2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12H.05 Phase II Study on Platinum-Pemetrexed and Lorlatinib Combination in ALK-Positive NSCLC Extracranially Progressing on Lorlatinib

EP.12H.05 Phase II Study on Platinum-Pemetrexed and Lorlatinib Combination in ALK-Positive NSCLC Extracranially Progressing on Lorlatinib

Back to course

Pdf Summary

The document outlines a Phase II multicenter study in Italy, exploring the effectiveness and safety of a combined treatment regimen for ALK-positive Non-Small Cell Lung Cancer (NSCLC) patients who experience extracranial progression on lorlatinib. Lorlatinib is a third-generation ALK inhibitor used for treating NSCLC, although resistance often develops, necessitating alternative therapies. The study investigates the addition of platinum/pemetrexed-based chemotherapy to lorlatinib to address this resistance.<br /><br />Approximately 45 patients with exclusively extracranial progression on lorlatinib and possibly stable brain metastases will be enrolled. The treatment includes an induction phase of four cycles with platinum/pemetrexed-based chemotherapy and lorlatinib, followed by a maintenance phase with pemetrexed and lorlatinib in 21-day cycles, continuing until further disease progression, unacceptable toxicity, or other specified endpoints occur.<br /><br />Participants will undergo baseline tumor imaging using CT and MRI. The primary endpoint is Progression Free Survival (PFS), while secondary endpoints include intracranial PFS, Overall Survival (OS), safety, and patient-reported outcomes like quality of life, assessed through standardized questionnaires. Exploratorily, the study will investigate genetic alterations of resistance using circulating tumor DNA at different stages.<br /><br />Adverse events will be documented following the NCI CTCAE guidelines, and genetic analysis will be conducted to explore resistance mechanisms. The study is approved through the Clinical Trials Information System and has begun patient enrollment as of March 2024, with trial updates to be presented at an upcoming Congress.

Asset Subtitle

Elisa Bertoli

Meta Tag

Speaker Elisa Bertoli

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

Phase II study

multicenter

Italy

ALK-positive NSCLC

lorlatinib resistance

platinum/pemetrexed chemotherapy

Progression Free Survival

genetic alterations

extracranial progression

patient-reported outcomes