This is a multicenter, phase 2 non-randomized study to investigate the clinical feasibility and therapeutic efficacy of employing a MDT-based strategy in unresectable stage III ALK positive NSCLC following neoadjuvant alectinib in combination with platinum-based chemotherapy. Participants in this study must not have received any previous systemic anticancer therapy before enrollment.
The study will consist of a 42-day screening period, a neoadjuvant treatment period, a local radical treatment period, a post-local treatment period, a safety follow-up visit occurring 28 days after the final dose of alectinib, and a survival follow-up period.
In the neoadjuvant treatment period, participants will be provided with alectinib (600mg PO BID for 3 cycles) plus platinum-based chemotherapy for a maximum of 3 cycles (each cycle is 21 days).
Following the completion of neoadjuvant therapy, all participants who are reassessed by MDT to be resectable after neoadjuvant treatment and have adequate lung functions would be provided with definite surgery. Otherwise, patients would be provided with radical radiotherapy through MDT discussion.
For the surgery cohort, participants meet both the R0 resection, the pathological assessment criteria of pCR and have two consecutive landmark ctDNA tests that are negative will receive surveillance after surgery. Participants who do not meet all the above conditions will receive alectinib after surgery, adjuvant treatment should be initiated ideally 4-12 weeks after surgery, or according to local standard of care, treatment will continue until completion of treatment period (24 months), disease recurrence, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first.
For the radical radiotherapy cohort, participants will receive alectinib after radiotherapy, adjuvant treatment should be initiated ideally 4-12 weeks after surgery, or according to local standard of care, the treatment will continue until completion of treatment period (24 months), disease progression, unacceptable toxicity, death, or withdrawal from the study, whichever occurs first.
Signed Informed Consent Form
Age ≥ 18 years at time of signing Informed Consent Form
Ability to comply with the study protocol
Eligible to receive a platinum-based chemotherapy according to local labels or guidelines
Any exclusion criteria based on local labels or guidelines for chemotherapy
Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 90 days after the final dose of alectinib or or according to local labels or guidelines for chemotherapy longer), whichever is longer.
Any history of previous NSCLC and/or any history of prior treatment for NSCLC (participants must be newly diagnosed with unresectable Stage III disease)
Pleural effusion
Single group
After neoadjuvant alpelisib combined with chemotherapy, a multidisciplinary decision was made
DrugFor patients who have undergone three treatment cycles of neoadjuvant alaftinib combined with chemotherapy and have been evaluated by MDT as being resectable with good lung function, definitive surgery can be performed. Otherwise, the MDT will discuss with the patient to provide radical radiotherapy as the treatment option.
24-month EFS rate
EFS is defined as the time frame from initiation of study treatment to any of the following events: progression of disease, recurrence disease, the occurrence of a new primary NSCLC or death due to any cause. Progression / recurrence will be assessed per RECIST 1.1.
Secondary Efficacy Objectives-Surgical rate
defined as the proportion of participants who underwent curative-intent surgical resection (R0) following the completion of neoadjuvant treatment.
Secondary Efficacy Objectives-ORR to neoadjuvant
defined as the percentage of participants who attain a CR or PR in the neoadjuvant stage, as determined by investigators according to RECIST v1.1.
Secondary Efficacy Objectives-EFS
defined as time from initiation of study treatment to any of the following events: progression of disease, recurrence disease, the occurrence of a new primary NSCLC or death due to any cause. Progression/recurrence will be assessed per RECIST 1.1.
Secondary Efficacy Objectives-MPR rate
defined as the number of participants with \<10% residual tumor cells in primary lung cancer as evaluated by thoracic pathologists, divided by the number of all participants who underwent surgery.
AE and SAE and AESI
1. Incidence, type, and severity of (serious) adverse events according to NCI CTCAE v5.0. 2. Adverse events of special interest (AESI) for this study are as follows: Cases of potential drug-induced liver injury, Suspected transmission of an infectious agent by the study drug.
Peripheral blood MRD, paired tissue whole-genome sequencing (WGS)，changes in the immune microenvironment before and after treatment (RNA-seq).
Peripheral blood MRD，By comparing whole-genome sequencing (WGS，specifically for cases with significant residual tumor post-treatment) data of tissue samples before and after treatment, this study aims to evaluate the evolutionary characteristics of large-scale genomic structural variations, including copy number variations (CNVs)，Analyze the dynamic evolution of CD4+/CD8+ lymphocytes, tertiary lymphoid structures (TLS), and the stromal microenvironment, and explore their correlations with clinical efficacy.
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Wen-zhao ZHONG
Lead sponsor
Guangdong Provincial People's Hospital
Sponsor institution
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