In a potentially practice-changing development for oncology, Merck announced that its Phase 3 KEYNOTE-B15 trial (also known as EV-304) has met its primary and key secondary endpoints. The study demonstrated that the combination of KEYTRUDA® (pembrolizumab) and the antibody-drug conjugate Padcev® (enfortumab vedotin-ejfv) significantly improved survival outcomes for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC) when used as a perioperative treatment.
A New Standard for High-Risk Patients
The trial evaluated the efficacy of the KEYTRUDA plus Padcev regimen administered both before (neoadjuvant) and after (adjuvant) surgery, compared to the current standard of care—neoadjuvant chemotherapy (gemcitabine plus cisplatin) followed by surgery.
Results showed a statistically significant and clinically meaningful improvement in:
- Event-Free Survival (EFS): The time patients lived without disease progression or recurrence.
- Overall Survival (OS): The total length of time patients lived following treatment.
- Pathologic Complete Response (pCR): The rate at which no traces of cancer were found in tissue samples following neoadjuvant therapy and surgery.
Read More: Merck’s Application for KEYTRUDA® (pembrolizumab) Receives US FDA’s Priority Review
Addressing an Unmet Medical Need
Bladder cancer affected more than 600,000 people globally in 2022, with approximately 25% of cases diagnosed as muscle-invasive. While neoadjuvant cisplatin-based chemotherapy followed by surgery is the current standard, nearly half of those patients eventually experience cancer recurrence.
The KEYNOTE-B15 trial enrolled 808 patients, randomizing them to receive either the experimental combination therapy or the standard chemotherapy protocol. By treating the cancer early and aggressively both before and after surgical intervention, researchers aim to eliminate micrometastases and prevent the disease from returning.
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Safety and Regulatory Next Steps
The safety profile for the combination was reported as consistent with previous studies for both KEYTRUDA and Padcev, with no new safety signals identified. Common side effects associated with this combination in previous trials have included rash, peripheral neuropathy, and fatigue.
Merck, in collaboration with Pfizer and Astellas, plans to share these results with global regulatory authorities to seek approval for this new indication. Detailed data from the KEYNOTE-B15 trial will also be presented at an upcoming medical meeting.
This success builds upon the combination’s previous approvals for locally advanced or metastatic urothelial cancer and for cisplatin-ineligible MIBC patients. If approved for cisplatin-eligible patients, the regimen could become the first immunotherapy-plus-ADC combination to extend survival in the perioperative setting for this specific population.
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