Phase 2 Study of Amivantamab Plus Lazertinib in Previously Treated Patients With EGFR-Mutant Lung Cancers With Brain and Leptomeningeal Metastases

Abstract

Introduction: Despite improved central nervous system (CNS) disease control with osimertinib, 20% of patients will develop CNS progression. Amivantamab and lazertinib have demonstrated activity in patients with EGFR-mutant lung cancer. This trial evaluated amivantamab and lazertinib in patients with new or progressive CNS metastases after prior therapy (NCT04965090).

Methods: We evaluated amivantamab and lazertinib in two cohorts: patients with (1) brain metastases (BrM) or (2) leptomeningeal disease (LMD) diagnosed by cytology in patients with lung cancers with sensitizing EGFR-activating mutations or exon 20 insertions. The primary end point was composite best overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 and Response Assessment in Neuro-Oncology brain metastases or Response Assessment in Neuro-Oncology leptomeningeal metastases. Secondary end points were toxicity, systemic ORR, CNS ORR, time on treatment, progression-free survival (PFS), CNS PFS, and overall survival.

Results: We treated 20 patients with BrM and 21 patients with LMD. Of the patients, 41% had EGFR del19, 37% L858R, 12% ex20ins, and 10% uncommon mutations. Median lines of prior therapy were 2 (range 1-7). The ORR by a combination of Response Evaluation Criteria in Solid Tumors and Response Assessment in Neuro-Oncology brain metastases/Response Assessment in Neuro-Oncology leptomeningeal metastases was 50% (95% confidence interval [CI], 27%-73%) for patients with BrM and 33% (95% CI, 15%-57%) for patients with LMD, respectively. The median PFS was 5.8 months (95% CI, 3.6-not reached [NR]) and 7.8 months (95% CI, 4.2-12.2) for the BrM and LMD cohorts, respectively. Median overall survival was 17.4 months (15.4-NR) in the BrM cohort and 14.4 months (8.9-NR) in the LMD cohort.

Conclusions: Amivantamab plus lazertinib has antitumor activity in patients with EGFR-mutant lung cancers who develop new or progressing BrM or LMD. This trial demonstrates the feasibility of including patients with LMD in prospective clinical trials.

Keywords: Brain metastases; EGFR; Leptomeningeal disease; Targeted therapy.