Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201)

Background POD1UM-201, an open-label, single-arm, phase II multiregional study, evaluated efficacy and tolerability of retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in chemotherapy-naive patients with recurrent locally advanced or metastatic Merkel ce...

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Main Authors: Federica Morano, Celeste Lebbe, Mark Cornfeld, Shailender Bhatia, Melissa Burgess, Giovanni Grignani, Piotr Rutkowski, Francesca Spada, Michele Guida, Chuan Tian, Caroline Gaudy-Marqueste, Roberta Depenni, Henri Montaudié, Jennifer Pulini, Francesco Spagnolo, Cecilia C S Yeung
Format: Article
Language:English
Published: BMJ Publishing Group 2025-08-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/13/8/e012478.full
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author Federica Morano
Celeste Lebbe
Mark Cornfeld
Shailender Bhatia
Melissa Burgess
Giovanni Grignani
Piotr Rutkowski
Francesca Spada
Michele Guida
Chuan Tian
Caroline Gaudy-Marqueste
Roberta Depenni
Henri Montaudié
Jennifer Pulini
Francesco Spagnolo
Cecilia C S Yeung
author_facet Federica Morano
Celeste Lebbe
Mark Cornfeld
Shailender Bhatia
Melissa Burgess
Giovanni Grignani
Piotr Rutkowski
Francesca Spada
Michele Guida
Chuan Tian
Caroline Gaudy-Marqueste
Roberta Depenni
Henri Montaudié
Jennifer Pulini
Francesco Spagnolo
Cecilia C S Yeung
author_sort Federica Morano
collection DOAJ
description Background POD1UM-201, an open-label, single-arm, phase II multiregional study, evaluated efficacy and tolerability of retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in chemotherapy-naive patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).Methods Patients were enrolled across 34 sites in the USA, Canada, and Europe. Eligible patients were ≥18 years with confirmed recurrent advanced locoregional or metastatic MCC not amenable to surgery or radiation therapy, had not received previous systemic treatment, had measurable disease, and Eastern Cooperative Oncology Group performance status 0–1. Retifanlimab 500 mg was administered intravenously every 4 weeks (Q4W) for up to 2 years. The primary endpoint was objective response rate (ORR). Key secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.Results A total of 101 patients were enrolled between February 12, 2019, and June 16, 2021, with a median duration of follow-up for response of 22.2 (range: 1.1–55.3) months. ORR was 54.5% (95% CI: 44.2% to 64.4%; n=55), including 18 patients (17.8%) with complete responses (CRs) and 37 (36.6%) with partial responses (PRs). DCR was 60.4% (95% CI: 50.2% to 70.0%; n=61). Median DOR was not reached (95% CI: 14.0 months to not estimable (NE)) in patients who achieved CR and was 25.3 months (95% CI: 14.2 months to NE) in those with PR. With a median follow-up of 9.3 (range: 0.0–57.1) months, the estimated median PFS was 16.0 months (95% CI: 9.0 months to 32.2). Median OS was not reached with 63% of patients alive at 3 years. The safety profile was representative of the PD-(ligand)1 inhibitor class, with grade 3 immune-related adverse events occurring in 11 patients (10.9%).Conclusions Retifanlimab 500 mg Q4W led to frequent and durable responses in chemotherapy-naive patients with advanced MCC with an acceptable safety profile. Retifanlimab represents a new immunotherapy option for patients with locally advanced or metastatic MCC.Trial registration number NCT03599713; EudraCT 2018-001627-39
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series Journal for ImmunoTherapy of Cancer
spelling doaj-art-d31c1df8ab704d1b8d77c76d3449f6a22025-08-20T03:41:54ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-08-0113810.1136/jitc-2025-012478Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201)Federica Morano0Celeste Lebbe1Mark Cornfeld2Shailender Bhatia3Melissa Burgess4Giovanni Grignani5Piotr Rutkowski6Francesca Spada7Michele Guida8Chuan Tian9Caroline Gaudy-Marqueste10Roberta Depenni11Henri Montaudié12Jennifer Pulini13Francesco Spagnolo14Cecilia C S Yeung159 Oncologia Medica 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy3 Université Paris Cité, AP-HP Dermato-oncology, CIC, Cancer Institute AP-HP. Nord-Paris Cité, INSERM U1342 – Equipe 1 – CNRS EMR8000, Saint Louis Hospital, Paris, France14 Incyte Corporation, Wilmington, Delaware, USA1 Department of Medicine, Division of Hematology/Oncology, University of Washington, Seattle, Washington, USA8 UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA1 Department of Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy2 Department of Soft Tissue/Bone Sarcoma and Melanoma, The Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Warsaw, Poland12 Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO), IRCCS, Milan, Italy4 Unit Melanoma and Rare Tumors, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy14 Incyte Corporation, Wilmington, Delaware, USA5 APHM, Service de Dermatologie et de Cancérologie Cutanée, Aix-Marseille University, Marseille, France11 Department of Oncology and Haematology, Division of Oncology, University Hospital of Modena, Modena, Italy10 Department of Dermatology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, Nice, France14 Incyte Corporation, Wilmington, Delaware, USA6 Medical Oncology 2, IRCCS Ospedale Policlinico San Martino, Genoa, Italy13 Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center and Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USABackground POD1UM-201, an open-label, single-arm, phase II multiregional study, evaluated efficacy and tolerability of retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in chemotherapy-naive patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).Methods Patients were enrolled across 34 sites in the USA, Canada, and Europe. Eligible patients were ≥18 years with confirmed recurrent advanced locoregional or metastatic MCC not amenable to surgery or radiation therapy, had not received previous systemic treatment, had measurable disease, and Eastern Cooperative Oncology Group performance status 0–1. Retifanlimab 500 mg was administered intravenously every 4 weeks (Q4W) for up to 2 years. The primary endpoint was objective response rate (ORR). Key secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.Results A total of 101 patients were enrolled between February 12, 2019, and June 16, 2021, with a median duration of follow-up for response of 22.2 (range: 1.1–55.3) months. ORR was 54.5% (95% CI: 44.2% to 64.4%; n=55), including 18 patients (17.8%) with complete responses (CRs) and 37 (36.6%) with partial responses (PRs). DCR was 60.4% (95% CI: 50.2% to 70.0%; n=61). Median DOR was not reached (95% CI: 14.0 months to not estimable (NE)) in patients who achieved CR and was 25.3 months (95% CI: 14.2 months to NE) in those with PR. With a median follow-up of 9.3 (range: 0.0–57.1) months, the estimated median PFS was 16.0 months (95% CI: 9.0 months to 32.2). Median OS was not reached with 63% of patients alive at 3 years. The safety profile was representative of the PD-(ligand)1 inhibitor class, with grade 3 immune-related adverse events occurring in 11 patients (10.9%).Conclusions Retifanlimab 500 mg Q4W led to frequent and durable responses in chemotherapy-naive patients with advanced MCC with an acceptable safety profile. Retifanlimab represents a new immunotherapy option for patients with locally advanced or metastatic MCC.Trial registration number NCT03599713; EudraCT 2018-001627-39https://jitc.bmj.com/content/13/8/e012478.full
spellingShingle Federica Morano
Celeste Lebbe
Mark Cornfeld
Shailender Bhatia
Melissa Burgess
Giovanni Grignani
Piotr Rutkowski
Francesca Spada
Michele Guida
Chuan Tian
Caroline Gaudy-Marqueste
Roberta Depenni
Henri Montaudié
Jennifer Pulini
Francesco Spagnolo
Cecilia C S Yeung
Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201)
Journal for ImmunoTherapy of Cancer
title Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201)
title_full Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201)
title_fullStr Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201)
title_full_unstemmed Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201)
title_short Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201)
title_sort phase ii study of retifanlimab in patients with recurrent locally advanced or metastatic merkel cell carcinoma pod1um 201
url https://jitc.bmj.com/content/13/8/e012478.full
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