13. Long-term efficacy, safety and predictors of response to amivantamab among patients with post-platinum EGFR exon 20 insert (Ex20ins)-mutated advanced non-small cell lung cancer (aNSCLC) — CHRYSALIS (NCT02609776)

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Publication Date


Publication Title

OTCC Conference April 14-16; Ontario, Canada. 2023


oregon; chiles


  1. Background and Objectives: Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, is approved for patients with aNSCLC harboring EGFR Ex20ins mutations and progressed on prior platinum-based chemotherapy (PBC). This report presents long-term results.

Methods: Patients with EGFR Ex20ins aNSCLC whose disease progressed on PBC and who received the approved amivantamab dose of 1050mg (1400mg, ≥80 kg) by 08Jun2020 were included. Response was investigator-assessed per RECIST v1.1.

Results: By Sep2022 (N=114), median follow-up was 19.2 months, with 48 (42%) patients alive. Investigator-assessed overall response rate (ORR) 37% (95%CI, 28–46), median response duration 12.5 months (95%CI, 6.9–19.3), median progression-free survival 6.9 months (95%CI, 5.6–8.8), and median overall survival 23 months (95%CI, 18.5–29.5). Activity (ORR) was observed across subgroups, including elderly (32%/33% for age ≥65/≥75, respectively), heavily pretreated (53% >2 prior lines, 42% prior immunotherapy, 52% prior EGFR TKI therapy), or patients sensitive/resistant to prior PBC (36%/31%, respectively). No new safety signals detected. Rash (89%) and infusion-related reactions (67%) remained most frequent toxicities.

There are 48 (42%) patients on amivantamab for ≥12 (28-day) cycles. Treatment is ongoing in 15 (13%) (11 responders, 4 with stable disease as best response) who have received ami for a median 2.6 years. An analysis comparing patients without/with sustained clinical benefit (≥12 cycles on amivantamab) will be presented, including plasma ctDNA data.

Conclusions: Amivantamab demonstrated robust efficacy, consistently observed across PBC patients with EGFR Ex20ins NSCLC, including elderly, multiple prior lines, or platinum sensitive or refractory. A subgroup derived long-term benefit; the mechanisms to be explored further.

Clinical Institute



Earle A. Chiles Research Institute



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