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Lorlatinib After Failure of First-line Second-generation ALK Kinase Inhibitor in Patients With Advanced ALK-positive Non-small Cell Lung Cancer | Clinical Trials | Clareo Health

COMPLETEDPHASE2

Lorlatinib After Failure of First-line Second-generation ALK Kinase Inhibitor in Patients With Advanced ALK-positive Non-small Cell Lung Cancer

A Phase II Non-randomized, Single Group Assignment, Open-label, Multicenter Study of Efficacy and Safety of Lorlatinib Monotherapy After Failure of First-line Second-generation ALK Kinase Inhibitor in Patients With Advanced ALK-positive Non-small Cell Lung Cancer

NCT04111705•Intergroupe Francophone de Cancerologie Thoracique

View on ClinicalTrials.gov

Summary

Crizotinib is a first-generation ALK tyrosine kinase inhibitor (ITK-ALK). It is the standard first-line treatment for patients with advanced NSCLC with ALK gene rearrangement. Alectinib, ceritinib and brigatinib are second-generation ITK-ALK. They have been shown to be effective in the first line of treatment in randomized trials. Alectinib has shown superiority to crizotinib as the first line of treatment in three randomized therapeutic trials, positioning this ITK-ALK as the treatment of choice in first-line treatment. Despite the effectiveness of these new treatments, all patients will virtually experience a relapse. There is no data on second-generation TKI-ALK resistance mechanisms when given as first-line treatment and the best therapeutic strategy for progression is undefined.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Signed Written Informed Consent:
•* Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
•* Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing
•5. Tumor Sample Requirement: Tumour biopsy sampling on fresh tissue (FFPE blocks required) at time of progression on first-line TKI is mandatory. Tumour biopsy should be exploitable for molecular analysis. If the tumour biopsy is not exploitable, the inclusion will be allowed if two blood samples are provided for tumoral cfDNA analysis. The Sponsor will monitor a posteriori the exploitability of provided tumour biopsies and will investigate the impossibility to perform or repeat tissue tumor sampling.
•6. Age ≥18 years.
•7. Life expectancy of at least 12 weeks, in the opinion of the Investigator.
•8. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2
•9. Adequate Bone Marrow Function, including:
•* Absolute Neutrophil Count (ANC) ≥1.5 x 109/L;
•* Platelets ≥100 x 109/L;
+16 more criteria

Exclusion Criteria

•3. Disease Status Requirements: Disease progression meeting RECISTv1.1 after first-line alectinib or brigatinib only. No prior chemotherapy is allowed in the metastatic disease setting.
•1. Patients who experienced a clinical benefit of less than 6 months with front-line alectinib or brigatinib.
•2. Participants with disease progression on front-line treatment with 2G ALK-TKI i.e. brigatinib or alectinib limited to CNS or one non-CNS site (oligometastasis) and eligible to a local ablative treatment (surgery or stereotaxic radiotherapy).
•3. Transdifferentiation into small cell lung cancer.
•4. Spinal cord compression is excluded unless the patient demonstrates good pain control attained through therapy and there is stabilization or recovery of neurological function for the 4 weeks prior to study entry.
•5. Patients with symptomatic and neurologically instable CNS metastases or leptomeningeal metastasis (including patients that require increasing doses of steroids within one week prior to Day 0 of screening phase and during the screening phase to manage CNS symptoms).
•6. Major surgery within 35 days of study entry. Minor surgical procedures (eg, port insertion, mediastinoscopy, surgical procedure for re-sampling) are not excluded, but sufficient time at investigator discretion should have passed for wound healing.
•7. Radiation therapy within 2 weeks of study entry (except palliative to relieve bone pain). Palliative radiation (≤15 fractions) must have been completed at least 48 hours prior to study entry. Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry.
•8. Prior therapy with an antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including, but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4.
•9. Active and clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness.
+10 more criteria

Locations (32)

Angers - CHU

Angers, France

Annecy - CH

Annecy, France

Bayonne - CH

Bayonne, France

Besançon - CHU

Besançon, France

Bordeaux - CHU Hôpital Haut-Lévèque

Bordeaux, France

Boulogne - Ambroise Paré

Boulogne-Billancourt, France

Caen - CHU Côte de Nacre

Caen, France

Colmar - CH

Colmar, France

Créteil - CHI

Créteil, France

Dijon - CRLCC

Dijon, France

Key Dates

Start Date

August 5, 2020

Primary Completion Date

August 11, 2022

Completion Date

December 15, 2024

Last Updated

April 1, 2025

Enrollment

ACTUAL participants

Conditions

Non Small Cell Lung Cancer Metastatic

Interventions

Lorlatinib

DRUG

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NCT03808662

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ACTIVE_NOT_RECRUITINGPHASE2

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: April 1, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Lorlatinib After Failure of First-line Second-generation ALK Kinase Inhibitor in Patients With Advanced ALK-positive Non-small Cell Lung Cancer

Inclusion Criteria

Exclusion Criteria

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