| World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access |
| Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc |
| Journal website https://www.wjon.org |
Review
Volume 15, Number 4, August 2024, pages 527-542
Opportunities and Challenges in the Development of Antibody-Drug Conjugate for Triple-Negative Breast Cancer: The Diverse Choices and Changing Needs
Table
| ADC | Target | Antibody | Payload | Linker | DAR | Clinical trial identifier | Phase | Patient cohort | Patients number | Main results of the clinical trial |
|---|---|---|---|---|---|---|---|---|---|---|
| ADC: antibody-drug conjugate; TNBC: triple-negative breast cancer; DAR: drug to antibody ratio; HER: human epidermal growth factor; TROP2: trophoblast surface antigen 2; FRα: folate receptor α; EGFR: epidermal growth factor receptor; ROR2: receptor tyrosine kinase-like orphan receptor 2; BC: breast cancer; NA: not available; PFS: progression-free survival; OS: overall survival; HR: hormone receptor. | ||||||||||
| Trastuzumab deruxtecan (DS-8201a) | HER2 | Trastuzumab | Deruxtecan (topoisomerase I inhibitor) | Proteolytically cleavable | 7 - 8 | NCT02564900 | I | Pre-treated metastatic breast, gastric, gastroesophageal cancers | 278 | Controllable safety, and satisfactory objective response rate |
| NCT03734029 | III | HER2-low expression, metastatic BC | 540 | Compared with chemotherapy, PFS and OS were significantly improved | ||||||
| Trastuzumab duocarmazine (SYD985) | HER2 | Trastuzumab | Duocarmycin (DNA alkylating agent) | Proteolytically cleavable | 7 - 8 | NCT02277717 | I | Locally advanced or metastatic BC | 185 | Both HER2-positive and negative patients showed objective response; controllable safety |
| NCT03262935 | III | HER2-positive advanced or metastatic BC | 436 | PFS was significantly improved compared to conventional chemotherapy | ||||||
| Sacituzumab govitecan (IMMU-132) | TROP-2 | Sacituzumab | SN-38 (topoisomerase I inhibitor) | Cleavable, pH sensitive | 7.6 | NCT01631552 | I/II | Metastatic TNBC | 108 | Objective response and clinical efficacy; bone marrow toxicity |
| NCT02574455 | III | Recurrent metastatic TNBC | 468 | Compared to chemotherapy, PFS and OS were significantly improved; bone marrow toxicity and diarrhea | ||||||
| Datopotamab deruxtecan (DS-1062) | TROP-2 | Datopotamab | Deruxtecan (topoisomerase I inhibitor) | Proteolytically cleavable | 4 | NCT03401385 | I | Advanced or metastatic TNBC | 44 | Preliminary results showed good objective response rate and controllable safety |
| NCT05374512 | III | Locally recurrent, inoperable or metastasis TNBC | 600 | NA | ||||||
| Patritumab deruxtecan (U3-1402) | HER3 | Patritumab | Deruxtecan (topoisomerase I inhibitor) | Proteolytically cleavable | 7 - 8 | NCT02980341 | I/II | HER3-positive metastatic BC | 180 | Objective response in HR+/HER2−, HER2+ and TNBC patients |
| Ladiratuzumab vedotin (SGN-LIV1a) | Estrogen-regulated LIV-1 protein (LIV-1) | Ladiratuzumab | Monomethyl auristatin E (microtubule inhibitor) | Proteolytically cleavable | 4 | NCT01969643 | I | Locally advanced or metastatic BC | 89 | Interim results showed good tolerability and significant antitumor activity |
| NCT03310957 | I/II | Advanced or metastatic TNBC | 97 | The combination with pembrolizumab (PD-1 monoclonal antibody) showed antitumor efficacy and safety | ||||||
| Enfortumab vedotin-ejfv | Nectin cell adhesion molecule 4 (nectin-4) | Enfortumab | Monomethyl auristatin E (microtubule inhibitor) | Proteolytically cleavable | 3.8 | NCT04225117 (EV-202) | II | HR+/HER2- BC, and TNBC | 240 | NA |
| Mirvetuximab soravtansine (IMGN853) | FRα | Mirvetuximab | Ravtansine (DM4) (microtubule inhibitor) | Cleavable | 2 | NCT03106077 | II | FRα-positive, advanced TNBC | 96 | Terminated due to low frequency of FRα positivity and the lack of response |
| Farletuzumab ecteribulin (MORAb-202) | FRα | Farletuzumab | Eribulin (microtubule inhibitor) | Proteolytically cleavable | 4 | NCT04300556 | I/II | FRα-positive, advanced solid tumors (including TNBC) | 196 | NA |
| AVID100 | EGFR | MAB100 | Mertansine (DM1) (microtubule inhibitor) | Proteolytically cleavable | NA | NCT03094169 | I/II | Advanced epithelial tumors (including TNBC) | 90 | NA |
| Ozuriftamab vedotin (CAB-ROR2-ADC) | ROR2 | Ozuriftamab | Monomethyl auristatin E (microtubule inhibitor) | Proteolytically cleavable | NA | NCT03504488 | I/II | TNBC, non-small-cell lung carcinoma | 120 | NA |
| Anti-CA6-DM4 immuno-conjugate (SAR566658) | Tumor-associated Sialoglycoprotein CA6 | DS6 | Ravtansine (DM4) (microtubule inhibitor) | Cleavable, glutathione dependent | 1 | NCT02984683 | II | CA6- positive, metastatic TNBC | 23 | Discontinued due to limited efficacy |