The data will be featured Monday June 3, in the official press program of the American Society of Clinical Oncology (ASCO) Annual Meeting and be presented as a Late-Breaking oral presentation (Abstract #LBA4505) and have been submitted for publication in a peer-reviewed journal.
Despite recent advances in treatment, approximately 80 percent of people do not respond to PD-1/L1 inhibitors, which are the standard of care after platinum-containing therapy has failed as an initial treatment for advanced disease.1,2,3 These patients have few treatment options and new therapies are urgently needed.
Enfortumab vedotin is an investigational antibody-drug conjugate (ADC) that targets Nectin-4, a protein that is highly expressed in urothelial cancers.4,5 Based on the results of the EV-201 trial, the companies plan to submit a Biologics License Application (BLA) for enfortumab vedotin to the U.S. Food and Drug Administration (FDA) this year. Based on preliminary results from the phase 1 EV-101 trial, the FDA granted enfortumab vedotin Breakthrough Therapy designation for people with locally advanced or metastatic urothelial cancer whose disease has progressed during or following checkpoint inhibitor therapy.
“Outcomes for patients diagnosed with locally advanced or metastatic urothelial cancer are generally poor, and treatment options after initial chemotherapy and immunotherapy are very limited,” said Daniel 2 P. Petrylak, M.D., Professor of Medicine and of Urology, Yale Cancer Center, New Haven. “These data have the potential to change the treatment course of advanced urothelial cancer, and it is gratifying to see these results for patients.”“Even with the recent introduction of new therapies, there remains a need for continued innovation in the treatment of urothelial cancer, and if approved, we hope to bring this potential treatment to physicians and patients as quickly as possible,” said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head at Astellas.
“We are encouraged that enfortumab vedotin is the first novel therapy to demonstrate substantial clinical activity in these difficult-to-treat patients who currently have limited treatment options,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics.A global, randomized phase 3 confirmatory clinical trial (EV-301) is ongoing and is intended to support global registrations. Another trial (EV-103) is underway to evaluate enfortumab vedotin in earlier lines of treatment for patients with locally advanced or metastatic urothelial cancer, including in combination with pembrolizumab and/or platinum chemotherapy in newly diagnosed patients as well as patients who progressed from earlier-stage disease.
EV-201 Study Results
In the first cohort of the EV-201 study, 125 patients were treated with enfortumab vedotin. The primary endpoint of confirmed objective response rate (ORR) was 44 percent per blinded independent central review (BICR) [(55/125; 95% CI: 35.1-53.2)]. The overall duration of response (DoR), a key secondary endpoint, was 7.6 months (range 0.95-11.3+).
Most responses occurred within the first cycle of treatment, and were observed across all pre-specified patient subgroups irrespective of lines of therapy, response to prior PD-1/L1 inhibitor, or presence of liver metastases:
• Three or more prior therapies: 41 percent ORR (26/63)
• Non-responders to PD-1/L1 inhibitors: 41 percent ORR (41/100)
• Liver metastases: 38 percent ORR (19/50)
Median overall survival (OS) was 11.7 months (95% CI:9.1-not reached), and the median progression-free survival (PFS) was 5.8 months (95% CI:4.9-7.5).
• The most common treatment-related adverse events (AEs) occurring in more than 40 percent of patients were fatigue (50 percent (62/125)); alopecia (49 percent (61/125)); rash (48 percent (60/125)); decreased appetite (44 percent (55/125)); taste distortion (40 percent (50/125)); and peripheral neuropathy (50 percent (63/125)).
• Most peripheral neuropathy (94 percent) and rash (75 percent) were less than or equal to Grade 2 in severity. Hyperglycemia occurred in 11 percent of patients (14/125).
• The most common severe AEs (defined as greater than or equal to Grade 3) were: neutropenia – experienced by 8 percent of patients (10/125); anemia in 7 percent of patients (9/125); and fatigue in 6 percent of patients (7/125). One death due to interstitial lung disease occurred outside the safety-reporting period and was confounded by prolonged high-dose steroid use and suspected pneumonia.
1. Kim HS, Seo HK, Immune checkpoint inhibitors for urothelial carcinoma. Investig Clin Urol 2018 Sep;59(5):285-296
2. Alhalabi O, Shah AY, Lemke EA, Gao J. Current and Future Landscape of Immune Checkpoint Inhibitors in Urothelial Cancer. Oncology (Williston Park). 2019 Jan 17;33(1):11-8
3. National Comprehensive Cancer Network. Bladder Cancer (Version 3.2019).
4. Vlachostergios P, Jakubowski C, Niaz J, et al. (2018). Antibody-Drug Conjugates in Bladder Cancer. Bladder Cancer (Version 4.2018).
5. Astellas Pharma Global Development, Inc. Bladder Cancer (2019).
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