallow oral medications.
  • Evidence or history of uncontrolled, clinically significant hematological, renal, hepatic, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, coagulation, neurologic, dermatologic, autoimmune, or allergic disease
  • Individuals who are pregnant or breastfeeding.

Interventions

DRUGVS-7375

VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.

DRUGCetuximab

Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR).

DRUGCarboplatin + Pemetrexed + Pembrolizumab

A combination therapy regimen used as a first-line treatment for advanced non-squamous non-small cell lung cancer.

DRUGGemcitabine

A chemotherapy used for the treatment of several types of cancer including advanced or metastatic pancreatic ductal adenocarcinoma.

DRUGGemcitabine + Nab-paclitaxel

A chemotherapy regimen used for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma.


Locations(12)

Cedars-Sinai Medical Center

Los Angeles, California, United States

Johns Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Univ of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, United States

SCRI Oncology Partners

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Peninsula and Southeast Oncology

Frankston, Victoria, Australia

View Full Details on ClinicalTrials.gov

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NCT07020221


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