Efficacy and Safety of Ensartinib Combined With Anlotinib in Lorlatinib-Resistant ALK-Positive NSCLC

Co-hort 1: Strict co-hort Inclusion criteria1：Histologically or cytologically confirmed stage IIIB-IV non-small cell lung cancer; Inclusion criteria2：Age ≥ 18 years at the time of signing the informed consent form; Inclusion criteria3：ALK-positive status confirmed by tissue samples or blood tests at each centre; Inclusion criteria4：History of resistance to lorlatinib treatment; prior use of ensartinib is not permitted; patients must have received a maximum of two other ALK-TKIs; prior receipt of ≤2 courses of chemotherapy is permitted; ECOG Performance Status (PS) score between 0 and 2, with no deterioration within 2 weeks prior to study entry;

Co-hort 2 (Compassionate Use Cohort):

Inclusion criteria1： Resistance to lorlatinib treatment; Inclusion criteria2： No restrictions on prior use of ensartinib or the number of prior lines of other ALK-TKIs and chemotherapy; Inclusion criteria3：Subjects with concomitant leptomeningeal metastases may be enrolled. For patients with leptomeningeal metastases (LM), diagnosis must be based on the three criteria outlined in the EANO-ESMO guidelines: clinical presentation, cranial imaging, and cerebrospinal fluid cytology. Tissue samples must not be derived from tumour sites that have previously undergone radiotherapy; however, new lesions arising after local treatment may be included; Inclusion criteria4：ECOG performance status of 0-4; Inclusion criteria5： Adequate organ system function, as determined by the investigator; Inclusion criteria6：All other inclusion criteria are consistent with items 1, 2 and 3 of Cohort 1.

Exclusion criteria1：Concurrent malignant tumours. Exclusion criteria2：Patients with leptomeningeal metastases (LM) who are unable to undergo contrast-enhanced MRI.

Exclusion criteria3：Patients who have undergone surgery within 4 weeks prior to treatment with the study drug, except for minor procedures deemed by the investigator not to preclude participation in the trial; or patients scheduled to undergo major surgery during the study period.

Exclusion criteria4：Patients who have experienced a marked deterioration in symptoms or signs within 2 weeks prior to screening and are deemed by the investigator to be unsuitable for participation in the trial.