Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
oregon; portland; chiles
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 = 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.
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.
Earle A. Chiles Research Institute
Park, Keunchil; Haura, Eric B; Leighl, Natasha B; Mitchell, Paul; Shu, Catherine A; Girard, Nicolas; Viteri, Santiago; Han, Ji-Youn; Kim, Sang-We; Lee, Chee Khoon; Sabari, Joshua K; Spira, Alexander I; Yang, Tsung-Ying; Kim, Dong-Wan; Lee, Ki Hyeong; Sanborn, Rachel E; Trigo, José; Goto, Koichi; Lee, Jong-Seok; Yang, James Chih-Hsin; Govindan, Ramaswamy; Bauml, Joshua M; Garrido, Pilar; Krebs, Matthew G; Reckamp, Karen L; Xie, John; Curtin, Joshua C; Haddish-Berhane, Nahor; Roshak, Amy; Millington, Dawn; Lorenzini, Patricia; Thayu, Meena; Knoblauch, Roland E; and Cho, Byoung Chul, "Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study." (2021). Articles, Abstracts, and Reports. 5132.