Neoadjuvant KRAS G12C Directed Therapy With Adagrasib (MRTX849) With or Without Nivolumab

NCT05472623 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: IRB00306149
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label phase 2 clinical trial evaluating the clinical safety, feasibility and efficacy of neoadjuvant Adagrasib alone or in combination with nivolumab in patients with NSCLC with KRAS G12C mutation.

Conditions

Resectable Non-Small Cell Lung Cancer

Keywords

Adagrasib; Nivolumab; Neoadjuvant; Resectable; NSCLC

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (pCR) rate

  Number of patients with absence of any residual viable tumor (0%) as determined by pathologic review of surgical resection specimens divided by total number of patients in each arm started on investigational therapy.

  Within 90 days of surgery

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Arm A treatment: Oral Adagrasib 600 mg twice daily for 6 weeks prior to surgery. Surgical Resection, then standard postoperative therapy(chemo +/- RT).

Drug: Adagrasib

Arm B

ACTIVE COMPARATOR

Arm B treatment: Oral Adagrasib 400 mg twice daily for 6 weeks and IV Nivolumab 240mg every 2 weeks for 3 doses prior to surgery. Surgical Resection, then standard postoperative therapy(chemo +/- RT).

Combination Product: Adagrasib/Nivolumab

Interventions

Adagrasib DRUG

Oral Adagrasib 600 mg twice daily for 6 weeks prior to surgery.

Arm A

Adagrasib/Nivolumab COMBINATION_PRODUCT

Oral Adagrasib 400 mg twice daily for 6 weeks and IV nivolumab 240mg every 2 weeks for 3 doses prior to surgery.

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Histologically confirmed diagnosis of NSCLC (squamous or nonsquamous) with KRAS G12C mutation.
• Diagnostic core biopsy specimens must be reviewed by a faculty pathologist at the enrolling/treating institution, and biopsy tissue must be available for further biomarker evaluation. If no archived tissue is available, patients will require a repeat biopsy prior to initiation of study treatment. See section 6.5.1 and lab manual for details of pretreatment biopsy tissue required.
• KRAS G12C mutation determined by any CLIA-certified testing platform on patient tumor tissue or plasma sample.
• Stage IB-IIIA NSCLC
• T2aN0, T3N0, T1-2N1, T3-4N1, T1-2N2. This includes T2aN0 tumors ≥3 cm. Subjects with N3 nodal involvement are not included.
• Primary resection option for potential cure as assessed by a faculty surgeon at treating institution.
• ECOG performance status 0-1 (See Appendix B)
• Adequate organ function within the screening period as follows:
• Leukocytes ≥ 2,000/mm3
• Absolute neutrophil count (ANC) ≥ 1000/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9 g/dL
• Creatinine ≤ 1.5 x institutional upper limit of normal (ULN) or creatinine clearance (CrCl) ≥60 mL/min
• Total Bilirubin ≤ 1.5 x institutional ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)

You may not qualify if:

• Patients presenting with any of the following will not be included in the study:
• NSCLC not amenable to curative intent resection based on evaluation by faculty surgeon at treating institution.
• This includes any patient with pathologically confirmed N3 disease.
• Prior systemic treatment for lung cancer including chemotherapy, immune checkpoint inhibitor therapy, or a therapy targeting KRAS G12C mutation.
• Prior thoracic radiation.
• Any concurrent malignancies for which active therapy is being received.
• Exceptions: non-melanoma skin cancers; in situ dysplasia of the bladder, gastric, breast, colon, or cervix
• Brain metastases at time of screening.
• All patients must have brain imaging prior to enrollment (MRI brain or CT brain with contrast preferred).
• Active or prior documented autoimmune or inflammatory disease as follows (Arm B only):
• Medically relevant autoimmune disease requiring systemic treatment within 2 years prior to the first dose of study treatment.
• Systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration (Arm B only). Inhaled or topical steroids are permitted.
• Adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Major surgery within 4 weeks prior to first dose of study treatment.
• History of allogeneic transplant or primary immunodeficiency.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Mirati Therapeutics Inc.: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Interventions

adagrasib; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kristen Marrone

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will enroll patients with newly diagnosed, biopsy-proven stage IB-IIIA NSCLC deemed surgically resectable and fit for surgery by a multidisciplinary thoracic oncology team. The study will accrue 42 patients to the following two arms sequentially: * Arm A: oral Adagrasib 600 mg twice daily for 6 weeks prior to surgery (21 patients) * Arm B: oral Adagrasib 400 mg twice daily for 6 weeks and IV nivolumab 240 mg every 2 weeks for 3 doses prior to surgery (21 patients)

Study Record Dates

• First Submitted: July 21, 2022
• First Posted: July 25, 2022
• Study Start: March 21, 2023
• Primary Completion: June 1, 2025
• Study Completion: September 1, 2025
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)