Clinical trial NCT04620330: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
KRAS Activating Mutation
Keywords: NSCLC
KRAS-G12V
G12V
BRAF
V600E
KRAS
Lead sponsor: Verastem, Inc.
Sponsor class: INDUSTRY
First posted: 2020-11-06
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC
timeFrame: From start of treatment to confirmation of response; 24 weeks
measure: To evaluate the initial efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC
timeFrame: From start of treatment to confirmation of response; 24 weeks
measure: To determine efficacy in KRAS-other (non-G12V) NSCLC
timeFrame: From start of treatment to confirmation of response; 24 weeks
measure: To determine the efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC
timeFrame: From start of treatment to confirmation of response; 24 weeks
Secondary outcomes:
measure: 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
timeFrame: 24 weeks
measure: Overall Response Rate per RECIST 1.1 as assessed by Investigator
timeFrame: From start of treatment to confirmation of response; 24 weeks
measure: Duration of Response (DOR)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: Greater than or equal to 8 weeks
measure: Progression Free Survival (PFS)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center-Duchossois Center for Advanced Medicine
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Baton Rouge
country: United States
facility: Hematology/Oncology Clinic, LLP
state: Louisiana
city: Columbia
country: United States
facility: Maryland Oncology Hematology P.A
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Cancer Institute/Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Lake Success
country: United States
facility: Northwell Health-Monter Cancer Center
state: New York
city: Columbus
country: United States
facility: Zangmeister Cancer Center
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Univ. of Pittsburgh Med Center
state: Pennsylvania
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Assoc.
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology Ft Worth Cancer Center
state: Texas
city: Grapevine
country: United States
facility: Texas Oncology
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Hopital Nord Marseille
city: Paris
country: France
facility: Hopital Cochin
city: Saint-Herblain
country: France
facility: Institute De Cancerologie De L'Ouest Site Paul Papin Oncologie Medicale
city: Villejuif
country: France
facility: Cancerologie Gustave Roussy - Cancer Medicine
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Leipzig
country: Germany
facility: Universitatsklinkum Leipzig
city: Straße
country: Germany
facility: Evangelisches Klinkum Bethel
city: Orbassano
country: Italy
facility: Azienda Ospedaliera Universitaria
state: Torino
city: Meldola
country: Italy
facility: Irccs, Irts
city: Parma
country: Italy
facility: UOC di Oncologia Medica
city: Verona
country: Italy
facility: Centro Ricerche Cliniche di Verona
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Coruña
country: Spain
facility: Complejo Hospitalario Universiario a Coruna Teresa
city: Córdoba
country: Spain
facility: Hospital 12 de Octubre
city: Málaga
country: Spain
facility: Universitario de Teatinos
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de la Macarena
Study officials:
affiliation: University of Colorado, Denver
name: Ross Camidge, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Verastem, Inc.
name: MD Verastem
role: STUDY_DIRECTOR
References:
citation: 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.