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

Non Small Cell Lung Cancer Clinical Trial

— RAMP202  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04620330
• Other study ID #: VS-6766-202
• Status: Completed
• Phase: Phase 2
• Start date: December 31, 2020
• Est. completion date: December 12, 2023

Study information

• Verified date: January 2024
• Source: Verastem, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: December 12, 2023
• Est. primary completion date: August 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• KRAS Activating Mutation
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
France	Centre Leon Berard	Lyon
France	Hopital Nord Marseille	Marseille
France	Hopital Cochin	Paris
France	Institute De Cancerologie De L'Ouest Site Paul Papin Oncologie Medicale	Saint-Herblain
France	Cancerologie Gustave Roussy - Cancer Medicine	Villejuif
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Universitatsklinkum Leipzig	Leipzig
Germany	Evangelisches Klinkum Bethel	Straße
Italy	Irccs, Irts	Meldola
Italy	Azienda Ospedaliera Universitaria	Orbassano	Torino
Italy	UOC di Oncologia Medica	Parma
Italy	Centro Ricerche Cliniche di Verona	Verona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital 12 de Octubre	Córdoba
Spain	Complejo Hospitalario Universiario a Coruna Teresa	Coruña
Spain	Universitario de Teatinos	Málaga
Spain	Hospital Universitario Virgen de la Macarena	Sevilla
United States	Emory University School of Medicine	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Hematology/Oncology Clinic, LLP	Baton Rouge	Louisiana
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Chattanooga Oncology Hematology Assoc.	Chattanooga	Tennessee
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Medical Center-Duchossois Center for Advanced Medicine	Chicago	Illinois
United States	Maryland Oncology Hematology P.A	Columbia	Maryland
United States	Zangmeister Cancer Center	Columbus	Ohio
United States	Texas Oncology	Dallas	Texas
United States	Henry Ford Cancer Institute/Henry Ford Health System	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Texas Oncology Ft Worth Cancer Center	Fort Worth	Texas
United States	Texas Oncology	Grapevine	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Northwell Health-Monter Cancer Center	Lake Success	New York
United States	Rocky Mountain Cancer Centers	Lone Tree	Colorado
United States	Tennessee Oncology	Nashville	Tennessee
United States	Illinois Cancer Specialists	Niles	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Univ. of Pittsburgh Med Center	Pittsburgh	Pennsylvania
United States	Northwest Cancer Specialists, P.C.	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Verastem, Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	From start of treatment to confirmation of response; 24 weeks
Primary	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	From start of treatment to confirmation of response; 24 weeks
Primary	To determine efficacy in KRAS-other (non-G12V) NSCLC	Confirmed overall response rate per RECIST 1.1	From start of treatment to confirmation of response; 24 weeks
Primary	To determine the efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC	Confirmed overall response rate per RECIST 1.1	From start of treatment to confirmation of response; 24 weeks
Secondary	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)	24 weeks
Secondary	Overall Response Rate per RECIST 1.1 as assessed by Investigator	Proportioned subjects achieving a CR or PR as assess by the investigator	From start of treatment to confirmation of response; 24 weeks
Secondary	Duration of Response (DOR)	Time of first response to PD as assessed by the IRC	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
Secondary	Disease Control Rate (DCR)	CR and PR stable disease as assessed by the IRC	Greater than or equal to 8 weeks
Secondary	Progression Free Survival (PFS)	From the time of first dose of study intervention to PD or death from any cause	Up to 5 years
Secondary	Overall Survival (OS)	From time of first dose of study intervention to death	Up to 5 years