Actively Recruiting
Phase II Study of Adagrasib and Stereotactic Radiosurgery for Patients With Metastatic KRAS G12C-mutated Non-Small Cell Lung Cancer With Untreated Brain Metastases
Led by Ryan Gentzler, MD · Updated on 2026-04-08
30
Participants Needed
3
Research Sites
52 weeks
Total Duration
On this page
Sponsors
R
Ryan Gentzler, MD
Lead Sponsor
M
Mirati Therapeutics Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the combination of stereotactic radiosurgery (SRS) and the drug adagrasib for treating brain metastases in patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC). This phase 2 trial aims to assess how well this treatment controls intracranial disease. The study plans to enroll 30 patients to better understand the effects of this combined approach. All participants will receive oral adagrasib at a dose of 600mg twice daily in treatment cycles. SRS will be delivered as part of standard care, occurring between 4 weeks before and up to 3 weeks after starting adagrasib. Adagrasib dosing will pause the day before and the day of SRS treatment. There is no set maximum duration for receiving adagrasib. Some patients may have had SRS prior to joining the study. Participants will be monitored closely with evaluations of disease control in the brain at 3 months as the primary outcome. Additional measures include overall response rates, progression-free survival, overall survival, and adverse events over 52 months. Researchers will collect health data throughout to assess treatment impact and safety. Participation involves ongoing assessments and treatments under medical supervision until study completion or discontinuation.
CONDITIONS
Brief Title
Adagrasib + SRS for Patients With Metastatic KRAS G12C-mutated NSCLC With Untreated Brain Metastases
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Provide written informed consent and HIPAA authorization.
- Age 18 years or older.
- ECOG Performance Status of 0 or 1 within 28 days before registration.
- Confirmed stage IV non-small cell lung cancer or metastatic recurrence after earlier treatment.
- Presence of KRAS G12C mutation verified by tissue or blood testing.
- At least one untreated brain metastasis measuring at least 2mm without any single lesion larger than 3 cm.
- Brain metastases suitable for stereotactic radiosurgery (SRS) or previously treated with SRS within specific timeframes.
- No contraindications to SRS; able to hold anticoagulation for treatment if needed.
- Received no more than two prior lines of systemic therapy for metastatic disease.
- Adequate organ function based on laboratory tests.
- Negative pregnancy test for females of childbearing potential.
- Willingness to use effective contraception or abstain if applicable.
- HIV patients with undetectable viral load on therapy are eligible.
- Hepatitis B or C infection must be controlled or cured.
- Ability to understand and comply with study procedures.
You will not qualify if you...
- Prior treatment with a KRAS G12C tyrosine kinase inhibitor.
- Active infection requiring systemic therapy (except controlled HIV or hepatitis).
- Uncontrolled or significant recent illness.
- Prolonged QTc interval over 480 milliseconds or congenital Long QT Syndrome.
- Receiving radiation to extra-cranial lesions at enrollment for pain or prevention.
- Use of strong CYP3A enzyme inhibitors or inducers that cannot be switched.
- Treatment with any investigational drug within 28 days prior to registration.
- Pregnant or breastfeeding women.
- Other malignancies that could interfere with safety or study results as judged by physician.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - No maximum duration; ongoing until disease progression or discontinuation
Participants receive oral adagrasib 600mg twice daily in cycles and stereotactic radiosurgery (SRS) as standard of care. SRS may occur between 4 weeks before and up to 3 weeks after starting adagrasib. Adagrasib is paused the day before and the day of SRS. Treatment duration has no maximum limit.
Visits as needed for treatment and monitoring
Trial Site Locations
Total: 3 locations
1
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Actively Recruiting
2
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
Actively Recruiting
3
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Actively Recruiting
Research Team
R
Ryan Gentzler, MD, MS
A
Amber Ryba
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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