%0 Journal Article
%A Park, Keunchil
%A Haura, Eric B
%A Leighl, Natasha B
%A Mitchell, Paul
%A Shu, Catherine A
%A Girard, Nicolas
%A Viteri, Santiago
%A Han, Ji-Youn
%A Kim, Sang-We
%A Lee, Chee Khoon
%A Sabari, Joshua K
%A Spira, Alexander I
%A Yang, Tsung-Ying
%A Kim, Dong-Wan
%A Lee, Ki Hyeong
%A Sanborn, Rachel E
%A Trigo, José
%A Goto, Koichi
%A Lee, Jong-Seok
%A Yang, James Chih-Hsin
%A Govindan, Ramaswamy
%A Bauml, Joshua M
%A Garrido, Pilar
%A Krebs, Matthew G
%A Reckamp, Karen L
%A Xie, John
%A Curtin, Joshua C
%A Haddish-Berhane, Nahor
%A Roshak, Amy
%A Millington, Dawn
%A Lorenzini, Patricia
%A Thayu, Meena
%A Knoblauch, Roland E
%A Cho, Byoung Chul
%T Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.
%D 2021
%U https://hdl.handle.net/10668/27014
%X 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. 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. In the efficacy population (n = 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 = 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. 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.
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