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

NCT ID: NCT04302025

Last Updated: 2026-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

99 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-06

Study Completion Date

2030-05-30

Brief Summary

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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.

Detailed Description

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Conditions

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Non-small Cell Lung Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Alectinib

Intervention Type DRUG

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

Resection

Intervention Type PROCEDURE

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

Chemotherapy

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Entrectinib

Intervention Type DRUG

Participants will receive oral entrectinib daily.

Resection

Intervention Type PROCEDURE

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

Chemotherapy

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Entrectinib

Intervention Type DRUG

Participants will receive oral entrectinib daily.

Resection

Intervention Type PROCEDURE

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

Chemotherapy

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Vemurafenib

Intervention Type DRUG

Participants will receive oral vemurafenib BID.

Cobimetinib

Intervention Type DRUG

Participants will receive oral cobimetinib daily.

Resection

Intervention Type PROCEDURE

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

Chemotherapy

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Pralsetinib

Intervention Type DRUG

Participants will receive oral pralsetinib daily.

Resection

Intervention Type PROCEDURE

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

Chemotherapy

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

Atezolizumab will be administered by intravenous (IV) infusion.

SBRT

Intervention Type DRUG

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

Resection

Intervention Type PROCEDURE

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

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.

Group Type EXPERIMENTAL

Resection

Intervention Type PROCEDURE

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

Chemotherapy

Intervention Type DRUG

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

Divarasib

Intervention Type 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.

Interventions

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Alectinib

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

Intervention Type DRUG

Entrectinib

Participants will receive oral entrectinib daily.

Intervention Type DRUG

Vemurafenib

Participants will receive oral vemurafenib BID.

Intervention Type DRUG

Cobimetinib

Participants will receive oral cobimetinib daily.

Intervention Type DRUG

Pralsetinib

Participants will receive oral pralsetinib daily.

Intervention Type DRUG

Atezolizumab

Atezolizumab will be administered by intravenous (IV) infusion.

Intervention Type DRUG

SBRT

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

Intervention Type DRUG

Resection

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

Intervention Type PROCEDURE

Chemotherapy

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

Intervention Type DRUG

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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 mediastinoscopyor endo- bronchial ultrasonography is highly encouraged for participants with radiographically suspected mediastinal nodal disease (ie, 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 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


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status WITHDRAWN

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, California, United States

Site Status WITHDRAWN

USC Norris Cancer Center

Los Angeles, California, United States

Site Status WITHDRAWN

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status WITHDRAWN

University of California Los Angeles - Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

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

Orange, California, United States

Site Status RECRUITING

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status RECRUITING

UCSF Helen Diller Family CCC

San Francisco, California, United States

Site Status WITHDRAWN

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

Aurora, Colorado, United States

Site Status WITHDRAWN

Yale Cancer Center

New Haven, Connecticut, United States

Site Status RECRUITING

MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)

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

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, United States

Site Status RECRUITING

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States

Site Status RECRUITING

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Site Status RECRUITING

Boston Medical Center

Boston, Massachusetts, United States

Site Status WITHDRAWN

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Karmanos Cancer Institute - Farmington Hills/Weisberg Cancer Treatment Center

Farmington Hills, Michigan, United States

Site Status WITHDRAWN

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Ellis Fischel Cancer Center

Columbia, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center - Washington University Medical Campus

St Louis, Missouri, United States

Site Status RECRUITING

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status RECRUITING

Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

New York, New York, United States

Site Status RECRUITING

Columbia University Medical Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status WITHDRAWN

Ohio State University

Columbus, Ohio, United States

Site Status RECRUITING

AHN Cancer Institute ? Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status COMPLETED

Baptist Clinical Research Institute

Memphis, Tennessee, United States

Site Status RECRUITING

Tennessee Oncology - Nashville

Nashville, Tennessee, United States

Site Status WITHDRAWN

Kelsey Seybold Clnic

Houston, Texas, United States

Site Status WITHDRAWN

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status WITHDRAWN

Lumi Research

Kingwood, Texas, United States

Site Status WITHDRAWN

Virginia Cancer Specialists (Fairfax) - USOR

Fairfax, Virginia, United States

Site Status RECRUITING

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status WITHDRAWN

Countries

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United States

Central Contacts

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Reference Study ID Number: ML41591 https://forpatients.roche.com/

Role: CONTACT

888-662-6728

Other Identifiers

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ML41591

Identifier Type: -

Identifier Source: org_study_id

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