EV-103 Cohort A: Long-term Outcomes of EV Plus Pembrolizumab in First-line mUC

After approximately 4 years of follow-up data, enfortumab vedotin (EV) plus pembrolizumab continues to demonstrate promising survival trends with durable responses in first-line cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma (la/mUC).

New data from the EV-103 dose escalation/cohort A are presented at the American Society of Clinical Oncology 2023 Annual Meeting.

EV plus pembrolizumab has shown a manageable safety profile and promising antitumor activity in EV-103 dose escalation/cohort A and cohort K.

Shilpa Gupta, MD, and colleagues reported updated safety, efficacy, and survival data, as well as subsequent therapies for dose escalation/cohort A after nearly 4 years of follow-up. Patients initially received 3-week cycles of EV (1.25 mg/kg on days 1 and 8) in combination with pembrolizumab (day 1).

The primary end point was safety and tolerability, while secondary end points included confirmed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

As of September 2022, Dr. Gupta and colleagues reported that 45 patients with first-line cisplatin-ineligible la/mUC received treatment. All patients discontinued treatment and 18 patients remain on the study. After a median follow-up of 47 months, the confirmed ORR after a median of 9 cycles was 73% (95% CI, 58.1-85.4). Median PFS was 12.7 months (95% CI, 6.11 to not reached) with a 12-month PFS of 55.0% (95% CI, 38.84-68.85). Median OS was 26.1 months (95% CI, 15.51 to not reached) with a 12-month OS of 83.4% (95% CI, 68.25-91.72).

The most commonly reported treatment-related adverse events (trAEs) for EV were skin reactions (66.7%), peripheral neuropathy (62.2%), and ocular disorders (40.0%), while the most common trAEs of special interest for pembrolizumab were severe skin reactions (24.4%), pneumonitis (8.9%), colitis (6.7%), and hypothyroidism (6.7%).

Additionally, researchers shared that 60% of patients received subsequent cancer-related therapies, including systemic therapy (48.9%), surgery (8.9%), and palliative radiotherapy (8.9%). The most common second-line therapies were pembrolizumab (17.8%), carboplatin-based therapy (11.1%), and EV (6.7%).

“These results are concordant with previously reported dose escalation/cohort A data by investigator assessment and support the evaluation of EV plus pembrolizumab in ongoing phase 3 studies in UC,” study authors concluded.