2. Academic Validation
  3. Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma

Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma

  • J Immunother Cancer. 2023 Oct;11(10):e007637. doi: 10.1136/jitc-2023-007637.
Philip Clingan 1,  Rahul Ladwa 2,  Daniel Brungs 1 3,  Dean Laurence Harris 4,  Margaret McGrath 5,  Susan Arnold 6,  Jermaine Coward 7,  Samuel Fourie 8,  Andriy Kurochkin 9,  Daniel R Malan 10,  Andrew Mant 11,  Vinay Sharma 12,  Hong Shue 13,  Andrea Tazbirkova 14,  Miguel-Angel Berciano-Guerrero 15,  Chaiyut Charoentum 16,  Stéphane Dalle 17,  Arunee Dechaphunkul 18,  Oleksandr Dudnichenko 19,  Piotr Koralewski 20,  Iwona Lugowska 21,  Henri Montaudié 22,  Eva Muñoz-Couselo 23,  Virote Sriuranpong 24,  James Oliviero 25,  Jayesh Desai 26
Affiliations

Affiliations

  • 1 Southern Medical Day Care Centre, Wollongong, New South Wales, Australia.
  • 2 Princess Alexandra Hospital, University of Queensland, Brisbane, Queensland, Australia.
  • 3 Graduate School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia.
  • 4 Christchurch Hospital, Christchurch, New Zealand.
  • 5 Medical Oncology, Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, Queensland, Australia.
  • 6 Exellentis Clinical Trial Consultants, George, South Africa.
  • 7 ICON Cancer Centre, South Brisbane, Queensland, Australia.
  • 8 Wilgers Oncology Centre, Pretoria, South Africa.
  • 9 Municipal Nonprofit Enterprise of Sumy Regional Council Sumy Regional Clinical Oncology Dispensary, Sumy, Ukraine.
  • 10 Phoenix Pharma, Port Elizabeth, South Africa.
  • 11 Medical Oncology Unit, Eastern Health, Melbourne, Victoria, Australia.
  • 12 Wits Clinical Research Chris Hani Baragwanath Clinical Trial Site, Johannesburg, South Africa.
  • 13 Sunshine Coast Haematology and Oncology Clinic, Buderim, Queensland, Australia.
  • 14 Medical Oncology, Pindara Private Hospital, Gold Coast, Queensland, Australia.
  • 15 Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain.
  • 16 Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand.
  • 17 Hospices Civils de Lyon - Hopital Lyon Sud, Pierre-Bénite, France.
  • 18 Songklanagarind Hospital, Prince of Songkla University, Songkhla, Thailand.
  • 19 Kharkiv Medical Academy of Postgraduate Education, Chair of Oncology and Children's Oncology, Clinical base State institution "VT Zaycev Institute of General and Urgent Surgery of National Academy Medical Sciences of Ukraine", Kharkiv, Ukraine.
  • 20 Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o., Oddział Onkologii Klinicznej z Pododdziałem Dziennym, Kraków, Poland.
  • 21 Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy, Oddział Badań Wczesnych Faz, Warsaw, Poland.
  • 22 Centre Hospitalier Universitaire de Nice - Hôpital l'Archet, Nice, France.
  • 23 Hospital Universitario Vall d'Hebron, Passeig de la Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • 24 King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
  • 25 Checkpoint Therapeutics Inc, Waltham, Massachusetts, USA jfo@checkpointtx.com.
  • 26 Department of Medical Oncology, Peter MacCallum Cancer Centre; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
PMID: 37848259 DOI: 10.1136/jitc-2023-007637
Abstract

Background: Programmed cell death receptor-1 (PD-1)-blocking antibodies are approved to treat metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) cases ineligible for curative surgery or radiation. Notwithstanding, some patients experience inadequate responses or severe immune-related adverse events (AEs), indicating the need for improved therapies. Cosibelimab is a high-affinity programmed cell death-ligand 1 (PD-L1)-blocking antibody that activates innate and adaptive immunity by blocking PD-L1 interaction with PD-1 and B7-1 receptors. It is an unmodified immunoglobulin G1 subtype with a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Here, we present results of the pivotal study of patients with metastatic CSCC from an open-label, multicenter, multiregional, multicohort, phase 1 trial of cosibelimab.

Methods: In this trial, participants with metastatic CSCC received cosibelimab 800 mg intravenously every 2 weeks. Primary endpoint was objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, V.1.1. Secondary endpoints included duration of response (DOR) and safety.

Results: Objective response was observed in 37 of 78 participants (47.4% (95% CI: 36.0% to 59.1%)), with median follow-up of 15.4 months (range: 0.4 to 40.5) as of data cut-off. Median DOR was not reached (range: 1.4+ to 34.1+ months), with response ongoing in 73.0% of participants. Common treatment-emergent AEs (≥15%) were fatigue (26.9%), rash (16.7%), and anemia (15.4%). Eighteen participants (23.1%) experienced immune-related AEs (grade 3: n=2 (2.6%); no grade 4/5). No treatment-related deaths were reported.

Conclusions: Cosibelimab demonstrated clinically meaningful ORR and DOR and was associated with a manageable safety profile.

Trial registration number: NCT03212404.

Keywords

Immune Checkpoint Inhibitors; Immunotherapy; Programmed Cell Death 1 Receptor; Skin Neoplasms.

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