Enfortumab Vedotin Approved in China for Locally Advanced/Metastatic Urothelial Cancer

On August 13, 2024, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration approved enfortumab vedotin (Padcev) for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received prior treatment with platinum-containing chemotherapy and PD-1 or PD-L1 inhibitors.¹

The regulatory decision was supported by findings from the randomized, global, phase 3 EV-301 trial (NCT03474107) and the Chinese phase 2 EV-203 trial (NCT04995419). The single-arm EV-203 trial served as a bridging trial to EV-301 and investigated the Nectin-4–directed antibody-drug conjugate (ADC) in Chinese patients with locally advanced or metastatic urothelial cancer who had previously been exposed to a PD-1/PD-L1 inhibitor and platinum-based chemotherapy.

EV-203 met its primary end point, with a statistically significant overall response rate (ORR) benefit observed in patients who received enfortumab vedotin monotherapy (n = 40) compared with historical controls. The ORR was 37.5% (95% CI, 22.7%-54.2%), including a complete response in 1 patient and a partial response in 14 patients. The efficacy and pharmacokinetic data from EV-203 were consistent with global data reported with enfortumab vedotin in this population. Furthermore, investigators observed no new safety signals, and most treatment-related adverse effects (TRAEs) were grade 1 or 2. Two patients discontinued treatment because of treatment-related hyperglycemia/rash and acute coronary syndrome.

“This approval, based on a global phase 3 registration study as well as a bridging study in Chinese patients, is a milestone event where patients will now have access to this new ADC treatment in China,” professor Guo Jun, principal investigator of the EV-203 trial and director of the Department of Melanoma and Urological Oncology at Beijing Cancer Hospital in China, stated in a news release.

The EV-301 trial investigated enfortumab vedotin vs physician’s choice of chemotherapy (paclitaxel, vinflunine, or docetaxel) in 608 patients with locally advanced or metastatic urothelial cancer who had previously received platinum-containing therapies and a PD-1/PD-L1 inhibitor.

Patients in the enfortumab vedotin arm (n = 301) achieved a longer median overall survival compared with those in the chemotherapy arm (n = 307), at 12.88 months (95% CI, 10.58-15.21) vs 8.97 months (95% CI, 8.05-10.74), respectively (HR, 0.70; 95% CI, 0.56-0.89; P = .001).2 The median progression-free survival was 5.55 months (95% CI, 5.32-5.82) in the investigational arm vs 3.71 months (95% CI, 3.52-3.94) in the chemotherapy arm (HR, 0.62; 95% CI, 0.51-0.75; P < .001).

The confirmed overall response was higher with enfortumab vedotin vs chemotherapy, at 40.6% (95% CI, 34.9%-46.5%) and 17.9% (95% CI, 13.7%-22.8%), respectively (P < .001). The disease control rates in the respective arms were 71.9% (95% CI, 66.3%-77.0%) and 53.4% (95% CI, 47.5%-59.2%; P < .001). Moreover, the median duration of response in those who achieved a complete or partial response was 7.39 months in the enfortumab vedotin arm vs 8.11 months in the chemotherapy arm.

TRAEs were observed in 93.9% of patients in the enfortumab vedotin arm vs 91.8% of those in the chemotherapy arm. Grade 3 or higher AEs were reported in 51.4% and 49.8% of patients in these respective arms.

The most common adverse effects experienced in the enfortumab vedotin arm (n = 296) were alopecia (any grade, 45.3%; grade ≥3, 0%), peripheral sensory neuropathy (33.8%; 3.0%), pruritus (32.1%; 1.4%), fatigue (31.1%; 6.4%), reduced appetite (30.7%; 3.0%), diarrhea (24.3%; 3.4%), dysgeusia (24.3%; 0%), nausea (22.6%; 1.0%), maculopapular rash (16.2%; 7.4%), anemia (11.5%; 2.7%), decreased neutrophil count (10.1%; 6.1%), neutropenia (6.8%; 4.7%), decreased white cell count (5.4%; 1.4%), and febrile neutropenia (0.7%; 0.7%).

“Enfortumab vedotin will benefit patients in our country, bringing a new treatment to those with locally advanced or metastatic urothelial carcinoma who have previously received platinum-containing chemotherapy and PD-1/PD-L1 inhibitors,” professor Dingwei Ye, academic leader of the Department of Urology and principal expert of Urological Oncology MDT Management at Fudan University-Affiliated Cancer Hospital in China, added in the news release.¹

References

1. China’s National Medical Products Administration (NMPA) approves PADCEV (enfortumab vedotin) for treatment of locally advanced or metastatic urothelial cancer. News release. Astellas Pharma, Inc. August 19, 2024. Accessed August 20, 2024. https://newsroom.astellas.us/2024-08-19-Chinas-National-Medical-Products-Administration-NMPA-Approves-PADCEV-TM-enfortumab-vedotin-for-Treatment-of-Locally-Advanced-or-Metastatic-Urothelial-Cancer
2. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med. 2021;384(12):1125-1135. doi:10.1056/NEJMoa2035807