Clinical Trials /

A Study of VS-6766 v. VS-6766 + Defactinib in Recurrent G12V or Other KRAS-Mutant Non-Small Cell Lung Cancer

NCT04620330

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of VS-6766 v. VS-6766 + Defactinib in Recurrent G12V or Other KRAS-Mutant Non-Small Cell Lung Cancer
  • Official Title: A Phase 2 Study of VS-6766 (Dual RAF/MEK Inhibitor) as a Single Agent and In Combination With Defactinib (FAK Inhibitor) in Recurrent KRAS-Mutant (KRAS-MT) Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: VS-6766-202
  • NCT ID: NCT04620330

Conditions

  • Non Small Cell Lung Cancer
  • KRAS Activating Mutation

Interventions

DrugSynonymsArms
VS-6766Part A
VS-6766 and DefactinibVS-6766 and VS-6063Part A

Purpose

This study will assess the safety and efficacy of 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, non-randomized, open-label Phase 1b/2 study designed to evaluate
      safety and tolerability and efficacy of VS-6766 versus VS-6766 in combination with defactinib
      in subjects with KRAS-MT NSCLC following treatment with an appropriate platinum-based regimen
      and an approved immune checkpoint inhibitor (CPI).
    

Trial Arms

NameTypeDescriptionInterventions
Part AExperimentalTo determine the optimal regimen, either VS-6766 monotherapy or VS-6766 in combination with defactinib, for subsequent evaluation for efficacy in the expansion phase (Part B).
  • VS-6766
  • VS-6766 and Defactinib
Part BExperimentalTo determine the efficacy of the optimal regimen identified from Part A
  • VS-6766
  • VS-6766 and Defactinib

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female subjects ≥ 18 years of age

          -  Histologic or cytologic evidence of NSCLC

          -  Known KRAS 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 or KRAS

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: To determine the optimal regimen, either VS-6766 monotherapy or VS-6766 in combination with defactinib,
Time Frame:From start of treatment to confirmation of response; 24 weeks
Safety Issue:
Description:Confirmed overall response rate per RECIST 1.1

Secondary Outcome Measures

Measure:Overall Response Rate as assessed by Investigator
Time Frame:From start of treatment to confirmation of response; 24 weeks
Safety Issue:
Description:Proportioned subjects achieving a CR or PR as assess by the investigator
Measure:Duration of Response (DOR)
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
Safety Issue:
Description:Time of first response to PD as assessed by the IRC
Measure:Disease Control Rate (DCR)
Time Frame:Greater than or equal to 8 weeks
Safety Issue:
Description:CR and PR stable disease as assessed by the IRC
Measure:Progression Free Survival (PFS)
Time Frame:Up to 5 years
Safety Issue:
Description:From the time of first dose of study intervention to PD or death from any cause
Measure:Overall Survival (OS)
Time Frame:Up to 5 years
Safety Issue:
Description:From time of first dose of study intervention to death

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Verastem, Inc.

Trial Keywords

  • NSCLC
  • KRAS-G12V
  • G12V

Last Updated

April 9, 2021