Amivantamab in egfr exon 20 insertion- mutated non-small-cell lung cancer progressing on platinum chemotherapy: Initial results from the chrysalis phase i study

Keunchil Park, Eric B. Haura, Natasha B. Leighl, Paul Mitchell, Catherine A. Shu, Nicolas Girard, Santiago Viteri, Ji Youn Han, Sang We Kim, Chee Khoon Lee, Joshua K. Sabari, Alexander I. Spira, Tsung Ying Yang, Dong Wan Kim, Ki Hyeong Lee, Rachel E. Sanborn, Jose Trigo, Koichi Goto, Jong Seok Lee, James Chih-Hsin YangRamaswamy Govindan, Joshua M. Bauml, Pilar Garrido, Matthew G. Krebs, Karen L. Reckamp, John Xie, Joshua C. Curtin, Nahor Haddish-Berhane, Amy Roshak, Dawn Millington, Patricia Lorenzini, Meena Thayu, Roland E. Knoblauch, Byoung Chul Cho

Research output: Contribution to journalArticlepeer-review

333 Scopus citations


PURPOSE Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine kinase inhibitors. Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor's extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site. METHODS CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with EGFR Exon20ins NSCLC. The primary end points were dose-limiting toxicity and overall response rate. We report findings from the postplatinum EGFR Exon20ins NSCLC population treated at the recommended phase II dose of 1,050 mg amivantamab (1,400 mg, $ 80 kg) given once weekly for the first 4 weeks and then once every 2 weeks starting at week 5. RESULTS In the efficacy population (n 5 81), the median age was 62 years (range, 42-84 years); 40 patients (49%) were Asian, and the median number of previous lines of therapy was two (range, 1-7). The overall response rate was 40% (95% CI, 29 to 51), including three complete responses, with a median duration of response of 11.1 months (95% CI, 6.9 to not reached). The median progression-free survival was 8.3 months (95% CI, 6.5 to 10.9). In the safety population (n 5 114), the most common adverse events were rash in 98 patients (86%), infusion-related reactions in 75 (66%), and paronychia in 51 (45%). The most common grade 3-4 adverse events were hypokalemia in six patients (5%) and rash, pulmonary embolism, diarrhea, and neutropenia in four (4%) each. Treatment-related dose reductions and discontinuations were reported in 13% and 4% of patients, respectively. CONCLUSION Amivantamab, via its novel mechanism of action, yielded robust and durable responses with tolerable safety in patients with EGFR Exon20ins mutations after progression on platinum-based chemotherapy.

Original languageEnglish
Pages (from-to)3391-3402
Number of pages12
JournalJournal of Clinical Oncology
Issue number30
StatePublished - Oct 20 2021


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