Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Sotorasib

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

To determine the recommended phase 2 dose (RP2D) for avutometinib (VS 6766) in combination with sotorasib in KRAS G12C inhibitor naïve and exposed patients

To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients

To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients

To determine the recommended phase 2 dose (RP2D) for avutometinib (VS-6766) in combination with sotorasib and defactinib in KRAS G12C inhibitor exposed patients

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

avutometinib and sotorasib

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

avutometinib and sotorasib and defactinib

Verastem Call Center

Jennifer Hege

David Andorsky, MD

Jeannette Crawford

Joshua Reuss, MD

Laura Lozano

Rajat Malhotra, MD

Teresa Saavedra

Nicholas Farrell, MD

Dana Farber Cancer Institute

Mark Awad, MD

Meir Stauss

Shirish Gadgeel, MD

Kayla McDonald

Girum Lemma, MD

Rose Tipton

Ramaswamy Govindan, MD

Alex Adjei

Alex Adjei, MD

Miranda Bean

Asrar AlAhmadi, MD

Maureen Lisowski

John Sprandio, MD

Beckie Banas

Benjamin Jacobs, MD

Amy Ressel

Jeffrey Yorio, MD

Alicia Latham

Stephen Richey, MD

Shelly Maxfield

John Lijo, MD

Natasha Holt

Jerome Goldschmidt, MD

Carrie Friedman

Alexander Spira, MD

Jade Mosselmans

Veerle Surmont

Alexis Cortot, MD

Marie Wislez, MD

Jaafar Bennouna, MD

Laurie Steinbusch

Joachim Aerts, MD

Rosario García Campelo

Rosario García Campelo, MD

Antonio Calles

Antonio Calles, MD

Manuel Dómine Gómez

Manuel Dómine Gómez, MD

Jose Carlos Benitez Montañez

Teresa García Manrique, MD

Samreen Ahmed, MD

Anna Minchom, MD

MD Verastem

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.

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.

Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients

A Phase 1/2 Study of Avutometinib (VS-6766) in Combination With Sotorasib With or Without Defactinib in Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer (NSCLC)

Assessment of Dose-limiting toxicities (DLTs)

Confirmed overall response rate per RECIST 1.1

Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale

Time of first response to PD as assessed per RECIST 1.1

CR and PR stable disease as assessed per RECIST 1.1

From the time of first dose of study intervention to PD or death from any cause

From time of first dose of study intervention to death

Area under plasma Concentration (AUC) 0 to t

Amgen

Verastem, Inc.

Spots Global Cancer Trial Database for avutometinib and sotorasib and defactinib