cisplatin in cisplatin-eligible MIBC¶

Abstract: LBA630 · Session: Oral Abstract Session — Urothelial / Bladder, Day 2 (Fri Feb 27, 2026), Moscone West · Embargo: lifted on presentation

Headline: Perioperative EV + pembro produced an EFS HR of 0.53 (95% CI 0.41–0.70, p<0.001) vs gem/cis with cystectomy, with 24-month OS already separating (86.9% vs 81.3%) — the regimen displaces cisplatin chemo as the new perioperative standard in cisplatin-eligible MIBC.

At a glance¶

Sponsor: Merck (pembrolizumab) + Pfizer / Astellas (enfortumab vedotin)
PI / presenter: Matthew Galsky (Mount Sinai) — presented the LBA630 oral
NCT ID: NCT04700124
Phase: 3
Design: Open-label, 1:1 randomization, perioperative (neoadjuvant + adjuvant) EV + pembro vs neoadjuvant gem/cis → cystectomy
N: ~857 randomized, cisplatin-eligible MIBC
Primary endpoint(s): EFS (event-free survival) and pCR; key secondary OS
Comparator: Gemcitabine + cisplatin neoadjuvant (the prior NCCN standard)
Indication: Muscle-invasive urothelial carcinoma (MIBC), cisplatin-eligible
Line: Perioperative (curative intent)

Headline result¶

EFS HR 0.53 (95% CI 0.41–0.70, p<0.001), with the pCR advantage already foreshadowed at SUO 2025. 24-month OS 86.9% (EV+pembro) vs 81.3% (gem/cis) — interim, with OS-mature follow-up expected at ASCO 2026 main meeting (May 29–Jun 2). Safety was consistent with the EV+pembro 1L mUC profile (KEYNOTE-A39 / EV-302); cystectomy completion rates were preserved.

Mechanism / class¶

Enfortumab vedotin: Nectin-4-directed ADC with MMAE payload (Pfizer/Astellas/Seagen legacy). Pembrolizumab: anti-PD-1. The combination is the same backbone that displaced platinum chemo in metastatic urothelial via EV-302 (ASCO 2023 Plenary, NEJM 2024). KEYNOTE-B15 / EV-304 moves the regimen from metastatic into curative-intent perioperative MIBC.

Trial design deep dive¶

Study architecture. Open-label Ph3, 1:1 randomization, ~857 cisplatin-eligible MIBC patients. Experimental arm received neoadjuvant EV + pembro (typically 4 cycles) → radical cystectomy + pelvic lymph node dissection → adjuvant EV + pembro continuation; control arm received neoadjuvant gemcitabine + cisplatin → cystectomy with no adjuvant systemic therapy by protocol. Stratification factors per ClinicalTrials.gov: PD-L1 status, geographic region, and renal function / cisplatin-fitness category. Blinding: open-label (chemotherapy backbone is not maskable).

Endpoint definitions. Dual primary endpoints: pathologic complete response (pCR, ypT0N0 at cystectomy by central pathology) and event-free survival (EFS, defined as time from randomization to disease progression precluding cystectomy, local/distant recurrence, or death). Key secondary: OS, pCR by PD-L1, safety, PRO.

Key subgroup analyses. - PD-L1 CPS high vs low — EFS benefit reportedly consistent across CPS strata (magnitude TBD in abstract). - Clinical T stage (cT2 vs cT3/T4a) — benefit preserved in higher-stage disease. - Node-positive (cN+) subset — TBD; cystectomy completion rates a key safety readout. - Age / renal-function subgroups within cisplatin-eligible band — TBD.

Comparator context. Gem/cis neoadjuvant has been NCCN-preferred for cisplatin-eligible MIBC since the SWOG-8710 / EORTC 30994 era; HR 0.53 represents the first head-to-head displacement of platinum chemo in this setting.

FDA / regulatory implications. Merck sNDA filing for pembro perioperative label expansion anticipated H1 2026; Pfizer/Astellas parallel EV sBLA filing expected. Priority review and Breakthrough Therapy designation plausible given EFS magnitude. NCCN bladder panel anticipated to elevate the regimen to preferred within 60–90 days of filing acceptance.

Discussant takeaway¶

Discussant (Thomas Powles, Barts) framed it as the "cisplatin displacement moment" for MIBC — the first regimen to clear gem/cis on EFS in a head-to-head perioperative Ph3. Andrea Apolo (NCI) reinforced the OS-direction signal and flagged the cisplatin-ineligible population (covered by VOLGA / NIAGARA) as the next frontier.

Practice-changing verdict¶

Yes. NCCN bladder guidelines anticipated to add perioperative EV+pembro as preferred regimen in cisplatin-eligible MIBC within 60–90 days. FDA sNDA filing expected H1 2026. The major open questions: cystectomy-sparing potential in cCR cases, and how this reads through to cisplatin-ineligible disease.

Cross-links¶

ASCO 2026 main: OS-mature update expected (forward-looking)
ESMO 2026: subgroup analyses / biomarker readouts likely
AACR 2026 GU sessions: Nectin-4 / ADC mechanism work
Other ASCO GU 2026 trials: IMvigor011 (ctDNA-guided adjuvant atezo); NIAGARA biomarker analyses