FDA approves pembrolizumab/enfortumab vedotin for frontline urothelial cancer

The FDA has granted an accelerated approval to the combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy.^1,2

An accelerated approval means that continued approval of the combination is eventually contingent on a confirmatory trial validating the regimen’s efficacy.

The approval was supported by results from combined dose escalation/cohort A and cohort K of the phase 1b /2 EV-103 trial (KEYNOTE-869; NCT03288545). An accelerated approval means that continued approval of the combination is eventually contingent on a confirmatory trial validating the regimen’s efficacy.

"Advanced-stage urothelial cancer is aggressive and associated with devastating outcomes," David R. Epstein, chief executive officer, Seagen, stated in a press release.² "In the EV-103 clinical trial, the use of Padcev in combination with pembrolizumab resulted in confirmed and durable tumor responses in over two-thirds of patients with advanced bladder cancer. Global enrollment in the confirmatory trial, EV-302, is complete. With this approval, we look forward to providing a new treatment option that helps address a high unmet need for these patients."

The dose escalation cohort and cohort A of EV-103 were single-arm cohorts in which all patients received enfortumab vedotin plus pembrolizumab. Cohort K randomized patients to enfortumab vedotin plus pembrolizumab or enfortumab vedotin alone.

The FDA efficacy analysis included 121 patients from these arms who had been treated with the combination regimen. These patients were systemic therapy–naive in the locally advanced or metastatic setting and were not eligible to receive cisplatin-containing chemotherapy.

The primary efficacy outcome was objective response rate (ORR) by RECIST v1.1 criteria. The ORR in the efficacy population was 68% (95% CI, 58.7-76.0). Of the responders, 12% had a complete response, and 55% of patients had a partial response.

In the dose escalation cohort + cohort A, the median duration of response was 22.1 months (range, 1.0+ to 46.3+). In cohort K the median duration of response was not reached (range, 1.2 to 24.1+).

Regarding safety, adverse events occurring in at least 20% of patients included, glucose increased (74%), aspartate aminotransferase increased (73%), rash (71%), hemoglobin decreased (69%), creatinine increased (69%), peripheral neuropathy (65%), lymphocytes decreased (64%), fatigue (60%), alanine aminotransferase increased (60%), sodium decreased (60%), lipase increased (59%), albumin decreased (59%), alopecia (52%), phosphate decreased (51%), decreased weight (48%), diarrhea (45%), pruritus (40%), decreased appetite (38%), nausea (36%), dysgeusia (35%), potassium decreased (35%), neutrophils decreased (32%), urinary tract infection (30%), constipation (27%), potassium increased (27%), calcium increased (27%), peripheral edema (26%), dry eye (25%), dizziness (23%), arthralgia (23%), and dry skin (21%).

"The accelerated approval for the combination of Padcev and pembrolizumab marks an important milestone for the approximately 8,000 to 9,000 patients in the United States with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy," Ahsan Arozullah, MD, MPH, senior vice president, head of oncology development, Astellas, said in the press release.² "This patient population now has an additional treatment option to treat advanced bladder cancer at first diagnosis of metastatic disease."

References

1. FDA grants accelerated approval to enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial carcinoma. Published online and accessed April 3, 2023. https://bit.ly/3MdWuAJ

2. FDA Grants Accelerated Approval for PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) for First-Line Treatment of Locally Advanced or Metastatic Urothelial Cancer. Published online and accessed April 3, 2023. https://prn.to/3KvpR0n