1. Amivantamab in EGFR Exon 20 Insertion–Mutated Non–Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study
- Author
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Meena Thayu, A. Roshak, Jose Manuel Trigo, Jong Seok Lee, Keunchil Park, Santiago Viteri, Ramaswamy Govindan, Natasha B. Leighl, Ji-Youn Han, Paul Mitchell, Nahor Haddish-Berhane, James Chih-Hsin Yang, Chee Khoon Lee, Roland Elmar Knoblauch, Patricia Lorenzini, Byoung Chul Cho, Dawn Millington, Nicolas Girard, Alexander I. Spira, Tsung-Ying Yang, Rachel E. Sanborn, Eric B. Haura, J.C. Curtin, Matthew G Krebs, Pilar Garrido, Koichi Goto, Sang-We Kim, Dong Wan Kim, Karen L. Reckamp, Ki Hyeong Lee, Joshua Bauml, Joshua K. Sabari, Catherine A. Shu, and John Xie
- Subjects
Adult ,Diarrhea ,Male ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Neutropenia ,Organoplatinum Compounds ,Hypokalemia ,03 medical and health sciences ,Exon ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Antibodies, Bispecific ,Platinum chemotherapy ,Humans ,Medicine ,Epidermal growth factor receptor ,Paronychia ,Lung cancer ,Aged ,Aged, 80 and over ,Manchester Cancer Research Centre ,biology ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Exons ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Injection Site Reaction ,Phase i study ,ErbB Receptors ,Mutagenesis, Insertional ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Retreatment ,Disease Progression ,Cancer research ,biology.protein ,Female ,Drug Eruptions ,Non small cell ,Pulmonary Embolism ,business ,Tyrosine kinase - 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.
- Published
- 2021