CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours : results of two multi-institutional Phase 1 trials
Segal, Neil H. (Memorial Sloan Kettering Cancer Center)
Melero, Ignacio (Universidad de Navarro)
Moreno, Victor (Hospital Universitario Fundación Jiménez Díaz)
Steeghs, Neeltje (The Netherlands Cancer Institute (Amsterdam, Països Baixos))
Marabelle, Aurelien (Université Paris-Saclay)
Rohrberg, Kristoffer (Copenhagen University Hospital-Rigshospitalet)
Rodriguez-Ruiz, Maria E. (Universidad de Navarra)
Eder, Joseph P. (Yale University Cancer Center)
Eng, Cathy (Vanderbilt Ingram Cancer Center (Estats Units d'Amèrica))
Manji, Gulam A. (Columbia University (Estats Units d'Amèrica))
Waterkamp, Daniel (Genentech (Estats Units d'Amèrica))
Leutgeb, Barbara (Hoffmann-La Roche (Suïssa))
Bouseida, Said (Hoffmann-La Roche (Suïssa))
Flinn, Nick (Hoffmann-La Roche (Suïssa))
Das Thakur, Meghna (Genentech (Estats Units d'Amèrica))
Elze, Markus C. (Hoffmann-La Roche (Suïssa))
Koeppen, Hartmut (Genentech (Estats Units d'Amèrica))
Jamois, Candice (Hoffmann-La Roche (Suïssa))
Martin-Facklam, Meret (Hoffmann-La Roche (Suïssa))
Lieu, Christopher H. (University of Colorado)
Calvo, Emiliano (Centro Integral Oncológico Clara Campal (Madrid))
Paz-Ares, Luis (Hospital Universitario 12 de Octubre (Madrid))
Tabernero, Josep (Vall d'Hebron Institut d'Oncologia)
Argilés Martínez, Guillem (Universitat Autònoma de Barcelona. Departament de Cirurgia)

Fecha:	2024
Resumen:	Cibisatamab is a bispecific antibody-based construct targeting carcinoembryonic antigen (CEA) on tumour cells and CD3 epsilon chain as a T-cell engager. Here we evaluated cibisatamab for advanced CEA-positive solid tumours in two open-label Phase 1 dose-escalation and -expansion studies: as a single agent with or without obinutuzumab in S1 (NCT02324257) and with atezolizumab in S2 (NCT02650713). Primary endpoints were safety, dose finding, and pharmacokinetics in S1; safety and dose finding in S2. Secondary endpoints were anti-tumour activity (including overall response rate, ORR) and pharmacodynamics in S1; anti-tumour activity, pharmacodynamics and pharmacokinetics in S2. S1 and S2 enrolled a total of 149 and 228 patients, respectively. Grade ≥3 cibisatamab-related adverse events occurred in 36% of S1 and 49% of S2 patients. The ORR was 4% in S1 and 7% in S2. In S2, patients with microsatellite stable colorectal carcinoma (MSS-CRC) given flat doses of cibisatamab and atezolizumab demonstrated an ORR of 14%. In S1 and S2, 40% and 52% of patients, respectively, developed persistent anti-drug antibodies (ADAs). ADA appearance could be mitigated by obinutuzumab-pretreatment, with 8% of patients having persistent ADAs. Overall, cibisatamab warrants further exploration in immunotherapy combination strategies for MSS-CRC. Cibisatamab is a T-cell bispecific antibody targeting the carcinoembryonic antigen (CEA) on tumor cells and CD3 epsilon chain on T cells. Here the authors report the results of two clinical trials of cibisatamab as monotherapy (NCT02324257) and in combination with atezolizumab (anti-PD-L1; NCT02650713) in patients with CEA-positive solid tumors.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Colon cancer ; Antibody therapy ; Cancer immunotherapy
Publicado en:	Nature communications, Vol. 15 (may 2024) , ISSN 2041-1723

DOI: 10.1038/s41467-024-48479-8
PMID: 38750034

14 p, 1.8 MB

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