Long-term efficacy, safety, and predictors of response to amivantamab among patients with post-platinum EGFR Ex20ins-mutated advanced NSCLC

Background: Amivantamab (ami), an EGFR and MET bispecific antibody with immune cell-directing activity, is approved to treat patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations (Ex20ins) who progressed on prior platinum-based chemotherapy. This report presents long-term results for this population. Methods: Pts with EGFR Ex20ins advanced NSCLC whose disease progressed on platinum-based chemotherapy were recruited in CHRYSALIS. Pts who received the approved phase II dose of 1050 mg (1400 mg, ≥80 kg) by 08 Jun 2020 were included. Response was assessed by investigator per RECIST v1.1. Results: As of Sep 2022, among 114 pts included, the median follow-up was 19.2 months and 48 (42%) pts alive. Investigator-assessed overall response rate (ORR) was 37% (95% CI, 28–46), with median duration of response of 12.5 months (95% CI, 6.9–19.3), median progression-free survival of 6.9 months (95% CI, 5.6–8.8), and median overall survival of 23 months (95% CI, 18.5–29.5). Activity was observed across subgroups, including the elderly (ORR of 32% and 33% for age ≥65 and ≥75, respectively), heavily pretreated pts (ORR of 53% for \u3e2 prior lines, 42% for prior immunotherapy, and 52% for prior EGFR TKI therapy), or those sensitive or resistant to prior platinum-based chemotherapy (ORR of 36% and 31%, respectively). No new safety signals were detected, with rash (all grades, 89%) and infusion-related reactions (67%) remaining the most frequent toxicities. There are 48 (42%) pts on ami for ≥12 (28-day) cycles. Treatment is ongoing in 15 (13%) pts (11 responders and 4 with stable disease as best response) who have received ami for a median of 2.6 years. An analysis comparing pts without and with sustained clinical benefit (≥12 cycles on ami) will presented at the meeting, including plasma ctDNA data. Conclusions: Ami demonstrated robust efficacy that was consistently observed across post-platinum patients with EGFR Ex20ins NSCLC, including the elderly, those with multiple prior lines, or those who were platinum sensitive or refractory. A subgroup derived long-term benefit; the mechanisms for which will be explored further