Phase 2 study of amivantamab plus lazertinib in previously-treated patients with EGFR mutant lung cancers with brain and leptomeningeal metastases

Abstract

Background: 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 2 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 endpoint was composite best overall response rate (ORR) per RECIST v 1.1 and RANO-BM or -LM. Secondary endpoints were toxicity, systemic ORR, CNS ORR, time on treatment (ToT), progression-free survival (PFS), CNS PFS, and overall survival (OS).

Results: We treated 20 pts with BrM and 21 pts with LMD. 41% had EGFR del19, 37% L858R, 12% ex20ins, and 10% uncommon mutations. Median lines of prior therapy: 2 (range 1-7). The ORR by a combination of RECIST and RANO-BM/RANO-LM respectively for pts with BrM was 50% (95% CI, 27-73%) and 33% (95% CI, 15-57%) for pts with LMD. 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 OS was 17.4 months (15.4-NR) in the BrM cohort and 14.4 months (8.9-NR) in the LMD cohort.

Conclusions: Amivantamab+lazertinib has anti-tumor activity in patients with EGFR-mutant lung cancers who develop new or progressing brain or leptomeningeal metastases. This trial demonstrates the feasibility of including patients with LMD in prospective clinical trials.