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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05074810
Other study ID # VS-6766-203
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date April 12, 2022
Est. completion date April 2027

Study information

Verified date May 2024
Source Verastem, Inc.
Contact Verastem Call Center
Phone 781-292-4204
Email clinicaltrials@verastem.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C Non-Small Cell Lung Cancer (NSCLC) in patients who have been exposed to prior G12C inhibitor and those who have not been exposed to prior G12C inhibitor.


Description:

This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C mutant NSCLC.


Recruitment information / eligibility

Status Recruiting
Enrollment 153
Est. completion date April 2027
Est. primary completion date September 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Male or female patients = 18 years of age - Histologic or cytologic evidence of NSCLC - Known KRAS G12C mutation - Have not received a KRAS inhibitor to be included in Part A (avutometinib + sotorasib) and Part B (avutometinib + sotorasib + defactinib), Cohort 1 - Received at least 1 dose of a G12C inhibitor to be included in Part A (avutometinib + sotorasib + defactinib) and Part B, Cohort 2 - Must have received appropriate treatment with at least one prior systemic regimen, but no more than 2 prior regimens, for Stage 3B-C or 4 NSCLC - 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, minor surgery within 2 weeks (excluding placement of vascular access) - History of treatment with a direct and specific inhibitor of MEK - Exposure to strong CYP3A4 inhibitors or inducers within 14 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 - Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active - Active skin disorder that has required systemic therapy within the past year - History of rhabdomyolysis - Concurrent ocular disorders - Concurrent heart disease or severe obstructive pulmonary disease - Inability to swallow oral medications - Female patients that are pregnant or breastfeeding - Previously treated with sotorasib and were dose reduced due to toxicity

Study Design


Intervention

Drug:
avutometinib and sotorasib
The RP2D of avutometinib + sotorasib determined in Part A will be used in Part B dose expansion
avutometinib and sotorasib and defactinib
The RP2D of avutometinib + sotorasib + defactinib determined in Part A will be used in Part B dose expansion

Locations

Country Name City State
Belgium University Hospital Gent Gent
France CHRU of Lille Lille
France Hôpital Cochin Paris
France Hôpital Foch Suresnes
Netherlands Leids Universitair Medisch Centrum Leiden
Netherlands Erasmus MC Rotterdam
Spain Hospital Teresa Herrera (C.H.U.A.C) A Coruña
Spain Hospital General Universitario Gregorio Marañón Madrid
Spain Hospital Universitario Fundación Jiménez Díaz Madrid
Spain Hospital Universitario Virgen De La Victoria Málaga
Spain Hospital Universitario Virgen de la Macarena Sevilla
United Kingdom University of Leicester Leicester
United Kingdom Royal Marsden Hospital London
United Kingdom Royal Marsden Hospital Sutton
United States Illinois Cancer Specialists Arlington Heights Illinois
United States Texas Oncology Austin Texas
United States Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care Blacksburg Virginia
United States Dana Farber Cancer Institute Boston Massachusetts
United States Rocky Mountain Cancer Center, LLP Boulder Colorado
United States Consultants in Medical Oncology & Hematology Broomall Pennsylvania
United States Cleveland Clinic Taussig Cancer Center Cleveland Ohio
United States Ohio State University Brain and Spine Hospital Columbus Ohio
United States Henry Ford Health System Detroit Michigan
United States Virginia Cancer Specialists, PC Fairfax Virginia
United States Texas Oncology - Fort Worth Cancer Center Fort Worth Texas
United States Alliance Cancer Specialists, Horsham Pennsylvania
United States Texas Oncology Longview Texas
United States Maryland Oncology & Hematology, P.A. Rockville Maryland
United States Washington University School of Medicine Saint Louis Missouri
United States Georgetown University Medical Center Washington District of Columbia
United States MedStar Washington Hospital Center, MedStar Georgetown Cancer Institute, Washington District of Columbia
United States Minnesota Oncology Hematology, P.A Woodbury Minnesota

Sponsors (2)

Lead Sponsor Collaborator
Verastem, Inc. Amgen

Countries where clinical trial is conducted

United States,  Belgium,  France,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Part A: To determine RP2D for avutometinib in combination with sotorasib and the Alt-RP2D for avutometinib in combination with sotorasib and defactinib Assessment of Dose-limiting toxicities (DLTs) From start of treatment to confirmation of RP2D; 28 days
Primary Part B: To determine the efficacy of the RP2D and/or Alt-RP2D identified from Part A Confirmed overall response rate per RECIST 1.1 From start of treatment to confirmation of response; 16 weeks
Secondary Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs) Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale 24 months
Secondary Duration of Response (DOR) Time of first response to PD as assessed per RECIST 1.1 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 per RECIST 1.1 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 24 months
Secondary Overall Survival (OS) From time of first dose of study intervention to death Up to 5 years
Secondary Plasma Pharmacokinetics (PK) of avutometinib, sotorasib, defactinib and relevant metabolites - Tmax time of Maximum concentration (Tmax) 10 weeks
Secondary Plasma Pharmacokinetics (PK) of avutometinib, sotorasib, defactinib and relevant metabolites -AUC Area under plasma Concentration (AUC) 0 to t 10 weeks
Secondary Plasma Pharmacokinetics (PK) of avutometinib, sotorasib, defactinib and relevant metabolites half-life concentration Half-life (T1/2) 10 weeks
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