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

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ELCC Conference; March 29; Copenhagen, Denmark. 2023: 30.


oregon; chiles


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 >2 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.

Clinical Institute



Earle A. Chiles Research Institute




Lopez PG, Girard N, Cho BC, Sabari J, Spira A, Sanborn RE, Goto K, Yang JC, Curtin J, Lyu X, He A, Penton J, Edwards J, Massin GL, Xia K, Chioda M, Thayu M, Knoblauch RE, Mahadevia P, Leighl N.

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