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History of Changes for Study: NCT03924895
Perioperative Pembrolizumab (MK-3475) Plus Cystectomy Versus Cystectomy Alone in Cisplatin-ineligible Participants With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905)
Latest version (submitted September 23, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 22, 2019 None (earliest Version on record)
2 April 30, 2019 Oversight and Study Status
3 May 30, 2019 Outcome Measures and Study Status
4 June 27, 2019 Recruitment Status, Study Status and Contacts/Locations
5 July 23, 2019 Study Status and Contacts/Locations
6 August 7, 2019 Study Status and Contacts/Locations
7 August 21, 2019 Contacts/Locations and Study Status
8 August 29, 2019 Contacts/Locations and Study Status
9 September 5, 2019 Contacts/Locations and Study Status
10 September 13, 2019 Contacts/Locations and Study Status
11 September 19, 2019 Contacts/Locations and Study Status
12 September 27, 2019 Contacts/Locations and Study Status
13 October 3, 2019 Study Status and Contacts/Locations
14 October 10, 2019 Contacts/Locations and Study Status
15 October 16, 2019 Contacts/Locations and Study Status
16 October 25, 2019 Contacts/Locations and Study Status
17 October 30, 2019 Contacts/Locations and Study Status
18 November 7, 2019 Study Status and Contacts/Locations
19 November 13, 2019 Contacts/Locations and Study Status
20 November 22, 2019 Contacts/Locations and Study Status
21 December 5, 2019 Study Status and Contacts/Locations
22 December 11, 2019 Contacts/Locations and Study Status
23 December 22, 2019 References, Contacts/Locations and Study Status
24 December 27, 2019 Contacts/Locations and Study Status
25 January 17, 2020 Study Status and Contacts/Locations
26 January 27, 2020 Contacts/Locations and Study Status
27 January 30, 2020 Contacts/Locations and Study Status
28 February 17, 2020 Contacts/Locations and Study Status
29 February 26, 2020 Contacts/Locations and Study Status
30 March 6, 2020 Contacts/Locations and Study Status
31 March 12, 2020 Contacts/Locations and Study Status
32 March 20, 2020 Contacts/Locations and Study Status
33 March 27, 2020 Contacts/Locations and Study Status
34 April 2, 2020 Contacts/Locations and Study Status
35 April 17, 2020 Contacts/Locations and Study Status
36 April 23, 2020 Contacts/Locations and Study Status
37 April 29, 2020 Contacts/Locations and Study Status
38 May 7, 2020 Study Status and Contacts/Locations
39 May 15, 2020 Contacts/Locations and Study Status
40 May 22, 2020 Contacts/Locations and Study Status
41 May 28, 2020 Contacts/Locations and Study Status
42 June 23, 2020 Study Status and Contacts/Locations
43 July 7, 2020 Arms and Interventions, Study Identification, Contacts/Locations, Outcome Measures, Study Status, Eligibility, Study Design and Sponsor/Collaborators
44 July 10, 2020 Contacts/Locations and Study Status
45 July 22, 2020 Contacts/Locations and Study Status
46 July 31, 2020 Contacts/Locations and Study Status
47 August 13, 2020 Study Status and Eligibility
48 August 20, 2020 Contacts/Locations and Study Status
49 September 4, 2020 Contacts/Locations and Study Status
50 September 10, 2020 Contacts/Locations and Study Status
51 September 18, 2020 Contacts/Locations and Study Status
52 November 4, 2020 Study Status and Contacts/Locations
53 November 12, 2020 Contacts/Locations and Study Status
54 November 20, 2020 Contacts/Locations and Study Status
55 November 25, 2020 Contacts/Locations and Study Status
56 December 2, 2020 Contacts/Locations and Study Status
57 December 9, 2020 Contacts/Locations and Study Status
58 December 17, 2020 Contacts/Locations and Study Status
59 December 23, 2020 Contacts/Locations and Study Status
60 December 30, 2020 Contacts/Locations and Study Status
61 January 7, 2021 Study Status and Contacts/Locations
62 January 13, 2021 Contacts/Locations and Study Status
63 January 22, 2021 Contacts/Locations and Study Status
64 January 29, 2021 Contacts/Locations and Study Status
65 February 12, 2021 Contacts/Locations and Study Status
66 February 19, 2021 Contacts/Locations and Study Status
67 February 26, 2021 Contacts/Locations and Study Status
68 March 5, 2021 Contacts/Locations and Study Status
69 March 19, 2021 Contacts/Locations and Study Status
70 April 1, 2021 Contacts/Locations and Study Status
71 April 9, 2021 Study Status and Contacts/Locations
72 April 22, 2021 Contacts/Locations, Eligibility and Study Status
73 April 30, 2021 Contacts/Locations and Study Status
74 May 6, 2021 Contacts/Locations and Study Status
75 May 13, 2021 Contacts/Locations and Study Status
76 May 21, 2021 Contacts/Locations and Study Status
77 May 28, 2021 Contacts/Locations and Study Status
78 June 11, 2021 Contacts/Locations and Study Status
79 June 18, 2021 Contacts/Locations and Study Status
80 June 24, 2021 Contacts/Locations and Study Status
81 July 2, 2021 Contacts/Locations and Study Status
82 July 15, 2021 Contacts/Locations and Study Status
83 July 22, 2021 Contacts/Locations and Study Status
84 July 30, 2021 Contacts/Locations and Study Status
85 August 5, 2021 Contacts/Locations and Study Status
86 August 13, 2021 Contacts/Locations and Study Status
87 August 20, 2021 Contacts/Locations and Study Status
88 August 27, 2021 Contacts/Locations and Study Status
89 September 3, 2021 Contacts/Locations and Study Status
90 September 9, 2021 Contacts/Locations and Study Status
91 September 14, 2021 Study Status and Study Identification
92 September 23, 2021 Study Status
93 September 30, 2021 Contacts/Locations and Study Status
94 October 8, 2021 Contacts/Locations and Study Status
95 October 21, 2021 Contacts/Locations and Study Status
96 October 27, 2021 Contacts/Locations and Study Status
97 November 10, 2021 Contacts/Locations and Study Status
98 November 18, 2021 Contacts/Locations and Study Status
99 November 25, 2021 Contacts/Locations and Study Status
100 December 3, 2021 Contacts/Locations and Study Status
101 December 9, 2021 Contacts/Locations and Study Status
102 December 17, 2021 Contacts/Locations and Study Status
103 December 29, 2021 Contacts/Locations and Study Status
104 January 6, 2022 Study Status
105 January 17, 2022 Contacts/Locations, Study Identification and Study Status
106 January 21, 2022 Contacts/Locations and Study Status
107 February 11, 2022 Outcome Measures, Contacts/Locations, Study Status, Study Identification, Eligibility, Study Design, Conditions and Study Description
108 February 24, 2022 Contacts/Locations and Study Status
109 March 4, 2022 Contacts/Locations and Study Status
110 March 11, 2022 Contacts/Locations and Study Status
111 March 17, 2022 Contacts/Locations and Study Status
112 March 24, 2022 Contacts/Locations and Study Status
113 April 1, 2022 Contacts/Locations and Study Status
114 April 6, 2022 Study Status and Contacts/Locations
115 April 13, 2022 Contacts/Locations and Study Status
116 April 21, 2022 Contacts/Locations and Study Status
117 June 9, 2022 Contacts/Locations and Study Status
118 June 23, 2022 Contacts/Locations and Study Status
119 July 13, 2022 Contacts/Locations and Study Status
120 July 22, 2022 Contacts/Locations and Study Status
121 August 11, 2022 Contacts/Locations and Study Status
122 September 2, 2022 Study Status and Contacts/Locations
123 September 15, 2022 Contacts/Locations and Study Status
124 September 23, 2022 Contacts/Locations and Study Status
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Study NCT03924895
Submitted Date:  April 22, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: 3475-905
Brief Title: Perioperative Pembrolizumab (MK-3475) Plus Cystectomy Versus Cystectomy Alone in Cisplatin-ineligible Participants With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905)
Official Title: A Phase 3 Randomized Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin-ineligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-905)
Secondary IDs: MK-3475-905 [Merck Protocol Number]
2018-003809-26 [EudraCT Number]
KEYNOTE-905 [Merck]
Open or close this module Study Status
Record Verification: April 2019
Overall Status: Not yet recruiting
Study Start: June 14, 2019
Primary Completion: February 12, 2025 [Anticipated]
Study Completion: February 16, 2026 [Anticipated]
First Submitted: April 22, 2019
First Submitted that
Met QC Criteria:
April 22, 2019
First Posted: April 23, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
April 22, 2019
Last Update Posted: April 23, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Merck Sharp & Dohme LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief 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).
Detailed Description:
Open or close this module Conditions
Conditions: Urinary Bladder Cancer, Muscle-invasive
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Pembrolizumab (MK-3475)
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 610 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Pembrolizumab + Surgery
Participants receive 3 preoperative cycles of pembrolizumab, followed by standard of care surgery, followed by up to 14 cycles of postoperative pembrolizumab.
Drug: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle
Other Names:
  • KEYTRUDA®
  • MK-3475
Procedure: Surgery (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.
Active Comparator: Surgery alone
Participants receive standard of care surgery alone.
Procedure: Surgery (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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Pathological Complete Response (pCR) Rate in All Participants
[ Time Frame: Up to approximately 3 months (Time of surgery) ]

Pathological complete response rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0) in examined tissue from RC and PLND, as determined centrally.
2. Pathologic Complete Response Rate in Participants Whose Tumors Express PD-L1 Combined Positive Score (CPS) ≥10
[ Time Frame: Up to approximately 3 months (Time of surgery) ]

Pathological complete response rate is defined as the percentage of participants having pCR. pCR is defined as pT0 in examined tissue from RC and PLND, as determined centrally.
3. Event-Free Survival (EFS) in All Participants
[ Time Frame: Up to approximately 5.5 years ]

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, gross residual disease left behind at the time of surgery, local or distant recurrence based on blinded independent central review (BICR) assessments, or death due to any cause.
4. Event-Free Survival in Participants Whose Tumors Express PD-L1, CPS ≥10
[ Time Frame: Up to approximately 5.5 years ]

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, gross residual disease left behind at the time of surgery, local or distant recurrence based on blinded independent central review (BICR) assessments, or death due to any cause.
Secondary Outcome Measures:
1. Overall Survival (OS) in All Participants
[ Time Frame: Up to approximately 6.5 years ]

OS is defined as the time from randomization to death due to any cause.
2. Overall Survival in Participants Whose Tumors Express PD-L1, CPS ≥10
[ Time Frame: Up to approximately 6.5 years ]

OS is defined as the time from randomization to death due to any cause.
3. Disease-Free Survival (DFS) in All Participants
[ Time Frame: Up to approximately 5.5 years ]

DFS is defined as the time from first post-surgery baseline scan until:

  • local or distant recurrence as assessed by imaging (BICR) and/or biopsy
  • Death due to any cause
4. Disease-Free Survival in Participants Whose Tumors Express PD-L1, CPS ≥10
[ Time Frame: Up to approximately 5.5 years ]

DFS is defined as the time from first post-surgery baseline scan until:

  • local or distant recurrence as assessed by imaging (BICR) and/or biopsy
  • Death due to any cause
5. Pathologic Downstaging (pDS) Rate in All Participants
[ Time Frame: Up to approximately 3 months (Time of surgery) ]

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.
6. Pathologic Downstaging (pDS) Rate in Participants Whose Tumors Express PD-L1, CPS ≥10
[ Time Frame: Up to approximately 3 months (Time of surgery) ]

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.
7. Number of Participants Experiencing Adverse Events (AEs)
[ Time Frame: Up to approximately 6.5 years ]

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.
8. Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs)
[ Time Frame: Up to approximately 1 year ]

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.
9. Number of Participants Experiencing Perioperative Complications
[ Time Frame: Up to approximately 1 year ]

The number of participants who experience perioperative complications will be presented.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Histologically confirmed diagnosis of muscle invasive bladder cancer (T2-T4aN0M0) 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 contain any neuroendocrine component are not eligible.
  • 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
    • CTCAE v.4 Grade ≥2 peripheral neuropathy
    • New York Heart Association (NYHA) Class III heart failure
  • Transurethral resection (TUR) of a bladder tumor that is submitted and adequate for evaluation of histology, muscle invasion and PD-L1 status
  • ECOG performance status of 0, 1, or 2
  • Adequate organ function

Exclusion Criteria:

  • Known additional non-urothelial malignancy that is progressing or has required active treatment ≤3 years of study randomization, with certain exceptions
  • Received any prior systemic anti-neoplastic treatment for muscle-invasive bladder cancer (MIBC)
  • Received prior therapy with a 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 anti-cancer therapy including investigational agents within 3 years prior to randomization
  • Received any prior radiotherapy to the bladder
  • 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
  • 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
  • Hypersensitivity to monoclonal antibodies (including pembrolizumab) and/or any of their excipients
  • 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 (non-infectious) pneumonitis that required steroids, or current pneumonitis.
  • Active infection requiring systemic therapy
Open or close this module Contacts/Locations
Study Officials: Medical Director
Study Director
Merck Sharp & Dohme LLC
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Supporting Information:
Time Frame:
Access Criteria:
URL: http://engagezone.msd.com/ds_documentation.php
Open or close this module References
Links:
Available IPD/Information:

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