Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Cisplatin-ineligible Participants With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)

  • STATUS
    Recruiting
  • End date
    May 12, 2027
  • participants needed
    836
  • sponsor
    Merck Sharp & Dohme Corp.
Updated on 18 January 2021
Investigator
Toll Free Number
Primary Contact
Greater Baltimore Medical Center ( Site 0014) (9.3 mi away) Contact
+163 other location

Summary

A global, randomized phase III study to evaluate perioperative pembrolizumab with radical cystectomy + pelvic lymph node dissection (RC+PLND) versus RC+PLND alone in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC).

Details
Treatment Pembrolizumab, Enfortumab vedotin, Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
Clinical Study IdentifierNCT03924895
SponsorMerck Sharp & Dohme Corp.
Last Modified on18 January 2021

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Eligibility

Yes No Not Sure

Inclusion Criteria

Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Is your age greater than or equal to 18 yrs?
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have any of these conditions: Do you have Urinary Bladder Cancer, Muscle-invasive??
Do you have Urinary Bladder Cancer, Muscle-invasive?
Gender: Male or Female
Histologically confirmed diagnosis of muscle-invasive bladder cancer (MIBC) cT2-T4aN0M0 or cT1-T4aN1M0 with predominant (50%) urothelial histology. Participants with mixed histology are eligible provided the urothelial component is 50%. Urothelial carcinomas not originating from the bladder are not eligible. Participants whose tumors show any of the following variant histologies are not eligible: plasmacytoid, clear cell, lipid rich, giant cell, sarcomatoid, and/or neuroendocrine component
Clinically non-metastatic 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
Impaired renal function with measured or calculated CrCl 30 to 59 mL/min
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 and adequate to determine determine pathologic stage pT2-T4a or pT1, urothelial histology, and PD-L1 status. For confirmation of stages T2-T4a, TUR biopsy samples must include detrusor muscle
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 120 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 60 days after the last dose of enfortumab vedotin. 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

Known additional non-urothelial malignancy that is progressing or has required active treatment 3 years of study randomization, with certain exceptions
N2 or M1 disease
Received any prior systemic antineoplastic treatment for muscle-invasive bladder cancer (MIBC)
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 co-inhibitory 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 vaccine within 30 days prior to the first dose of study drug
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 ( Grade 3) hypersensitivity to any enfortumab vedotin 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
History of uncontrolled diabetes
History of (noninfectious) pneumonitis that required steroids, or current pneumonitis
Active infection requiring systemic therapy
Has had an allogenic tissue/solid organ transplant
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