A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Inclusion Criteria for Neoadjuvant Therapy:
• Pathologically documented NSCLC:
• Newly diagnosed early-stage NSCLC stages IB, IIA, IIB, IIIA, or selected IIIB (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) NSCLC staging system
• T4 primary NSCLC will be allowed only on the basis of size. Invasion of the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodules in a different ipsilateral lobe is not permitted
• All participants will undergo clinical staging using computed tomography (CT) and positron emission tomography (PET) scanning, as well as brain imaging using magnetic resonance imaging (MRI). Invasive mediastinal staging by either mediastinoscopy or endo-bronchial ultrasonography is highly encouraged for participants with radiographically suspected mediastinal nodal disease (i.e., N2) but not mandated if the CT or PET scans showed no evidence of N2 disease
• Molecular testing results from clinical laboratory improvement amendments (CLIA)-certified laboratories and showing at least one of the following abnormalities: ALK fusion, ROS1 fusion, NTRK1/2/3 fusion; BRAF V600 mutation, RET fusion, PD-L1 expression in ≥ 1% tumor cells as determined by Food and Drug Administration (FDA)-approved test, KRAS G12C mutation
• Measurable disease, as defined by RECIST v1.1
• NSCLC must have a solid or subsolid appearance on CT scan and cannot have a purely ground glass opacity appearance. For subsolid lesions, the tumor size (i.e., clinical T stage) should be measured based on the solid component only, exclusive of the ground glass opacity component
• Evaluated by the attending surgeon prior to study enrollment to verify that the primary tumor and any involved lymph nodes are technically completely resectable and verify that the participant is medically operable
• Adequate pulmonary function to be eligible for surgical resection with curative intent
• Adequate cardiac function to be eligible for surgical resection with curative intent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate hematologic and end-organ function
• Negative hepatitis B surface antigen (HBsAg) test at screening for cohort
• Negative total hepatitits B core antibody (HBcAb) test at screening for cohort, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test at screening
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening
• Male participants must be willing to use acceptable methods of contraception
• Female participants of childbearing potential must agree to use acceptable methods of contraception
• Inclusion Criteria for Adjuvant Therapy (TKI Cohorts and KRAS G12C cohort [if continuing on Divarasib]):
• Participants whose tumors lack radiographic progression
• ECOG Performance Status of 0 or 1
• Adequate hematologic and end-organ function

You cannot join if

• NSCLC that is clinically T4 by virtue of mediastinal organ invasion or Stage IIIB by virtue of N3 disease
• Any prior therapy for lung cancer, including chemotherapy, targeted therapy, immunotherapy, or radiotherapy, within 2 years
• Participants with prior lung cancer
• Major surgical procedure within 28 days prior to Cycle 1, Day 1
• Malignancies other than the disease under study within 3 years prior to Cycle 1, Day 1, with the exception of participants with a negligible risk of metastasis or death and with expected curative outcome
• Treatment with an investigational agent for any condition within 4 weeks prior to Cycle 1, Day 1
• Participants known to be positive for human immunodeficiency virus (HIV) are excluded if they meet any of the following criteria: cluster of differentiation 4 (CD4)+ T-cell count of <350 cells/microliters (cells/µL); detectable HIV viral load; history of an opportunistic infection within the past 12 months; on stable antiretroviral therapy for <4 weeks
• Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infections, or any active infection that, in the opinion of the investigator, could impact participant safety
• Pregnant or lactating, or intending to become pregnant during the study

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

divarasib. An orally available inhibitor of the oncogenic KRAS substitution mutation, G12C, with potential antineoplastic activity. Upon oral administration, divarasib selectively targets the KRAS G12C mutant and inhibits KRAS G12C mutant-dependent signaling. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis. NCI Drug Dictionary

Treatments listed in the registry

• Alectinib (Drug): Participants will receive oral alectinib twice per day (BID).
• Entrectinib (Drug): Participants will receive oral entrectinib daily.
• Vemurafenib (Drug): Participants will receive oral vemurafenib BID.
• Cobimetinib (Drug): Participants will receive oral cobimetinib daily.
• Pralsetinib (Drug): Participants will receive oral pralsetinib daily.
• Atezolizumab (Drug): Atezolizumab will be administered by intravenous (IV) infusion.
• SBRT (Drug): Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab.
• Resection (Procedure): Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC.
• Chemotherapy (Drug): Participants will receive SOC chemotherapy as determined by the treating physician.
• Divarasib (Drug): Participants in the KRAS G12C cohort will receive oral divarasib for approximately 8 weeks until the day before surgery as neoadjuvant therapy up to 3 years as adjuvant therapy.

Non Randomized · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• surgery: Part of the study plan
• radiation: Part of the study plan

Main goals

• Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR) (After surgical resection (approximately study Week 8))
• Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR) (After surgical resection (approximately study Week 8))
• KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs) (After surgical resection (approximately study Week 8))
• KRAS G12C Cohort: Percentage of Participants Without Delays of Surgery due to Treatment-related AEs as Reported by the Investigator (After surgical resection (approximately study Week 8))

Other goals

• Proportion of Participants With MPR
• Proportion of Participants With pCR
• Pathological Regression Based on Weighted % Viable Tumor Cell Assessment
• Investigator-assessed Response Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
• Disease-free Survival (DFS)
• Event-free Survival (EFS)
• Overall Survival (OS)
• Percentage of Participants With AEs
• Nodal Downstaging
• Circulating tumor DNA (ctDNA) Clearance Rate
• KRAS G12C Cohort: Plasma Concentration of Divarasib at Specified Timepoints

Planned enrollment: 99 (estimated).

• University of California Los Angeles - Jonsson Comprehensive Cancer Center, Los Angeles, California
• The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange, Orange, California
• UC Davis Comprehensive Cancer Center, Sacramento, California
• Yale Cancer Center, New Haven, Connecticut
• MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center), Washington D.C., District of Columbia
• Moffitt Cancer Center, Tampa, Florida
• Northwestern University, Chicago, Illinois
• Northwestern Medicine Cancer Center Kishwaukee, DeKalb, Illinois
• Northwestern Medicine Cancer Center Delnor, Geneva, Illinois
• Northwestern Medicine Cancer Center Warrenville, Warrenville, Illinois
• Dana-Farber Cancer Institute, Boston, Massachusetts
• University of Michigan, Ann Arbor, Michigan
• Mayo Clinic, Rochester, Minnesota
• Ellis Fischel Cancer Center, Columbia, Missouri
• Siteman Cancer Center - Washington University Medical Campus, St Louis, Missouri
• Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
• Laura and ISAAC Perlmutter Cancer Center at NYU Langone., New York, New York
• Columbia University Medical Center, New York, New York
• Memorial Sloan Kettering Cancer Center, New York, New York
• Ohio State University, Columbus, Ohio
• Baptist Clinical Research Institute, Memphis, Tennessee
• University of Texas MD Anderson Cancer Center, Houston, Texas
• Virginia Cancer Specialists (Fairfax) - USOR, Fairfax, Virginia

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT04302025
• NCI Drug Dictionary: C173995

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 12, 2026. Public record; not medical advice.