PMID- 37848259
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231025
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 11
IP  - 10
DP  - 2023 Oct
TI  - Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic 
      cutaneous squamous cell carcinoma.
LID - 10.1136/jitc-2023-007637 [doi]
LID - e007637
AB  - 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.
CI  - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Clingan, Philip
AU  - Clingan P
AD  - Southern Medical Day Care Centre, Wollongong, New South Wales, Australia.
FAU - Ladwa, Rahul
AU  - Ladwa R
AD  - Princess Alexandra Hospital, University of Queensland, Brisbane, Queensland, 
      Australia.
FAU - Brungs, Daniel
AU  - Brungs D
AD  - Southern Medical Day Care Centre, Wollongong, New South Wales, Australia.
AD  - Graduate School of Medicine, University of Wollongong, Wollongong, New South 
      Wales, Australia.
FAU - Harris, Dean Laurence
AU  - Harris DL
AD  - Christchurch Hospital, Christchurch, New Zealand.
FAU - McGrath, Margaret
AU  - McGrath M
AD  - Medical Oncology, Gallipoli Medical Research Foundation, Greenslopes Private 
      Hospital, Greenslopes, Queensland, Australia.
FAU - Arnold, Susan
AU  - Arnold S
AD  - Exellentis Clinical Trial Consultants, George, South Africa.
FAU - Coward, Jermaine
AU  - Coward J
AD  - ICON Cancer Centre, South Brisbane, Queensland, Australia.
FAU - Fourie, Samuel
AU  - Fourie S
AD  - Wilgers Oncology Centre, Pretoria, South Africa.
FAU - Kurochkin, Andriy
AU  - Kurochkin A
AD  - Municipal Nonprofit Enterprise of Sumy Regional Council Sumy Regional Clinical 
      Oncology Dispensary, Sumy, Ukraine.
FAU - Malan, Daniel R
AU  - Malan DR
AD  - Phoenix Pharma, Port Elizabeth, South Africa.
FAU - Mant, Andrew
AU  - Mant A
AD  - Medical Oncology Unit, Eastern Health, Melbourne, Victoria, Australia.
FAU - Sharma, Vinay
AU  - Sharma V
AD  - Wits Clinical Research Chris Hani Baragwanath Clinical Trial Site, Johannesburg, 
      South Africa.
FAU - Shue, Hong
AU  - Shue H
AD  - Sunshine Coast Haematology and Oncology Clinic, Buderim, Queensland, Australia.
FAU - Tazbirkova, Andrea
AU  - Tazbirkova A
AD  - Medical Oncology, Pindara Private Hospital, Gold Coast, Queensland, Australia.
FAU - Berciano-Guerrero, Miguel-Angel
AU  - Berciano-Guerrero MA
AUID- ORCID: 0000-0002-5437-5196
AD  - Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University 
      Hospitals, IBIMA, Malaga, Spain.
FAU - Charoentum, Chaiyut
AU  - Charoentum C
AD  - Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, 
      Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand.
FAU - Dalle, Stephane
AU  - Dalle S
AD  - Hospices Civils de Lyon - Hopital Lyon Sud, Pierre-Benite, France.
FAU - Dechaphunkul, Arunee
AU  - Dechaphunkul A
AD  - Songklanagarind Hospital, Prince of Songkla University, Songkhla, Thailand.
FAU - Dudnichenko, Oleksandr
AU  - Dudnichenko O
AD  - 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.
FAU - Koralewski, Piotr
AU  - Koralewski P
AD  - Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o., Oddzial 
      Onkologii Klinicznej z Pododdzialem Dziennym, Krakow, Poland.
FAU - Lugowska, Iwona
AU  - Lugowska I
AD  - Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut 
      Badawczy, Oddzial Badan Wczesnych Faz, Warsaw, Poland.
FAU - Montaudie, Henri
AU  - Montaudie H
AD  - Centre Hospitalier Universitaire de Nice - Hopital l'Archet, Nice, France.
FAU - Munoz-Couselo, Eva
AU  - Munoz-Couselo E
AD  - Hospital Universitario Vall d'Hebron, Passeig de la Vall d'Hebron, Vall d'Hebron 
      Institute of Oncology (VHIO), Barcelona, Spain.
FAU - Sriuranpong, Virote
AU  - Sriuranpong V
AD  - King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
FAU - Oliviero, James
AU  - Oliviero J
AUID- ORCID: 0009-0009-9857-1189
AD  - Checkpoint Therapeutics Inc, Waltham, Massachusetts, USA jfo@checkpointtx.com.
FAU - Desai, Jayesh
AU  - Desai J
AD  - Department of Medical Oncology, Peter MacCallum Cancer Centre; Sir Peter 
      MacCallum Department of Oncology, The University of Melbourne, Melbourne, 
      Victoria, Australia.
LA  - eng
SI  - ClinicalTrials.gov/NCT03212404
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Squamous Cell/drug therapy
MH  - B7-H1 Antigen/metabolism
MH  - Programmed Cell Death 1 Receptor/therapeutic use
MH  - *Skin Neoplasms/drug therapy
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Immune Checkpoint Inhibitors/therapeutic use
PMC - PMC10582968
OTO - NOTNLM
OT  - Immune Checkpoint Inhibitors
OT  - Immunotherapy
OT  - Programmed Cell Death 1 Receptor
OT  - Skin Neoplasms
COIS- Competing interests: PC has nothing to disclose. RL has received honoraria from 
      AstraZeneca/MedImmune, Bristol Myers Squibb Foundation, MSD, and Sanofi; has 
      served as a consultant and/or scientific advisor for AstraZeneca/MedImmune and 
      Roche; and has received compensation for travel, accommodations, and other 
      expenses from MSD. DB has nothing to disclose. DLH has served as a consultant 
      and/or scientific advisor for Checkpoint Therapeutics. MM has nothing to 
      disclose. SA has nothing to disclose. JC has nothing to disclose. SF has nothing 
      to disclose. AK has nothing to disclose. DRM has nothing to disclose. AM has 
      nothing to disclose. VSh has served as a speaker for Elekta. HS has nothing to 
      disclose. AT has nothing to disclose. M-AB-G has served as a consultant and/or 
      scientific advisor for BMS, Eisai, MSD, Novartis, and Pierre Fabre and has 
      received research funding from Novartis. CC has received grant/research support 
      from AstraZeneca, Novartis, and Roche. SD has received institutional research 
      grants from BMS and MSD; has served as a consultant and/or scientific advisor for 
      BMS, MSD, and Pierre Fabre; and has received compensation for congress attendance 
      from BMS and MSD. AD has nothing to disclose. OD has nothing to disclose. PK has 
      nothing to disclose. IL has financial or non-financial interests in Agenus, BMS, 
      Janssen, MacroGenics, MSD, Pfizer, and Roche. HM has received honoraria from BMS, 
      Merck Serono, MSD, Novartis, and Pierre Fabre; has received institutional support 
      from BMS, Canceropole PACA, and Societe Francaise de Dermatologie; has served as 
      a consultant for BMS, Merck Serono, MSD, Novartis, and Pierre Fabre; has served 
      on a data safety monitoring board/advisory board for Novartis and Pierre Fabre; 
      and has received travel grants from Novartis and Pierre Fabre. EM-C has served as 
      a consultant and/or scientific advisor for MBS, MSD, Novartis, Pierre Fabre, and 
      Sanofi; has received honoraria from MBS, MSD, Novartis, Pierre Fabre, and Sanofi; 
      and has received compensation for travel, accommodations, and other expenses from 
      MSD. VSr has nothing to disclose. JO is an employee of Checkpoint Therapeutics 
      and holds stocks and other ownership interests in the company; has served in 
      leadership roles at Checkpoint Therapeutics; and has received compensation for 
      travel, accommodations, and other expenses from Checkpoint Therapeutics. JD has 
      served as a consultant and/or scientific advisor for Amgen, Bayer, BeiGene, 
      Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Merck KGaA, Novartis, 
      Novotech, Pfizer, Pierre Fabre, and Roche/Genentech; has served on a data safety 
      monitoring board/advisory board for Boehringer Ingelheim and Pfizer; has served 
      as a board director for Cancer Trials Australia and ANZSA; and has received 
      institutional grant/research support from AstraZeneca/MedImmune, BeiGene, BMS, 
      GlaxoSmithKline, Lilly, Novartis, and Roche.
EDAT- 2023/10/18 00:43
MHDA- 2023/10/23 01:18
PMCR- 2023/10/17
CRDT- 2023/10/17 20:53
PHST- 2023/09/15 00:00 [accepted]
PHST- 2023/10/23 01:18 [medline]
PHST- 2023/10/18 00:43 [pubmed]
PHST- 2023/10/17 20:53 [entrez]
PHST- 2023/10/17 00:00 [pmc-release]
AID - jitc-2023-007637 [pii]
AID - 10.1136/jitc-2023-007637 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2023 Oct;11(10):e007637. doi: 10.1136/jitc-2023-007637.