Status:
Open
Clinicaltrials.gov identifier:
Sponsor:
Astellas Pharma Global Development
Enrollment:
608
Study Design:
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.
Rationale:
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.
Endpoints:
The primary end point was overall survival (OS).
Comments:
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.
Results:
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.
