NCT04700124 · CITED IN SOURCE DOCUMENTS

Perioperative Enfortumab Vedotin (EV) Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Chemotherapy for Cisplatin-Eligible Muscle Invasive Bladder Cancer (MIBC) (MK-3475-B15/ KEYNOTE-B15 / EV-304)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-07-16

The purpose of this study is to assess the antitumor efficacy and safety of perioperative enfortumab vedotin (EV) plus pembrolizumab and radical cystectomy (RC) + pelvic lymph node dissection (PLND) compared with the current standard of care (neoadjuvant chemotherapy \[gemcitabine plus cisplatin\] and RC + PLND) for participants with MIBC who are cisplatin-eligible. The primary hypothesis is perioperative EV and pembrolizumab and RC + PLND (Arm A) will achieve superior event free survival (EFS) compared with neoadjuvant gemcitabine + cisplatin and RC + PLND (Arm B).

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: Inclusion Criteria: * Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology. * Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis * Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND) * Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Have adequate organ function. Exclusion Criteria: * Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions * Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) * Has ≥N2 disease or metastatic disease (M1) as identified by imaging * Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol * Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder * Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC * Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention * Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection. Hepatitis B infection or known active Hepatitis C infection * Has a known psychiatric or substance abuse disorder * Has had an allogenic tissue/solid organ transplant * Has ongoing sensory or motor neuropathy Grade 2 or higher * Has active keratitis (superficial punctate keratitis) or corneal ulcerations * Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to \<8% with associated diabetes symptoms
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants receive 4 cycles (each cycle length = 21 days) of EV intravenous (IV) infusion plus pembrolizumab IV infusion preoperatively, followed by RC + PLND, followed by 5 cycles of adjuvant EV IV infusion plus 13 cycles of adjuvant pembrolizumab IV infusion postoperatively. The total treatment duration is up to approximately 1 year.
intervention Names
Biological: Pembrolizumab
Biological: Enfortumab vedotin (EV)
Procedure: RC + PLND
label
Arm A: Perioperative EV+ Pembrolizumab and RC + PLND
type
EXPERIMENTAL
description
Participants receive 4 cycles (each cycle length = 21 days) of standard of care (SOC) chemotherapy (gemcitabine IV infusion plus cisplatin IV infusion) preoperatively, followed by RC + PLND. The total treatment duration is up to approximately 3 months.
intervention Names
Procedure: RC + PLND
Drug: Gemcitabine
Drug: Cisplatin
label
Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm A: Perioperative EV+ Pembrolizumab and RC + PLND
description
200 mg of Pembrolizumab IV infusion, on Day 1 Q3W for 4 cycles (each cycle length = 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 Q3W for 13 cycles in postoperative phase (up to approximately 9 months). The total duration of treatment is up to approximately 1 year.
name
Pembrolizumab
other Names
KEYTRUDA®
MK-3475
type
BIOLOGICAL
arm Group Labels
Arm A: Perioperative EV+ Pembrolizumab and RC + PLND
description
1.25 mg/kg of EV IV infusion, on Day 1 and Day 8 Q3W for 4 cycles (each cycle length = 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 and Day 8 Q3W for 5 cycles (each cycle length = 21 days) in postoperative phase (up to approximately 4 months). The total duration of treatment is up to approximately 7 months.
name
Enfortumab vedotin (EV)
other Names
Padcev
type
BIOLOGICAL
arm Group Labels
Arm A: Perioperative EV+ Pembrolizumab and RC + PLND
Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND
description
Curative intent RC + PLND surgery will be administered to all participants randomized to Arm A and B after completion of preoperative systemic treatment (RC + PLND to be done approximately at 15 weeks from randomization).
name
RC + PLND
other Names
Surgery
type
PROCEDURE
arm Group Labels
Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND
description
1000 mg/m\^2 of Gemcitabine IV infusion, Day 1 and Day 8 Q3W for 4 cycles in preoperative phase (up to approximately 3 months)
name
Gemcitabine
other Names
Gemzar
type
DRUG
arm Group Labels
Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND
description
70 mg/m\^2 of Cisplatin IV infusion, Day 1, Q3W for 4 cycles in preoperative phase (up to approximately 3 months)
name
Cisplatin
other Names
Platinol®
Platinol®-AQ
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE
masking Description: Open label

primary Purpose

TREATMENT

Enrollment

count: 808
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
EFS is defined as the time from randomization to the first occurrence of following events: radiographic disease progression precluding RC + PLND, failure to undergo surgery in participants with residual disease, gross residual disease left behind at time of surgery, local or distant recurrence based on blinded independent central review (BICR) or death due to any cause.
measure
Event-Free Survival (EFS)
time Frame
Up to ~68 months

secondary Outcomes

description
pCR rate is defined as defined as the proportion of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from radical cystectomy (RC) + pelvic lymph node dissection (PLND), as assessed by blinded central pathologic review.
measure
Pathologic Complete Response (pCR) Rate
time Frame
Up to ~47 months
description
OS is defined as the time from randomization to death due to any cause.
measure
Overall Survival (OS)
time Frame
Up to ~68 months
description
DFS is defined as the time from postsurgery baseline scan until the first occurrence of either local/distant recurrence as assessed by BICR imaging and/or biopsy or death from any cause.
measure
Disease Free Survival (DFS)
time Frame
From ~12 months to up to ~68 months
description
pDS is defined as participants with \<pT2 (includes pT0, pTis, pTa, and pT1) and N0 in examined tissue from RC plus PLND, based on central pathologic review.
measure
Pathologic Downstaging (pDS) Rate
time Frame
Up to ~47 months
description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be presented.
measure
Number of Participants Who Experienced An Adverse Event (AE) (Arm A only)
time Frame
Up to ~68 months
description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be presented.
measure
Number of Participants Who Discontinued Study Treatment Due to An AE (Arm A only)
time Frame
Up to ~68 months
description
Perioperative complications are defined as both intraoperative and postoperative complications, potentially contributing to increased length of inpatient care and/or delay of adjuvant therapy. The number of participants experiencing perioperative complications will be presented.
measure
Number of Participants Experiencing Perioperative Complications
time Frame
Up to ~68 months
description
The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer participants. Participant responses to questions 29 ("How would you rate your overall health during the past week?") and 30 ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). A higher score indicates a better overall health/quality of life status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined scores will be presented.
measure
Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score
time Frame
Baseline, Up to ~68 months
description
The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=not at all to 4=very much). A higher score indicates a better quality of life. The change from baseline in physical function (EORTC QLQ-C30 Items 1-5) score will be presented.
measure
Change from Baseline in EORTC QLQ-C30 Physical Functioning Scale
time Frame
Baseline, Up to ~68 months
description
The BCI is a 36-item validated, condition-specific health questionnaire to assess the quality of life among participants with bladder cancer. The BCI contains 3 domains: urinary (14 items), bowel (10 items), and sexual (12 items) with function (Likert response scale: 0 \[Never\] - 4 \[Always\]) and bother (Likert response scale: 0 \[No problem\] - 4 \[Big problem\]) subdomains. The domain and subdomain scores are standardized to a 0 to 100 point scale where higher scores correspond better functioning and health-related qualify of life. The change from baseline in the combined scores of the urinary, bowel, and sexual domains of the BCI will be presented.
measure
Change From Baseline in Urinary, Bowel and Sexual Domains per Bladder Cancer Index (BCI)
time Frame
Baseline, Up to ~68 months
description
The EQ-5D-5L VAS records the respondent's self-rated health on a 10 centimeter (cm) vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine". The change from baseline in EQ-5D-5L VAS will be presented.
measure
Change from Baseline in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS)
time Frame
Baseline, Up to ~68 months
description
The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and " Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a better level of role functioning. Change from baseline in the role functioning (EORTC QLQ-C30 Items 6-7) combined score will be presented.
measure
Change from Baseline in EORTC QLQ-C30 Role Functioning Combined Score (Items 6-7)
time Frame
Baseline, Up to ~68 months

Full study description

brief Summary: The purpose of this study is to assess the antitumor efficacy and safety of perioperative enfortumab vedotin (EV) plus pembrolizumab and radical cystectomy (RC) + pelvic lymph node dissection (PLND) compared with the current standard of care (neoadjuvant chemotherapy \[gemcitabine plus cisplatin\] and RC + PLND) for participants with MIBC who are cisplatin-eligible. The primary hypothesis is perioperative EV and pembrolizumab and RC + PLND (Arm A) will achieve superior event free survival (EFS) compared with neoadjuvant gemcitabine + cisplatin and RC + PLND (Arm B).

Source references

references

citation
Galsky MD, Valderrama BP, Maruzzo M, Font A, Ciuleanu T, Chatzkel J, Koie T, Hoimes CJ, Puente J, Zakharia Y, Rosenbaum E, Boehm K, Loriot Y, Bedke J, Powles TB, Necchi A, Wiechno P, Alvarez-Fernandez C, Kim TH, Oliveira N, Flaig TW, Wirtz HS, Mihm M, Huang Q, Rogiers A, Homet Moreno B, Gomez de Liano A; KEYNOTE-B15/EV-304 Investigators. Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer. N Engl J Med. 2026 Jul 23;395(4):338-348. doi: 10.1056/NEJMoa2601486.
pmid
42485627
type
DERIVED