Trial Results Support Ongoing Investigation of Enfortumab Vedotin-ejfv, Pembrolizumab for First-Line Advanced Urothelial Cancer

New data from the phase 1b/2 EV-103 clinical trial cohort K support ongoing research into the use of enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab, and enfortumab vedotin-ejfv alone in patients with unresectable locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based chemotherapy.

Results demonstrated a 64.5% confirmed objective response rate (ORR) in patients treated with the investigational combination. The data were highlighted in a late-breaking presentation at the European Society for Medical Oncology Congress 2022.

“Nearly 65% of patients who were treated with enfortumab vedotin and pembrolizumab responded to this combination, with almost 11% showing no detectable cancer following treatment,” said Margorie Green, senior vice president and head of late-stage development at Seagen, in a press release. “These study results represent an encouraging finding for people with advanced urothelial cancer who are not eligible for cisplatin treatment.”

The confirmed ORR was the primary endpoint of cohort K, with 10.5% of patients experiencing a complete response and 53.9% of patients experiencing a partial response. The median duration of response (DOR) was not reached.

All-grade treatment-related adverse events (TRAEs) of special interest for enfortumab vedotin-ejfv in combination with pembrolizumab were skin reactions (67.1%), peripheral neuropathy (60.5%), ocular disorders (26.3%), hyperglycemia (14.5%), and infusion-related reactions (3.9%). Pembrolizumab AEs of special interest were consistent with previously observed safety data from monotherapy with the exception of severe skin reactions.

Cohort K of the trial also included a monotherapy arm in which 73 patients were treated with enfortumab vedotin-ejfv alone, although the study was not designed to support a formal comparison between the 2 arms. Results from this cohort showed a 45.2% confirmed ORR, with 4.1% of patients experiencing a complete response and 41.1% of patients experiencing a partial response. The median DOR was 13.2 months.

All-grade TRAEs of special interest for enfortumab vedotin-ejfv were peripheral neuropathy (54.8%), skin reactions (45.2%), ocular disorders (28.8%), hyperglycemia (11%), and infusion-related reactions (5.5%).

“We’re pleased that this combination provided a meaningful benefit to this group of advanced bladder cancer patients in this study, and we will continue to investigate enfortumab vedotin plus pembrolizumab through our collaboration,” said Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, in the press release.

Additional secondary endpoints in Cohort K included progression-free survival (PFS) and overall survival (OS). Among patients treated with both enfortumab vedotin-ejfv and pembrolizumab, median PFS was not reached, and median OS was 22.3 months. Among those treated with enfortumab vedotin-ejfv alone, median PFS was 8 months and median OS was 21.7 months.

TRAEs of any grade that occurred in more than 20% of patients treated with enfortumab vedotin-ejfv alone or in combination with pembrolizumab were fatigue, peripheral sensory neuropathy, alopecia, rash maculo-papular, pruritus, dysgeusia, decreased weight, diarrhea, decreased appetite, nausea, and dry eye.

In February 2020, the FDA granted Breakthrough Therapy Designation to enfortumab vedotin-ejfv in combination with pembrolizumab for patients with unresectable la/mUC who are ineligible to receive cisplatin-based chemotherapy in the first-line setting. The designation is based on results from the dose-escalation cohort and expansion cohort A in the phase 1b/2 EV-103 trial.

“We’re encouraged by these positive findings from the combination of enfortumab vedotin and pembrolizumab in people with advanced urothelial cancer who historically have had limited treatment options in the first-line setting, and we intend to discuss these results with regulatory authorities,” said Ahsan Arozullah, MD, MPH, senior vice president and head of development therapeutic areas at Astellas, in the press release.

REFERENCE

Seagen, Astellas, and Merck Announce Results of Clinical Trial Investigating Padcev (enfortumab vedotin-ejfv) with Keytruda (pembrolizumab) and Padcev as Monotherapy in First-Line Advanced Urothelial Cancer. News release. Merck; September 12, 2022. Accessed September 13, 2022. https://www.merck.com/news/seagen-astellas-and-merck-announce-results-of-clinical-trial-investigating-padcev-enfortumab-vedotin-ejfv-with-keytruda-pembrolizumab-and-padcev-as-monotherapy-in-first-line-advanced/