Study EV-103 Cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC)

There is a critical need for effective and tolerable 1L treatment options in la/mUC. Both EV and P have independently shown an OS benefit in previously treated la/mUC. EV preclinical studies have shown hallmarks of immune cell death potentially augmented by PD-1/PD-L1 inhibitors. Results from a previous cohort formed the rationale for this randomized Cohort K. Previously untreated cisplatin-ineligible pts with la/mUC were randomized 1:1 to EV (1.25 mg/kg) as monotherapy on Days 1 and 8 or in combination with P (200 mg) on Day 1 of 3-week cycles (EV-103, NCT03288545). The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by BICR. Secondary endpoints included duration of response (DOR) and safety (treatment-related adverse events, TRAEs). There were no formal statistical comparisons between treatment arms. 149 pts were treated: EV+P n=76; EV n=73. Confirmed ORR (95%CI) for EV+P, 64.5% (52.7, 75.1), median DOR was not reached. Confirmed ORR (95%CI) for EV, 45.2% (33.5, 57.3) and median DOR (95%CI) 13.2 mos (6.1, 16.0). TRAEs of special interest included skin reactions (EV+P, n=51 [67.1%]; EV, n=33 [45.2%]), peripheral neuropathy (EV+P, n=46 [60.5%]; EV, n=40 [54.8%]), ocular disorders (eg, dry eye and blurred vision; EV+P, n=20 [26.3%]; EV, n=21 [28.8%]), and hyperglycemia (EV+P, n=11 [14.5%]; EV, n=8 [11.0%]). The majority of treatment-related AESIs were Grade ≤2.Table: LBA73EV+PEV mono(N=76)(N=73)Confirmed ORR, % (95% CI)64.5 (52.7, 75.1)45.2 (33.5, 57.3)Best overall response per BICR, %Complete Response10.54.1Partial Response53.941.1Stable Disease22.434.2Progressive Disease7.99.6Not Evaluable3.96.8No Assessment1.34.1Median (range) time to ORR, mos2.1 (1.1, 6.6)2.1 (1.9, 15.4)Median (range) treatment duration, mos9.0 (0.6, 26.1+)5.5 (0.5, 26.9+)Median (95%CI) follow-up, mos14.8 (12.9, 17.3)15.0 (12.7, 17.4)Data cutoff: June 10, 2022; +Pts remain on treatment. Open table in a new tab Data cutoff: June 10, 2022; +Pts remain on treatment. EV+P showed high ORR with rapid responses and median DOR not reached in a 1L cisplatin-ineligible population. The safety profile was tolerable and generally consistent with the known profile for EV+P. EV monotherapy was consistent with prior experience. These data support ongoing investigations of 1L EV+P in patients with la/mUC who have a high unmet need.