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Completed

NCT Number: NCT05375994

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

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.

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Key information

Conditions

Non Small Cell Lung Cancer Advanced Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung KRAS Activating Mutation Lung Diseases Lung Neoplasms Malignant Neoplasm of Lung Malignant Neoplastic Disease Metastatic Cancer Neoplasm Metastasis Neoplasms Neoplasms by Site Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

UCSF Thoracic Oncology, San Francisco, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • 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

  • 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
  • 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

Treatment and study plan

avutometinib (VS-6766) and adagrasib

Drug

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

Other names: KRAS G12C Inhibitor, adagrasib, KRAZATI®

Primary outcomes

  1. 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

    Assessment of Dose-limiting toxicities (DLTs)

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

    Time frame: From start of treatment to confirmation of response; 16 weeks

    Confirmed overall response rate per RECIST 1.1

Secondary outcomes

  1. To characterize the safety and toxicity profile:

    Time frame: 24 Months

    • 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)

  2. ECG QT Interval

    Time frame: 24 months

    Corrected ECG QT interval by Fredericia (QTcF)

  3. 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

  4. Disease Control Rate (DCR)

    Time frame: Greater than or equal to 8 weeks

    CR and PR stable disease as assessed per RECIST 1.1

  5. Progression Free Survival (PFS)

    Time frame: 24 months

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

  6. Overall Survival (OS)

    Time frame: Up to 5 years

    From time of first dose of study intervention to death

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

    Time frame: 10 weeks

    time of Maximum concentration (Tmax)

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

    Time frame: 10 weeks

    Area under plasma Concentration (AUC) 0 to t

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

    Time frame: 10 weeks

    concentration Half-life (T1/2)

  10. Clinical Benefit Rate

    Time frame: ≥ 6 months

    defined as Complete Response+Partial Response +Stable Disease

Sponsors and collaborators

Lead sponsor

Verastem, Inc.

Industry

Collaborators

  • Mirati Therapeutics Inc.

Registry information

Official study 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)

Acronym: RAMP204

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
May 17, 2022
Registry last updated
Jul 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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