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Non Small Cell Lung CancerPhase 1/2RAMP204NCT05375994

Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients

A Phase 1/2 study testing avutometinib (VS-6766) and adagrasib in people with Non Small Cell Lung Cancer and KRAS Activating Mutation, run by Verastem, Inc. at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with G12C Non-Small Cell Lung Cancer (NSCLC) who have been exposed to prior G12C inhibitor and experienced progressive disease. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
avutometinib (VS-6766) and adagrasib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
8 sitesUnited States
Study dates
1 Aug 2022to 15 Jun 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female subjects ≥ 18 years of age
  • Histologic or cytologic evidence of NSCLC
  • Known KRAS G12C mutation
  • The subject must have received prior therapy with a KRAS G12C inhibitor and experienced progression
  • Must have received appropriate treatment with at least one prior systemic regimen, but no more than 3 prior regimens, for Stage 3B-C or 4 NSCLC
  • Measurable disease according to RECIST 1.1
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  • 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

Who cannot join

  • Prior chemotherapy, targeted therapies, radiotherapy, immunotherapy or treatment with an investigational agent within 14 days of receipt of study drug (within 6 weeks for nitrosoureas, mitomycin C and chest radiation; within 6 months prior to Cycle 1 Day 1 for chest radiation > 30Gy)
  • History of prior malignancy, with the exception of curatively treated malignancies
  • Major surgery within 4 weeks (excluding placement of vascular access)
  • Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy
  • Exposure to strong inhibitors of breast cancer resistance protein (BCRP) within 14 days prior to the first dose and during the course of therapy
  • Symptomatic brain metastases requiring steroids or other local interventions within the 2 weeks prior to initiation of therapy
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  • 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 1 year
  • History of rhabdomyolysis or interstitial lung disease
  • Concurrent ocular disorders
  • Concurrent heart disease or severe obstructive pulmonary disease
  • Subjects with the inability to swallow oral medications

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • University of Colorado Hospital Anschutz Cancer Pavllion

    Aurora, Colorado, 80045

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 275514

  • Virginia Cancer Specialists, NEXT Oncology

    Fairfax, Virginia, 22031

  • Mayo Clinic Cancer Center

    Jacksonville, Florida, 32224

  • Medical College Wisconsin

    Milwaukee, Wisconsin, 53226

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • UCSF Thoracic Oncology

    San Francisco, California, 94158

Other trials in United States

About this study

Official title: A Phase 1/2 Study of Avutometinib (VS-6766) in Combination With Adagrasib in Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer (NSCLC) (RAMP 204)

This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with G12C Non-Small Cell Lung Cancer (NSCLC) who have been exposed to prior G12C inhibitor and experienced progressive disease.

Read the detailed description

This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety, tolerability and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with KRAS G12C mutant NSCLC who have been exposed to prior G12C inhibitor and experienced progressive disease.

Being tested
avutometinib (VS-6766) and adagrasib
Keywords
NSCLC, KRAS G12C, Non Small Cell Lung Cancer, Metastatic Cancer, Adagrasib, Avutometinib (VS-6766)
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis, Lung Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • avutometinib (VS-6766) and adagrasibDrug

    Also called KRAS G12C Inhibitor, adagrasib, KRAZATI®

    The RP2D of VS-6766 + adagrasib determined in Part A will be used in Part B dose expansion

Study groups in NCT05375994
Study groupRoleWhat they receive
avutometinib(VS-6766)+adagrasibExperimentalTo determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients
Receives: Drug: avutometinib (VS-6766) and adagrasib
avutometinib (VS-6766)+adagrasib RP2DExperimentalTo determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients
Receives: Drug: avutometinib (VS-6766) and adagrasib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib

    Assessment of Dose-limiting toxicities (DLTs)

    Measured: From start of treatment to confirmation of RP2D; 28 days

  2. To determine the efficacy of the optimal regimen identified from Part A

    Confirmed overall response rate per RECIST 1.1

    Measured: From start of treatment to confirmation of response; 16 weeks

Secondary outcomes (10)

  1. To characterize the safety and toxicity profile:

    • Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs) assessed by the toxicity grading of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0)
    • Severity of Adverse events (AEs) and Serious Adverse Events (SAEs) by toxicity grade assessed by the toxicity grading of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0)
    • Duration of Adverse events (AEs) and Serious Adverse Events (SAEs)
    • Incidence of clinically significant changes in lab parameters
    • Incidence of abnormal vital signs (including systolic and diastolic blood pressure in mmHg)

    Measured: 24 Months

  2. ECG QT Interval

    Corrected ECG QT interval by Fredericia (QTcF)

    Measured: 24 months

  3. Duration of Response (DOR)

    Time of first response to PD as assessed per RECIST 1.1

    Measured: 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

  4. Disease Control Rate (DCR)

    CR and PR stable disease as assessed per RECIST 1.1

    Measured: Greater than or equal to 8 weeks

  5. Progression Free Survival (PFS)

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

    Measured: 24 months

  6. Overall Survival (OS)

    From time of first dose of study intervention to death

    Measured: Up to 5 years

  7. Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Tmax

    time of Maximum concentration (Tmax)

    Measured: 10 weeks

  8. Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - AUC

    Area under plasma Concentration (AUC) 0 to t

    Measured: 10 weeks

  9. Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Half-life

    concentration Half-life (T1/2)

    Measured: 10 weeks

  10. Clinical Benefit Rate

    defined as Complete Response+Partial Response +Stable Disease

    Measured: ≥ 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2022
  2. Study start1 Aug 2022
  3. Primary completion15 Jun 2026
  4. Study completion15 Jun 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05375994
Sponsor's protocol ID
VS-6766-204
Acronym
RAMP204
Status last verified
Jun 2026
First submitted
2 May 2022
Last updated
2 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing avutometinib (VS-6766) and adagrasib in people with Non Small Cell Lung Cancer and KRAS Activating Mutation, run by Verastem, Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib (time frame: From start of treatment to confirmation of RP2D; 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05375994.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.

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