2. Academic Validation
  3. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study

Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study

  • J Clin Oncol. 2021 Oct 20;39(30):3391-3402. doi: 10.1200/JCO.21.00662.
Keunchil Park 1,  Eric B Haura 2,  Natasha B Leighl 3,  Paul Mitchell 4,  Catherine A Shu 5,  Nicolas Girard 6,  Santiago Viteri 7,  Ji-Youn Han 8,  Sang-We Kim 9,  Chee Khoon Lee 10,  Joshua K Sabari 11,  Alexander I Spira 12,  Tsung-Ying Yang 13,  Dong-Wan Kim 14,  Ki Hyeong Lee 15,  Rachel E Sanborn 16,  José Trigo 17,  Koichi Goto 18,  Jong-Seok Lee 19,  James Chih-Hsin Yang 20,  Ramaswamy Govindan 21,  Joshua M Bauml 22,  Pilar Garrido 23,  Matthew G Krebs 24,  Karen L Reckamp 25,  John Xie 26,  Joshua C Curtin 26,  Nahor Haddish-Berhane 26,  Amy Roshak 26,  Dawn Millington 26,  Patricia Lorenzini 26,  Meena Thayu 26,  Roland E Knoblauch 26,  Byoung Chul Cho 27
Affiliations

Affiliations

  • 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 Oncológico 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 Ramón 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 Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
PMID: 34339292 DOI: 10.1200/JCO.21.00662
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P9977
    99.90%, EGFR-MET Dual Antibody