CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: Results of two multi-institutional Phase 1 trials Journal Article
| 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. |
| Article Title: | CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: Results of two multi-institutional Phase 1 trials |
| 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. © The Author(s) 2024. |
| Keywords: | adult; aged; aged, 80 and over; middle aged; major clinical study; clinical trial; fatigue; advanced cancer; diarrhea; drug efficacy; drug safety; monotherapy; solid tumor; cancer adjuvant therapy; cancer patient; pancreas cancer; antineoplastic agent; neoplasm; neoplasms; cd3 antigen; cd8+ t lymphocyte; t lymphocyte; low drug dose; metastasis; pharmacodynamics; gene expression; nausea; vomiting; antineoplastic combined chemotherapy protocols; incidence; carcinoembryonic antigen; cohort analysis; dexamethasone; antineoplastic activity; monoclonal antibody; arthralgia; asthenia; chill; colorectal carcinoma; drug dose escalation; dyspnea; fever; pruritus; cancer inhibition; cytokine; immunology; antigen; multicenter study; microsatellite instability; immunogenicity; drug response; drug clearance; sepsis; open study; methylprednisolone; safety; maximum tolerated dose; phase 1 clinical trial; tumor; corticosteroid; disease control; dose calculation; antibody; national health organization; dysgeusia; hypertensive factor; respiratory failure; cell adhesion molecule; lung lesion; decreased appetite; drug; cytokine release syndrome; exploration; overall response rate; antibodies, bispecific; antibodies, monoclonal, humanized; Common Terminology Criteria for Adverse Events; bispecific antibody; infusion related reaction; very elderly; humans; human; male; female; article; evaluation study; rna sequencing; obinutuzumab; x-ray computed tomography; atezolizumab; drug antibody; ecog performance status; maximum concentration; cd3 complex; cibisatamab |
| Journal Title: | Nature Communications |
| Volume: | 15 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-05-15 |
| Start Page: | 4091 |
| Language: | English |
| DOI: | 10.1038/s41467-024-48479-8 |
| PUBMED: | 38750034 |
| PROVIDER: | scopus |
| PMCID: | PMC11096172 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
