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

Guangzhou Medical University

Status and phase

Not yet enrolling

Phase 4

Conditions

NSCLC

Treatments

Drug: lorlatinib

Drug: lorlatinib plus chemotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT06893354

LORLAL-001-V1

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.