Enfortumab Vedotin Plus Keytruda Achieves 91% Disease Control Rate in First-Line Cisplatin-Ineligible Advanced Urothelial Cancer

Today, Seagen and Astellas jointly announced that the antibody-drug conjugate (ADC) enfortumab vedotin, co-developed by the two companies, in combination with Merck & Co.’s blockbuster PD-1 inhibitor Keytruda (pembrolizumab), achieved positive trial results as a first-line treatment for patients with advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-based chemotherapy. The confirmed objective response rate (ORR) was 71%.

Urothelial carcinoma is the most common type of bladder cancer, accounting for 90% of all cases. Last year, there were approximately 549,000 new patients worldwide, and about 200,000 deaths resulted from this disease. The first-line treatment typically recommended is cisplatin-based chemotherapy; if patients cannot undergo this treatment due to health reasons, carboplatin-based chemotherapy becomes their next option. However, fewer than half of the patients respond to carboplatin-based regimens, and their prognosis is worse compared to those receiving cisplatin-based therapy.

Enfortumab vedotin is an antibody-drug conjugate (ADC) that links an anti-Nectin-4 monoclonal antibody to the microtubule-disrupting agent MMAE. It utilizes Seagen’s proprietary antibody-conjugation technology. Nectin-4, a cell adhesion molecule expressed on the surface of various solid tumors and highly expressed in urothelial carcinoma, is an ADC target identified by Astellas. This therapy has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA). Recently, the FDA granted Priority Review to its Biologics License Application (BLA) for the treatment of patients with urothelial carcinoma whose disease has progressed following prior chemotherapy and PD-1/PD-L1 inhibitor therapy.

▲Mechanism of Action of Enfortumab Vedotin (Image source: Seattle Genetics official website)

In this open-label, Phase 1 clinical trial named EV-103, enfortumab vedotin, either as monotherapy or in combination with Keytruda, was used to treat patients with advanced or metastatic urothelial carcinoma who were ineligible for first-line cisplatin-based chemotherapy due to health reasons. The trial results demonstrated that the combination of enfortumab vedotin and Keytruda reduced tumor size in the majority of cancer patients. The overall response rate (ORR) reached 71% (32/45; 95% CI: 55.7, 83.6). Among these, the complete response rate was 13%, the partial response rate was 58%, 22% of patients achieved stable disease, and the disease control rate reached 91%.

“These data are encouraging and support our further exploration of the potential of combining Keytruda with enfortumab vedotin as a platinum-free chemotherapy regimen,” said Dr. Roger Dansey, Chief Medical Officer at Seagen.

References:

[1] Seattle Genetics and Astellas Announce Results from Phase 1 Trial of Investigational Agent Enfortumab Vedotin in Combination with Immune Therapy Pembrolizumab as First-Line Treatment for Advanced Bladder Cancer. Retrieved September 28, 2019, from https://www.businesswire.com/news/home/20190927005519/en

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