PEARL: A Multicenter Phase 2 Study of Lorlatinib in Patients with ALK-Rearranged NSCLC and Central Nervous System Disease

Chang Lu ¹, Hong-Hong Yan ¹, Chan-Yuan Zhang ²

⁰Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

Clinical Lung Cancer +

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December 25, 2024

View abstract on PubMed

Summary

Lorlatinib shows promise for treating ALK-positive non-small cell lung cancer with brain metastases. This study evaluates its efficacy and safety using new CNS response criteria.

Area Of Science

Oncology
Translational Research
Clinical Trials

Background

Patients with ALK-rearranged non-small cell lung cancer (ALK+ NSCLC) and central nervous system (CNS) metastases often have poor performance status, limiting clinical trial participation.
There is a critical need for improved and validated assessment criteria for CNS response in ALK+ NSCLC.
Lorlatinib has demonstrated systemic activity in ALK+ NSCLC patients.

Purpose Of The Study

To evaluate the efficacy and safety of lorlatinib in ALK+ NSCLC patients with progressive brain metastases (BM) and leptomeningeal metastases (LM).
To assess intracranial objective response rate (ORR) using refined CNS response evaluation criteria.
To conduct biomarker analyses for insights into response and resistance mechanisms.

Main Methods

A multicenter, open-label, single-arm, prospective Phase II trial (PEARL study, CTONG2303).
Fifty eligible subjects divided into BM (n=30) and LM (n=20) cohorts.
Key inclusion criteria: ALK+ NSCLC, progressive CNS metastases, ECOG performance status 0-2 (BM) or 0-3 (LM).
Primary endpoint: Intracranial ORR per modified RECIST v1.1 (BM) and RANO-LM criteria (LM).

Main Results

This section is not available in the provided abstract.

Conclusions

The PEARL study will evaluate lorlatinib's efficacy in CNS metastases for ALK+ NSCLC.
Refined CNS response evaluation criteria will be utilized.
Biomarker analyses will offer insights into response and resistance mechanisms.

Keywords:

ALK TKI ALK fusion CNS metastases Leptomeningeal metastases Non-small cell lung cancer