CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: results of two multi-institutional Phase 1 trials

Neil H. Segal (), Ignacio Melero, Victor Moreno, Neeltje Steeghs, Aurelien Marabelle, Kristoffer Rohrberg, Maria E. Rodriguez-Ruiz, Joseph P. Eder, Cathy Eng, Gulam A. Manji, Daniel Waterkamp, Barbara Leutgeb, Said Bouseida, Nick Flinn, Meghna Thakur, Markus C. Elze, Hartmut Koeppen, Candice Jamois, Meret Martin-Facklam, Christopher H. Lieu, Emiliano Calvo, Luis Paz-Ares, Josep Tabernero and Guillem Argilés
Additional contact information
Neil H. Segal: United States; Weill Cornell Medical College
Ignacio Melero: Clínica Universidad de Navarra and CIMA University of Navarra
Victor Moreno: Hospital Fundación Jiménez Díaz
Neeltje Steeghs: Netherlands Cancer Institute
Aurelien Marabelle: Université Paris-Saclay
Kristoffer Rohrberg: Copenhagen University Hospital - Rigshospitalet
Maria E. Rodriguez-Ruiz: Clínica Universidad de Navarra and CIMA University of Navarra
Joseph P. Eder: Yale University Cancer Center
Cathy Eng: Vanderbilt Ingram Cancer Center
Gulam A. Manji: Columbia University
Daniel Waterkamp: Inc.
Barbara Leutgeb: Ltd
Said Bouseida: Ltd
Nick Flinn: Ltd
Meghna Thakur: Inc.
Markus C. Elze: Ltd
Hartmut Koeppen: Inc.
Candice Jamois: Ltd
Meret Martin-Facklam: Ltd
Christopher H. Lieu: Aurora
Emiliano Calvo: Centro Integral Oncológico Clara Campal
Luis Paz-Ares: University Hospital 12 de Octubre
Josep Tabernero: Vall d’Hebron Hospital Campus and Institute of Oncology (VHIO)
Guillem Argilés: Vall d’Hebron Hospital Campus and Institute of Oncology (VHIO)

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-48479-8

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