ADCs

CEACAM5

Carcinoembryonic antigen (CEA)-related cell adhesion molecule 5 (CEACAM5) is a cell surface glycoprotein that is overexpressed on tumor cells and is associated with tumor differentiation, invasion, and metastasis.1,2 While expression of CEACAM5 is high in several tumor types, including gastrointestinal, lung, and pancreatic cancers, expression in normal epithelial tissues is low.3-5 Thus, CEACAM5 presents an attractive target for anticancer therapy.

M9140 – CEACAM5 ADC

M9140 is an investigational CEACAM5 ADC that is designed to deliver a cytotoxic topoisomerase 1 (TOP1) inhibitor payload to CEACAM5-expressing tumor cells.6-8 The TOP1 inhibitor payload enters the nucleus and disrupts DNA replication and repair, thereby killing CEACAM5-expressing tumor cells.6-8 The payload can also enter and kill neighboring tumor cells via a bystander effect.6

CLINICAL TRIALS

M9140 in Advanced Solid Tumors

M9140 monotherapy is being investigated in a Phase 1, multicenter, open-label, first-in-human study in patients with advanced solid tumors.

The 8th edition of Takeda's Global Brand Guidelines

VIEWPOINTS ON CANCER

Investigational compounds are not approved by any health authority. Safety and efficacy have not been established.

Abbreviations:

ADC, antibody drug conjugate; CEACAM5, carcinoembryonic antigen-related cell adhesion molecule 5.

References:

  1. Tchoupa TA, Schuhmacher T, Hauck CR. Signaling by epithelial members of the CEACAM family - mucosal docking sites for pathogenic bacteria. Cell Commun Signal. 2014;12:27.
  2. Beauchemin N, Arabzadeh A. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev. 2013;32(3-4):643-671.
  3. Decary S, Berne P-F, Nicolazzi C, et al. Preclinical activity of SAR408701: a novel anti-CEACAM5-maytansinoid antibody-drug conjugate for the treatment of CEACAM5-positive epithelial tumors. Clin Cancer Res. 2020;26(24):6589-6599.
  4. Gazzah A, Bedard PL, Hierro C, et al. Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: first-in-human dose-escalation study. Ann Oncol. 2022;33(4):416-425.
  5. Hammarström S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999;9(2):67-81.
  6. Abuhelwa Z, Alloghbi A, Nagasaka M. A comprehensive review on antibody-drug conjugates (ADCs) in the treatment landscape of non-small cell lung cancer (NSCLC). Cancer Treat Rev. 2022;106:102393.
  7. Lambert JM, Berkenblit A. Antibody-drug conjugates for cancer treatment. Annu Rev Med. 2018;69:191-207.
  8. Pommier Y. Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006;6(10):789-802.
  9. Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors. ClinicalTrials.gov identifier: NCT05464030. Updated February 27, 2023. Accessed April 28, 2023. https://clinicaltrials.gov/ct2/show/NCT05464030