open access publication

Article, 2024

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

Nature Communications, ISSN 2041-1723, Volume 15, 1, Page 4091, 10.1038/s41467-024-48479-8

Contributors

Segal, Neil Howard 0000-0002-3047-2303 (Corresponding author) [1] [2] Melero, I Herrera 0000-0002-1360-348X [3] [4] Moreno, Victor [5] Steeghs, Neeltje 0000-0003-2989-2279 [6] Marabelle, Aurélien 0000-0002-5816-3019 [7] Rohrberg, Kristoffer Staal 0000-0002-5448-9003 [8] Rodriguez-Ruiz, Maria Esperanza 0000-0002-9765-2499 [4] Eder, Joseph Paul 0000-0002-7805-0986 [9] Eng, Cathy 0000-0003-2335-0612 [10] Manji, Gulam Abbas [11] Waterkamp, Daniel [12] Leutgeb, Barbara [13] Bouseida, Said [13] Flinn, Nick [13] Das Thakur, Meghna [12] Elze, Markus C 0000-0003-1843-271X [13] Koeppen, Hartmut 0000-0003-0923-3110 [12] Jamois, Candice 0000-0001-7018-9687 [13] Martin-Facklam, Meret [13] Lieu, Christopher Hanyoung 0000-0002-4852-4642 [14] Calvo, Emiliano 0000-0003-4921-829X [15] Paz-Ares, Luis G [16] Tabernero, Josep 0000-0002-2495-8139 [17] Argiles, Guillem [17] [18]

Affiliations

  1. [1] Cornell University
    2. [NORA names: United States; America, North; OECD];
  2. [2] Memorial Sloan Kettering Cancer Center
    3. [NORA names: United States; America, North; OECD];
  3. [3] Centro de Investigación Biomédica en Red de Cáncer
    4. [NORA names: Spain; Europe, EU; OECD];
  4. [4] Clínica Universidad de Navarra
    5. [NORA names: Spain; Europe, EU; OECD];
  5. [5] Hospital Universitario Fundación Jiménez Díaz
    6. [NORA names: Spain; Europe, EU; OECD];

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.

Keywords

CD3, CD3 epsilon chain, MSS-CRC, ORR, S1, S2, S2 patients, Secondary endpoints, T cells, T-cell engagers, activity, adverse events, anti-drug antibodies, anti-tumor activity, antibodies, antigen, appearance, atezolizumab, carcinoembryonic antigen, carcinoma, cells, chain, colorectal carcinoma, combination strategies, dose, dose-finding, endpoint, engagement, epsilon chain, events, exploration, findings, flat dose, grade, immunotherapy, immunotherapy combination strategies, microsatellite, microsatellite stable colorectal carcinomas, obinutuzumab, patients, persistent ADAs, pharmacodynamics, pharmacokinetics, phase 1 dose-escalation, phase 1 trial, primary endpoint, results, safety, solid tumors, strategies, study, tumor, tumor cells

Funders

  • Roche (United States)

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