Lorlatinib in Combination With Chemotherapy in Participants With Metastatic Anaplastic Lymphoma Kinase Positive (ALK+) Non-small Cell Lung Cancer (NSCLC) Who Progressed on Single-agent Lorlatinib — NSCLC  

Lung Cancer Clinical Trial

Official title: Phase II Study of Lorlatinib in Combination With Chemotherapy in Participants With Metastatic Anaplastic Lymphoma Kinase Positive (ALK+) Non-small Cell Lung Cancer (NSCLC) Who Progressed on Single-agent Lorlatinib

Status Withdrawn

Clinical Trial Summary

This clinical trial is an open-label, single arm study evaluating the safest dose of lorlatinib in combination with standard of care chemotherapy in participants with metastatic anaplastic lymphoma kinase positive (ALK+) NSCLC who progressed on prior therapy of lorlatinib alone. The main goals of this study are to:

• Evaluate the safety and tolerability of lorlatinib in combination with standard of care chemotherapy.

• Evaluate how well the combination of lorlatinib and standard of care chemotherapy works to treat metastatic anaplastic lymphoma kinase positive (ALK+) NSCLC.

• Evaluate the pharmacokinetics (PK) of lorlatinib when given in combination with standard of care chemotherapy.

Clinical Trial Description

Lorlatinib is a kinase inhibitor with in vitro activity against ALK and ROS1. This study's aim is to evaluate the safety of lorlatinib given in combination with platinum-based standard of care chemotherapy in participants with metastatic anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer who progressed after receiving lorlatinib alone.

There will be a lead-in portion for the first six participants treated. Lead-in participants will receive an assigned starting dose of lorlatinib by mouth once daily throughout each cycle. In addition, a platinum-based standard of care chemotherapy regimen, to include carboplatin or cisplatin as well as pemetrexed, will be given intravenously every 3 weeks. A cycle is defined as 3 weeks. After tolerability is confirmed in the lead-in with the first 6 participants on trial, the next 9 participants may begin at an increased starting dose of lorlatinib by mouth once daily. After 4 cycles of oral lorlatinib and intravenous platinum-based standard of care chemotherapy and intravenous pemetrexed, the participant will move into the maintenance regimen. The maintenance regimen will include continuing on daily oral lorlatinib plus intravenous pemetrexed every 3 weeks until disease progression or intolerable toxicity or other reason for discontinuation. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Non-small Cell Lung Cancer

• NCT number: NCT05948462
• Study type: Interventional
• Source: SCRI Development Innovations, LLC
• Status: Withdrawn
• Phase: Phase 2
• Start date: November 2023
• Completion date: September 2025