A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer
- Conditions
- KRAS Activating MutationNon Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT04620330
- Lead Sponsor
- Verastem, Inc.
- Brief Summary
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.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1: avutometinib (VS-6766) monotherapy avutometinib (VS-6766) in patients with NSCLC KRAS-G12V tumor Arm 2: avutometinib (VS-6766) in combination with defactinib avutometinib (VS-6766) and Defactinib in patients with a NSCLC KRAS-G12V tumor Arm 3: avutometinib (VS-6766) in combination with defactinib avutometinib (VS-6766) and Defactinib in patients with a NSCLC KRAS-other (non-G12V) tumor Arm 4: avutometinib (VS-6766) in combination with defactinib avutometinib (VS-6766) and Defactinib in patients with a NSCLC BRAF-V600E tumor Arm 5:avutometinib (VS-6766) in combination with defactinib avutometinib (VS-6766) and Defactinib in patients with a NSCLC BRAF-non-V600E tumor
- Primary Outcome Measures
Name Time Method To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC From start of treatment to confirmation of response; 24 weeks Confirmed overall response rate per RECIST 1.1
To evaluate the initial efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC From start of treatment to confirmation of response; 24 weeks Confirmed overall response rate per RECIST 1.1
To determine efficacy in KRAS-other (non-G12V) NSCLC From start of treatment to confirmation of response; 24 weeks Confirmed overall response rate per RECIST 1.1
To determine the efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC From start of treatment to confirmation of response; 24 weeks Confirmed overall response rate per RECIST 1.1
- Secondary Outcome Measures
Name Time Method To characterize the safety and toxicity profile of VS-6766 as a monotherapy and in combination with defactinib in KRAS-MT NSCLC and in BRAF-MT NSCLC 24 weeks Adverse events (AEs), serious AEs (SAEs), vital signs, physical examinations, clinical laboratory values, and tolerability (dose interruptions/reductions)
Overall Response Rate per RECIST 1.1 as assessed by Investigator From start of treatment to confirmation of response; 24 weeks Proportioned subjects achieving a CR or PR as assess by the investigator
Duration of Response (DOR) Time from the first documentation of response to first documentation of progressive disease or death due to any cause, greater than or equal to 6 months Time of first response to PD as assessed by the IRC
Disease Control Rate (DCR) Greater than or equal to 8 weeks CR and PR stable disease as assessed by the IRC
Progression Free Survival (PFS) Up to 5 years From the time of first dose of study intervention to PD or death from any cause
Overall Survival (OS) Up to 5 years From time of first dose of study intervention to death
Related Research Topics
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Trial Locations
- Locations (43)
City of Hope
🇺🇸Duarte, California, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Rocky Mountain Cancer Centers
🇺🇸Lone Tree, Colorado, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Florida Cancer Specialists
🇺🇸Saint Petersburg, Florida, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center-Duchossois Center for Advanced Medicine
🇺🇸Chicago, Illinois, United States
Illinois Cancer Specialists
🇺🇸Niles, Illinois, United States
Hematology/Oncology Clinic, LLP
🇺🇸Baton Rouge, Louisiana, United States
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