Keytruda (pembrolizumab) + Padcev (enfortumab vedotin-ejfv) reduced risk of death by more than half versus chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer

Findings from its first pre-specified analysis showed that Keytruda plus enfortumab vedotin significantly improved overall survival (OS), reducing the risk of death by 53% compared to chemotherapy (median OS, 31.5 months vs. 16.1 months, respectively), an improvement in median OS of more than 15 months; (HR=0.47 [95% CI, 0.38-0.58]; p<0.00001). keytruda plus enfortumab vedotin also achieved a significant improvement in progression-free survival (pfs), reducing the risk of disease progression or death by 55% (median pfs, 12.5 months vs. 6.3 months, respectively); (hr="0.45" [95% ci, 0.38-0.54]; p><0.00001).

Results were consistent across all predefined subgroups, including patients who may or may not be eligible for treatment with cisplatin-based chemotherapy, patients whose tumors expressed both high (Combined Positive Score [CPS] greater than 10) or low (CPS less than c10) levels of PD-L1, and patients with or without liver metastases. These late-breaking data are being presented for the first time during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2023 (abstract #LBA6) and are included in the official ESMO Press Briefing.

“As an investigator in this trial and a physician who treats patients with advanced urothelial cancer, I can attest to the challenging nature of this diagnosis for patients and their families,” said Dr. Thomas Powles, KEYNOTE-A39 primary investigator, professor of Genitourinary Oncology and director, Barts Cancer Center. “These results, showing a 53% reduction in the risk of death for the combination compared to chemotherapy, are striking and may open a new chapter for the treatment of these patients diagnosed with advanced urothelial carcinoma, who face an urgent need for new therapies.”

“Our goal is to extend the lives of patients with cancer, and these unambiguous survival findings from KEYNOTE-A39 showing that Keytruda plus enfortumab vedotin reduced the risk of death by half when compared to chemotherapy are important to patients and the medical community alike,” said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “These results – the first positive Phase III results combining a PD-1 inhibitor and an antibody-drug conjugate in this patient population – have the potential to change the treatment paradigm for previously untreated patients with advanced urothelial cancer regardless of whether patients are eligible or ineligible for cisplatin.”

The Phase III KEYNOTE-A39 trial is intended to serve as the basis for global regulatory submissions and as the confirmatory trial for the current U.S. accelerated approval of Keytruda plus enfortumab vedotin as first-line treatment for patients with la/mUC who are not eligible to receive cisplatin-containing chemotherapy. The accelerated approval is based on data from the KEYNOTE-869 trial (also known as EV-103) dose escalation cohort, Cohort A and Cohort K. As announced, data spanning more than 15 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the ESMO Congress 2023.