From a first-in-human, phase I dose-escalation and dose-expansion study, Park et al. reported the safety and efficacy of amivantamab, an EGFR-MET bispecific antibody with immune cell–directing activity, in advanced (post-platinum) NSCLC patients with EGFR exon 20 insertion mutations. Amivantamab showed a tolerable safety profile consistent with on-target toxicities from EGFR and MET pathway inhibition. In the efficacy population (n= 81), the objective response rate was 40%, with 3 complete responses and 29 partial responses. The median duration of response was 11.1 months, and the median progression-free survival was 8.3 months, leading to FDA approval.
Contributed by Shishir Pant
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, ³ 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.
Author Info: (1) Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. (2) H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. (3) Princess Margare
Author Info: (1) Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. (2) H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. (3) Princess Margaret Cancer Centre, Toronto, Canada. (4) Olivia Newton-John Cancer Wellness and Research Centre, Austin Hospital, Heidelberg, Australia. (5) Columbia University Medical Center, New York, NY. (6) Institut Curie, Paris, France. (7) Instituto Oncolgico Dr Rosell, Hospital Universitari Dexeus, Grupo QuironSalud, Barcelona, Spain. (8) National Cancer Center, Gyeonggi-do, South Korea. (9) Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. (10) St George Hospital, Kogarah, Australia. (11) New York University School of Medicine, New York, NY. (12) Virginia Cancer Specialists Research Institute, US Oncology Research, Fairfax, VA. (13) Taichung Veterans General Hospital, Taiwan, China. (14) Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea. (15) Chungbuk National University Hospital, Cheongju, South Korea. (16) Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR. (17) Hospital Universitario Virgen de la Victoria y Regional, IBIMA, Malaga, Spain. (18) National Cancer Center Hospital East, Kashiwa, Japan. (19) Seoul National University Bundang Hospital, Seongnam, South Korea. (20) National Taiwan University Cancer Center, Taiwan, China. (21) Washington University School of Medicine, St Louis, MO. (22) Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. (23) Hospital Universitario Ramn y Cajal, IRYCIS, Madrid, Spain. (24) Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester and The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. (25) City of Hope Comprehensive Cancer Center, Duarte, CA. (26) Janssen R&D, Spring House, PA. (27) Janssen R&D, Spring House, PA. (28) Janssen R&D, Spring House, PA. (29) Janssen R&D, Spring House, PA. (30) Janssen R&D, Spring House, PA. (31) Janssen R&D, Spring House, PA. (32) Janssen R&D, Spring House, PA. (33) Janssen R&D, Spring House, PA. (34) Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
