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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06305767




Registration number
NCT06305767
Ethics application status
Date submitted
5/03/2024
Date registered
12/03/2024
Date last updated
15/11/2024

Titles & IDs
Public title
A Clinical Study of V940 Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)
Scientific title
A Phase 1/2 Study of V940 Plus Pembrolizumab With or Without Enfortumab Vedotin in Muscle-Invasive Urothelial Carcinoma (MIUC) (INTerpath-005)
Secondary ID [1] 0 0
V940-005
Secondary ID [2] 0 0
V940-005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Other - V940
Other interventions - Placebo
Treatment: Other - Enfortumab Vedotin
Treatment: Surgery - Surgery (RC plus PLND)

Experimental: Adjuvant Cohort: Pembrolizumab + V940 - Adjuvant Cohort 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 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.

Active comparator: Adjuvant Cohort: Pembrolizumab + Placebo - Adjuvant Cohort 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.

Experimental: Perioperative Cohort: Pembrolizumab + V940 + Enfortumab Vedotin (EV) and Surgery - Curative intent surgery (radical cystectomy \[RC\] plus pelvic lymph node dissection \[PLND\]) will be administered to all participants in the Perioperative Cohort. RC plus PLND will be performed approximately 15 weeks after allocation to the Perioperative Cohort and within 6 weeks of the last dose of neoadjuvant V940 plus pembrolizumab plus EV treatment. Adjuvant V940 plus pembrolizumab plus EV treatment will begin within 8 weeks of completing RC plus PLND. Pembrolizumab will be administered via IV infusion at a dose of 200 mg on Day 1 of every 3-week cycle for up to 4 neoadjuvant cycles and up to 13 adjuvant cycles. V940 will be administered at a dose of 1 mg every 3 weeks for a total of up to 9 doses in the neoadjuvant and adjuvant periods. EV will be administered via IV infusion at a dose of 1.25 mg/kg on Day 1 and Day 8 of every 3-week cycle for up to 4 neoadjuvant cycles and up to 5 adjuvant cycles. The total duration of treatment is up to approximately 16 months.


Treatment: Other: Pembrolizumab
Administered via IV infusion at a dose of 400 mg on Day 1 of every 6-week cycle for up to 9 adjuvant cycles for Adjuvant Cohort participants, or at a dose of 200 mg on Day 1 of every 3-week cycle for up to 4 neoadjuvant cycles, and up to 13 adjuvant cycles for Perioperative Cohort participants.

Treatment: Other: V940
Administered via IM injection at a dose of 1 mg every 3 weeks for a total of up to 9 adjuvant doses for Adjuvant Cohort participants, or at a dose of 1 mg every 3 weeks for a total of up to 9 doses in the neoadjuvant and adjuvant periods for Perioperative Cohort participants.

Other interventions: Placebo
V940 diluent only (saline and/or dextrose) administered via IM injection Q3W for up to 9 doses.

Treatment: Other: Enfortumab Vedotin
Administered via IV infusion at a dose of 1.25 mg/kg on Day 1 and Day 8 of every 3-week cycle for up to 4 neoadjuvant cycles, and up to 5 adjuvant cycles for Perioperative Cohort participants.

Treatment: Surgery: Surgery (RC plus PLND)
Curative intent surgery (RC plus PLND) will be administered to all participants in the Perioperative Cohort and will be done in accordance with the American Urological Association/American Society for Radiation Oncology/American Society of Clinical Oncology/Society of Urologic Oncology guidelines.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adjuvant Cohort: Disease Free Survival (DFS)
Timepoint [1] 0 0
Up to approximately 28 months
Primary outcome [2] 0 0
Perioperative Cohort: Number of Participants Who Experience an Adverse Event (AE)
Timepoint [2] 0 0
Up to approximately 19 months
Primary outcome [3] 0 0
Perioperative Cohort: Number of Participants Who Discontinue Study Treatment Due to AE
Timepoint [3] 0 0
Up to approximately 16 months
Secondary outcome [1] 0 0
Adjuvant Cohort: Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 28 months
Secondary outcome [2] 0 0
Adjuvant Cohort: Distant Metastasis-Free Survival (DMFS)
Timepoint [2] 0 0
Up to approximately 28 months
Secondary outcome [3] 0 0
Adjuvant Cohort: Number of Participants Who Experience an AE
Timepoint [3] 0 0
Up to approximately 16 months
Secondary outcome [4] 0 0
Adjuvant Cohort: Number of Participants Who Discontinue Study Treatment Due to an AE
Timepoint [4] 0 0
Up to approximately 13 months
Secondary outcome [5] 0 0
Perioperative Cohort: Pathologic Complete Response (pCR) Rate
Timepoint [5] 0 0
Up to approximately 18 weeks
Secondary outcome [6] 0 0
Perioperative Cohort: Pathologic Downstaging (pDS) Rate
Timepoint [6] 0 0
Up to approximately 18 weeks

Eligibility
Key inclusion criteria
The main inclusion criteria include but are not limited to the following:

* Must provide blood samples per protocol, to enable V940 production, and circulating tumor deoxyribonucleic acid testing
* Has an Eastern Cooperative Oncology Group performance status of 0 to 2 assessed within 7 days before randomization
* Must provide a formalin-fixed paraffin-embedded tumor tissue sample for next generation sequencing

Adjuvant Cohort:

* Has MIUC
* Has dominant histology of urothelial carcinoma (UC)
* Has high-risk pathologic disease after radical resection
* For participants who have not received cisplatin-based neoadjuvant chemotherapy, are ineligible to receive cisplatin according to protocol pre-defined criteria

Perioperative Cohort:

* Has MIBC
* Has a histological diagnosis of UC
* Is deemed eligible for RC and PLND and agrees to undergo curative intent standard RC and PLND and neoadjuvant and adjuvant treatment per protocol
* Is ineligible to receive cisplatin according to protocol pre-defined criteria
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The main exclusion criteria include but are not limited to the following:

* 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 current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy
* Has active hepatitis B and hepatitis C virus infection

Adjuvant Cohort:

* Has received prior systemic anticancer therapy
* Has received prior neoadjuvant therapy, with the exception of neoadjuvant cisplatin-based chemotherapy for MIUC
* Has severe hypersensitivity to either V940 or pembrolizumab (MK-3475) and/or any of their excipients

Perioperative Cohort:

* Has received any prior systemic treatment, cancer vaccine treatment, chemoradiation, and/or radiation therapy treatment for MIBC
* Has severe hypersensitivity to either V940, pembrolizumab, or EV and/or any of their excipients
* Has ongoing sensory or motor neuropathy
* Has active keratitis or corneal ulcerations

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/03/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
8/04/2031
Actual
Sample size
Target
230
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Macquarie University-MQ Health Clinical Trials Unit ( Site 1803) - Macquarie University
Recruitment hospital [2] 0 0
Westmead Hospital-Department of Medical Oncology ( Site 1802) - Westmead
Recruitment hospital [3] 0 0
One Clinical Research ( Site 1807) - Nedlands
Recruitment postcode(s) [1] 0 0
2109 - Macquarie University
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Canada
State/province [10] 0 0
British Columbia
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Chile
State/province [12] 0 0
Region M. De Santiago
Country [13] 0 0
Chile
State/province [13] 0 0
Valparaiso
Country [14] 0 0
Colombia
State/province [14] 0 0
Cesar
Country [15] 0 0
Colombia
State/province [15] 0 0
Distrito Capital De Bogota
Country [16] 0 0
Colombia
State/province [16] 0 0
Valle Del Cauca
Country [17] 0 0
France
State/province [17] 0 0
Haute-Garonne
Country [18] 0 0
France
State/province [18] 0 0
Ile-de-France
Country [19] 0 0
France
State/province [19] 0 0
Maine-et-Loire
Country [20] 0 0
France
State/province [20] 0 0
Nord
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
Germany
State/province [22] 0 0
Bayern
Country [23] 0 0
Germany
State/province [23] 0 0
Sachsen-Anhalt
Country [24] 0 0
Germany
State/province [24] 0 0
Sachsen
Country [25] 0 0
Germany
State/province [25] 0 0
Berlin
Country [26] 0 0
Italy
State/province [26] 0 0
Lazio
Country [27] 0 0
Italy
State/province [27] 0 0
Liguria
Country [28] 0 0
Italy
State/province [28] 0 0
Lombardia
Country [29] 0 0
Italy
State/province [29] 0 0
Napoli
Country [30] 0 0
Italy
State/province [30] 0 0
Milano
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Seoul
Country [32] 0 0
New Zealand
State/province [32] 0 0
Auckland
Country [33] 0 0
Peru
State/province [33] 0 0
Lima
Country [34] 0 0
Poland
State/province [34] 0 0
Kujawsko-pomorskie
Country [35] 0 0
Poland
State/province [35] 0 0
Mazowieckie
Country [36] 0 0
Poland
State/province [36] 0 0
Swietokrzyskie
Country [37] 0 0
Poland
State/province [37] 0 0
Wielkopolskie
Country [38] 0 0
Poland
State/province [38] 0 0
Zachodniopomorskie
Country [39] 0 0
Spain
State/province [39] 0 0
Barcelona
Country [40] 0 0
Spain
State/province [40] 0 0
Madrid, Comunidad De
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid
Country [42] 0 0
Spain
State/province [42] 0 0
Sevilla
Country [43] 0 0
Sweden
State/province [43] 0 0
Stockholms Lan
Country [44] 0 0
Sweden
State/province [44] 0 0
Uppsala Lan
Country [45] 0 0
Turkey
State/province [45] 0 0
Ankara
Country [46] 0 0
Turkey
State/province [46] 0 0
Istanbul
Country [47] 0 0
Turkey
State/province [47] 0 0
Izmir
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Devon
Country [49] 0 0
United Kingdom
State/province [49] 0 0
England
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Glasgow City
Country [51] 0 0
United Kingdom
State/province [51] 0 0
London, City Of
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
ModernaTX, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Researchers are looking for new ways to treat people with high-risk muscle-invasive urothelial carcinoma (MIUC). Urothelial carcinoma is a type of bladder cancer that begins in cells that line the inside of the bladder and other parts of the urinary tract, such as part of the kidneys, ureters, and urethra. People with MIUC usually have chemotherapy before surgery, then surgery to remove the cancer. Chemotherapy is a type of medicine to destroy cancer cells or stop them from growing. After surgery, some people receive more treatment to prevent cancer from returning. Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Enfortumab vedotin (EV) is an antibody drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. Researchers want to learn if giving V940 (the study treatment) with pembrolizumab can prevent MIUC from returning after surgery. V940 (also called mRNA-4157) is designed to treat each person's cancer by helping the person's immune system identify and kill cancer cells based on certain proteins found on those cancer cells.

The goals of this study are to learn if people who receive V940 and pembrolizumab are alive and cancer free longer than those who receive placebo and pembrolizumab, and to learn about the safety of V940, pembrolizumab, and EV, and if people tolerate them.
Trial website
https://clinicaltrials.gov/study/NCT06305767
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06305767