Enfortumab vedotin approved in China for urothelial carcinoma

China’s National Medical Products Administration’s (NMPA’s) Center for Drug Evaluation (CDE) has approved enfortumab vedotin (Padcev, EV) for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who have undergone prior treatment with platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.¹

The EV-301 trial showed that treatment with enfortumab vedotin improved overall survival and progression-free survival compared with treatment with chemotherapy.

"On August 13, 2024, the NMPA officially approved the use of enfortumab vedotin for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (la/mUC) after prior treatment with platinum-containing chemotherapy and PD-1/PD-L1 inhibitors. 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 antibody-drug conjugate (ADC) treatment in China,” said Guo Jun, MD, PhD, in a news release on the approval.¹ Jun is the principal investigator of the EV-203 trial and the director of the department of melanoma and urological oncology at Beijing Cancer Hospital in China.

The approval for EV is supported by findings from the global phase 3 EV-301 trial (NCT03474107) and the phase 2 EV-203 bridging trial (NCT04995419) in Chinese patients.

Data from the EV-301 trial showed that treatment with EV improved overall survival (OS) and progression-free survival (PFS) compared with treatment with chemotherapy.² Specifically, the median OS in the EV cohort was 12.88 months vs 8.97 months with chemotherapy (HR, 0.70; 95% CI, 0.56-0.89; P = .001). Additionally, the median PFS was 5.55 months in the EV arm compared with 3.71 months in the chemotherapy arm (HR, 0.62; 95% CI, 0.51-0.75; P < .001).

Regarding safety, 93.9% of patients in the EV arm and 91.8% of patients in the chemotherapy arm experienced a treatment-related adverse event. Grade 3 or higher adverse events were experienced by 51.4% of patients in the EV arm and 49.8% of patients in the chemotherapy arm.

In total, global, open-label, phase 3 EV-301 enrolled 608 patients with la/mUC who were randomly assigned 1:1 to receive either EV (n = 301) at a dose of 1.25 mg/kg of body weight on days 1, 8, and 15 of a 28-day cycle or to chemotherapy (n = 307) with standard docetaxel, paclitaxel, or vinflunine. The median follow-up was 11.1 months. The primary end point for the trial was OS.

The EV-203 trial served as a bridging trial to EV-301. In total, the single-arm, phase 2 EV-203 trial enrolled 40 Chinese patients with la/mUC who previously received platinum-based chemotherapy and a PD-1/PD-L1 inhibitor.

Overall, the EV-203 trial met its primary end point by demonstrating a confirmed objective response rate of 37.5% (95% CI, 22.7%-54.2%) among patients who were treated with EV. This included 1 patient (2.5%) who achieved a complete response and 14 patients (35.0%) who achieved a partial response.

Regarding safety, the majority of treatment-related adverse events (TRAEs) were grade 1-2. TRAEs that led to study discontinuation were experienced by 2 patients, which were due to acute coronary syndrome and hyperglycemia/rash.

Ahsan Arozullah, MD, MPH, senior vice president and head of oncology development at Astellas, concluded in the news release on the approval,¹ "We remain committed to driving scientific progress that leads to meaningful changes in the course of cancer across the globe. The approval of enfortumab vedotin by the CDE provides patients in China with another treatment option for locally advanced or metastatic urothelial cancer, providing hope of better outcomes for those affected by this condition."

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. Published online August 19, 2024. Accessed August 20, 2024. https://www.prnewswire.com/news-releases/chinas-national-medical-products-administration-nmpa-approves-padcev-enfortumab-vedotin-for-treatment-of-locally-advanced-or-metastatic-urothelial-cancer-302225531.html

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