Pembrolizumab + Enfortumab Vedotin + Surgery for Bladder Cancer

Recruiting in Palo Alto (17 mi)

+249 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Merck Sharp & Dohme Corp.

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for adults with muscle-invasive bladder cancer who can't take cisplatin or choose not to. They must be able to undergo surgery, have good organ function, and an ECOG status of 0-2. Women must use effective contraception or abstain from sex if they're of childbearing potential; men also have similar requirements if receiving enfortumab vedotin.

Inclusion Criteria

A WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention

My bladder cancer has not spread, as confirmed by scans.

My organs are working well.

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Exclusion Criteria

My diabetes is not under control.

I have had radiation therapy to my bladder before.

I have received a transplant from another person.

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Treatment Details

Interventions

Enfortumab Vedotin (Monoclonal Antibodies)
Pembrolizumab (Monoclonal Antibodies)
Radical Cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND] (Surgery)

Trial OverviewThe study tests perioperative pembrolizumab (a drug) alone or combined with enfortumab vedotin (another drug), plus bladder removal surgery against surgery alone. The goal is to see which approach leads to better survival without the disease progressing.

Participant Groups

3Treatment groups

Experimental Treatment

Active Control

Group I: Arm C: Enfortumab Vedotin + Pembrolizumab + SurgeryExperimental Treatment1 Intervention

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.

Group II: Arm A: Pembrolizumab + SurgeryExperimental Treatment2 Interventions

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.

Group III: Arm B: Surgery aloneActive Control1 Intervention

Participants receive standard of care surgery alone.

Enfortumab Vedotin is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Padcev for: