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

Eligibility: Inclusion Criteria
  •   Key
  •   * 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.