Enfortumab Vedotin, a Nectin-4–directed antibody-drug conjugate approved for urothelial cancer, targets Nectin-4 expression in various solid tumors, including breast cancer. In the EV-202 study, enfortumab vedotin monotherapy was assessed in TNBC and HR+/HER2- breast cancer. The primary endpoint was the confirmed objective response rate (ORR), with secondary endpoints including duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety/tolerability. The results presented at ASCO 2024 were as follows:

Efficacy outcomes of TNBC and HR+/HER2-ve cancer: Enfortumab vedotin demonstrated antitumor activity in both the TNBC and HR+/HER2-ve cancer cohorts. Nectin-4 was highly expressed in both cohorts, and expression was similar between responders and non-responders

• ORR: 19% TNBC and 15.6% for HR+/HER2-ve cancer

• PFS: 3.5 for TNBC and 5.4 months for HR+/HER2-ve cancer

• OS: 12.9 for TNBC and 19.8 months for HR+/HER2-ve cancer

Safety overview: Safety remained manageable and consistent in both cohorts.

KOL insights

“Response rates and PFS of Enfortumab vedotin, independent of nectin expression in HR+ and TNBC. Unclear what the strategy of sequencing would be with this agent, although has significant efficacy.” –Expert Opinion.

“Enfortumab vedotin had modest activity in unselected HER2 negative MBC. Encouraging signal in TNBC deserves further exploration +/-CPI. Biomarkers can potentially optimize ADC development”–Expert Opinion.

Conclusion- Enfortumab vedotin, a targeted antibody-drug conjugate directed at Nectin-4, showed promising antitumor activity in both triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer groups. However, it fell short of the prespecified objective response rate (ORR) threshold. Nonetheless, safety remained manageable and consistent across both cohorts.