Induction Lorlatinib in Stage III Non-small Cell Lung Cancer

January 16, 2026 updated by: Wen-zhao ZHONG, Guangdong Provincial People's Hospital

Induction Lorlatinib for ALK Fusion Locally Advanced Non-small Cell Lung Cancer: A Prospective, Single Arm, Open-label Phase 2 Study

A prospective, single-arm, open-label phase 2 study that evaluates the efficacy and safety of induction Lorlatinib in stage III non-small cell lung cancer and explores the clinical feasibility of dynamic ctDNA and multidisciplinary assessment in guiding local treatments.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Simon two-stage was applied to estimate the required sample size for the study. Overall an estimated 43 patients were required and at least 12 patients achieved pathological complete response would be deemed as positive result. Patients will be provided 3 cycles induction Lorlatinib 100mg and then assessed whether patients would be eligible for radical surgery or local radiotherapy through multidisciplinary evaluation. After local intervention, patients could choose consolidation treatment of Lorlatinib for up to 2 years or adjuvant doublet chemotherapy for up to 4 cycles. Dynamic blood samples will be collected before and after induction Lorlatinib as well as consolidation treatment. The primary endpoints is pCR for patients who received radical surgery.

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijin
      • Beijin, Beijin, China, 100730
        • Peking Union Medical College Hospital
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • Guangdong Provincial People's Hospital
      • Guangzhou, Guangdong, China
        • Guangzhou Twelfth People's Hospital
    • Hunan
      • Changsha, Hunan, China, 410011
        • The Second Xiangya Hospital Of Central South University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age :18 Years to 75 Years;
  • ECOG physical score 0-2 points; expected survival time ≥ 1 year;
  • Pathologically confirmed diagnosis with Stage III NSCLC which harbored ALK fusion detected by next generation sequencing (NGS) or immunohistochemistry (IHC) with or without FISH. Suspected N2 (station 2/4/7) for stage III disease should be confirmed by either mediastinoscopy or EBUS.
  • At least one measurable target lesion according to the RECIST 1.1 standard;
  • The main organ function meets the following criteria: 1) blood routine: absolute value of neutrophils ≥ 1.5 × 109 / L, platelets ≥ 75 × 109 / L, hemoglobin ≥ 80 g / L; 2) blood biochemistry: total bilirubin ≤ 1.5 times the upper limit of normal value, aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times the upper limit of normal value (if liver metastasis, ≤ upper limit of normal value 5 times), serum creatinine ≤ 1.5 times the upper limit of normal;
  • Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.

Exclusion Criteria:

  • Stage I, stage II and metastatic stage IV NSCLC;
  • Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
  • Patients who have previously used any other anti-tumor drugs or received surgery/radiotherapy;
  • Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections.
  • Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy;
  • Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
  • Patients with low compliance or willingness to take the drugs and surveillance.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Arm
Patients will receive 12-week induction Lorlatinib followed by radical surgery or local radiotherapy or continue Lorlatinib through MDT and optional consolidation lorlatinib for up to 2 years.
Drug: Lorlatinib
Patients were assigned to receive oral lorlatinib at a dose of 100 mg daily in a course of treatment that was measured in cycles of 28 days. 3 cycles of induction treatment will be required for the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological Complete Response (pCR)
Time Frame: After surgery (approximately 2 weeks)
The pathological complete response is defined as the absence of residual tumor in both lung and regional lymph nodes after induction treatment and radical surgery.
After surgery (approximately 2 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: After last dose of induction treatment (approximately 1 week)
ORR is the number of participants with a Complete Response (CR) and Partial Response (PR) divided by the total number of enrolled participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared to baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions.
After last dose of induction treatment (approximately 1 week)
Dynamic ctDNA alteration
Time Frame: From induction treatment till completion of consolidation lorlatinib (approximately 2.5 years)
The exploratory ctDNA alteration will be stratified into three parts. 1) Induction period: overall ctDNA clearance rate (before and after induction treatment); 2) Posttreatment period: ctDNA clearance rate after local treatment; 3) Consolidation period: 1-year and 2-year ctDNA positive rate during consolidation treatment.
From induction treatment till completion of consolidation lorlatinib (approximately 2.5 years)
Overall Survival (OS)
Time Frame: From date of induction treatment till the date of death from any cause, assessed up to 60 months.
OS was assessed from initiation of treatment to death as a result of any cause.
From date of induction treatment till the date of death from any cause, assessed up to 60 months.
Adverse Events (AEs)
Time Frame: From Initiation of induction treatment till treatment discontinuation, assessed up to 24 months.
Incidence of AE/SAE which has been confirmed correlation with Lorlatinib or local treatment.
From Initiation of induction treatment till treatment discontinuation, assessed up to 24 months.
Progression-free Survival (PFS)
Time Frame: From date of induction treatment till the date of first documented disease progression or death, whichever came first, assessed up to 48 months
The period after initiation of induction treatment till the time of disease progress or any cause of death.
From date of induction treatment till the date of first documented disease progression or death, whichever came first, assessed up to 48 months
Event-free Survival (EFS)
Time Frame: From date of radical surgery till the date of first documented disease relapse, assessed up to 48 months
The period after radical surgery till the time of disease relapse with either local recurrence or distant metastasis.
From date of radical surgery till the date of first documented disease relapse, assessed up to 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangdong Provincial People's Hospital

Collaborators

Peking Union Medical College Hospital
Second Xiangya Hospital of Central South University
Guangzhou No.12 People's Hospital

Investigators

  • Principal Investigator: Wen-Zhao Zhong, MD., Guangdong Provincial People's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2023

Primary Completion (Actual)

December 31, 2025

Study Completion (Estimated)

April 30, 2026

Study Registration Dates

First Submitted

February 12, 2023

First Submitted That Met QC Criteria

February 21, 2023

First Posted (Actual)

February 23, 2023

Study Record Updates

Last Update Posted (Actual)

January 20, 2026

Last Update Submitted That Met QC Criteria

January 16, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LORIN

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Partial clinicopathological data of participants will be presented in the corresponding manuscript.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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