A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer

Phase 2

Recruiting

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Atezolizumab; Drug: Vemurafenib (Enrollment closed); Drug: Pralsetinib (Enrollment closed); Drug: Alectinib; Drug: Entrectinib; Procedure: Resection; Drug: SBRT; Drug: Divarasib; Drug: Cobimetinib (Enrollment closed); Drug: Chemotherapy

• Registration Number: NCT04302025
• Lead Sponsor: Genentech, Inc.

Brief Summary

This trial will evaluate the efficacy and safety of various therapies in patients with Stage IB, IIA, IIB, IIIA, or selected IIIB resectable and untreated non-small cell lung cancer (NSCLC) tumors that meet protocol-specified biomarker criteria

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-03-06
• Study First Submitted QC: 2020-03-06
• Study First Posted: 2020-03-10
• Study Start: 2020-11-06
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-29
• Last Update Posted: 2024-05-01
• Primary Completion: 2025-12-30
• Study Completion: 2029-03-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 125

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ALK Cohort	Resection	Participants will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
ALK Cohort	Chemotherapy	Participants will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
ROS 1 Cohort	Resection	Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
ROS 1 Cohort	Chemotherapy	Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
NTRK Cohort	Resection	Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
NTRK Cohort	Chemotherapy	Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
BRAF Cohort (Enrollment closed, no participants enrolled)	Resection	Participants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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. Enrollment closed.
BRAF Cohort (Enrollment closed, no participants enrolled)	Chemotherapy	Participants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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. Enrollment closed.
RET Cohort (Enrollment closed)	Resection	Participants will receive up to 8 weeks of pralsetinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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. Enrollment closed.
RET Cohort (Enrollment closed)	Chemotherapy	Participants will receive up to 8 weeks of pralsetinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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. Enrollment closed.
PD-L1 Cohort	Atezolizumab	Participants with positive PD-L1 in ≥1% tumor cells will receive 4 cycles of atezolizumab neoadjuvant treatment. During neoadjuvant Cycle 1 of atezolizumab, patients will also receive low-dose SBRT (8Gy X 3). Adjuvant treatment consists of SOC treatment as determined by the investigator, per NCCN guidelines
PD-L1 Cohort	SBRT	Participants with positive PD-L1 in ≥1% tumor cells will receive 4 cycles of atezolizumab neoadjuvant treatment. During neoadjuvant Cycle 1 of atezolizumab, patients will also receive low-dose SBRT (8Gy X 3). Adjuvant treatment consists of SOC treatment as determined by the investigator, per NCCN guidelines
PD-L1 Cohort	Resection	Participants with positive PD-L1 in ≥1% tumor cells will receive 4 cycles of atezolizumab neoadjuvant treatment. During neoadjuvant Cycle 1 of atezolizumab, patients will also receive low-dose SBRT (8Gy X 3). Adjuvant treatment consists of SOC treatment as determined by the investigator, per NCCN guidelines
KRAS G12C Cohort	Resection	Participants will receive up to 8 weeks of divarasib as neoadjuvant treatment before undergoing surgical resection per standard of care. PD-L1 negative patients whose tumors have pathological response or lack radiographic progression will be have the option of continuing divarasib for up to 2 years as adjuvant therapy. For patients who test positive PD-L1, they will have the option to receive Atezolizumab for up to 16 cycles.
KRAS G12C Cohort	Divarasib	Participants will receive up to 8 weeks of divarasib as neoadjuvant treatment before undergoing surgical resection per standard of care. PD-L1 negative patients whose tumors have pathological response or lack radiographic progression will be have the option of continuing divarasib for up to 2 years as adjuvant therapy. For patients who test positive PD-L1, they will have the option to receive Atezolizumab for up to 16 cycles.
BRAF Cohort (Enrollment closed, no participants enrolled)	Cobimetinib (Enrollment closed)	Participants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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. Enrollment closed.
BRAF Cohort (Enrollment closed, no participants enrolled)	Vemurafenib (Enrollment closed)	Participants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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. Enrollment closed.
RET Cohort (Enrollment closed)	Pralsetinib (Enrollment closed)	Participants will receive up to 8 weeks of pralsetinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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. Enrollment closed.
ALK Cohort	Alectinib	Participants will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
ROS 1 Cohort	Entrectinib	Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.
NTRK Cohort	Entrectinib	Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. 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.

Primary Outcome Measures

Name	Time	Method
Tyrosine kinase inhibitor (TKI) cohort: Proportion of Participants with Major Pathologic Response (MPR)	After surgical resection (approximately study Week 8)	MPR is defined as \</=10% residual viable tumor cells as scored by local pathologists
Checkpoint inhibitor (CPI) cohort: Pathological complete response (pCR)	After surgical resection (approximately study Week 8)	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
KRAS cohort: Percentage of participants with 3-5 grade Adverse Events	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 Outcome Measures

Name	Time	Method
Pathological Complete Response (pCR) as Assessed by Local and Central Pathology Laboratories	At the time of surgical resection (approximately study Week 8)	Defined as the absence of any viable tumor in main tumor bed at the time of surgical resection, as assessed by local and central pathology laboratories
Disease-Free Survival (DFS)	From the first date of no disease to local or distant recurrence or death from any cause, whichever occurs first, through the end of the study (up to 8 years)
Event-Free Survival (EFS)	From first dose of study treatment to first documented disease progression per RECIST v1.1, or local or distant disease recurrence as determined by investigator, or death from any cause, whichever occurs first, through the end of study (up to 8 years)
Overall Survival (OS)	From the first dose of study medication to death from any cause, through the end of the study (up to 8 years)
Percentage of Participants with Adverse Events (AEs)	Up to 8 years
Nodal downstaging, defined as percentage of patients with reduced stages in mediastinal nodes at surgery	After surgical resection (approximately study Week 8)
Circulating tumor DNA ctDNA Clearance Rate	Prior to surgery (before study Week 8)
KRAS G12C cohort: Plasma concentration of divarasib at specified timepoints	Cycle 1 Day 1, Cycle 2 Day 1 (Cycle= 28 days)
Proportion of Participants with MPR	After surgical resection (approximately study Week 8)	Defined as ≤10% residual viable tumor cells) based on surgical resection as defined by Hellmann et al. (2014) and Travis et al. (2020) TKI cohorts: MPR will be scored by a central pathology committee consensus read CPI cohort: MPR will be scored by local pathologists and central pathology committee consensus read KRAS G12C cohort: MPR will be scored by local pathologists and central pathology committee consensus read
Proportion of Participants with pCR	After surgical resection (approximately study Week 8)	defined as lack of any viable tumor cells on review of H\&E slides after complete evaluation of a resected lung cancer specimen, including all sampled regional lymph nodes TKI cohorts: pCR will be scored by local pathologists and a central pathology committee consensus read CPI cohort: pCR will be scored by a central pathology committee consensus read KRAS G12C cohort: pCR will be scored by local pathologists and a central pathology committee consensus read
Pathological Regression Based on Weighted % Viable Tumor Cell Assessment	After surgical resection (approximately study Week 8)
Investigator-Assessed Response Objective Response Rate (ORR) per RECIST v1.1	After neoadjuvant treatment (after approximately study Week 8)

Trial Locations

Locations (34)

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

UCLA Hematology Oncology; 🇺🇸 Los Angeles, California, United States

Karmanos Cancer Institute - Farmington Hills/Weisberg Cancer Treatment Center; 🇺🇸 Farmington Hills, Michigan, United States

Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Dana-Farber Cancer Institute; Brigham and Women's Cancer Center; 🇺🇸 Boston, Massachusetts, United States

Boston Medical Center; 🇺🇸 Boston, Massachusetts, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Sylvester Comprehensive Cancer Center - Deerfield Beach; 🇺🇸 Miami, Florida, United States

MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center); 🇺🇸 Washington, District of Columbia, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Lumi Research; 🇺🇸 Kingwood, Texas, United States

Ohio State University; Hemat/Onc; 🇺🇸 Columbus, Ohio, United States

Dartmouth Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States

Baptist Clinical Research Institute; 🇺🇸 Memphis, Tennessee, United States

Washington University School of Medicine; Sitemann Cancer Center; 🇺🇸 Saint Louis, Missouri, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Laura and ISAAC Perlmutter Cancer Center at NYU Langone.; 🇺🇸 New York, New York, United States

University of Missouri Health Care; Ellis Fischel Cancer Center; 🇺🇸 Columbia, Missouri, United States

USC Norris Cancer Center; 🇺🇸 Los Angeles, California, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange; 🇺🇸 Orange, California, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Northwestern University; Robert H. Lurie Comp Can Ctr; 🇺🇸 Chicago, Illinois, United States

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

UC Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

UCSF; 🇺🇸 San Francisco, California, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

HCA Midwest Health; 🇺🇸 Kansas City, Missouri, United States

Tennessee Oncology - Nashville; 🇺🇸 Nashville, Tennessee, United States