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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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. - Must have received ≥1 prior line of standard systemic therapy for advanced or metastatic disease or experienced cancer progression within 6 months of neoadjuvant or adjuvant therapy. - 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 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

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
VS-7375 Dose Escalation 		To determine the recommended phase 2 dose (RP2D) for VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation.
  • Drug: VS-7375
    VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.
Experimental
Cetuximab + VS-7375 Dose Escalation 		To determine the recommended phase 2 dose (RP2D) for cetuximab + VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation.
  • Drug: VS-7375
    VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.
  • Drug: Cetuximab
    Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR).
    Other names:
    • Erbitux
Experimental
VS-7375 Recommended Phase 2 Dose Expansion 		To determine the efficacy of VS-7375 at the recommended phase 2 dose (RP2D) in patients with advanced PDAC and NSCLC harboring a KRAS G12D mutation.
  • Drug: VS-7375
    VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.
Experimental
Cetuximab + VS-7375 Recommended Phase 2 Dose Expansion 		To determine the efficacy of cetuximab +VS-7375 at the recommended phase 2 dose (RP2D) in patients with advanced CRC harboring a KRAS G12D mutation.
  • Drug: VS-7375
    VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.
  • Drug: Cetuximab
    Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR).
    Other names:
    • Erbitux

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Leon Pappas, MD
617-724-4000
lpappas3@mgb.org

More Details

Status
Recruiting
Sponsor
Verastem, Inc.

Study Contact

Verastem Call Center
1 781 292 4204
clinicaltrials@verastem.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.