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NCT04302025PHASE2Recruiting

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

Genentech, Inc.

Start Date

11/6/2020

Completion Date

5/30/2030

Summary

This trial will evaluate the efficacy and safety of various therapies in participants with Stage IB, IIA, IIB, IIIA, or selected IIIB resectable and untreated NSCLC tumors that meet protocol-specified biomarker criteria.

Eligibility Criteria

Age Range: 18 years to No maximum

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 Exclusion Criteria * 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

Interventions

DRUG

Alectinib

DRUG

Entrectinib

DRUG

Vemurafenib

DRUG

Cobimetinib

DRUG

Pralsetinib

DRUG

Atezolizumab

DRUG

SBRT

PROCEDURE

Resection

DRUG

Chemotherapy

DRUG

Divarasib

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Conditions

Non-small Cell Lung Cancer

Locations

City of Hope Comprehensive Cancer Center

Duarte, California 91010

United States

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, California 92618

United States

USC Norris Cancer Center

Los Angeles, California 90033

United States

Cedars-Sinai Medical Center

Los Angeles, California 90048

United States

University of California Los Angeles - Jonsson Comprehensive Cancer Center

Los Angeles, California 90095

United States

The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange

Orange, California 92868

United States

UC Davis Comprehensive Cancer Center

Sacramento, California 95817

United States

UCSF Helen Diller Family CCC

San Francisco, California 94158

United States

University of Colorado - Anschutz Medical Campus (University of Colorado Health Sciences Center)

Aurora, Colorado 80045

United States

Yale Cancer Center

New Haven, Connecticut 06511

United States

MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)

Washington D.C., District of Columbia 20007

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Northwestern University

Chicago, Illinois 60611

United States

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois 60115

United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois 60134

United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois 60555

United States

Boston Medical Center

Boston, Massachusetts 02118

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

University of Michigan

Ann Arbor, Michigan 48109

United States

Karmanos Cancer Institute - Farmington Hills/Weisberg Cancer Treatment Center

Farmington Hills, Michigan 48334

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Ellis Fischel Cancer Center

Columbia, Missouri 65201

United States

Siteman Cancer Center - Washington University Medical Campus

St Louis, Missouri 63108

United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire 03756

United States

Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

New York, New York 10016

United States

Columbia University Medical Center

New York, New York 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44016

United States

Ohio State University

Columbus, Ohio 43210

United States

AHN Cancer Institute ? Allegheny General Hospital

Pittsburgh, Pennsylvania 15212

United States

Baptist Clinical Research Institute

Memphis, Tennessee 38120

United States

Tennessee Oncology - Nashville

Nashville, Tennessee 37203

United States

Kelsey Seybold Clnic

Houston, Texas 77025

United States

University of Texas MD Anderson Cancer Center

Houston, Texas 77030-4008

United States

Baylor College of Medicine

Houston, Texas 77030

United States

Lumi Research

Kingwood, Texas 77339

United States

Virginia Cancer Specialists (Fairfax) - USOR

Fairfax, Virginia 22031

United States

Seattle Cancer Care Alliance

Seattle, Washington 98109

United States