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

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

  • Pancreatic Ductal Adenocarcinoma
  • Non Small Cell Lung Cancer
  • Colorectal Cancer
  • Solid Tumor, Adult
  • G12D Mutated KRAS

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