KRAS Activating Mutation, Non Small Cell Lung Cancer
Conditions
Keywords
NSCLC, KRAS-G12V, G12V, BRAF, V600E, KRAS
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).
Interventions
Monotherapy
Combination therapy
Sponsors
Verastem, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to 5 years | From the time of first dose of study intervention to PD or death from any cause |
| 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 Survival (OS) | Up to 5 years | From time of first dose of study intervention to death |
| 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 |
Countries
France, Germany, Italy, Spain, United States
Outcome results
None listed