Amivantamab in EGFR Exon 20 Insertion–Mutated Non–Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. Issue 30 (20th October 2021)

• Record Type: Journal Article
• Authors: 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.; Cho, Byoung Chul;
• Is Part Of: Journal of clinical oncology. Volume 39:Issue 30(2021)
• Page Start: 3391
• Page End: 3402
• Publication Date: 2021-10-20
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.21.00662
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : 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.