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.
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
Monotherapy
Combination therapy
To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC
Confirmed overall response rate per RECIST 1.1
Time frame: From start of treatment to confirmation of response; 24 weeks
To evaluate the initial efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC
Confirmed overall response rate per RECIST 1.1
Time frame: From start of treatment to confirmation of response; 24 weeks
To determine efficacy in KRAS-other (non-G12V) NSCLC
Confirmed overall response rate per RECIST 1.1
Time frame: From start of treatment to confirmation of response; 24 weeks
To determine the efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC
Confirmed overall response rate per RECIST 1.1
Time frame: From start of treatment to confirmation of response; 24 weeks
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
Adverse events (AEs), serious AEs (SAEs), vital signs, physical examinations, clinical laboratory values, and tolerability (dose interruptions/reductions)
Time frame: 24 weeks
Overall Response Rate per RECIST 1.1 as assessed by Investigator
Proportioned subjects achieving a CR or PR as assess by the investigator
Time frame: From start of treatment to confirmation of response; 24 weeks
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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 D.C., District of Columbia, United States
Florida Cancer Specialists
Fort Myers, Florida, United States
Florida Cancer Specialists
St. 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
...and 35 more locations
Duration of Response (DOR)
Time of first response to PD as assessed by the IRC
Time frame: 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
Disease Control Rate (DCR)
CR and PR stable disease as assessed by the IRC
Time frame: Greater than or equal to 8 weeks
Progression Free Survival (PFS)
From the time of first dose of study intervention to PD or death from any cause
Time frame: Up to 5 years
Overall Survival (OS)
From time of first dose of study intervention to death
Time frame: Up to 5 years