Evaluation of Alectinib and Chemotherapy Efficacy and Safety in Resectable Stage I-III ALK-Positive Non-Small Cell Lung Cancer Patients

The primary objectives of this study are to evaluate the efficacy and safety of various therapeutic approaches in patients with resectable non-small cell lung cancer (NSCLC) characterized by anaplastic lymphoma kinase (ALK) positivity. In Cohort B1, the study aims to assess the safety of alectinib in combination with chemotherapy in patients with completely resected Stage II, IIIA, and selected IIIB disease. In Cohort B2, the primary goal is to evaluate the efficacy of neoadjuvant treatment using alectinib combined with chemotherapy in patients with resectable Stage II, IIIA, and selected IIIB disease.

Secondary objectives include:

• In Cohort B1: evaluating the efficacy of alectinib combined with chemotherapy followed by alectinib monotherapy, and assessing the safety of this sequential regimen.
• In Cohort B2: evaluating the efficacy of neoadjuvant alectinib and chemotherapy followed by adjuvant alectinib monotherapy, and assessing the safety of this combined approach.
• In Cohort B2: assessing the safety and feasibility of surgery following neoadjuvant treatment with alectinib and chemotherapy.

This clinical trial involves 96 participants diagnosed with resectable non-small cell lung cancer (NSCLC). The study population includes both male and female individuals within the 3 to 17 age range. Participants are categorized into two cohorts to evaluate alectinib in combination with chemotherapy. Cohort B1 consists of patients with completely resected Stage II, Stage IIIA, or selected Stage IIIB (T3N2) adenocarcinoma who exhibit an ECOG performance status of 0 or 1. Cohort B2 includes patients undergoing neoadjuvant treatment for the same stages of disease. All participants must have a documented ALK fusion.

This Phase I-III, multicenter study is designed to evaluate the efficacy and safety of various therapies in patients with resectable non-small cell lung cancer (NSCLC). The research is divided into two specific cohorts based on biomarker status, specifically focusing on patients with documented anaplastic lymphoma kinase (ALK) fusion. Cohort B1 focuses on evaluating the safety of alectinib in combination with chemotherapy following complete resection, while Cohort B2 evaluates the efficacy of neoadjuvant treatment using alectinib and chemotherapy in resectable stages. The investigated medicinal products include cisplatin, carboplatin, and pemetrexed administered via intravenous infusion, alongside oral alectinib. The study duration is estimated to extend from March 2025 through July 2033. Clinical assessments include monitoring for adverse events, pathologic complete response, disease-free survival, and overall survival. Participants undergo screening to verify eligibility, including histopathological confirmation of non-squamous adenocarcinoma and assessment of ECOG performance status. The trial involves various follow-up assessments to track safety parameters and clinical responses.

Alectinib is administered as a hard capsule at an oral dose of 1200 mg.

Pemetrexed is provided as a solution for infusion and is administered via intravenous infusion at a dose of 500 mg/m².

Carboplatin is administered as a solution for infusion via intravenous infusion at a dose of 750 mg.

Cisplatin is administered as a solution for infusion via intravenous infusion at a dose of 75 mg/m².

In this study involving patients with resectable stage I-III non-small cell lung cancer, efficacy and safety assessments are differentiated by cohort. For Cohort B1, the primary evaluation focuses on the incidence, type, and severity of adverse events using the NCI CTCAE v5.0, with onset monitored up to 28 days after the final dose of chemotherapy. Secondary efficacy measures for Cohort B1 include investigator-assessed disease-free survival, disease-free rates at intervals of 1, 2, 3, 4, and 5 years, and overall survival.

For Cohort B2, the primary efficacy endpoint is the investigator-assessed pathologic complete response. Secondary efficacy parameters include investigator-assessed major pathological response, pathologic complete response and major pathologic response via independent review, investigator-assessed overall response rate per RECIST v1.1, investigator-assessed event-free survival, and overall survival. Additional secondary assessments for Cohort B2 involve the frequency of surgery completion, the length of treatment-related surgical delays, the incidence of operative and post-operative complications, and reasons for surgical cancellations.

Safety assessments across both cohorts include monitoring the change from baseline in target safety parameters, specifically vital signs, clinical laboratory test results, and ECG parameters. Baseline is defined as the last assessment conducted prior to the first treatment.