Multidisciplinary Treatment of Stage III ALK+ NSCLC With Neoadjuvant Alectinib and Chemotherapy

NCT07573696 | Not Yet Recruiting Phase 2

• 1 other identifier: KY2026-147-02
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Nonsmall Cell Lung Cancer Stage III

Outcome Measures

Primary Outcomes (1)

• 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.

  From enrollment to the end of treatment at about 120 weeks(Preoperative treatment lasted for 9 weeks, MDT + surgery was assumed for 2 weeks, and continuous treatment began within 12 weeks after surgery and lasted for approximately 96 weeks.)

Secondary Outcomes (6)

• Secondary Efficacy Objectives-Surgical rate

  From enrollment to the end of treatment at 10 weeks（Each cycle lasts for 3 weeks, and there are a total of 3 cycles，and MDT assessment need 1 week）.

• Secondary Efficacy Objectives-ORR to neoadjuvant

  From enrollment to the end of treatment at 10 weeks（Each cycle lasts for 3 weeks, and there are a total of 3 cycles，and MDT assessment need 1 week）.

• Secondary Efficacy Objectives-EFS

  From enrollment to the end of treatment at about 120 weeks(Preoperative treatment lasted for 9 weeks, MDT + surgery was assumed for 2 weeks, and continuous treatment began within 12 weeks after surgery and lasted for approximately 96 weeks.)

• Secondary Efficacy Objectives-MPR rate

  From enrollment to the end of treatment at 10 weeks（Each cycle lasts for 3 weeks, and there are a total of 3 cycles，and MDT assessment need 1 week）.

• Secondary Efficacy Objectives-pCR rate

  From enrollment to the end of treatment at 10 weeks（Each cycle lasts for 3 weeks, and there are a total of 3 cycles，and MDT assessment need 1 week）.

Other Outcomes (2)

• AE and SAE and AESI

  From enrollment to 28 days after the last dose (about 124 weeks for each participant)

• Peripheral blood MRD, paired tissue whole-genome sequencing (WGS)，changes in the immune microenvironment before and after treatment (RNA-seq).

  Peripheral blood MRD：enrollment, after neoadjuvant therapy, post-surgery Tissue：enrollment, after surgery or radical radiotherapy

Study Arms (1)

Alectinib plus Chemotherapy

EXPERIMENTAL

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).

Drug: After neoadjuvant alpelisib combined with chemotherapy, a multidisciplinary decision was made

Interventions

After neoadjuvant alpelisib combined with chemotherapy, a multidisciplinary decision was made DRUG

For 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.

Alectinib plus Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• 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
• Cytologically and/or histologically documented locally advanced, unresectable Stage III NSCLC
• Staging should be based on Version 8 of the American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system.
• Participants with T4 primary NSCLC with a separate nodule in a different ipsilateral lobe are not eligible.
• Documented ALK fusion positivity by an eligible result from:
• ○ Previously obtained local test results as ordered by a healthcare provider from a high-quality and appropriately validated ALK fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments Certified or equivalent laboratory. Acceptable local test methods include the following
• Next-generation sequencing; immunohistochemistry; fluorescence in situ hybridization; reverse transcription-polymerase chain reaction; NanoString.
• Only National Medical Products Administration (NMPA)-approved tests for ALK fusions are acceptable.
• Identification of a specific gene fusion partner is required (exceptions: ALK immunohistochemistry and certain PCR tests for which the gene fusion partner is not pre-specified as part of the test design). The use of positional 5/3 imbalance probe gene expression is not acceptable.
• Eastern Cooperative Oncology Group Performance Status of 0, or 1
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• 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.
• ○ Women of childbearing potential must have a negative serum pregnancy test result prior to enrollment and within 7 days prior to the first dose of alectinib.
• Any history of previous NSCLC and/or any history of prior treatment for NSCLC (participants must be newly diagnosed with unresectable Stage III disease)
• Any evidence of Stage IV disease, including, but not limited to, the following:
• Pleural effusion
• Pericardial effusion
• Brain metastases
• History of intracranial hemorrhage or spinal cord hemorrhage
• Bone metastases
• Distant metastases
• If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (T4 disease):
• ○ When pleural fluid is visible on both the CT scan and chest X-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative.
• Participants with exudative pleural effusions are excluded regardless of cytology.
• Participants with effusions that are minimal (i.e., not visible on chest X-ray) that are too small to safely tap are eligible.

Sponsors & Collaborators

• Wen-zhao ZHONG: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

WEN ZHAO ZHONG, MD

CONTACT

86-020-83525815; gdphgcp@gdph.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 12, 2026
• First Posted: May 7, 2026
• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): February 8, 2030
• Study Completion (Estimated): August 7, 2030
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share