ALK-positive, Locally Advanced or Metastatic (TNM Stage IIIB-IV) Non-small Cell Lung Cancer That Has Developed Resistance to Prior Treatment With Lorlatinib
Conditions
Keywords
Lorlatinib resistance, Ensartinib, Anlotinib, ALK-positive non-small cell lung cancer
Brief summary
ALK TKIs, particularly second- and third-generation ALK TKIs, have significantly improved progression-free survival (PFS) in patients with advanced ALK-positive non-small cell lung cancer (NSCLC). However, patients continue to face challenges related to drug resistance and disease progression; in the CROWN study, 40% of patients still experienced disease progression within five years. There are currently no standard treatment recommendations for this patient population. This study retrospectively evaluated the efficacy and safety of ensartinib combined with anlotinib as a second-line treatment in patients who had developed resistance to lorlatinib. The inclusion criteria for data collection were patients aged ≥18 years with histologically confirmed stage IIIB-IV ALK-positive NSCLC who had developed resistance to lorlatinib; prior to lorlatinib treatment, patients could have received up to two other ALK-TKIs, excluding ensartinib.
Interventions
DRUGCombined group of ensatinib and arotinib
Ensatinib is administered at a dose of 225 mg once daily, either on an empty stomach or with food; anlotinib is administered at a dose of 10 mg once daily, in 21-day cycles; treatment continues until disease progression, the occurrence of intolerable toxicity, withdrawal at the discretion of the investigator or the subject, loss to follow-up, initiation of other anticancer therapy, or death.
Sponsors
Qiming Wang
Betta Pharmaceuticals Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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 criteria
1：Concurrent malignant tumours.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | After the patients were enrolled according to the inclusion criteria, the tumor assessment will be conducted every 6 weeks, and the maximum duration of the assessment is 6 months until the patients have disease progression or cannot tolerate the treatmen | If the patient has available imaging results from within 28 days prior to the first dose (bone scans may be accepted if performed within 2 months prior to the first dose), repeat imaging is not required. Tumour assessment should be performed every 6 weeks (±4 days) until tumour progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary endpoints include progression-free survival (PFS) | The assessment was conducted every 2 cycles (6 weeks and 24 days), and the maximum duration of the assessment was 6 months until the patient's condition progressed or could not tolerate the treatment. As of June 2028, the follow-up work has been complete | Progression-free survival (PFS): defined as the time from randomisation to the first occurrence of objective tumour progression or death, whichever comes first. |
| Overall survival (OS) | The assessment was conducted every 2 cycles (6 weeks and 24 days), and the maximum duration of the assessment was 6 months until the patient's condition progressed or could not tolerate the treatment. As of June 2028, the follow-up work has been complete | Overall survival (OS): defined as the time from randomisation to the patient's death from any cause. |
| Duration of Response (DOR) | The assessment was conducted every 2 cycles (6 weeks and 24 days), and the maximum duration of the assessment was 6 months until the patient's condition progressed or could not tolerate the treatment. As of June 2028, the follow-up work has been complete | Duration of Response (DOR): Defined as the time from the first assessment of complete response (CR) or partial response (PR) until the first assessment of disease progression (PD) or death from any cause. |
| Disease Control Rate (DCR) | The assessment was conducted every 2 cycles (6 weeks and 24 days), and the maximum duration of the assessment was 6 months until the patient's condition progressed or could not tolerate the treatment. As of June 2028, the follow-up work has been complete | Disease Control Rate (DCR): Defined as the proportion of patients who achieve complete response (CR), partial response (PR) or stable disease (SD) following treatment and maintain this status for a certain period. |
| Safety assessment | At the end of the first cycle (24 days in each cycle), a safety follow-up (telephone follow-up) was conducted within 28 days after the last administration. | Safety assessment: A summary of patients' physical examinations, electrocardiograms, ECOG scores, vital signs, adverse events and abnormal laboratory test results. All adverse events should be graded for severity in accordance with NCI CTCAE version 4.03. |
Contacts
CONTACTQiming Wang Qiming Wang
Outcome results
None listed