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Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study

Passaro A 1 , Wang J 2 , Wang Y 3 , Lee SH 4 , Melosky B 5 , Shih JY 6 Show all authors , Wang J 7 , Azuma K 8 , Juan-Vidal O 9 , Cobo M 10 , Felip E 11 , Girard N 12 , Cortot AB 13 , Califano R 14 , Cappuzzo F 15 , Owen S 16 , Popat S 17 , Tan JL 18 , Salinas J 19 , Tomasini P 20 , Gentzler RD 21 , William WN 22 , Reckamp KL 23 , Takahashi T 24 , Ganguly S 25 , Kowalski DM 26 , Bearz A 27 , MacKean M 28 , Barala P 29 , Bourla AB 30 , Girvin A 29 , Greger J 29 , Millington D 31 , Withelder M 29 , Xie J 30 , Sun T 30 , Shah S 29 , Diorio B 30 , Knoblauch RE 29 , Bauml JM 29 , Campelo RG 32 , Cho BC 33 , MARIPOSA-2 Investigators

Affiliations 

  • 1 Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan, Italy. Electronic address: antonio.passaro@ieo.it
  • 2 Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
  • 3 Department of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
  • 4 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  • 5 British Columbia Cancer Agency, Vancouver, Canada
  • 6 Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
  • 7 Fudan University Shanghai Cancer Center, Shanghai, China
  • 8 Kurume University School of Medicine, Kurume, Japan
  • 9 Hospital Universitari i Politécnic La Fe, Valencia, Spain
  • 10 Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain
  • 11 Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain
  • 12 Institut Curie, Institut du Thorax Curie-Montsouris, Paris, France; Paris Saclay University, UVSQ, Versailles, France
  • 13 University of Lille, CHU Lille, CNRS, Inserm, Institut Pasteur de Lille, UMR9020-UMR1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000 Lille, France
  • 14 Department of Medical Oncology, Christie NHS Foundation Trust and Division of Cancer Sciences, The University of Manchester, Manchester, UK
  • 15 IRCCS Regina Elena National Cancer Institute, Rome, Italy
  • 16 Department of Medical Oncology, McGill University Health Centre, Montreal, Quebec, Canada
  • 17 Royal Marsden Hospital NHS Foundation Trust and The Institute of Cancer Research, London, UK
  • 18 Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 19 Centro de Especialidades Medicas Ambulatorias e Investigación Clínica, Córdoba, Argentina
  • 20 Multidisciplinary Oncology and Therapeutic Innovations Department, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Marseille, France
  • 21 Hematology/Oncology, University of Virginia Cancer Center, Charlottesville, VA, USA
  • 22 Centro Oncológico BP, Beneficência Portuguesa de São Paulo, and Grupo Oncoclínicas, São Paulo, Brazil
  • 23 Cedars-Sinai Medical Center, Los Angeles, USA
  • 24 Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi, Japan
  • 25 Tata Medical Center, Kolkata, India
  • 26 Department of Lung Cancer and Thoracic Tumours, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
  • 27 Medical Oncology, Centro di Riferimento Oncologico-CRO, Aviano, Italy
  • 28 Edinburgh Cancer Centre, Western General Hospital, Edinburgh, UK
  • 29 Janssen Research & Development, Spring House, PA, USA
  • 30 Janssen Research & Development, Raritan, NJ, USA
  • 31 Janssen Research & Development, San Diego, CA, USA
  • 32 University Hospital A Coruña, A Coruña, Spain
  • 33 Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
Ann Oncol, 2024 Jan;35(1):77-90.
PMID: 37879444 DOI: 10.1016/j.annonc.2023.10.117

Abstract

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial.

PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion.

RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy.

CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.

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

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