Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients
RAMP204
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)
1 other identifier
interventional
85
1 country
8
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2022
Typical duration for phase_1
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 2, 2022
CompletedFirst Posted
Study publicly available on registry
May 17, 2022
CompletedStudy Start
First participant enrolled
August 1, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 24, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2026
CompletedMay 18, 2025
May 1, 2025
3.4 years
May 2, 2022
May 13, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib
Assessment of Dose-limiting toxicities (DLTs)
From start of treatment to confirmation of RP2D; 28 days
To determine the efficacy of the optimal regimen identified from Part A
Confirmed overall response rate per RECIST 1.1
From start of treatment to confirmation of response; 16 weeks
Secondary Outcomes (10)
To characterize the safety and toxicity profile:
24 Months
ECG QT Interval
24 months
Duration of Response (DOR)
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)
Greater than or equal to 8 weeks
Progression Free Survival (PFS)
24 months
- +5 more secondary outcomes
Study Arms (2)
avutometinib(VS-6766)+adagrasib
EXPERIMENTALTo determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients
avutometinib (VS-6766)+adagrasib RP2D
EXPERIMENTALTo determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients
Interventions
The RP2D of VS-6766 + adagrasib determined in Part A will be used in Part B dose expansion
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Verastem, Inc.lead
- Mirati Therapeutics Inc.collaborator
Study Sites (8)
UCSF Thoracic Oncology
San Francisco, California, 94158, United States
University of Colorado Hospital Anschutz Cancer Pavllion
Aurora, Colorado, 80045, United States
Mayo Clinic Cancer Center
Jacksonville, Florida, 32224, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 275514, United States
Virginia Cancer Specialists, NEXT Oncology
Fairfax, Virginia, 22031, United States
Medical College Wisconsin
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
MD Verastem
Verastem, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 2, 2022
First Posted
May 17, 2022
Study Start
August 1, 2022
Primary Completion
December 24, 2025
Study Completion
January 1, 2026
Last Updated
May 18, 2025
Record last verified: 2025-05