2. Academic Validation
  3. Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A

Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A

  • ESMO Open. 2022 Oct;7(5):100563. doi: 10.1016/j.esmoop.2022.100563.
D V T Catenacci 1,  Y-K Kang 2,  H H Yoon 3,  B Y Shim 4,  S T Kim 5,  D-Y Oh 6,  A I Spira 7,  S V Ulahannan 8,  E J Avery 9,  P M Boland 10,  J Chao 11,  H C Chung 12,  F Gardner 13,  S J Klempner 14,  K-W Lee 15,  S C Oh 16,  J Peguero 17,  M B Sonbol 18,  L Shen 19,  M Moehler 20,  J Sun 21,  D Li 21,  M K Rosales 21,  H Park 22
Affiliations

Affiliations

  • 1 Department of Medicine, The University of Chicago Medical Centre, Chicago, USA. Electronic address: [email protected].
  • 2 Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • 3 Division of Medical Oncology, Mayo Clinic Comprehensive Cancer Center, Rochester, USA.
  • 4 Medical Oncology, The Catholic University of Korea St. Vincent's Hospital, Suwon, Republic of Korea.
  • 5 Hematology and Oncology, Samsung Medical Center, Seoul, Republic of Korea.
  • 6 Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea.
  • 7 Virginia Cancer Specialists Research Institute, Fairfax, USA.
  • 8 University of Oklahoma Health Sciences Center - Stephenson Cancer Center, Oklahoma City, USA.
  • 9 Division of Hematology and Oncology, Nebraska Hematology-Oncology, Lincoln, USA.
  • 10 Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, USA.
  • 11 Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, USA.
  • 12 Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • 13 Medical Oncology, Florida Cancer Specialists, Cape Coral, USA.
  • 14 Mass General Hospital Cancer Center, Massachusetts General Hospital, Boston, USA.
  • 15 Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam.
  • 16 Oncology, Korea University Guro Hospital, Seoul, Republic of Korea.
  • 17 Medical Oncology, Oncology Consultants, Houston, USA.
  • 18 Internal Medicine Department, Mayo Clinic Cancer Center, Phoenix, USA.
  • 19 Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China.
  • 20 Johannes-Gutenberg University, Mainz, Germany.
  • 21 MacroGenics, Inc., Rockville, USA.
  • 22 Department of Medicine, Washington University School of Medicine, St. Louis, USA.
PMID: 36029651 DOI: 10.1016/j.esmoop.2022.100563
Abstract

Background: Human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric and gastroesophageal adenocarcinoma (GEA) is globally treated with chemotherapy plus trastuzumab. Novel therapeutic strategies strive to not only optimize efficacy, but also limit toxicities. In MAHOGANY cohort A, margetuximab, an Fc-engineered, anti-HER2 monoclonal antibody (mAb) was combined with retifanlimab, an anti-programmed cell death protein 1 mAb, in the first-line HER2-positive/programmed death-ligand 1 (PD-L1)-positive GEA.

Patients and methods: MAHOGANY cohort A part 1 is a single-arm trial to evaluate margetuximab plus retifanlimab in patients with HER2 immunohistochemistry 3+, PD-L1-positive (combined positive score ≥1%), and non-microsatellite instability-high tumors. Primary objectives for cohort A were safety/tolerability and the confirmed objective response rate (ORR).

Results: As of 3 August 2021, 43 patients were enrolled and received margetuximab/retifanlimab. Nine grade 3 treatment-related adverse events (TRAEs) were reported in eight (18.6%) patients and eight serious TRAEs in seven (16.3%) patients. There were no grade 4/5 TRAEs. Three patients discontinued margetuximab/retifanlimab because of immune-related adverse events. The ORR by independent assessment was 53% [21/40 (95% confidence interval (CI) 36.1-68.5)], with a median duration of response of 10.3 months (95% CI 4.6-not evaluable); disease control rate was 73% [29/40 (95% CI 56.1-85.4)]. The study sponsor discontinued the study in advance of the planned enrollment when it became apparent that the study design would no longer meet the requirements for drug approval because of recent advances in the treatment of GEA.

Conclusions: The chemotherapy-free regimen of combined margetuximab/retifanlimab as first-line treatment in double biomarker-selected patients demonstrated a favorable toxicity profile compared with historical outcomes using chemotherapy plus trastuzumab. The ORR observed in this study compares favorably versus ORR observed with other chemotherapy-free approaches.

Keywords

first-line therapy; human epidermal growth factor receptor 2; margetuximab; metastatic gastroesophageal adenocarcinoma; programmed death-ligand 1; retifanlimab.

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