Astellas and Pfizer’s Padcev-Keyrtruda combo gains FDA Priority Review for muscle-invasive bladder cancer

Astellas Pharma Inc. (TSE: 4503), headquartered in Tokyo, and Pfizer Inc. (NYSE: PFE), headquartered in New York, announced that the US FDA has granted Priority Review to a supplemental Biologics License Application (sBLA) to the Nectin-4-directed antibody-drug conjugate (ADC) Padcev (enfortumab vedotin-ejfv). The sBLA is for Padcev’s use in combination with Keytruda (pembrolizumab) as perioperative treatment for muscle-invasive bladder cancer (MIBC) regardless of cisplatin eligibility. The filing also covers Keytruda QLEX (pembrolizumab and berahyaluronidase alfa-pmph), a subcutaneous co-formulation. The US FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of August 17, 2026.

The sBLA expands on an existing approval granted in November 2025, under which the combination is indicated as perioperative treatment for cisplatin-ineligible patients with MIBC. The current submission seeks to remove the cisplatin-eligibility restriction, extending the potential indication to the broader MIBC population.

The supporting data package draws on two Phase III trials. The pivotal dataset for the cisplatin-eligible expansion comes from the EV-304/KEYNOTE-B15 trial (NCT04700124), an open-label, randomized, controlled study comparing perioperative enfortumab vedotin plus pembrolizumab against neoadjuvant gemcitabine and cisplatin chemotherapy in patients with MIBC eligible for cisplatin-based treatment. Results presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) showed a 47% reduction in the risk of tumor recurrence, progression, or death — the trial’s primary endpoint of event-free survival (EFS) — and a 35% reduction in the risk of death compared with standard-of-care chemotherapy. The combination produced a pathological complete response (pCR) rate of 55.8% versus 32.5% in the chemotherapy arm at the time of surgery. The trial’s primary EFS endpoint was defined as the time from randomization to progression precluding radical cystectomy (RC), failure to undergo RC with residual disease, gross residual disease at surgery, local or distant recurrence per blinded independent central review, or death from any cause. No new safety signals were identified relative to the established profile of the combination.

The cisplatin-ineligible component of the sBLA package rests on data from KEYNOTE-905/EV-303, presented at ESMO 2025 and published concurrently in the New England Journal of Medicine. That Phase III trial enrolled cisplatin-ineligible patients with MIBC and compared perioperative enfortumab vedotin plus pembrolizumab against radical cystectomy alone. EFS favored the combination with a hazard ratio of 0.40 (95% CI: 0.28–0.57; p < 0.0001), with a pCR rate of 57.1% versus 8.6% in the control arm, and a downstaging rate of 65.9% versus 12.6%. Those data formed the basis of the November 2025 approval in the cisplatin-ineligible population and now contribute to the broader perioperative sBLA.

Research context

The perioperative setting in MIBC has historically been contested terrain for novel agents. Checkpoint inhibitor monotherapy trials in the neoadjuvant setting, including studies of atezolizumab and nivolumab, did not produce results that altered the standard of care. The combination of an ADC with a PD-1 inhibitor represents a mechanistically distinct approach: enfortumab vedotin delivers the microtubule-disrupting payload monomethyl auristatin E (MMAE) selectively to Nectin-4-expressing cells, which are highly expressed in bladder cancer, while pembrolizumab provides checkpoint blockade. Unlike platinum-based regimens, the combination does not require renal function thresholds that exclude a meaningful share of the MIBC population, which is the basis for the cisplatin-eligibility-agnostic framing of the current sBLA.

The combination already holds approvals for locally advanced or metastatic urothelial cancer (la/mUC) in the US, EU, Japan, and other markets, and enfortumab vedotin retains a monotherapy indication for previously treated la/mUC patients. The perioperative MIBC program therefore builds on a well-characterized safety and efficacy profile across multiple urothelial cancer settings. Known toxicities include peripheral neuropathy, skin reactions — including a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis — hyperglycemia, and pneumonitis/interstitial lung disease, each of which requires monitoring and dose management per the current prescribing information.

The August 2026 PDUFA date positions a potential decision ahead of major oncology congresses in the second half of 2026. Astellas and Pfizer have indicated they plan to discuss the EV-304 data with additional global health authorities for potential regulatory filings outside the US. If approved in the broader MIBC indication, the combination would hold perioperative coverage across the full MIBC population — cisplatin-eligible and ineligible alike — a position no other regimen currently occupies in the US market.