Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients (RAMP203)

January 8, 2026 updated by: Verastem, Inc.

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
153

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Belgium
      • Ghent, Belgium, 9000
        • University Hospital Gent
      • Liège, Belgium, 4000
        • CHU de Liege
  • France
      • Lille, France, 59037
        • CHRU of Lille
      • Paris, France, 75014
        • Hôpital Cochin
      • Suresnes, France, 92150
        • Hôpital Foch
  • Netherlands
      • Leiden, Netherlands, 2333 ZA
        • Leids Universitair Medisch Centrum
      • Rotterdam, Netherlands, 3015 GD
        • Erasmus MC
  • Spain
      • A Coruña, Spain, 15006
        • Hospital Teresa Herrera (C.H.U.A.C)
      • Madrid, Spain, 28040
        • Hospital Universitario Fundación Jiménez Díaz
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañón
      • Málaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria
      • Seville, Spain, 41009
        • Hospital Universitario Virgen De La Macarena
  • United Kingdom
      • Leicester, United Kingdom, LE2 7LX
        • University of Leicester
      • London, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital
      • Sutton, United Kingdom, SM2 5PT
        • Royal Marsden Hospital
  • United States
    • Colorado
      • Boulder, Colorado, United States, 80303
        • Rocky Mountain Cancer Center, LLP
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Georgetown University Medical Center
      • Washington D.C., District of Columbia, United States, 20010
        • MedStar Washington Hospital Center, MedStar Georgetown Cancer Institute,
    • Illinois
      • Arlington Heights, Illinois, United States, 60005
        • Illinois Cancer Specialists
    • Maryland
      • Rockville, Maryland, United States, 20850
        • Maryland Oncology & Hematology, P.A.
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • Minnesota
      • Woodbury, Minnesota, United States, 55125
        • Minnesota Oncology Hematology, P.A
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
      • Columbus, Ohio, United States, 43210
        • Ohio State University Brain and Spine Hospital
    • Pennsylvania
      • Broomall, Pennsylvania, United States, 19008
        • Consultants in Medical Oncology & Hematology
      • Horsham, Pennsylvania, United States, 19044
        • Alliance Cancer Specialists,
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Fort Worth, Texas, United States, 76104
        • Texas Oncology - Fort Worth Cancer Center
      • Longview, Texas, United States, 75601
        • Texas Oncology
    • Virginia
      • Blacksburg, Virginia, United States, 24060
        • Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC
    • Washington
      • Vancouver, Washington, United States, 98684
        • Northwest Cancer Specialists

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female patients ≥ 18 years of age
  • Histologic or cytologic evidence of NSCLC
  • Known KRAS G12C mutation
  • Either exposed or not exposed to a KRAS inhibitor to be included in Part A (avutometinib + sotorasib + defactinib) and not exposed to KRAS inhibitor to be included in Part B (avutometinib + sotorasib + defactinib), Cohort 1
  • Received at least 1 dose of a G12C inhibitor to be included in Part B, Cohort 2 (avutometinib + sotorasib + defactinib)
  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: avutometinib (VS-6766)+sotorasib
To determine the recommended phase 2 dose (RP2D) for avutometinib (VS 6766) in combination with sotorasib in KRAS G12C inhibitor naïve and exposed patients
Drug: avutometinib and sotorasib
The RP2D of avutometinib + sotorasib determined in Part A will be used in Part B dose expansion
Other Names:
  • AMG 510
  • VS-6766
  • LUMAKRAS™
Experimental: avutometinib (VS-6766)+sotorasib - KRAS G12C inhibitor naïve
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients
Drug: avutometinib and sotorasib
The RP2D of avutometinib + sotorasib determined in Part A will be used in Part B dose expansion
Other Names:
  • AMG 510
  • VS-6766
  • LUMAKRAS™
Experimental: avutometinib (VS-6766)+sotorasib - KRAS G12C inhibitor exposed
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients
Drug: avutometinib and sotorasib
The RP2D of avutometinib + sotorasib determined in Part A will be used in Part B dose expansion
Other Names:
  • AMG 510
  • VS-6766
  • LUMAKRAS™
Experimental: avutometinib (VS-6766)+sotorasib+defactinib
To determine the recommended phase 2 dose (RP2D) for avutometinib (VS-6766) in combination with sotorasib and defactinib in KRAS G12C inhibitor exposed patients
Drug: avutometinib and sotorasib and defactinib
The RP2D of avutometinib + sotorasib + defactinib determined in Part A will be used in Part B dose expansion
Other Names:
  • AMG 510
  • VS-6063
  • VS-6766
  • LUMAKRAS™
Experimental: avutometinib (VS-6766)+sotorasib+defactinib - KRAS G12C inhibitor naive
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients
Drug: avutometinib and sotorasib and defactinib
The RP2D of avutometinib + sotorasib + defactinib determined in Part A will be used in Part B dose expansion
Other Names:
  • AMG 510
  • VS-6063
  • VS-6766
  • LUMAKRAS™
Experimental: avutometinib (VS-6766)+sotorasib+defactinib - KRAS G12C inhibitor exposed
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients
Drug: avutometinib and sotorasib and defactinib
The RP2D of avutometinib + sotorasib + defactinib determined in Part A will be used in Part B dose expansion
Other Names:
  • AMG 510
  • VS-6063
  • VS-6766
  • LUMAKRAS™

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part A: To determine RP2D for avutometinib in combination with sotorasib and the Alt-RP2D for avutometinib in combination with sotorasib and defactinib
Time Frame: From start of treatment to confirmation of RP2D; 28 days
Assessment of Dose-limiting toxicities (DLTs)
From start of treatment to confirmation of RP2D; 28 days
Part B: To determine the efficacy of the RP2D and/or Alt-RP2D identified from Part A
Time Frame: From start of treatment to confirmation of response; 16 weeks
Confirmed overall response rate per RECIST 1.1
From start of treatment to confirmation of response; 16 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to 5 years
From time of first dose of study intervention to death
Up to 5 years
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 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
Disease Control Rate (DCR)
Time Frame: Greater than or equal to 8 weeks
CR and PR stable disease as assessed per RECIST 1.1
Greater than or equal to 8 weeks
Progression Free Survival (PFS)
Time Frame: 24 months
From the time of first dose of study intervention to PD or death from any cause
24 months
Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 24 months
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
Plasma Pharmacokinetics (PK) of avutometinib, sotorasib, defactinib and relevant metabolites - Tmax
Time Frame: 10 weeks
time of Maximum concentration (Tmax)
10 weeks
Plasma Pharmacokinetics (PK) of avutometinib, sotorasib, defactinib and relevant metabolites -AUC
Time Frame: 10 weeks
Area under plasma Concentration (AUC) 0 to t
10 weeks
Plasma Pharmacokinetics (PK) of avutometinib, sotorasib, defactinib and relevant metabolites half-life
Time Frame: 10 weeks
concentration Half-life (T1/2)
10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Verastem, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Amgen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: MD Verastem, Verastem, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 12, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 29, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 29, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2021

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 8, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VS-6766-203

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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