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

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.

Interventions

• VS-7375 · DRUG

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

• Cetuximab · DRUG

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

• Carboplatin + Pemetrexed + Pembrolizumab · DRUG

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

• Gemcitabine · DRUG

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

• Gemcitabine + Nab-paclitaxel · DRUG

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

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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.

Sites (14)

• Cedars-Sinai Medical Center, Los Angeles, California · RECRUITING
• Johns Hopkins University, Baltimore, Maryland · RECRUITING
• Massachusetts General Hospital, Boston, Massachusetts · RECRUITING
• University of Michigan, Ann Arbor, Michigan · RECRUITING
• Washington University School of Medicine, St Louis, Missouri · RECRUITING
• Laura & Isaac Perlmutter Cancer Center at NYU Langone, New York, New York · RECRUITING
• Univ of Pennsylvania, Abramson Cancer Center, Philadelphia, Pennsylvania · RECRUITING
• SCRI Oncology Partners, Nashville, Tennessee · RECRUITING
• MD Anderson Cancer Center, Houston, Texas · RECRUITING
• Huntsman Cancer Institute, Salt Lake City, Utah · RECRUITING
• University of Virginia, Charlottesville, Virginia · RECRUITING
• Virginia Cancer Specialists, Fairfax, Virginia · RECRUITING
• Virginia Mason Medical Center, Seattle, Washington · RECRUITING
• Peninsula and Southeast Oncology, Frankston, Victoria, Australia · RECRUITING