This is a Phase II, open-label, multicenter, multi cohort, study of VS-6063 (defactinib), a focal adhesion kinase inhibitor, in patients with KRAS mutant non-small cell lung cancer (NSCLC). NSCLC with a KRAS mutation is required for study entry and subjects will be enrolled into 1 of 4 cohorts based on the status of their INK4a/Arf and p53 mutations. The purpose of this study is to demonstrate if VS-6063 (defactinib) improves PFS within each cohort. The safety and tolerability of VS-6063, tumor response rate, progression free survival and overall survival will also be assessed. The pharmacodynamic effects of VS-6063 (defactinib) will be examined in a tumor biopsy and a blood sample.
Eleven subjects will be enrolled into one of four cohorts: Cohort A (KRAS mutation, wild type INK4a/ARF and wildtype p53), Cohort B (KRAS mutation, INK4s/ARF mutation and wild type p53), Cohort C (KRAS mutation, wild type INK4a/ARF and p53 mutation), and Cohort D (KRAS mutation, INK4a/ARF mutation and p53 mutation). If \>/= 4 patients demonstrate PFS at 12 weeks in each cohort, an additional 23 subjects will be enrolled.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
University of Colorado Cancer Center, Anschutz Medical Campus
Denver, Colorado, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Washington University School of Medicine
St Louis, Missouri, United States
Knight Cancer Institute, Oregon Health and Science University
Portland, Oregon, United States
University of Pittsburgh Medical Center Cancer Center
Pittsburgh, Pennsylvania, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Demonstrate that VS-6063 (defactinib), will improve PFS at 12 weeks (PFS12) within each cohort.
Time frame: From baseline through 12 weeks of treatment
Evaluate the response rate (RR)
RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.
Time frame: Every 6 weeks from baseline through the end of treatment, an expected average of 4 months
Evaluate progression free survival
PFS will be estimated in each cohort using Kaplan-Meier product limit estimates.
Time frame: From the date of first treatment to the date of progression including death from any cause, expected average at least 4 months
Evaluate Overall Survival (OS)
OS in each cohort will be estimated using Kaplan-Meier product limit estimates.
Time frame: OS will be calculated from the date of first treatment to the date of death from any cause, expected average of at least 12 months. Patients who did not experience death will be censored at the last follow-up time.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.