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

NCT07671560 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2026-252
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

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.

Conditions

ALK-positive, Locally Advanced or Metastatic (TNM Stage IIIB-IV) Non-small Cell Lung Cancer That Has Developed Resistance to Prior Treatment With Lorlatinib

Keywords

Lorlatinib resistance; Ensartinib; Anlotinib; ALK-positive non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  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.

  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

Secondary Outcomes (5)

• 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

• 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

• 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

• 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

• 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.

Study Arms (2)

Strict Queue

OTHER

Patients with a performance status (ECOG) score of 0-2 and brain parenchymal metastases were enrolled in Cohort 1.

Drug: Combined group of ensatinib and arotinib

Compassionate Use Cohort

OTHER

Patients with a performance status (ECOG) score of 0-4 and leptomeningeal metastases were enrolled in Cohort 2 (compassionate use cohort).

Drug: Combined group of ensatinib and arotinib

Interventions

Combined group of ensatinib and arotinib DRUG

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.

Compassionate Use Cohort; Strict Queue

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Co-hort 2 (Compassionate Use Cohort):

Sponsors & Collaborators

• Qiming Wang: lead
• Betta Pharmaceuticals Co., Ltd.: collaborator

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Qiming Wang Qiming Wang

CONTACT

13783590691; qimingwang1006@126.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Department

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: June 26, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 26, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share