A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer (RAMP202)

• ClinicalTrials.gov Identifier: NCT04620330
• Recruitment Status: Completed
• First Posted: November 6, 2020
• Last Update Posted: January 12, 2024
• Sponsor: Verastem, Inc.
• Information provided by (Responsible Party): Verastem, Inc.

Tracking Information

• First Submitted Date: November 5, 2020
• First Posted Date: November 6, 2020
• Last Update Posted Date: January 12, 2024
• Actual Study Start Date: December 31, 2020
• Actual Primary Completion Date: August 29, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 22, 2022)

• To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From start of treatment to confirmation of response; 24 weeks ]
  Confirmed overall response rate per RECIST 1.1

Original Primary Outcome Measures (submitted: November 5, 2020)

• 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 ]
  Confirmed overall response rate per RECIST 1.1
• Part B: To determine the efficacy of the optimal regimen identified from Part A [ Time Frame: From start of treatment to confirmation of response; 24 weeks ]
  Confirmed overall response rate per RECIST 1.1

Current Secondary Outcome Measures (submitted: June 22, 2022)

• 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 [ Time Frame: 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 [ Time Frame: 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 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 ]
  Time of first response to PD as assessed by the IRC
• Disease Control Rate (DCR) [ Time Frame: Greater than or equal to 8 weeks ]
  CR and PR stable disease as assessed by the IRC
• Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
  From the time of first dose of study intervention to PD or death from any cause
• Overall Survival (OS) [ Time Frame: Up to 5 years ]
  From time of first dose of study intervention to death

Original Secondary Outcome Measures (submitted: November 5, 2020)

• Overall Response Rate as assessed by Investigator [ Time Frame: 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 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 8 months ]
  Time of first response to PD as assessed by the IRC
• Disease Control Rate (DCR) [ Time Frame: Greater than or equal to 8 weeks ]
  CR and PR stable disease as assessed by the IRC
• Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
  From the time of first dose of study intervention to PD or death from any cause
• Overall Survival (OS) [ Time Frame: Up to 5 years ]
  From time of first dose of study intervention to death

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer
• Official Title: A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) as a Single Agent and In Combination With Defactinib (FAK Inhibitor) in Recurrent KRAS-Mutant (KRAS-MT) and BRAF-Mutant (BRAF-MT) Non-Small Cell Lung Cancer (NSCLC) (RAMP 202)
• 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).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non Small Cell Lung Cancer
• KRAS Activating Mutation

Intervention

• Drug: avutometinib (VS-6766)
  Monotherapy
• Drug: avutometinib (VS-6766) and Defactinib
  Combination therapy
  Other Name: avutometinib (VS-6766) and VS-6063

Study Arms

• Experimental: Arm 1: avutometinib (VS-6766) monotherapy
  in patients with NSCLC KRAS-G12V tumor
  Intervention: Drug: avutometinib (VS-6766)
• Experimental: Arm 2: avutometinib (VS-6766) in combination with defactinib
  in patients with a NSCLC KRAS-G12V tumor
  Intervention: Drug: avutometinib (VS-6766) and Defactinib
• Experimental: Arm 3: avutometinib (VS-6766) in combination with defactinib
  in patients with a NSCLC KRAS-other (non-G12V) tumor
  Intervention: Drug: avutometinib (VS-6766) and Defactinib
• Experimental: Arm 4: avutometinib (VS-6766) in combination with defactinib
  in patients with a NSCLC BRAF-V600E tumor
  Intervention: Drug: avutometinib (VS-6766) and Defactinib
• Experimental: Arm 5:avutometinib (VS-6766) in combination with defactinib
  in patients with a NSCLC BRAF-non-V600E tumor
  Intervention: Drug: avutometinib (VS-6766) and Defactinib

• Publications *: Capelletto E, Bironzo P, Denis L, Koustenis A, Bungaro M, Novello S. Single agent VS-6766 or VS-6766 plus defactinib in KRAS-mutant non-small-cell lung cancer: the RAMP-202 phase II trial. Future Oncol. 2022 May;18(16):1907-1915. doi: 10.2217/fon-2021-1582. Epub 2022 Mar 14.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 11, 2024): 90
• Original Estimated Enrollment (submitted: November 5, 2020): 100
• Actual Study Completion Date: December 12, 2023
• Actual Primary Completion Date: August 29, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Italy, Spain, United States

Administrative Information

• NCT Number: NCT04620330
• Other Study ID Numbers: VS-6766-202
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Verastem, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Verastem, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ross Camidge, MD, PhD; University of Colorado, Denver
• Study Director: MD Verastem; Verastem, Inc.

• PRS Account: Verastem, Inc.
• Verification Date: January 2024