Recruiting
Phase 2

Multiple Therapies

Sponsor:

Genentech, Inc.

Code:

NCT04302025

Conditions

Non-small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Alectinib

Entrectinib

Vemurafenib

Cobimetinib

Pralsetinib

Study Details

Brief 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.

Conditions

Non-small Cell Lung Cancer

Study ID

NCT04302025

Start date

Nov 6, 2020

Status verified date

Aug, 2026

Completion date

May 30, 2030

Anticipated

Primary completion date

Nov 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

99 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: ALK Cohort (Enrolment Closed)

Participants will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care (SOC). All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with alectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of alectinib.

Enrolment Closed.

experimental: ROS 1 Cohort (Enrolment Closed)

Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib.

Enrolment Closed.

experimental: NTRK Cohort (Enrolment Closed)

Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib.

Enrolment Closed.

experimental: BRAF Cohort (No Participants Enrolled, Cohort Closed)

Participants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with vemurafenib plus cobimetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of of vemurafenib plus cobimetinib.

Cohort closed.

experimental: RET Cohort (Cohort closed)

Participants will receive up to 8 weeks of pralsetinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with pralsetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of pralsetinib.

Cohort closed.

experimental: PD-L1 Cohort (Enrolment Closed)

Participants with positive programmed death-ligand 1 (PD-L1) in ≥1% tumor cells will receive 4 cycles of atezolizumab neoadjuvant treatment. During neoadjuvant Cycle 1 of atezolizumab, participants will also receive low-dose stereotactic body radiation therapy (SBRT) (8 gray \[Gy\] X 3). Adjuvant treatment consists of SOC treatment as determined by the investigator, per National Comprehensive Cancer Network (NCCN) guidelines.

Enrolment Closed.

experimental: KRAS G12C Cohort

Participants will receive up to 8 weeks of divarasib as neoadjuvant treatment before undergoing surgical resection per SOC. PD-L1 negative participants whose tumors have pathological response or lack radiographic progression will be have the option of continuing divarasib alone for up to 3 years or 1-4 cycles of SOC chemotherapy followed by divarasib for 3 years as adjuvant therapy. For participants who test positive PD-L1, they will have the option to receive 1-4 cycles of SOC chemotherapy followed by atezolizumab for up to 16 cycles or SOC alone.

Interventions

Alectinib

Participants will receive oral alectinib twice per day (BID).

Entrectinib

Participants will receive oral entrectinib daily.

Vemurafenib

Participants will receive oral vemurafenib BID.

Cobimetinib

Participants will receive oral cobimetinib daily.

Pralsetinib

Participants will receive oral pralsetinib daily.

Atezolizumab

Atezolizumab will be administered by intravenous (IV) infusion.

SBRT

Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab.

Resection

Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC.

Chemotherapy

Participants will receive SOC chemotherapy as determined by the treating physician.

Divarasib

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.

Primary outcome measure

  • Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR) [ Time Frame: After surgical resection (approximately study Week 8) ]
  • Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR) [ Time Frame: After surgical resection (approximately study Week 8) ]
  • KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs) [ Time Frame: 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 [ Time Frame: After surgical resection (approximately study Week 8) ]

Central Contacts and Locations

Central contacts

Reference Study ID Number: ML41591 https://forpatients.roche.com/ No attachments to email below.

888-662-6728global-roche-genentech-trials@gene.com

Locations

University of California Los Angeles - Jonsson Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90095

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

Recruiting

Orange, California, United States, 92868

UC Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06511

MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)

Recruiting

Washington D.C., District of Columbia, United States, 20007

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Northwestern Medicine Cancer Center Kishwaukee

Recruiting

DeKalb, Illinois, United States, 60115

Northwestern Medicine Cancer Center Delnor

Recruiting

Geneva, Illinois, United States, 60134

Northwestern Medicine Cancer Center Warrenville

Recruiting

Warrenville, Illinois, United States, 60555

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Ellis Fischel Cancer Center

Recruiting

Columbia, Missouri, United States, 65201

Siteman Cancer Center - Washington University Medical Campus

Recruiting

St Louis, Missouri, United States, 63108

Dartmouth Hitchcock Medical Center

Recruiting

Lebanon, New Hampshire, United States, 03756

Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

Recruiting

New York, New York, United States, 10016

Columbia University Medical Center

Recruiting

New York, New York, United States, 10032

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Ohio State University

Recruiting

Columbus, Ohio, United States, 43210

Baptist Clinical Research Institute

Recruiting

Memphis, Tennessee, United States, 38120

University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030-4008

Virginia Cancer Specialists (Fairfax) - USOR

Recruiting

Fairfax, Virginia, United States, 22031

More Information

Sponsor

Genentech, Inc.

Last update posted

Aug 11, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-04. This information was provided to ClinicalTrials.gov by Genentech, Inc. on 2026-08-11.