Explore the Mechanisms Underlying Disease Resistance and Potential Primary Resistance Mechanism of Induction Therapy Lorlatinib in Resectable Non-small Cell Lung Cancer (NSCLC) Harboring ALK Positive Mutation Revealed by Single-cell RNA Sequencing and Spatial Transcriptomics

NCT ID: NCT06893354

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-10
• Study Completion Date: 2027-07-20

Brief Summary

This is an open-label, randomized, single-center study. This translational study aims to explore tumor microenvironment remodelling after induction therapy lorlatinib and identify mechanisms of disease persistence and potential primary resistance mechanisms of lorlatinib as induction therapy treatment in surgically resectable ALK-rearranged NSCLC by single-cell RNA sequencing (scRNA-seq) and Spatial transcriptomics.

Detailed Description

to explore tumor microenvironment remodelling after induction therapy lorlatinib and identify mechanisms of disease persistence and potential primary resistance mechanisms of lorlatinib as induction therapy treatment in surgically resectable ALK-rearranged NSCLC by single-cell RNA sequencing (scRNA-seq) and Spatial transcriptomics.

Conditions

NSCLC

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

lorlatinib group

Group Type: EXPERIMENTAL

lorlatinib

Intervention Type: DRUG

Subjects will be registered to receive oral lorlatinib 100mg qd for 3 cycles of 4 weeks each (12 weeks total), and then underwent surgery.

lorlatinib plus chemotherapy group

Group Type: ACTIVE_COMPARATOR

lorlatinib plus chemotherapy

Intervention Type: DRUG

Subjects will be registered to receive oral lorlatinib 100mg qd for 3 cycles of 4 weeks each (12 weeks total) plus chemotherapy, and then underwent surgery.

Interventions

lorlatinib

Subjects will be registered to receive oral lorlatinib 100mg qd for 3 cycles of 4 weeks each (12 weeks total), and then underwent surgery.

Intervention Type: DRUG

lorlatinib plus chemotherapy

Subjects will be registered to receive oral lorlatinib 100mg qd for 3 cycles of 4 weeks each (12 weeks total) plus chemotherapy, and then underwent surgery.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female subjects who are ≥18 years of age；
• Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage IB-III) disease
• Clinical stage IIA/IIB/IIIA/IIIB assessed by EBUS-TBNA or PET(positron emission tomography)/CT can be resected.
• Documented ALK-fusion positive（ Ventana , assessed by a local laboratory）
• ECOG PS 0-1
• Performance status (ECOG) 0-1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing of lorlatinib
• Hematology , liver and kidney function are adequate for induction therapy .
• Cardiopulmonary function suitable for surgical treatment (ECG, echocardiography, pulmonary function or blood gas analysis).
• Be willing and able to provide written informed consent for the trial prior to any study specific procedures. The subject must also provide consent for correlative translational study.
• Female participants of childbearing potential must agree to use acceptable methods of contraception
• Male patients must be willing to use barrier contraception. Provide written informed consent.

Exclusion Criteria

• Mixed squamous cell carcinoma, large cell carcinoma, small cell lung cancer.
• Prior treatment with any systemic anti-cancer therapy for NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug.
• Pregnant female patients; breastfeeding female patients.
• Malignancies other than the disease under study within 3 years prior to Cycle 1, Day 1, with the exception of patients with a negligible risk of metastasis or death and with expected curative outcome
• Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infections, or any active infection that, in the opinion of the investigator, could impact participant safety
• Pregnant or lactating, or intending to become pregnant during the study Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Jianxing He

Chief physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Wenhua Liang, Doctor

Role: CONTACT

liangwh1987@163.com

020-81567210

Other Identifiers

LORLAL-001-V1

Identifier Type: -

Identifier Source: org_study_id