NCT06248606

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
19mo left

Started Aug 2024

Typical duration for phase_2

Geographic Reach
1 country

3 active sites

Status
recruiting

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

Study Progress56%
Aug 2024Feb 2028

First Submitted

Initial submission to the registry

January 31, 2024

Completed
8 days until next milestone

First Posted

Study publicly available on registry

February 8, 2024

Completed
6 months until next milestone

Study Start

First participant enrolled

August 6, 2024

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 25, 2027

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

February 25, 2028

Last Updated

April 8, 2026

Status Verified

April 1, 2026

Enrollment Period

2.6 years

First QC Date

January 31, 2024

Last Update Submit

April 2, 2026

Conditions

Non Small Cell Lung CancerNSCLCKRAS G12C

Outcome Measures

Primary Outcomes (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

    3 months

Secondary Outcomes (6)

  • Adverse events

    52 months

  • Intracranial overall response rate (ORR)

    52 months

  • Overall response rate (ORR)

    52 months

  • Progression free survival (PFS)

    52 months

  • Overall survival (OS)

    52 months

  • +1 more secondary outcomes

Study Arms (1)

Adagrasib + SRS (Stereotactic Radiosurgery)

EXPERIMENTAL

All 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.

Drug: AdagrasibRadiation: Stereotactic Radiosurgery

Interventions

AdagrasibDRUG

Adagrasib 600mg orally

Also known as: Krazati
Adagrasib + SRS (Stereotactic Radiosurgery)
Stereotactic RadiosurgeryRADIATION

Delivered as per standard of care

Also known as: SRS
Adagrasib + SRS (Stereotactic Radiosurgery)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • 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.
  • +14 more criteria

You may not qualify if:

  • 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

adagrasibRadiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

RadiotherapyTherapeuticsStereotaxic TechniquesNeurosurgical ProceduresSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Ryan Gentzler, MD, MS

    University of Virginia

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ryan Gentzler, MD, MS

CONTACT

434-924-4251rg2uc@uvahealth.org

Amber Ryba

CONTACT

317-634-5842aryba@hoosiercancer.org

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Sponsor-Investigator

Study Record Dates

First Submitted

January 31, 2024

First Posted

February 8, 2024

Study Start

August 6, 2024

Primary Completion (Estimated)

February 25, 2027

Study Completion (Estimated)

February 25, 2028

Last Updated

April 8, 2026

Record last verified: 2026-04

Locations

US(3)