NCT05948462

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

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• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: SCRI Development Innovations, LLC · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Lung Cancer
• Non-small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Lorlatinib	Participants will receive assigned dose of daily oral lorlatinib continuously for each cycle. Each cycle is 3 weeks.
DRUG	Cisplatin or Carboplatin	Participants will receive standard of care intravenous Cisplatin or Carboplatin, both chemotherapy medications, on day 1 of each cycle every 3 weeks, for Cycles 1-4. Each cycle is 3 weeks.
DRUG	Pemetrexed	Participants will receive intravenous Pemetrexed, a chemotherapy medication, on day 1 of each cycle. Each cycle is 3 weeks.

Timeline

• Start date: 2023-11-01
• Primary completion: 2025-03-01
• Completion: 2025-09-01
• First posted: 2023-07-17
• Last updated: 2023-12-13

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study