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Active, not recruitingNCT03924895Updated Jun 30, 2026Results posted

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)

A Phase 3 interventional study of Pembrolizumab and Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]) in Urinary Bladder Cancer, Muscle-invasive, sponsored by Merck Sharp & Dohme LLC. Active, not recruiting at 242 sites in 28 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-30.

Sponsored by Merck Sharp & Dohme LLC · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
595
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Urinary Bladder Cancer, Muscle-invasive

Keywords

  • Muscle-Invasive Bladder Cancer (MIBC)
  • Enfortumab vedotin (EV)
  • Pembrolizumab (MK-3475)
03

In context

Urinary Bladder Neoplasms

1,616 studies on the registry are indexed under Urinary Bladder Neoplasms; 421 are open to participants now.

This study's enrollment of 595 is above the median of 60 across 1,163 interventional studies indexed under Urinary Bladder Neoplasms.

Browse Urinary Bladder Neoplasms studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Have a histologically confirmed diagnosis of urothelial carcinoma/muscle-invasive bladder cancer [MIBC] (cT2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology to be confirmed by Blinded Independent Central Review (BICR) (central pathology and/or imaging).
  • Clinically nonmetastatic bladder cancer determined by imaging
  • Eligible for radical cystectomy (RC) + pelvic lymph node dissection (PLND), and agreement to undergo curative intent standard RC + PLND (including prostatectomy if applicable)

  • Ineligible for treatment with cisplatin, as defined by meeting at least one of the following criteria OR be eligible for treatment with cisplatin but decline treatment with cisplatin-based chemotherapy:

    • Impaired renal function with measured or calculated creatinine clearance (CrCl) 30 to 59 mL/min (calculated by Cockcroft-Gault method, Modification of Diet of Renal Disease [MDRD] equations, or measured by 24-hour urine collection)
    • Eastern Cooperative Oncology Group (ECOG) Performance Status 2
    • Common Terminology Criteria for Adverse Events (CTCAE) v.4 Grade ≥2 audiometric hearing loss
    • New York Heart Association (NYHA) Class III heart failure
  • Transurethral resection (TUR) of a bladder tumor that is submitted for central pathology assessment and adequate to determine urothelial histology and PD-L1 expression assessment
  • ECOG performance status of 0, 1, or 2
  • Adequate organ function
  • A male participant is eligible to participate if he agrees to use contraception and refrain from donating sperm during the intervention period and for at least 180 days after the last dose of enfortumab vedotin. If the male participants are receiving pembrolizumab only or undergoing surgery only, there are no contraception requirements
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a (woman of childbearing potential) WOCBP or a WOCBP who agrees to use a highly effective contraceptive method or be abstinent from heterosexual intercourse (as their preferred and usual lifestyle) during the intervention period and for at least 120 days after the last dose of pembrolizumab and at least 180 days after the last dose of enfortumab vedotin; whichever comes last. A female participant must agree not to donate eggs during this period as well
  • A WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention

Exclusion criteria

Exclusion Criteria:

  • Known additional nonurothelial malignancy that is progressing or has required active anticancer treatment ≤3 years of study randomization, with certain exceptions
  • Has ≥ N2 or metastatic disease (M1) as identified by imaging
  • Received any prior systemic treatment, chemoradiation, and/or radiation therapy for muscle-invasive bladder cancer (MIBC) or non-muscle invasive bladder cancer (NMIBC)
  • Received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor
  • Received prior systemic anticancer therapy including investigational agents within 3 years prior to randomization
  • Received any prior radiotherapy to the bladder
  • Received a partial cystectomy of the bladder to remove any non-muscle-invasive bladder cancer (NMIBC) or MIBC
  • Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  • Current participation in or participation in a study of an investigational agent or use of an investigational device within 4 weeks prior to the first dose of study intervention
  • Ongoing sensory or motor neuropathy Grade 2 or higher
  • Diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
  • Hypersensitivity to monoclonal antibodies (including pembrolizumab) and/or any of their excipients
  • Severe hypersensitivity (≥ Grade 3) to enfortumab vedotin or any excipient contained in the drug formulation of enfortumab vedotin
  • Active keratitis or corneal ulcerations. Participants with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator
  • Active autoimmune disease that has required systemic therapy in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic therapy and is allowed
  • Has uncontrolled diabetes
  • History of (noninfectious) pneumonitis that required steroids, or current pneumonitis
  • Active infection requiring systemic therapy
  • Has had an allogeneic tissue/solid organ transplant
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
595 participants (actual)

Study 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.

    Drug: Pembrolizumab · Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])

  • Active comparator
    Arm B: Surgery alone

    Participants receive standard of care surgery alone.

    Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])

  • 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.

    Drug: Enfortumab Vedotin

Interventions

  • DrugPembrolizumab

    Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.

    Also known as: KEYTRUDA®, MK-3475

  • ProcedureSurgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])

    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.

  • DrugEnfortumab Vedotin

    Enfortumab vedotin 1.25 mg/kg by intravenous (IV) infusion, given on Days 1 and 8 of each 21-day cycle.

    Also known as: Padcev, ASG-22CE, ASG-22ME

06

What researchers measure

Primary outcomes

  1. Event-Free Survival (EFS) Between Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery and Arm B: Surgery Alone

    EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes radical cystectomy + pelvic lymph node dissection (RC + PLND) surgery, failure to undergo RC + PLND surgery in participants with residual disease and any radiographic disease present (biopsy-proven muscle-invasive bladder cancer \[MIBC\] will be considered an event regardless of radiographic findings), gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy, or death due to any cause.

    Time frame: Up to approximately 53 months

Secondary outcomes

  1. EFS Between Arm A and Arm B

    EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes RC surgery or failure to undergo RC surgery in participants with residual disease (biopsy-proven muscle-invasive bladder cancer \[MIBC\] will be considered an event regardless of radiographic findings), gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy, or death due to any cause.

    Time frame: Up to approximately 6.75 years

  2. Overall Survival (OS) Between Arm C and Arm B

    OS is defined as the time from randomization to death due to any cause.

    Time frame: Up to approximately 7.6 years

  3. OS Between Arm A and Arm B

    OS is defined as the time from randomization to death due to any cause.

    Time frame: Up to approximately 7.6 years

  4. Pathologic Complete Response (pCR) Rate Between Arm C and Arm B

    Pathologic complete response rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as assessed by blind independent central review (BICR).

    Time frame: Up to approximately 53 monhts

  5. pCR Rate Between Arm A and Arm B

    Pathologic complete response rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as determined centrally.

    Time frame: Up to approximately 5.7 years

  6. Disease-Free Survival (DFS)

    DFS is defined as the time from first post-surgery baseline scan until: * local or distant recurrence as assessed by imaging and/or biopsy * Death due to any cause

    Time frame: Up to approximately 6.75 years

  7. Pathologic Downstaging (pDS) Rate Between Arm A and Arm B

    Pathologic downstaging rate is defined as the percentage of participants having pDS. pDS is defined as participants with a tumor classification of \<pT2 (includes pT0, pTis, pTa, pT1) and N0 in examined tissue from RC and PLND.

    Time frame: Up to approximately 5.7 years

  8. Pathologic Downstaging {pDS) Rate Between Arm C and Arm B

    Pathologic downstaging (pDS) is defined as participants with a tumor classification of \<pT2. The pathologic stage \<pT2 includes pT0 (No residual primary tumor found in the tissue examined), pTis (carcinoma in situ; a flat, non-invasive cancer confined to the epithelial lining), pTa (Non-invasive papillary carcinoma limited to the urothelium) pT1 (tumor has invaded the connective tissue beneath the urothelium, but not the muscle layer) and N0 (No cancer found in the examined lymph nodes) in examined tissue from RC and PLND. The \<pT2 category represents a better outcome than participants with residual muscle-invasive disease (pT2 or higher) and/or any nodal involvement (N1/N2). The percentage of participants with pDS is presented.

    Time frame: Up to approximately 53 months

  9. Number of Participants Experiencing Adverse Events (AEs)

    An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

    Time frame: Up to approximately 7.6 years

  10. Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs)

    An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

    Time frame: Up to approximately 1 year

  11. Number of Participants Experiencing Perioperative Complications

    The number of participants who experience perioperative complications will be presented.

    Time frame: Up to approximately 1 year

07

Results

Posted Jun 30, 2026

Participant flow

Participant flow — Overall Study
MilestoneArm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin (EV) + Pembrolizumab + Surgery
Started166259170
Treated166236170
Completed000
Not completed166259170
Withdrew: Death7410837
Withdrew: Withdrawal by subject383
Withdrew: Ongoing89143130

Outcome measures

PrimaryEvent-Free Survival (EFS) Between Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery and Arm B: Surgery Alone

EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes radical cystectomy + pelvic lymph node dissection (RC + PLND) surgery, failure to undergo RC + PLND surgery in participants with residual disease and any radiographic disease present (biopsy-proven muscle-invasive bladder cancer \[MIBC\] will be considered an event regardless of radiographic findings), gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy, or death due to any cause.

Time frame:
Up to approximately 53 months
Reported as:
Median · Months
Event-Free Survival (EFS) Between Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery and Arm B: Surgery Alone
MonthsArm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin + Pembrolizumab + Surgery
Event-Free Survival (EFS) Between Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery and Arm B: Surgery Alone—15.7 (10.3 to 20.5)NA (37.3 to NA)
Statistical analysis
  • Arm B: Surgery Alone vs Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery · Log Rank · p = <0.0001 (One-sided p-value based on log-rank test stratified by cisplatin status (cisplatin-ineligible vs cisplatin eligible but declined), tumor stage (T2N0 vs T3/T4aN0 vs T1-4aN1), and geographic regions (US vs EU vs MOW) with small strata collapsed) · Hazard ratio (hr): 0.40 · 95% CI 0.28 to 0.57
SecondaryEFS Between Arm A and Arm B

EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes RC surgery or failure to undergo RC surgery in participants with residual disease (biopsy-proven muscle-invasive bladder cancer \[MIBC\] will be considered an event regardless of radiographic findings), gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy, or death due to any cause.

Time frame:
Up to approximately 6.75 years

Results for this outcome have not been posted.

SecondaryOverall Survival (OS) Between Arm C and Arm B

OS is defined as the time from randomization to death due to any cause.

Time frame:
Up to approximately 7.6 years

Results for this outcome have not been posted.

SecondaryOS Between Arm A and Arm B

OS is defined as the time from randomization to death due to any cause.

Time frame:
Up to approximately 7.6 years

Results for this outcome have not been posted.

SecondaryPathologic Complete Response (pCR) Rate Between Arm C and Arm B

Pathologic complete response rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as assessed by blind independent central review (BICR).

Time frame:
Up to approximately 53 monhts
Reported as:
Number · Percentage of Participants
Pathologic Complete Response (pCR) Rate Between Arm C and Arm B
Percentage of ParticipantsArm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin + Pembrolizumab + Surgery
Pathologic Complete Response (pCR) Rate Between Arm C and Arm B—8.6 (4.9 to 13.8)57.1 (49.3 to 64.6)
Statistical analysis
  • Arm B: Surgery Alone vs Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery · Miettinen & Nurminen method · p = <0.000001 · Difference in percentage: 48.3 · 95% CI 39.5 to 56.5Arm C: EV+ Pembrolizumab +Surgery vs Arm B: Surgery Alone
SecondarypCR Rate Between Arm A and Arm B

Pathologic complete response rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as determined centrally.

Time frame:
Up to approximately 5.7 years

Results for this outcome have not been posted.

SecondaryDisease-Free Survival (DFS)

DFS is defined as the time from first post-surgery baseline scan until: * local or distant recurrence as assessed by imaging and/or biopsy * Death due to any cause

Time frame:
Up to approximately 6.75 years

Results for this outcome have not been posted.

SecondaryPathologic Downstaging (pDS) Rate Between Arm A and Arm B

Pathologic downstaging rate is defined as the percentage of participants having pDS. pDS is defined as participants with a tumor classification of \<pT2 (includes pT0, pTis, pTa, pT1) and N0 in examined tissue from RC and PLND.

Time frame:
Up to approximately 5.7 years

Results for this outcome have not been posted.

SecondaryPathologic Downstaging {pDS) Rate Between Arm C and Arm B

Pathologic downstaging (pDS) is defined as participants with a tumor classification of \<pT2. The pathologic stage \<pT2 includes pT0 (No residual primary tumor found in the tissue examined), pTis (carcinoma in situ; a flat, non-invasive cancer confined to the epithelial lining), pTa (Non-invasive papillary carcinoma limited to the urothelium) pT1 (tumor has invaded the connective tissue beneath the urothelium, but not the muscle layer) and N0 (No cancer found in the examined lymph nodes) in examined tissue from RC and PLND. The \<pT2 category represents a better outcome than participants with residual muscle-invasive disease (pT2 or higher) and/or any nodal involvement (N1/N2). The percentage of participants with pDS is presented.

Time frame:
Up to approximately 53 months
Reported as:
Number · Percentage of Participants
Pathologic Downstaging {pDS) Rate Between Arm C and Arm B
Percentage of ParticipantsArm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin + Pembrolizumab + Surgery
Pathologic Downstaging {pDS) Rate Between Arm C and Arm B—12.6 (8.1 to 18.5)65.9 (58.2 to 73.0)
Statistical analysis
  • Arm B: Surgery Alone vs Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery · Miettinen & Nurminen Method · p = <0.000001 (p-value is nominal) · Difference in percentage: 53.1 · 95% CI 44.0 to 61.2Arm C: EV+ Pembrolizumab +Surgery vs Arm B: Surgery Alone
SecondaryNumber of Participants Experiencing Adverse Events (AEs)

An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

Time frame:
Up to approximately 7.6 years

Results for this outcome have not been posted.

SecondaryNumber of Participants Discontinuing Study Drug Due to Adverse Events (AEs)

An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

Time frame:
Up to approximately 1 year

Results for this outcome have not been posted.

SecondaryNumber of Participants Experiencing Perioperative Complications

The number of participants who experience perioperative complications will be presented.

Time frame:
Up to approximately 1 year

Results for this outcome have not been posted.

Adverse events

Collected over Up to approximately 69 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm A: Pembrolizumab + Surgery76/166 (45.8%)107/163 (65.6%)143/163 (87.7%)
Arm B: Surgery Alone111/259 (42.9%)94/242 (38.8%)94/242 (38.8%)
Arm C: EV + Pembrolizumab + Surgery38/170 (22.4%)97/167 (58.1%)163/167 (97.6%)
Most frequent serious events
Showing 10 of 213
Most frequent serious events
EventArm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: EV + Pembrolizumab + Surgery
Urinary tract infectionInfections and infestations15/16317/24217/167
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)13/16311/2423/167
Acute kidney injuryRenal and urinary disorders5/1633/2428/167
PyelonephritisInfections and infestations7/1632/2426/167
SepsisInfections and infestations7/1637/2425/167
UrosepsisInfections and infestations3/1638/2427/167
PneumoniaInfections and infestations5/1632/2425/167
HydronephrosisRenal and urinary disorders5/1633/2421/167
Intestinal obstructionGastrointestinal disorders4/1632/2424/167
Postoperative wound infectionInfections and infestations4/1631/2421/167
Most frequent other events
Showing 10 of 48
Most frequent other events
EventArm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: EV + Pembrolizumab + Surgery
PruritusSkin and subcutaneous tissue disorders28/1631/24278/167
AlopeciaSkin and subcutaneous tissue disorders1/1630/24258/167
DiarrhoeaGastrointestinal disorders23/1637/24254/167
FatigueGeneral disorders26/16312/24254/167
AnaemiaBlood and lymphatic system disorders49/16327/24251/167
Decreased appetiteMetabolism and nutrition disorders23/1639/24247/167
DysgeusiaNervous system disorders5/1630/24247/167
ConstipationGastrointestinal disorders23/16318/24244/167
NauseaGastrointestinal disorders21/16316/24243/167
RashSkin and subcutaneous tissue disorders16/1632/24241/167

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Arm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin (EV) + Pembrolizumab + SurgeryTotal
Mean71.8 ± 7.971.9 ± 7.772.1 ± 7.971.9 ± 7.8
Sex: Female, Male
Sex: Female, Male(Participants)Arm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin (EV) + Pembrolizumab + SurgeryTotal
Female366633135
Male130193137460
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin (EV) + Pembrolizumab + SurgeryTotal
Hispanic or Latino315826
Not Hispanic or Latino155231160546
Unknown or Not Reported813223
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Arm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin (EV) + Pembrolizumab + SurgeryTotal
American Indian or Alaska Native0101
Asian16383185
Native Hawaiian or Other Pacific Islander0000
Black or African American1427
White148205132485
More than one race07411
Unknown or Not Reported1416
Cisplatin Status
Cisplatin Status(Participants)Arm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin (EV) + Pembrolizumab + SurgeryTotal
Cisplatin-Ineligible163223142528
Cisplatin-Eligible but Declined3362867
Tumor Clinical Stage
Tumor Clinical Stage(Participants)Arm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin (EV) + Pembrolizumab + SurgeryTotal
T2N012403082
T3/T4aN0150209133492
T1-4aN1410721
Geographic Region
Geographic Region(Participants)Arm A: Pembrolizumab + SurgeryArm B: Surgery AloneArm C: Enfortumab Vedotin (EV) + Pembrolizumab + SurgeryTotal
United States (US)19332173
European Union (EU)7311078261
Most of World (MOW)7411671261
08

Study locations

242 sites
  • University of South Alabama, Mitchell Cancer Institute ( Site 1582)
    Mobile, Alabama 36604, United States
  • CARTI Cancer Center ( Site 1577)
    Little Rock, Arkansas 72205, United States
  • St. Joseph Heritage Healthcare ( Site 0046)
    Fullerton, California 92835, United States
  • Scripps MD Anderson ( Site 0010)
    La Jolla, California 92037, United States
  • Hoag Memorial Hospital Presbyterian ( Site 1595)
    Newport Beach, California 92663, United States
  • John Wayne Cancer Institute ( Site 0075)
    Santa Monica, California 90404, United States
  • University of Colorado Hospital ( Site 0098)
    Aurora, Colorado 80045, United States
  • Georgetown University Medical Center ( Site 0022)
    Washington D.C., District of Columbia 20007, United States
  • Emory School of Medicine ( Site 0006)
    Atlanta, Georgia 30322, United States
  • John H. Stroger Jr. Hospital of Cook County ( Site 1551)
    Chicago, Illinois 60612, United States
  • University of Chicago ( Site 0068)
    Chicago, Illinois 60637, United States
  • Parkview Cancer Institute ( Site 0077)
    Fort Wayne, Indiana 46845, United States
  • Indiana University Melvin and Bren Simon Comprehensive Cancer Center ( Site 0004)
    Indianapolis, Indiana 46202, United States
  • Wichita Urology Group ( Site 0059)
    Wichita, Kansas 67226, United States
  • Tulane University School of Medicine ( Site 0088)
    New Orleans, Louisiana 70112, United States
  • New England Cancer Specialists ( Site 0070)
    Westbrook, Maine 04092, United States
  • Greater Baltimore Medical Center ( Site 0014)
    Baltimore, Maryland 21204, United States
  • Dana-Farber Cancer Institute ( Site 1596)
    Boston, Massachusetts 02215, United States
  • M Health Fairview Ridges Hospital ( Site 1555)
    Burnsville, Minnesota 55337, United States
  • Morristown Medical Center ( Site 0015)
    Morristown, New Jersey 07960, United States
  • UNM Comprehensive Cancer Center-Clinical Research Office ( Site 0045)
    Albuquerque, New Mexico 87106, United States
  • Northwell Health - Monter Cancer Center ( Site 0083)
    Lake Success, New York 11042, United States
  • New York University Perlmutter Cancer Center ( Site 0008)
    New York, New York 10016, United States
  • Icahn School of Medicine at Mount Sinai ( Site 0031)
    New York, New York 10029, United States
  • Cleveland Clinic Main ( Site 1576)
    Cleveland, Ohio 44195, United States
  • Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0021)
    Tulsa, Oklahoma 74146, United States
  • Providence Portland Medical Center [Portland, OR] ( Site 0095)
    Portland, Oregon 97213, United States
  • MidLantic Urology ( Site 0089)
    Bala-Cynwyd, Pennsylvania 19004, United States
  • Abramson Cancer Center of the University of Pennsylvania ( Site 0074)
    Philadelphia, Pennsylvania 19104, United States
  • Thomas Jefferson University ( Site 1579)
    Philadelphia, Pennsylvania 19107, United States
  • Fox Chase Cancer Center ( Site 0055)
    Philadelphia, Pennsylvania 19111, United States
  • Allegheny General Hospital ( Site 0048)
    Pittsburgh, Pennsylvania 15212, United States
  • Bon Secours St. Francis Health System ( Site 1572)
    Greenville, South Carolina 29607, United States
  • Carolina Urologic Research Center ( Site 0062)
    Myrtle Beach, South Carolina 29572, United States
  • Urology Associates [Nashville, TN] ( Site 0053)
    Nashville, Tennessee 37209, United States
  • Vanderbilt University Medical Center ( Site 0017)
    Nashville, Tennessee 37232, United States
  • Texas Oncology-Baylor Sammons Cancer Center ( Site 1552)
    Dallas, Texas 75246, United States
  • Inova Schar Cancer Institute ( Site 0007)
    Fairfax, Virginia 22031, United States
  • Charleston Area Medical Center ( Site 0023)
    Charleston, West Virginia 25304, United States
  • Asociación de Beneficencia Hospital Sirio Libanés ( Site 2102)
    Buenos Aires, Buenos Aires F.D. C1419AHN, Argentina
  • Western Sydney Local Health District ( Site 1259)
    Blacktown, New South Wales 2148, Australia
  • Macquarie University ( Site 1251)
    Macquarie Park, New South Wales 2109, Australia
  • Cairns Base Hospital ( Site 1257)
    Cairns, Queensland 4870, Australia
  • Mater Misericordiae Ltd ( Site 1258)
    South Brisbane, Queensland 4101, Australia
  • Eastern Health ( Site 1255)
    Box Hill, Victoria 3128, Australia
  • Monash Health ( Site 1260)
    Clayton, Victoria 3168, Australia
  • UCL Saint-Luc - Oncologie Medicale ( Site 0357)
    St-Lambrechts-Woluwe, Bruxelles-Capitale, Region de 1200, Belgium
  • CHU UCL Namur Site de Godinne ( Site 0354)
    Yvoir, Namur 5530, Belgium
  • AZ Maria Middelares Gent ( Site 0353)
    Ghent, Oost-Vlaanderen 9000, Belgium
  • UZ Leuven ( Site 0361)
    Leuven, Vlaams-Brabant 3000, Belgium
  • AZ Sint-Jan Brugge ( Site 0352)
    Bruges, West-Vlaanderen 8000, Belgium
  • AZ Delta vzw-Oncology ( Site 0362)
    Roeselare, West-Vlaanderen 8800, Belgium
  • Arthur J.E. Child Comprehensive Cancer Centre ( Site 0100)
    Calgary, Alberta T2N 5G2, Canada
  • BC Cancer Vancouver-Clinical Trials Unit ( Site 0121)
    Vancouver, British Columbia V5Z 4E6, Canada
  • Silverado Resarch Inc. ( Site 0111)
    Victoria, British Columbia V8T 2C1, Canada
  • Moncton Hospital - Horizon Health Network ( Site 0112)
    Moncton, New Brunswick E1C 6Z8, Canada
  • Sunnybrook Research Institute ( Site 0110)
    Toronto, Ontario M4N 3M5, Canada
  • Princess Margaret Cancer Centre ( Site 0107)
    Toronto, Ontario M5G 2M9, Canada
  • CIUSSS du Saguenay-Lac-St-Jean ( Site 0116)
    Chicoutimi, Quebec G7H 5H6, Canada
  • CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0105)
    Montreal, Quebec H1T 2M4, Canada
  • Jewish General Hospital ( Site 0120)
    Montreal, Quebec H3T 1E2, Canada
  • McGill University Health Centre ( Site 0123)
    Montreal, Quebec H4A 3J1, Canada
  • CIUSSS de l'Estrie-CHUS ( Site 0106)
    Sherbrooke, Quebec J1H 5N4, Canada
  • Fundacion Colombiana de Cancerología Clinica Vida ( Site 2003)
    Medellín, Antioquia 050030, Colombia
  • Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 2002)
    Bogotá, Bogota D.C. 111321, Colombia
  • IMAT S.A.S ( Site 2001)
    Montería, Departamento de Córdoba 230002, Colombia
  • Fundación Cardiovascular de Colombia ( Site 2004)
    Piedecuesta, Santander Department 681017, Colombia
  • Fundacion Valle del Lili- CIC-Fundacion Valle del Lili ( Site 2005)
    Cali, Valle del Cauca Department 760032, Colombia
  • Rigshospitalet University Hospital ( Site 0411)
    Copenhagen, Capital Region 2100, Denmark
  • Herlev og Gentofte Hospital. ( Site 0412)
    Herlev, Capital Region 2730, Denmark
  • Aarhus University Hospital Skejby ( Site 0418)
    Aarhus, Central Jutland 8200, Denmark
  • Odense Universitetshospital ( Site 0413)
    Odense, Region Syddanmark 5000, Denmark
  • Hopital de la Timone ( Site 0489)
    Marseille, Bouches-du-Rhone 13005, France
  • Centre Georges Francois Leclerc ( Site 0488)
    Dijon, Bourgogne-Franche-Comté 21000, France
  • Centre Francois Baclesse ( Site 0459)
    Caen, Calvados 14075, France
  • CHU Jean Minjoz ( Site 0455)
    Besançon, Doubs 25000, France
  • Institut de Cancerologie du Gard - CHU Caremeau ( Site 0490)
    Nîmes, Gard 30029, France
  • CHU de Bordeaux- Hopital Saint Andre ( Site 0456)
    Bordeaux, Gironde 33000, France
  • Institut Claudius Regaud IUCT Oncopole ( Site 0486)
    Toulouse, Haute-Garonne 31059, France
  • CHU de Montpellier - Hopital Saint-Eloi ( Site 0469)
    Montpellier, Herault 34295, France
  • C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0492)
    Rennes, Ille-et-Vilaine 35033, France
  • CHU Hotel Dieu Nantes ( Site 0458)
    Nantes, Loire-Atlantique 44093, France
  • Hopital Belle Isle ( Site 0452)
    Vantoux, Moselle 57070, France
  • C.H.U. Lyon Sud ( Site 0466)
    Pierre-Bénite, Rhone 69310, France
  • Institut Gustave Roussy ( Site 0487)
    Villejuif, Val-de-Marne 94800, France
  • CHU Cochin ( Site 0475)
    Paris, 75014, France
  • Hopital Europeen Georges Pompidou ( Site 0476)
    Paris, 75015, France
  • Hopital Bichat du Paris ( Site 0462)
    Paris, 75018, France
  • Klinikum Stuttgart - Katharinenhospital ( Site 0520)
    Stuttgart, Baden-Wurttemberg 70174, Germany
  • Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0549)
    Tübingen, Baden-Wurttemberg 72076, Germany
  • Universitaetsklinikum Erlangen ( Site 0546)
    Erlangen, Bavaria 91058, Germany
  • Klinikum der Universitaet Muenchen - Grosshadern ( Site 0548)
    Munich, Bavaria 81377, Germany
  • Universitaetsklinikum Wuerzburg ( Site 0547)
    Würzburg, Bavaria 97080, Germany
  • Universitaetsklinikum Bonn ( Site 0550)
    Bonn, North Rhine-Westphalia 53127, Germany
  • Universitaetsklinikum Carl Gustav Carus ( Site 0532)
    Dresden, Saxony 01307, Germany
  • Universitaetsklinikum Magdeburg A.o.R. ( Site 0535)
    Magdeburg, Saxony-Anhalt 39120, Germany
  • SRH Wald-Klinikum Gera-Zentrum für klinische Studien ( Site 0533)
    Gera, Thuringia 07548, Germany
  • Vivantes Klinikum am Urban ( Site 0529)
    Berlin, 10967, Germany
  • Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0528)
    Hamburg, 20246, Germany
  • SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 1010)
    Szeged, Csongrád megye 6720, Hungary

Showing the first 100 of 242 sites across 28 countries.

09

References and documents

Publications

  • Vulsteke C, Adra N, Danchaivijitr P, Sabadash M, Rodriguez-Vida A, Zhang Z, Atduev V, Goger YE, Rausch S, Kang SH, Loriot Y, Bedke J, Galsky MD, O'Donnell PH, von Amsberg G, Alimohamed N, Sulimka G, Gupta S, Paramonov V, Nakane K, Mihm M, Meng C, Huang CD, Ramamurthy C, Homet Moreno B, Ullen A; KEYNOTE-905/EV-303 Investigators. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026 Apr 2;394(13):1257-1269. doi: 10.1056/NEJMoa2511674. Epub 2026 Feb 18. PubMed 41707170 ↗
  • Galsky MD, Hoimes CJ, Necchi A, Shore N, Witjes JA, Steinberg G, Bedke J, Nishiyama H, Fang X, Kataria R, Sbar E, Jia X, Siefker-Radtke A. Perioperative pembrolizumab therapy in muscle-invasive bladder cancer: Phase III KEYNOTE-866 and KEYNOTE-905/EV-303. Future Oncol. 2021 Aug;17(24):3137-3150. doi: 10.2217/fon-2021-0273. Epub 2021 May 19. PubMed 34008425 ↗

Study documents

  • Protocol and statistical analysis plan · Apr 8, 2026

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 30, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03924895
Lead sponsor
Merck Sharp & Dohme LLC
Collaborators
Seagen Inc., Astellas Pharma Global Development, Inc.
Responsible party
Sponsor
First posted
Apr 23, 2019
Start date
Jul 24, 2019
Primary completion
Jun 6, 2025
Completion
Dec 15, 2027 (estimated)
Results posted
Jun 30, 2026
Last update
Jun 30, 2026

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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