Merck has revealed that the FDA has granted priority review to a supplemental Biologics License Application (sBLA) submitted for KEYTRUDA, Merck's anti-PD-1 therapy, in conjunction with Padcev (enfortumab vedotin-ejfv), an antibody-drug conjugate. The application seeks approval for treating adult patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Under the FDA's Real-Time Oncology Review (RTOR) program, this application is being expedited to enhance the efficiency of the review process, ensuring prompt availability of treatments for patients. The FDA has set a target action date of May 9, 2024, under the Prescription Drug User Fee Act (PDUFA).
The sBLA is grounded in data from the Phase 3 KEYNOTE-A39 trial (EV-302), conducted in collaboration with Seagen and Astellas. This trial demonstrated that KEYTRUDA plus enfortumab vedotin exhibited a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) compared to chemotherapy (gemcitabine plus cisplatin or carboplatin). These findings, presented as late-breaking data at the European Society for Medical Oncology Congress 2023, revealed that KEYTRUDA plus enfortumab vedotin significantly improved OS, with a 53% reduction in the risk of death compared to chemotherapy (median OS, 31.5 months vs. 16.1 months, respectively), representing an improvement of more than 15 months (HR=0.47 [95% CI, 0.38-0.58]; p<0.00001).
KEYTRUDA plus enfortumab vedotin also demonstrated 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). Consistent results were observed across all pre-defined subgroups, including patients eligible or not for cisplatin-based chemotherapy, those with varying levels of PD-L1 expression (Combined Positive Score [CPS] ≥10 or CPS <10), and patients with or without liver metastases.
The KEYNOTE-A39 trial is positioned as the foundation for global regulatory submissions for treating adult patients with la/mUC and serves as the confirmatory trial for the current U.S. accelerated approval of KEYTRUDA plus enfortumab vedotin for adult patients with la/mUC ineligible for cisplatin-containing chemotherapy, based on data from the KEYNOTE-869 trial (EV-103) dose escalation cohort, Cohort A, and Cohort K.
Merck, in collaboration with Seagen and Astellas, continues to evaluate this combination in an extensive clinical development program, including two Phase 3 clinical trials in muscle-invasive bladder cancer (KEYNOTE-B15 and KEYNOTE-905).
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