Astellas Pharma Global Development
This was an international open-label, phase 3 trial of enfortumab vedotin, an antibody drug conjugate that targets Nectin-4 and carries a Monomethyl Auristatin E (MMAE) Payload, a microtubule-disrupting agent, as compared to investigator’s chemotherapy of choice in patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-containing chemotherapy and had disease progression during or after treatment with a PD-1 or PD-L1 inhibitor. Patients were randomly assigned in a 1:1 ratio to receive enfortumab vedotin or docetaxel, paclitaxel, or vinflunine.
Patients with advanced urothelial carcinoma have poor overall survival when recurring after platinum-containing chemotherapy and programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor treatment. More novel therapies are needed.
The primary end point was overall survival (OS).
The FDA approved enfortumab vedotin for treatment of patients with locally advanced or metastatic UC previously treated with a PD-(L)1 inhibitor and platinum-containing CT in the (neo)adjuvant, locally advanced, or metastatic setting. A second antibody drug conjugate Sacituzumab Govitecan, that targets Targets Trop-2, with a SN-38 Payload, the active metabolite of irinotecan, was also recently approved for locally advanced or metastatic UC previously treated with a PD-L1 inhibitor and either platinum ineligible or previously treated with platinum-containing CT in the (neo)adjuvant, locally advanced, or metastatic setting.
301 patients were assigned to receive enfortumab vedotin and 307 to receive chemotherapy. As of July 15, 2020, a total of 301 deaths had occurred (134 in the enfortumab vedotin group and 167 in the chemotherapy group). At the prespecified interim analysis, the median follow-up was 11.1 months. OS was longer in the enfortumab vedotin group than in the chemotherapy group (median 12.88 vs. 8.97 months; hazard ratio for death, 0.70; 95% confidence interval [CI], 0.56 to 0.89; P = 0.001). Progression-free survival(PFS) was also longer in the enfortumab vedotin group than in the chemotherapy group (median 5.55 vs. 3.71 months; HR for progression or death, 0.62; 95% CI, 0.51 to 0.75; P<0.001). The study was halted by the IDMC at this analysis and it was recommended to the sponsor to allow crossover of patients on chemotherapy at PD to enfortumab vedotin.