The CHRYSALIS-2 trial (cohort C) investigated the combination of amivantamab and lazertinib in 105 patients with advanced non-small cell lung cancer (NSCLC) with atypical EGFR mutations, such as G719X (56%), L861X (26%), and S768I (23%), including single and combined mutations[1][2]. Patients had no more than two prior lines of therapy, including first- or second-generation EGFR inhibitors[1]. At a median follow-up of 16.1 months, the objective response rate (ORR) was 52% (95% CI: 42–62%), all partial responses[1][2]. Median duration of response was 14.1 months (95% CI: 9.5–26.2 months), median progression-free time (PFS) was 11.1 months (95% CI: 7.8–17.8 months), and median overall survival was not reached (95% CI: 22.8 months or more)[2]. In untreated patients, the ORR was 57% (95% CI: 42–71%), the median duration of response was 20.7 months, and the PFS was 19.5 months[2]. Another 35% of patients had stable disease[2]. The combination demonstrated clinically significant antitumor activity without new safety signals[1][2].