Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Participants Who Are Cisplatin-ineligible or Decline Cisplatin With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)

Conditions

• Urinary Bladder Cancer, Muscle-invasive

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Pembrolizumab — DRUG
  Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
• Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]) — PROCEDURE
  Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.
• Enfortumab Vedotin — DRUG
  Enfortumab vedotin 1.25 mg/kg by intravenous (IV) infusion, given on Days 1 and 8 of each 21-day cycle.

Study Details

This is a study of perioperative pembrolizumab or enfortumab vedotin in combination with pembrolizumab in participants who are cisplatin-ineligible or decline cisplatin with muscle-invasive bladder cancer (MIBC). The primary hypothesis is that perioperative pembrolizumab plus radical cystectomy (RC) plus pelvic lymph node dissection (PLND) and perioperative enfortumab vedotin in combination with pembrolizumab plus RC+PLND will achieve superior event-free survival (EFS) compared with RC+PLND alone. With Amendment 5, outcome measures for programmed cell death ligand 1 (PD-L1) combined positive score (CPS) were removed. With Amendment 8, the primary outcome measure of pathologic complete response (pCR) rates was changed to a secondary outcome measure.

Key Dates

Start date

Jul 24, 2019

Status verified

Aug 2025

Primary completion

Jun 6, 2025

Completion

Dec 15, 2027

Study Design

Enrollment

595 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A: Pembrolizumab + Surgery
  Participants receive 3 preoperative cycles of pembrolizumab, followed by standard of care surgery, followed by 14 cycles of postoperative pembrolizumab. Each cycle is 21 days.
• Active Comparator: Arm B: Surgery alone
  Participants receive standard of care surgery alone.
• Experimental: Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery
  Participants receive 3 preoperative cycles of enfortumab vedotin + pembrolizumab, followed by standard of care surgery, followed by 6 cycles of postoperative enfortumab vedotin + pembrolizumab, followed by 8 cycles of pembrolizumab alone. Each cycle is 21 days.

Primary Outcome Measure

Event-Free Survival (EFS) between Arm C and Arm B [ Time Frame: Up to approximately 6.75 years ]

Locations (39)

Related coverage on Hipa.ai

• Pembrolizumab Trial for Muscle-Invasive Bladder Cancer Reaches Primary…
  Pembrolizumab · Jun 6, 2025 · ClinicalTrials.gov

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