Clinical Trial 20530

Study Title

Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Alectinib, Entrectinib, or Vemurafenib Plus Cobimetinib in Patients with Stages I-III Non-Small Cell Lung Cancer with ALK, ROS1, NTRK, or BRAF V600E Molecular Alterations

Summary

This trial will evaluate the efficacy and safety of targeted therapies in participants with resectable Stage IIA, IIB, IIIA, and select IIIB (T3N2) resectable and untreated non-small cell lung cancer (NSCLC) tumors with selected molecular alterations.

Objective

The primary efficacy objective for this study is to evaluate the efficacy of each study treatment on the basis of the following endpoint: Determination of major pathologic response (MPR), (defined as less than or equal to 10% residual viable tumor cells) scored by a local pathologist, based on surgical resection as defined by Hellmann et al. 2014 and further outlines in the pathology standard operating procedure (SOP) Secondary Objectives: Pathological regression based on % viable tumor cell assessment (see pathology SOP) Investigator-assessed response ORR per RECIST v1.1 Pathological complete response (pCR), defined as the absence of residual invasive in situ cancer and all sampled regional lymph nodes (i.e., ypT0 ypN0 in the current AJCC staging system), as assessed by the investigator site pathology laboratory Disease-free survival (DFS), defined as the time from the first date of no disease (e.g., date of surgery or date of CR prior surgery) to local or distant recurrence or death due to any cause, whichever occurs first, as determined by the investigator during the adjuvant treatment and observation follow-up Event-free Survival (EFS), defined as the time from first dose to the first documented disease progression, per RECIST v1.1, or local or distant disease recurrence, as determined by the investigator, or death from any cause, whichever occurs first Overall survival (OS), defined as the time from first dose to death from any cause Exploratory Objectives: Evaluate the change in blood ctDNA from baseline to pre-surgery and the correlation with clinical outcome measures Evaluate the blood ctDNA status post-surgery and the correlation with clinical outcome measures Monitoring of ctDNA status and profiles in blood post-surgery over time and correlation with clinical outcome measures Safety Objectives: Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)