Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Atezolizumab

Alectinib

Pralsetinib

Entrectinib

Vemurafenib

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Tyrosine

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.

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.

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.

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.

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

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.

Participants will receive oral alectinib twice per day (BID)

Participants will receive oral entrectinib daily

Participants will receive oral vemurafenib BID

Vemurafenib (Enrollment closed)

Participants will receive oral cobimetinib daily

Cobimetinib (Enrollment closed)

Participants will receive oral pralsetinib daily

Pralsetinib (Enrollment closed)

Atezolizumab will be administered by intravenous (IV) infusion

Patients will receive SBRT given concurrently starting with the first dose of atezolizumab

SBRT

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

Resection

Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician

Chemotherapy

Participants in the KRAS G12C cohort will receive divarasib for approximately 8 weeks until the day before surgery.

Divarasib

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

Clinical Trials

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

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

NAUTIKA1: Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

MPR is defined as \</=10% residual viable tumor cells as scored by local pathologists

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

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

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer	NCT04302025	Non-small Cell ...	Alectinib Entrectinib Vemurafenib (En... Cobimetinib (En... Pralsetinib (En... Atezolizumab SBRT Resection Chemotherapy Divarasib	18 Years -	Genentech, Inc.
A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer	NCT04302025	Non-small Cell ...	Alectinib Entrectinib Vemurafenib (En... Cobimetinib (En... Pralsetinib (En... Atezolizumab SBRT Resection Chemotherapy Divarasib	18 Years -	Genentech, Inc.

Spots Global Cancer Trial Database for vemurafenib (enrollment closed)