Chemotherapy Combined with ICIs in First-line Alectinib Failed Patients with ALK-rearranged NSCLC

• The investigators collected data from patients with metastatic ALK fusion-positive non-small cell lung cancer (NSCLC) who received first-line Alectinib treatment between April 2017 and July 2021. Our analysis aimed to assess their clinical outcomes and explore the impact of 5' ALK on the treatment response to Alectinib.
• For patients who experienced disease progression after August 2021, they were treated with a combination of chemotherapy and PD-1 monoclonal antibodies with/without Bevacizumab or chemotherapy alone with/without Bevacizumab was observed and recorded data on progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and overall survival (OS) for these patients.
• The investigators collected pre-treatment biological samples for biomarker analysis, including FFPE samples for whole-genome sequencing (WGS), whole-exome sequencing (WES), RNA-seq, and multiplex fluorescence analysis. FFPE samples were also collected for PD-L1 testing. Additionally, pre-treatment blood samples were collected for cytokine analysis, as well as tumor mutational burden (TMB) and T-cell receptor (TCR) testing. The investigators aimed to evaluate the differences in these results between 3' ALK and 5' ALK.

Inclusion criteria

• ≥18，Advanced Non-small Cell Lung Cancer Confirmed by Histopathology
• ALK -arreaged confirmed by NGS;
• Received first line treatment Alectinib;
• Progressed from first-line alectinib;
• ECOG 0-1;
• Predicted survival ≥ 12 weeks;
• Adequate bone marrow hematopoiesis and organ function;
• Presence of measurable lesions according to RECIST 1.1;
• Subjects with stable brain metastases may be included in the study.
• Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.

Exclusion criteria

• Patient who do not have the samples for NGS to confirmed ALK status.
• Subjects who have received any of the following treatments must be excluded:

• Treatment with molecules such as EGFR, VEGFR antibodies within 4 weeks prior to the first dose of study drug.
• Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
• Presence of spinal cord compression or meningeal metastasis.
• History of other malignant tumors within 2 years.
• Adverse events (except alopecia of any degree) of CTCAE > grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
• History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
• The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
• Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
• Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
• Live vaccine was given 2 weeks before the first medication.
• Women who are breastfeeding or pregnant.
• Hypersensitivity to the test drug and the ingredients.
• Other conditions assessed by the investigator to be unsuitable for participation in the study.