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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: lorlatinib; Drug: lorlatinib plus chemotherapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Wenhua Liang, Doctor; Phone Number: 020-81567210; Email: liangwh1987@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lorlatinib group	Drug: 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.
Active Comparator: lorlatinib plus chemotherapy group	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single-cell RNA sequencing (scRNA-seq)	use the Singleron Matrix® Single Cell Processing System (Singeleron) according to the manufacturer's instructions to conduct the single-cell experiment and sequencing. It will be performed by an authorized, qualified independent laboratory.	Obtain the primary tumor tissue before drug administration; after the end of cycle 3（each cycle is 28 days) of induction therapy, the fresh tumor tissues will be collected immediately by surgical resection.

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 10, 2025
• Primary Completion (Estimated): July 20, 2027
• Study Completion (Estimated): July 20, 2027

Study Registration Dates

• First Submitted: March 7, 2025
• First Submitted That Met QC Criteria: March 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Resistance
• Other Study ID Numbers: LORLAL-001-V1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No