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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
99
Participants will receive oral alectinib twice per day (BID).
Participants will receive oral entrectinib daily.
Participants will receive oral vemurafenib BID.
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.
Time frame: 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.
Time frame: After surgical resection (approximately study Week 8)
KRAS Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs)
Time frame: 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
Time frame: After surgical resection (approximately study Week 8)
Proportion of Participants With MPR
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.
Time frame: After surgical resection (approximately study Week 8)
Proportion of Participants With pCR
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 a central pathology committee consensus read.
Reference Study ID Number: ML41591 https://forpatients.roche.com/
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Participants will receive oral cobimetinib daily.
Participants will receive oral pralsetinib daily.
Atezolizumab will be administered by intravenous (IV) infusion.
Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab.
Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC.
Participants will receive SOC chemotherapy as determined by the treating physician.
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.
City of Hope Comprehensive Cancer Center
Duarte, California, United States
WITHDRAWNCity of Hope - Orange County Lennar Foundation Cancer Center
Irvine, California, United States
WITHDRAWNUSC Norris Cancer Center
Los Angeles, California, United States
WITHDRAWNCedars-Sinai Medical Center
Los Angeles, California, United States
WITHDRAWNUniversity of California Los Angeles - Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGThe Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
Orange, California, United States
RECRUITINGUC Davis Comprehensive Cancer Center
Sacramento, California, United States
RECRUITINGUCSF Helen Diller Family CCC
San Francisco, California, United States
WITHDRAWNUniversity of Colorado - Anschutz Medical Campus (University of Colorado Health Sciences Center)
Aurora, Colorado, United States
WITHDRAWNYale Cancer Center
New Haven, Connecticut, United States
RECRUITING...and 28 more locations
Time frame: After surgical resection (approximately study Week 8)
Pathological Regression Based on Weighted % Viable Tumor Cell Assessment
Time frame: 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)
Time frame: After neoadjuvant treatment (after approximately study Week 8)
Pathological Complete Response (pCR) as Assessed by Local and Central Pathology Laboratories
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.
Time frame: At the time of surgical resection (approximately study Week 8)
Disease-free Survival (DFS)
Time frame: 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 9 years)
Event-free Survival (EFS)
Time frame: 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 9 years)
Overall Survival (OS)
Time frame: From the first dose of study medication to death from any cause, through the end of the study (up to 9 years)
Percentage of Participants With Adverse Events (AEs)
Time frame: Up to 9 years
Nodal Downstaging
Defined as percentage of participants with reduced stages in regional lymph nodes at surgery.
Time frame: After surgical resection (approximately study Week 8)
Circulating tumor DNA (ctDNA) Clearance Rate
Time frame: Prior to surgery (before study Week 8)
KRAS G12C Cohort: Plasma Concentration of Divarasib at Specified Timepoints
Time frame: Cycle 1 Day 1, Cycle 2 Day 1 (Cycle= 28 days)