Pembrolizumab in Muscle-invasive Bladder Cancer

NCT05406713 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GU20-444
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 4

Brief Summary

Subjects with cT2-T3N0M0 urothelial cancer of the bladder will be enrolled. After completing two cycles of pembrolizumab, subjects will undergo a restaging MRI of the abdomen and pelvis with a standard acquisition protocol (as outlined in the protocol) as well as CT chest. A CT of the abdomen and pelvis may be performed if there are contraindications to MRI. Patients will also undergo a restaging cystoscopy and biopsies/TURBT as outlined in the protocol. Patients achieving a clinical complete response to treatment (defined in the protocol) will proceed with "maintenance" single agent pembrolizumab followed by surveillance. All other patients will proceed with standard of care local therapy as per their treating physicians followed by "adjuvant" pembrolizumab.

Conditions

Muscle Invasive Bladder Carcinoma; Localized Cancer; Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

• Clinical Complete Response Rate (CRR)

  Estimate the clinical complete response rate defined as cT0 or cTa disease after pembrolizumab

  2 years

• Benefit from Treatment

  Estimate the ability of clinical complete response (cT0 or cTa) to predict benefit from treatment. For patients achieving a clinical complete response, benefit will be defined as 2 year metastasis-free survival in patients among the patients achieving a clinical complete response.

  2 years

Secondary Outcomes (20)

• Assess adverse events

  6 months

• Positive Predictive Value between PD-L1 Expression and clinical complete response

  2 years

• Positive Predictive Value between TMB and clinical complete response

  2 years

• Metastasis Free Survival

  2 years

• Metastasis Free Survival

  2 years

Study Arms (1)

Experimental Group

EXPERIMENTAL

Cycles 1-2 (Pembrolizumab): 400 mg of Pembrolizumab intravenously (Administered Day 1 of 42 day Cycle) If complete response of treatment is observed then maintenance therapy will be given. All other patients will receive with standard of care local therapy (cystectomy or chemo-radiation) as per their treating physicians followed by "adjuvant" pembrolizumab. Cycle 3-9 (Maintenance or Adjuvant Single agent Pembrolizumab): 400 mg of Pembrolizumab intravenously (Administered Day 1 of 42 day Cycle)

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

400 mg intravenously

Also known as: Keytruda

Experimental Group

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of ≤ 1 within 28 days prior to registration.
• Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder. Clinical stage cT2-3N0M0. N0 will be considered the absence of radiographically enlarged lymph nodes on baseline imaging. Patients with lymph nodes \<1 cm in long axis on imaging may be eligible but must be discussed with the sponsor investigator.
• Have undergone a standard of care maximal transurethral resection of bladder tumor ≤ 60 days prior C1D1. Maximal TURBT is defined as a macroscopically complete resection of bladder tumor when safely possibly per the treating urologist. Patients who cannot safely undergo maximal TURBT as per their treating urologist are eligible for enrollment but should be discussed with the sponsor investigator.
• All subjects must have adequate transurethral resection of bladder tumor tissue available for submission (i.e., at least 15 unstained slides or paraffin block) identified during screening. This tissue can be from the maximal restaging TURBT, a prior diagnostic TURBT revealing muscle-invasive bladder cancer, or both specimens. Subjects without available archival tissue must be discussed with the sponsor-investigator.
• Decline cisplatin-based neoadjuvant chemotherapy or be considered cisplatin-ineligible based on at least one of the following modified criteria (as ECOG 0-1 is required for eligibility):
• Creatinine clearance \< 60 mL/min (but ≥ 30 mL/min)
• Grade ≥ 2 hearing loss (per CTCAE criteria v5)
• Grade ≥ 2 neuropathy (per CTCAE criteria v5)
• New York Heart Association Class III heart failure
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
• Hematological
• Absolute Neutrophil Count (ANC): ≥ 1.5 x 10\^9/L
• Hemoglobin (Hgb): ≥ 9 g/dL

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Prior systemic chemotherapy for muscle-invasive urothelial cancer of the bladder.
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured. Patients with intermediate or lower risk prostate cancer as defined by the National Comprehensive Cancer Network (NCCN) risk stratification guidelines may be eligible for enrollment.
• Prior radiation therapy for bladder cancer.
• Active infection requiring systemic therapy.
• Has a known history of Hepatitis B or C. NOTE: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. NOTE: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• Has a known history of Human Immunodeficiency Virus (HIV) infection. NOTE: no testing for HIV is required unless mandated by local health authority.
• Has a known history of active TB (Bacillus Tuberculosis).
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• 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 a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Sponsors & Collaborators

• Matthew Galsky: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

City of Hope

Duarte, California, 91010, United States

Location

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Matthew D Galsky, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 9, 2022
• First Posted: June 6, 2022
• Study Start: July 13, 2022
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)