Publicaciones científicas

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

15-may-2024 | Revista: Nature Communications

Neil H Segal  1 , Ignacio Melero  2   3 , Victor Moreno  4 , Neeltje Steeghs  5 , Aurelien Marabelle  6 , Kristoffer Rohrberg  7 , Maria E Rodriguez-Ruiz  2 , Joseph P Eder  8 , Cathy Eng  9 , Gulam A Manji  10 , Daniel Waterkamp  11 , Barbara Leutgeb  12 , Said Bouseida  12 , Nick Flinn  12 , Meghna Das Thakur  11 , Markus C Elze  12 , Hartmut Koeppen  11 , Candice Jamois  12 , Meret Martin-Facklam  12 , Christopher H Lieu  13 , Emiliano Calvo  14 , Luis Paz-Ares  15 , Josep Tabernero  16 , Guillem Argilés  16   17


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.

CITA DEL ARTÍCULO  Nat Commun. 2024 May 15;15(1):4091. doi: 10.1038/s41467-024-48479-8