FDA approves expanded indication for Keytruda (pembrolizumab) + Padcev (enfortumab vedotin-ejfv) for the first-line treatment of adult patients with locally advanced or metastatic urothelial cancer. -Merck Inc., + Pfizer,

The approval is based on data from the Phase III KEYNOTE-A39 trial (also known as EV-302) in 886 patients with locally advanced or metastatic urothelial cancer, which was conducted in a research collaboration with Pfizer (previously Seagen) and Astellas. In the trial, Keytruda plus enfortumab vedotin demonstrated a statistically significant improvement in the trial’s major efficacy endpoints of overall survival (OS) and progression-free survival (PFS) versus platinum-based chemotherapy (gemcitabine plus cisplatin or carboplatin). Keytruda plus enfortumab vedotin reduced the risk of death by 53% (HR=0.47 [95% CI, 0.38-0.58]; p<0.0001) versus platinum-based chemotherapy. median os was 31.5 months (95% ci, 25.4-not reached) for keytruda plus enfortumab vedotin versus 16.1 months (95% ci, 13.9-18.3) for platinum-based chemotherapy. keytruda plus enfortumab vedotin reduced the risk of disease progression or death by 55% (hr="0.45" [95% ci, 0.38-0.54]; p><0.0001) versus platinum-based chemotherapy. median pfs was 12.5 months (95% ci, 10.4-16.6) for keytruda plus enfortumab vedotin versus 6.3 months (95% ci, 6.2-6.5) for platinum-based chemotherapy.></0.0001)></0.0001)>

The trial also demonstrated a statistically significant improvement in objective response rate (ORR) in patients randomized to receive Keytruda plus enfortumab vedotin compared with patients randomized to receive platinum-based chemotherapy.

The ORR was 68% (95% CI, 63-72) for Keytruda plus enfortumab vedotin versus 44% (95% CI, 40-49) for platinum-based chemotherapy (p<0.0001). for keytruda plus enfortumab vedotin, the complete response (cr) rate was 29% and the partial response (pr) rate was 39%, and for platinum-based chemotherapy, the cr rate was 12% and the pr rate was 32%. efficacy results (os, pfs and orr) were consistent across all stratified patient subgroups.></0.0001).>

Immune-mediated adverse reactions , which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda. Based on the severity of the adverse reaction, Keytruda should be withheld or permanently discontinued and corticosteroids administered if appropriate. Keytruda can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman.

“Advanced bladder cancer is a common cause of cancer-related death,” said Dr. Thomas Powles, primary investigator of KEYNOTE-A39, professor of Genitourinary Oncology and director, Barts Cancer Center. “The overall survival benefit seen in the KEYNOTE-A39 trial demonstrates the potential for Keytruda in combination with enfortumab vedotin to impact the first-line treatment of patients with locally advanced or metastatic urothelial cancer. In my opinion, this is a meaningful advancement over platinum-based chemotherapy in the systemic treatment of these patients.”

“The landmark findings from the KEYNOTE-A39 trial are the first positive Phase III results combining a PD-1 inhibitor and an antibody-drug conjugate as first-line treatment for patients with locally advanced or metastatic urothelial cancer. This combination has the potential to change the treatment paradigm in advanced urothelial cancer and to help these patients live longer,” said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Today’s approval reinforces the value of advancing novel combinations with Keytrruda to provide these patients with a treatment option.”