A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer

Purpose

This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer.

Conditions

  • Non Small Cell Lung Cancer
  • KRAS Activating Mutation

Eligibility

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

Inclusion Criteria

  • Male or female subjects ≥ 18 years of age - Histologic or cytologic evidence of NSCLC - Known KRAS or BRAF mutation - The subject must have received appropriate prior therapy - Measurable disease according to RECIST 1.1 - An Eastern Cooperative Group (ECOG) performance status ≤ 1 - Adequate organ function - Adequate recovery from toxicities related to prior treatments - Agreement to use highly effective method of contraceptive

Exclusion Criteria

  • Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy - History of prior malignancy, with the exception of curatively treated malignancies - Major surgery within 4 weeks (excluding placement of vascular access) - History of treatment with a direct and specific inhibitor of MEK, KRAS or BRAF except for treatment of BRAF V-600E mutant NSCLC - Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 7 days prior to the first dose and during the course of therapy - Symptomatic brain metastases requiring steroids or other local interventions. - Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy - Active skin disorder that has required systemic therapy within the past 1 year - History of rhabdomyolysis - Concurrent ocular disorders - Concurrent heart disease or severe obstructive pulmonary disease - Subjects with the inability to swallow oral medications

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm 1: avutometinib (VS-6766) monotherapy 		in patients with NSCLC KRAS-G12V tumor
  • Drug: avutometinib (VS-6766)
    Monotherapy
Experimental
Arm 2: avutometinib (VS-6766) in combination with defactinib 		in patients with a NSCLC KRAS-G12V tumor
  • Drug: avutometinib (VS-6766) and Defactinib
    Combination therapy
    Other names:
    • avutometinib (VS-6766) and VS-6063
Experimental
Arm 3: avutometinib (VS-6766) in combination with defactinib 		in patients with a NSCLC KRAS-other (non-G12V) tumor
  • Drug: avutometinib (VS-6766) and Defactinib
    Combination therapy
    Other names:
    • avutometinib (VS-6766) and VS-6063
Experimental
Arm 4: avutometinib (VS-6766) in combination with defactinib 		in patients with a NSCLC BRAF-V600E tumor
  • Drug: avutometinib (VS-6766) and Defactinib
    Combination therapy
    Other names:
    • avutometinib (VS-6766) and VS-6063
Experimental
Arm 5:avutometinib (VS-6766) in combination with defactinib 		in patients with a NSCLC BRAF-non-V600E tumor
  • Drug: avutometinib (VS-6766) and Defactinib
    Combination therapy
    Other names:
    • avutometinib (VS-6766) and VS-6063

More Details

Status
Completed
Sponsor
Verastem, Inc.

Study Contact

Detailed Description

This is a multicenter, open-label Phase 2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with KRAS and BRAF mutant NSCLC following treatment with an appropriate platinum-based regimen and an approved immune checkpoint inhibitor (CPI).