Pembrolizumab and EV With Radiation Therapy for MIBC Patients (PEVRAD)

NCT05879653 | Recruiting Phase 2 DMC

• 1 other identifier: IACT21079
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

This study is designed to assess the efficacy and safety of induction therapy with MK-3475 and ASG-22CE and radiation therapy with MK-3475 in patients with cT2-4aN0M0 muscle invasive bladder cancer who are unfit for or refuse radical cystectomy.

Conditions

Bladder Cancer

Keywords

Bladder preservation; Radiation therapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Bladder Intact Event-Free Survival (BI-EFS) rate

  To evaluate bladder intact event-free survival (BI-EFS) rate at 2 year after study enrollment assessed by cystoscopy, cytology, biopsy results by central pathology review, and imaging evaluation.

  2 years

Secondary Outcomes (13)

• Pathologic Complete Response (pCR) Rate at 38 weeks

  38 weeks

• Overall Survival (OS)

  2 years

• Metastasis-Free Survival (MFS)

  2 years

• Number of participants who experienced an adverse event (AE)

  2 years

• Number of participants who discontinued study intervention due to an AE

  2 years

Study Arms (1)

MK-3475 and ASG-22CE With Radiation Therapy

EXPERIMENTAL

Drug: MK-3475; Drug: ASG-22CE; Procedure: maximal TURBT; Radiation: Radiation therapy

Interventions

MK-3475 DRUG

During the induction phase, MK-3475 200 mg will be administered as four cycles of 3-weeks regimen, with ASG-22CE 1.25 mg/kg administered on Day 1 and Day 8 of each cycle. The treatment and maintenance phases will consist of 9 cycles of one course per 6 weeks, with MK-3475 400 mg administered on Day 1 of each course at Q6W.

Also known as: Pembrolizumab

MK-3475 and ASG-22CE With Radiation Therapy

ASG-22CE DRUG

During the induction phase, four cycles of 3-weeks regimen are administered, with ASG-22CE 1.25 mg/kg administered on Day 1 and Day 8 of each cycle.

Also known as: Enfortumab vedotin

MK-3475 and ASG-22CE With Radiation Therapy

maximal TURBT PROCEDURE

All participants who were not determined to have PD on imaging during the induction phase should have had a maximal TURBT performed at 13 (± 1week) weeks after the first dose of trial drug.

MK-3475 and ASG-22CE With Radiation Therapy

Radiation therapy RADIATION

Radiotherapy will be initiated no later than 8 weeks after maximal TUR-BT. In this trial, a total dose of 56 Gy will be delivered using 2 Gy per dose. 40 Gy/20 fr (2 Gy/fr) to the small pelvis followed by 16 Gy /8 fr (2 Gy/fr) to the whole bladder 5 times a week for 5 consecutive days using Three-Dimensional Conformal Radiation Therapy (3D-CRT).

MK-3475 and ASG-22CE With Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Male/female participants who are at least 18 years of age on the day of signing informed consent and who have a first confirmed diagnosis of MIBC with predominant urothelial histology obtained via a diagnostic or maximal TURBT within 90 days prior to enrollment.
• Note: Participants with mixed histology are eligible provided the urothelial component is ≥50%.
• Has clinically non-metastatic bladder cancer (N0M0) determined by imaging (CT of the chest and CTU/MRU of abdomen and pelvis), assessed by the site.
• Male participants:
• A male participant must agree to use a contraception and not to donate sperm during the administration of MK-3475 and ASG-22CE and for at least 90 days after the last dose of MK-3475 and for 6 months after ASG-22CE.
• Female participants:
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of MK3475 and for 6 months after ASG-22CE and RT.
• The participant provides written informed consent for the trial.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• Demonstrates adequate organ function. All screening laboratory tests should be performed within 10 days prior to the first dose of study intervention.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Medical Conditions
• Has the presence of diffuse CIS (multiple foci \[4 or greater\] of CIS) throughout the bladder.
• Has the presence of UC at any site outside of the urinary bladder in the previous 2 years except for Ta/T1/CIS of the upper tract if the patient has undergone a complete nephroureterectomy.
• Has the presence of any small cell or neuroendocrine component in the tumor tissue sample.
• Has a known additional malignancy that is progressing or has required active therapy within the past 3 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or other carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded. Participants with low-risk prostate cancer (T1-T2a, Gleason score ≤6, and PSA \<10 ng/mL) either treated with definitive intent any time before screening or untreated in active surveillance are not excluded.
• Has limited bladder function with frequency of small amounts of urine (\< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter.
• Has a history of radiation therapy to the pelvic region for any reason.
• Prior/Concomitant Therapy
• Has received prior pelvic/local radiation therapy or any antineoplastic treatment for MIBC.
• Note: Prior treatment for NMIBC with intravesical instillation therapy such as BCG or intravesical chemotherapy is permitted, but must be completed ≥28 days before the first dose of the trial drug. Prior systemic treatment received for treatment of NMIBC is not permitted.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
• Has received prior therapy with an ASG-22CE or other MMAE-containing ADCs.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.

Sponsors & Collaborators

• Kyoto University Hospital: lead
• University of Tsukuba: collaborator
• Osaka Metropolitan University: collaborator
• Kobe City Medical Center General Hospital: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (4)

Kobe City Medical Center General Hospital

Kobe, Hyōgo, 650-0047, Japan

RECRUITING

University of Tsukuba Hospital

Tsukuba, Ibaraki, 305-8576, Japan

RECRUITING

Kyoto University Hospital

Kyoto, Kyoto, 606-8507, Japan

RECRUITING

Osaka Metropolitan University Hospital

Osaka, Osaka, 545-8586, Japan

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

pembrolizumab; enfortumab vedotin; Radiotherapy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Takashi Kobayashi, MD,PhD

  Kyoto University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuki Kita, MD,PhD

CONTACT

81757513337; kitayuki@kuhp.kyoto-u.ac.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 10, 2023
• First Posted: May 30, 2023
• Study Start: October 1, 2023
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2027
• Last Updated: August 29, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

JP (4)