CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: results of two multi-institutional Phase 1 trials
Open accessAbstract
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.
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Bispecific T cell engagers provide a potential additional tool to direct immune cells into immune-cold tumours and could be combined with other forms of immunotherapy.
“These antibodies include bispecific T cell engagers (reviewed in9698) that provide a potential additional tool to direct immune cells into immune-cold tumours and could be combined with other forms of immunotherapies.99”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [99]
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- Authors
- Segal, N. H., Melero, I., Moreno, V., Steeghs, N., Marabelle, A., Rohrberg, K., Rodriguez-Ruiz, M. E., Eder, J. P., Eng, C., Manji, G. A., Waterkamp, D., Leutgeb, B., Bouseida, S., Flinn, N., Das Thakur, M., Elze, M. C., Koeppen, H., Jamois, C., Martin-Facklam, M., Lieu, C. H., Calvo, E., Paz-Ares, L., Tabernero, J., & Argilés, G.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Instituto de Salud Carlos III (ES)
- The Netherlands Cancer Institute (NL)
- Copenhagen University Hospital (DK)
- Clinica Universidad de Navarra (ES)
- Yale Cancer Center (US)
- Vanderbilt University (US)
- Columbia University (US)
- Genentech (US)
- F. Hoffmann-La Roche AG (CH)
- University of Colorado Denver (US)
- Hospital Universitario 12 De Octubre (ES)
- Vall d'Hebron Institute of Oncology (ES)
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Segal, Neil H.
- ORCID
- Segal, Neil H.
- Melero, Ignacio
- Moreno, Victor
- Steeghs, Neeltje
- Marabelle, Aurelien
- Rohrberg, Kristoffer
- Rodriguez-Ruiz, Maria E.
- Eder, Joseph P.
- Eng, Cathy
- Manji, Gulam A.
- Leutgeb, Barbara
- Bouseida, Said
- Elze, Markus C.
- Jamois, Candice
- Lieu, Christopher H.
- Calvo, Emiliano
- Paz-Ares, Luis
- Tabernero, Josep
- Argilés, Guillem
- Venue
- Nature Communications
- Published
- 2024-05-15
- Volume
- 15
- Issue
- 1
- Pages
- 4091-4091
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC11096172
- OpenAlex
- W4396934258
- Cited by
- 80
- References
- 27
- Citations by year
- 2026: 48 · 2025: 26 · 2024: 6
- FWCI
- 13.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- F Hoffmann-La Roche
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- bispecific antibodies, T-cell engagers, carcinoembryonic antigen, CD3, atezolizumab, obinutuzumab, anti-drug antibodies, dose escalation, pharmacokinetics, pharmacodynamics, antitumour activity, adverse events
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Carcinoembryonic Antigen, Female, Humans, Male, Middle Aged, Neoplasms, CD3 Complex, Antibodies, Bispecific, Antibodies, Monoclonal, Humanized
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