Enfortumab Vedotin Delivers 44% Objective Response Rate in Heavily Pretreated Advanced Urothelial Cancer, Offering New Hope Where Options Are Limited

Today, Seagen and Astellas announced preliminary Phase 2 clinical data for the investigational antibody-drug conjugate (ADC) enfortumab vedotin. The study demonstrated that this ADC achieved a 44% objective response rate in patients with metastatic urothelial carcinoma who had progressed even on immunotherapy. This study was highlighted as a key presentation at today’s ASCO Annual Meeting and featured in a special report on the conference’s official website.

Urothelial carcinoma is a common type of bladder cancer, and immunotherapies approved for its treatment are currently available. However, as noted in the official press release by ASCO, once advanced urothelial carcinoma progresses despite treatment with platinum-based chemotherapy and immune checkpoint inhibitors (which are effective in only approximately 20% of patients), patients are left with no therapeutic options.

Enfortumab vedotin has offered patients new hope. This antibody-drug conjugate targets Nectin-4, a protein highly expressed in urothelial carcinoma, and delivers the microtubule-disrupting agent MMAE into cancer cells to exert its cytotoxic effect. Based on results from a Phase 1 clinical trial, the U.S. FDA has granted it Breakthrough Therapy Designation for the treatment of locally advanced or metastatic urothelial carcinoma that has progressed following immunotherapy with immune checkpoint inhibitors.

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

In a Phase 2 clinical trial, the therapeutic potential of this antibody-drug conjugate was further validated. Among 125 patients, the objective response rate was 44%, including a complete response rate of 12%.

This therapy also holds significant promise for patients with various refractory conditions: the objective response rate was 41% in patients who had previously received at least three prior therapies; it was also 41% in patients who had failed PD-1 and PD-L1 inhibitors; and even in patients with liver metastases, the objective response rate reached 38%.

These results have greatly excited researchers. Many experts pointed out in the press release that for patients who have failed both chemotherapy and immunotherapy, their treatment options are extremely limited. The results of this study have brought new hope for treating these refractory patients!

Currently, this therapy is in Phase 3 clinical trials. Researchers also look forward to confirming its efficacy through large-scale studies. Meanwhile, based on the results of Phase 2 trials, Seagen and Astellas plan to submit a marketing application to the U.S. FDA this year.

References:

[1] Seattle Genetics and Astellas Announce Antibody-Drug Conjugate Enfortumab Vedotin Produced Tumor Response Rate of 44 Percent in Patients with Most Common Type of Advanced Urothelial (Bladder) Cancer, Retrieved June 3, 2019, from https://seattlegenetics.gcs-web.com/news-releases/news-release-details/seattle-genetics-and-astellas-announce-antibody-drug-conjugate

[2] Novel Targeted-Antibody Treatment Produced Responses in Nearly Half of Patients With Advanced Urothelial Cancer, Retrieved June 3, 2019, from https://www.asco.org/about-asco/press-center/news-releases/novel-targeted-antibody-treatment-produced-responses-nearly

Original Title: ASCO | This ADC Brings a 44% Response Rate for Untreatable Bladder Cancer!

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