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

NCT04302025 | Recruiting Phase 2 FDA Drug

• 1 other identifier: ML41591
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 38

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

Outcome Measures

Primary Outcomes (4)

• Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR)

  MPR is defined as ≤ 10% residual viable tumor cells as scored by local pathologists.

  After surgical resection (approximately study Week 8)

• Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR)

  Scored by local pathologists; defined as lack of any viable tumor cells on review of hematoxylin and eosin (H\&E) slides after complete evaluation of a resected lung cancer specimen including all sampled regional lymph nodes.

  After surgical resection (approximately study Week 8)

• KRAS Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs)

  After surgical resection (approximately study Week 8)

• KRAS Cohort: Percentage of Participants Without Delays of Surgery due to Treatment-related Adverse Events as Reported by the Investigator

  After surgical resection (approximately study Week 8)

Secondary Outcomes (12)

• Proportion of Participants With MPR

  After surgical resection (approximately study Week 8)

• Proportion of Participants With pCR

  After surgical resection (approximately study Week 8)

• Pathological Regression Based on Weighted % Viable Tumor Cell Assessment

  After surgical resection (approximately study Week 8)

• Investigator-assessed Response Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  After neoadjuvant treatment (after approximately study Week 8)

• Pathological Complete Response (pCR) as Assessed by Local and Central Pathology Laboratories

  At the time of surgical resection (approximately study Week 8)

Study Arms (7)

ALK Cohort (Enrolment Closed)

EXPERIMENTAL

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.

Drug: Alectinib; Procedure: Resection; Drug: Chemotherapy

ROS 1 Cohort (Enrolment Closed)

EXPERIMENTAL

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.

Drug: Entrectinib; Procedure: Resection; Drug: Chemotherapy

NTRK Cohort (Enrolment Closed)

EXPERIMENTAL

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.

Drug: Entrectinib; Procedure: Resection; Drug: Chemotherapy

BRAF Cohort (No Participants Enrolled, Cohort Closed)

EXPERIMENTAL

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.

Drug: Vemurafenib; Drug: Cobimetinib; Procedure: Resection; Drug: Chemotherapy

RET Cohort (Cohort closed)

EXPERIMENTAL

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.

Drug: Pralsetinib; Procedure: Resection; Drug: Chemotherapy

PD-L1 Cohort (Enrolment Closed)

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: SBRT; Procedure: Resection

KRAS G12C Cohort

EXPERIMENTAL

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.

Procedure: Resection; Drug: Chemotherapy; Drug: Divarasib

Interventions

Alectinib DRUG

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

ALK Cohort (Enrolment Closed)

SBRT DRUG

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

PD-L1 Cohort (Enrolment Closed)

Entrectinib DRUG

Participants will receive oral entrectinib daily.

NTRK Cohort (Enrolment Closed); ROS 1 Cohort (Enrolment Closed)

Vemurafenib DRUG

Participants will receive oral vemurafenib BID.

BRAF Cohort (No Participants Enrolled, Cohort Closed)

Cobimetinib DRUG

Participants will receive oral cobimetinib daily.

BRAF Cohort (No Participants Enrolled, Cohort Closed)

Pralsetinib DRUG

Participants will receive oral pralsetinib daily.

RET Cohort (Cohort closed)

Atezolizumab DRUG

Atezolizumab will be administered by intravenous (IV) infusion.

PD-L1 Cohort (Enrolment Closed)

Resection PROCEDURE

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

ALK Cohort (Enrolment Closed); BRAF Cohort (No Participants Enrolled, Cohort Closed); KRAS G12C Cohort; NTRK Cohort (Enrolment Closed); PD-L1 Cohort (Enrolment Closed); RET Cohort (Cohort closed); ROS 1 Cohort (Enrolment Closed)

Chemotherapy DRUG

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

ALK Cohort (Enrolment Closed); BRAF Cohort (No Participants Enrolled, Cohort Closed); KRAS G12C Cohort; NTRK Cohort (Enrolment Closed); RET Cohort (Cohort closed); ROS 1 Cohort (Enrolment Closed)

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.

KRAS G12C Cohort

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (38)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

WITHDRAWN

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, California, 92618, United States

WITHDRAWN

USC Norris Cancer Center

Los Angeles, California, 90033, United States

WITHDRAWN

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

WITHDRAWN

University of California Los Angeles - Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

RECRUITING

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

Orange, California, 92868, United States

RECRUITING

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

UCSF Helen Diller Family CCC

San Francisco, California, 94158, United States

WITHDRAWN

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

Aurora, Colorado, 80045, United States

WITHDRAWN

Yale Cancer Center

New Haven, Connecticut, 06511, United States

RECRUITING

MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)

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

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, 60115, United States

RECRUITING

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, 60134, United States

RECRUITING

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555, United States

RECRUITING

Boston Medical Center

Boston, Massachusetts, 02118, United States

WITHDRAWN

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Karmanos Cancer Institute - Farmington Hills/Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

WITHDRAWN

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Ellis Fischel Cancer Center

Columbia, Missouri, 65201, United States

RECRUITING

Siteman Cancer Center - Washington University Medical Campus

St Louis, Missouri, 63108, United States

RECRUITING

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

New York, New York, 10016, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44016, United States

WITHDRAWN

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

AHN Cancer Institute ? Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

COMPLETED

Baptist Clinical Research Institute

Memphis, Tennessee, 38120, United States

RECRUITING

Tennessee Oncology - Nashville

Nashville, Tennessee, 37203, United States

WITHDRAWN

Kelsey Seybold Clnic

Houston, Texas, 77025, United States

WITHDRAWN

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4008, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

WITHDRAWN

Lumi Research

Kingwood, Texas, 77339, United States

WITHDRAWN

Virginia Cancer Specialists (Fairfax) - USOR

Fairfax, Virginia, 22031, United States

RECRUITING

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

WITHDRAWN

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

alectinib; entrectinib; Vemurafenib; cobimetinib; pralsetinib; atezolizumab; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 10, 2020
• Study Start: November 6, 2020
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): May 30, 2030
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (38)