A Study of Pembrolizumab (MK-3475) Plus V940 in Participants With Bladder Cancer Post-Radical Resection (V940-005)

• ClinicalTrials.gov Identifier: NCT06305767
• Recruitment Status: Recruiting
• First Posted: March 12, 2024
• Last Update Posted: June 10, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Collaborator: ModernaTX, Inc.
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: March 5, 2024
• First Posted Date: March 12, 2024
• Last Update Posted Date: June 10, 2024
• Actual Study Start Date: March 28, 2024
• Estimated Primary Completion Date: October 8, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 5, 2024)

Disease Free Survival (DFS) [ Time Frame: Up to approximately 28 months ]

DFS is defined as the time from randomization until death from any cause, or presence of disease per investigator assessment with muscle-invasive (≥pT2) disease in the urothelial tract (upper tract or lower tract) or high grade T1 disease in the upper tract on imaging and biopsy, and/or disease recurrence outside the urothelial tract on imaging with or without confirmation by biopsy. DFS will be reported for each arm.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 5, 2024)

• Overall Survival (OS) [ Time Frame: Up to approximately 28 months ]
  Overall survival is defined as the time from randomization to death due to any cause. OS will be reported for each arm.
• Distant Metastasis-Free Survival (DMFS) [ Time Frame: Up to approximately 28 months ]
  DMFS is defined as the time from randomization until death from any cause, or disease recurrence outside the urothelial tract on imaging with or without confirmation by biopsy, per investigator assessment. DMFS will be reported for each arm.
• Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 16 months ]
  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 AEs will be reported for each arm.
• Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 13 months ]
  An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an adverse event will be presented. The number of participants who discontinue study treatment due to an AE will be reported for each arm.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Pembrolizumab (MK-3475) Plus V940 in Participants With Bladder Cancer Post-Radical Resection (V940-005)
• Official Title: A Phase 2, Randomized, Double-blind, Placebo- and Active-comparator Controlled Clinical Study of Adjuvant V940 (mRNA-4157) Plus Pembrolizumab Versus Adjuvant Placebo Plus Pembrolizumab in Participants With High-risk Muscle-invasive Urothelial Carcinoma Post-radical Resection
• Brief Summary: The purpose of this study is to assess the safety and efficacy of V940 in combination with pembrolizumab (MK-3475) compared to pembrolizumab alone as an adjuvant treatment for participants with pathologic high-risk muscle-invasive urothelial carcinoma (MIUC) after radical resection. The primary study hypothesis is that V940 in combination with pembrolizumab results in a superior disease-free survival (DFS) as assessed by the investigator compared to pembrolizumab alone in participants with high-risk MIUC after radical resection.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Bladder Cancer

Intervention

• Biological: Pembrolizumab
  Administered via IV infusion at a dose of 400 mg on Day 1 of every 6-week cycle (Q6W) for up to 9 cycles.
  Other Names:

  • MK-3475
  • Keytruda®
• Biological: V940
  Administered via IM injection at a dose of 1 mg every 3 weeks (Q3W) for up to 9 doses.
• Other: Placebo
  V940 diluent only (saline and/or dextrose) administered via IM injection Q3W for up to 9 doses.

Study Arms

• Experimental: Pembrolizumab + V940
  Participants receive 400 mg of pembrolizumab via intravenous (IV) infusion on Day 1 of every 6-week cycle for up to 9 cycles, plus 1 mg of V940 via intramuscular (IM) injection once available every 3 weeks up to a total of 9 doses. V940 doses may begin as soon as Day 22 of Cycle 1. The total duration of treatment is up to approximately 13 months.
  Interventions:

  • Biological: Pembrolizumab
  • Biological: V940
• Active Comparator: Pembrolizumab + Placebo
  Participants receive pembrolizumab 400 mg via IV infusion on Day 1 of each 6-week cycle for up to 9 cycles. Placebo will be administered every 3 weeks up to a total of 9 doses. The total duration of treatment is up to approximately 13 months.
  Interventions:

  • Biological: Pembrolizumab
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 5, 2024): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 8, 2031
• Estimated Primary Completion Date: October 8, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Has muscle-invasive urothelial carcinoma (MIUC)
• Has dominant histology of UC
• Has high-risk pathologic disease after radical resection
• Must provide formalin-fixed paraffin-embedded (FFPE) tumor tissue sample for next generation sequencing (NGS)
• Must provide blood samples per protocol, to enable V940 production, and circulating tumor Deoxyribonucleic acid (ctDNA) testing
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before randomization

Exclusion Criteria:

• Has received prior systemic anticancer therapy
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Has known additional malignancy that is progressing or has required active treatment <3 years prior to study randomization
• Has severe hypersensitivity to either V940 or pembrolizumab and/or any of their excipients
• Has current pneumonitis/interstitial lung disease
• Has active infection requiring systemic therapy
• Has active hepatitis B and hepatitis C virus infection

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Australia, Canada, Chile, France, Germany, Italy, New Zealand, Poland, Spain, Sweden, United States

Administrative Information

• NCT Number: NCT06305767
• Other Study ID Numbers: V940-005; V940-005 ( Other Identifier: Merck ); U1111-1292-1952 ( Other Identifier: WHO ); 2023-505658-17 ( Other Identifier: EU CT )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: ModernaTX, Inc.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: June 2024