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

NCT07020221 · Verastem, Inc.
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Official title
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
About this study
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 criteria
Key Inclusion Criteria: * 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 Key Exclusion Criteria: * 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.
Study design
Enrollment target: 295 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-06-24
Estimated completion: 2028-12
Last updated: 2026-04-03
Interventions
Drug: VS-7375Drug: CetuximabDrug: Carboplatin + Pemetrexed + PembrolizumabDrug: GemcitabineDrug: Gemcitabine + Nab-paclitaxel
Primary outcomes
  • Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 (Up to 2.5 years)
  • Part A: To identify the MTD or MFD (Cycle 1 (each cycle is 21 days))
  • Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen (Up to 2.5 years)
Sponsor
Verastem, Inc. · industry
Contacts & investigators
ContactVerastem Call Center · contact · clinicaltrials@verastem.com · 1 781 292 4204
All locations (13)
Cedars-Sinai Medical CenterRecruiting
Los Angeles, California, United States
Johns Hopkins UniversityRecruiting
Baltimore, Maryland, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
University of MichiganRecruiting
Ann Arbor, Michigan, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Laura & Isaac Perlmutter Cancer Center at NYU LangoneRecruiting
New York, New York, United States
Univ of Pennsylvania, Abramson Cancer CenterRecruiting
Philadelphia, Pennsylvania, United States
SCRI Oncology PartnersRecruiting
Nashville, Tennessee, United States
MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
Huntsman Cancer InstituteRecruiting
Salt Lake City, Utah, United States
Virginia Cancer SpecialistsNot Yet Recruiting
Fairfax, Virginia, United States
Virginia Mason Medical CenterRecruiting
Seattle, Washington, United States
Peninsula and Southeast OncologyRecruiting
Frankston, Victoria, Australia
A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors · TrialPath