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Non Small Cell Lung CancerPhase 2NCT06248606

Adagrasib + SRS for Patients With Metastatic KRAS G12C-mutated NSCLC With Untreated Brain Metastases

A Phase 2 study testing Adagrasib and Stereotactic Radiosurgery in people with Non Small Cell Lung Cancer and NSCLC, run by Ryan Gentzler, MD at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a single arm phase 2 trial is to evaluate the efficacy of SRS plus adagrasib for the treatment of brain metastases for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC). A total of 30 patients will be enrolled on this study. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer, NSCLC, KRAS G12C
What is being tested?
Adagrasib and Stereotactic Radiosurgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
3 sitesUnited States
Study dates
6 Aug 2024to 25 Feb 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • ECOG Performance Status of 0-1 within 28 days prior to registration.
  • Confirmation of stage IV non-small cell lung cancer (NSCLC) per AJCC, 8th edition, or metastatic recurrence after treatment for earlier stage disease.
  • Known to have a KRAS G12C mutation. KRAS G12C mutation can be determined based on local tissue and/or ctDNA testing.
  • Presence of brain metastases that meet the following criteria:
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  • Patients must have at least 1 untreated enhancing intracranial lesion, per local radiology interpretation, measuring at least 2mm. NOTE: intracranial lesions do not need to be measurable by RECIST 1.1 criteria to be eligible.
  • Must have no single metastasis measuring larger than 3 cm.
  • Patients with surgically resected brain metastases are eligible provided there are additional brain metastases amenable to SRS
  • Patients with progression of previously radiated or surgically resected CNS metastases are eligible if solid component of lesion has enlarged and there is no concern for radionecrosis based on investigator discretion.
  • Patients who received SRS within 4 weeks prior to registration are eligible provided baseline brain MRI prior to SRS treatment is within 4 weeks of study registration and SRS treatment meets requirements in #7 below.
  • Symptomatic brain metastases are permitted if the following criteria are met:
  • No evidence of cerebral herniation or symptomatic leptomeningeal disease
  • No seizures within past 14 days; antiepileptic medications are permitted
  • Patients on steroids must have stable or improving neurologic symptoms that have not worsened during a steroid taper. Must be receiving the equivalent of dexamethasone 8 mg total daily dose or less at the time of registration.
  • CNS lesions have already been treated with SRS (within 3 weeks prior to Cycle 1 Day 1) or are amenable to SRS as determined by radiation oncologist and/or neurosurgeon. SRS treatment must use GammaKnife or linear accelerator-based treatments with nominal x-ray energy of 6MV or greater.
  • No contraindications to SRS. Patients on anticoagulation must be able to hold anticoagulation for SRS treatment based on investigator discretion.
  • Patients may be treatment-naïve OR have received up to 2 prior lines of systemic therapy. Treatment with systemic therapy for Stage I-III disease > 12 months prior to development of metastases do not count as a line of therapy. Treatment with platinum-doublet chemotherapy and checkpoint inhibitor immunotherapy (PD-1, PD-L1, CTLA-4, etc.) either in combination or sequentially counts as one line of therapy.
  • Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
  • Hemoglobin (Hgb): ≥ 8.0 g/dL in the absence of transfusions within 7 days prior to testing.
  • Calculated creatinine clearance: ≥ 60 mL/min
  • Bilirubin: ≤ 1.5 mg/dL
  • Aspartate aminotransferase (AST): ≤ 3.0 × ULN
  • Alanine aminotransferase (ALT): ≤ 3.0 × ULN
  • Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to treatment initiation.
  • Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from heterosexual activity or to use an effective method(s) of contraception. Males able to father a child who are sexually active with female of childbearing potential must be willing to abstain from heterosexual activity or to use an effective method(s) of contraception.
  • HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial. Testing is not required at screening unless mandated by local policy.
  • Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial. Testing is not required at screening unless mandated by local policy.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Who cannot join

  • Prior treatment with KRAS G12C tyrosine kinase inhibitor.
  • Active infection requiring systemic therapy with the exception of #13 and #14 above.
  • Uncontrolled, significant intercurrent or recent illness.
  • Prolonged QTc interval > 480 milliseconds or history of congenital Long QT Syndrome
  • Currently receiving radiation treatment at the time of enrollment to any extra-cranial lesion for prophylaxis or pain control. Patients may enroll after completion of palliative RT.
  • Ongoing need for treatment with concomitant medication known as a strong inhibitor or inducer of CYP3A enzyme and that cannot be switched to an alternative treatment prior to study enrollment. NOTE: Discontinuation of CYP3A4 inducers should occur a minimum of 7 days or 5 times their half-life, whichever is longer, prior to C1D1 study treatment.
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  • Treatment with any investigational drug within 28 days prior to registration.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Ryan Gentzler, MD, MS contact

434-924-4251

rg2uc@uvahealth.org

Amber Ryba contact

317-634-5842 ext. 13

aryba@hoosiercancer.org

United States3 sites, 3 recruiting

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

    Gracie Hockenberry, RN, mgt4n@virginia.edu

    Ryan Gentzler, MD

    Recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Sarah Jewell, 614-366-7421, sarah.jewell@osumc.edu

    Joshua Palmer, MD

    Recruiting

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

    Nicole Knight, 804-828-5773, nknight@vcu.edu

    Mariza Daras, MD

    Recruiting

Other trials in United States

About this study

Official title: Phase II Study of Adagrasib + Stereotactic Radiosurgery (SRS) for Patients With Metastatic KRAS G12C-mutated NSCLC With Untreated Brain Metastases

This is a single arm phase 2 trial is to evaluate the efficacy of SRS plus adagrasib for the treatment of brain metastases for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC). A total of 30 patients will be enrolled on this study.

Being tested
Adagrasib, Stereotactic Radiosurgery
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • AdagrasibDrug

    Also called Krazati

    Adagrasib 600mg orally

  • Stereotactic RadiosurgeryRadiation

    Also called SRS

    Delivered as per standard of care

Study groups in NCT06248606
Study groupRoleWhat they receive
Adagrasib + SRS (Stereotactic Radiosurgery)ExperimentalAll patients will receive oral adagrasib 600mg twice daily for every cycle and SRS which will be administered as standard of care. SRS will occur between 4 weeks prior to and up to 3 weeks after initiation of adagrasib. Patients may have received SRS prior to study enrollment. Cycle 1 Day 1 will begin on the first day of adagrasib dosing. Adagrasib should be held the day before and the day of SRS. There is no maximum duration of treatment.
Receives: Drug: Adagrasib; Radiation: Stereotactic Radiosurgery

What is being measured

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

  1. Intracranial disease control rate (DCR)

    Intracranial disease control rate (DCR) [complete response (CR) + partial response (PR) + stable disease (SD)] per RECIST 1.1 for intracranial lesions at 3 months

    Measured: 3 months

Secondary outcomes (6)

  1. Adverse events

    Safety and tolerability will be assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).

    Measured: 52 months

  2. Intracranial overall response rate (ORR)

    Intracranial overall response rate (icORR) will be measured by RECIST 1.1 criteria including only intracranial lesions. icORR is defined as the proportion of patients who have a partial or complete response (PR or CR) to therapy for intracranial lesions.

    Measured: 52 months

  3. Overall response rate (ORR)

    ORR will be measured by RECIST 1.1. ORR is defined as the proportion of patients who have a partial or complete response to therapy for all disease (systemic and intracranial lesions).

    Measured: 52 months

  4. Progression free survival (PFS)

    PFS is defined as time from the day of study treatment initiation until evidence of disease progression at any location per RECIST v1.1, or death from any cause.

    Measured: 52 months

  5. Overall survival (OS)

    OS will be calculated starting from the day of study treatment initiation until death from any cause.

    Measured: 52 months

  6. Intracranial progression free survival (PFS)

    Intracranial PFS is defined as time from the day of study treatment initiation until evidence of disease progression in the brain per RECIST 1.1 criteria including only intracranial lesions or death from any cause.

    Measured: 52 months

Timeline

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

  1. First posted8 Feb 2024
  2. Study start6 Aug 2024
  3. Primary completion25 Feb 2027 (estimated)
  4. Study completion25 Feb 2028 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06248606
Sponsor's protocol ID
HCRN LUN23-618
Status last verified
Apr 2026
First submitted
31 Jan 2024
Last updated
8 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Adagrasib and Stereotactic Radiosurgery in people with Non Small Cell Lung Cancer and NSCLC, run by Ryan Gentzler, MD at 3 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 29 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 8 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 phase mean?

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?

This study is still under way. Results are not available in the source record yet.

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

Contact Ryan Gentzler, MD, MS (434-924-4251, rg2uc@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intracranial disease control rate (DCR) (time frame: 3 months). 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 NCT06248606.

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 8 Apr 2026.

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