Subcutaneous versus Intravenous Amivantamab, both in Combination with Lazertinib, in Refractory EGFR-mutated NSCLC: Primary Results from the Phase 3 PALOMA-3 Study

Leighl NB 1 , Akamatsu H 2 , Lim SM 3 , Cheng Y 4 , Minchom AR 5 , Marmarelis ME 6 Show all authors , Sanborn RE 7 , Chih-Hsin Yang J 8 , Liu B 9 , John T 10 , Massutí B 11 , Spira AI 12 , Lee SH 13 , Wang J 14 , Li J 15 , Liu C 16 , Novello S 17 , Kondo M 18 , Tamiya M 19 , Korbenfeld E 20 , Moskovitz M 21 , Han JY 22 , Alexander M 23 , Joshi R 24 , Felip E 25 , Voon PJ 26 , Danchaivijitr P 27 , Hsu PC 28 , Silva Melo Cruz FJ 29 , Wehler T 30 , Greillier L 31 , Teixeira E 32 , Nguyen D 33 , Sabari JK 34 , Qin A 35 , Kowalski D 36 , Nahit Şendur MA 37 , Xie J 38 , Ghosh D 38 , Alhadab A 39 , Haddish-Berhane N 40 , Clemens PL 40 , Lorenzini P 40 , Verheijen RB 41 , Gamil M 40 , Bauml JM 40 , Baig M 38 , Passaro A 42 , PALOMA-3 Investigators

Affiliations 

  • 1 Princess Margaret Cancer Centre, Toronto, Canada
  • 2 Internal Medicine III, Wakayama Medical University, Wakayama, Japan
  • 3 Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
  • 4 Jilin Cancer Hospital, Changchun, China
  • 5 Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, UK
  • 6 Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • 7 Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
  • 8 Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
  • 9 Harbin Medical University Cancer Hospital, Harbin, China
  • 10 Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia
  • 11 Alicante University Dr. Balmis Hospital, ISABIAL, Alicante, Spain
  • 12 Virginia Cancer Specialists, Fairfax, VA, USA
  • 13 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  • 14 Fudan University Shanghai Cancer Center, Shanghai, China
  • 15 Sichuan Cancer Hospital, Sichuan, China
  • 16 Shengjing Hospital of China Medical University, Liao Ning Sheng, China
  • 17 Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano (TO), Italy
  • 18 Department of Respiratory Medicine, Fujita Health University School of Medicine, Aichi, Japan
  • 19 Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • 20 British Hospital of Buenos Aires - Central British Hospital, Buenos Aires, Argentina
  • 21 Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel
  • 22 National Cancer Center, Goyang, Republic of Korea
  • 23 Medical University of South Carolina, Charleston, SC, USA
  • 24 Cancer Research SA, Adelaide, Australia
  • 25 Medical Oncology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VIHO), Universitat Autonoma de Barcelona, Barcelona, Spain
  • 26 Department of Radiotherapy and Oncology, Sarawak General Hospital, Kuching, Sarawak, Malaysia
  • 27 Siriraj Hospital, Faculty of Medicine, Mahidol University Bangkok Noi Campus, Bangkok, Thailand
  • 28 Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
  • 29 Núcleo de Ensino e Pequisa, Instituto Brasileiro de Controle do Câncer, São Paulo, Brazil
  • 30 University Hospital of Giessen and Marburg, Giessen and Marburg, Germany
  • 31 Aix Marseille University, APHM, INSERM, CNRS, CRCM, Hôpital Nord, Multidisciplinary Oncology and Therapeutic Innovations Department, Marseille, France
  • 32 Medical Oncology, Hospital CUF Descobertas, Lisboa, Portugal
  • 33 City of Hope National Medical Center, Duarte, CA, USA
  • 34 Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA
  • 35 University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA
  • 36 Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
  • 37 Department of Medical Oncology, Ankara Yıldırım Beyazıt University, Ankara City Hospital, Ankara, Turkey
  • 38 Janssen Research & Development, Raritan, NJ, USA
  • 39 Janssen Research & Development, San Diego, CA, USA
  • 40 Janssen Research & Development, Spring House, PA, USA
  • 41 Janssen Research & Development, Leiden, The Netherlands
  • 42 European Institute of Oncology IRCCS, Milano, Italy
J Clin Oncol, 2024 Jun 10.
PMID: 38857463 DOI: 10.1200/JCO.24.01001

Abstract

PURPOSE: Phase 3 studies of intravenous amivantamab demonstrated efficacy across EGFR-mutated advanced non-small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy.

PATIENTS AND METHODS: Patients with EGFR-mutated advanced NSCLC who progressed following osimertinib and platinum-based chemotherapy were randomized 1:1 to receive subcutaneous or intravenous amivantamab, both combined with lazertinib. Co-primary pharmacokinetic noninferiority endpoints were trough concentrations (Ctrough; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUCD1-D15). Key secondary endpoints were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory endpoint.

RESULTS: Overall, 418 patients underwent randomization (subcutaneous group, n=206; intravenous group, n=212). Geometric mean ratios of Ctrough for subcutaneous to intravenous amivantamab were 1.15 (90% CI, 1.04-1.26) at cycle-2-day-1 and 1.42 (90% CI, 1.27-1.61) at cycle-4-day-1; the cycle-2 AUCD1-D15 was 1.03 (90% CI, 0.98-1.09). ORR was 30% in the subcutaneous and 33% in the intravenous group; median PFS was 6.1 and 4.3 months, respectively. OS was significantly longer in the subcutaneous versus intravenous group (hazard ratio for death, 0.62; 95% CI, 0.42-0.92; nominal P=0.02). Fewer patients in the subcutaneous group experienced infusion-related reactions (13% versus 66%) and venous thromboembolism (9% versus 14%) versus the intravenous group. Median administration time for first infusion was reduced to 4.8 minutes (range, 0-18) for subcutaneous amivantamab from 5 hours (range, 0.2-9.9) for intravenous amivantamab. During cycle-1-day-1, 85% and 52% of patients in the subcutaneous and intravenous groups, respectively, considered treatment convenient; end-of-treatment rates were 85% and 35%, respectively.

CONCLUSION: Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced infusion-related reactions, increased convenience, and prolonged survival.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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