A clinical study of V940 treatment and pembrolizumab in people with bladder cancer (V940-005)

2023-505658-17-00 Protocol V940-005 Therapeutic exploratory (Phase II) Ongoing, recruitment ended

Start 16 Apr 2024 · Status Ongoing, recruitment ended · 6 EU/EEA countries · 27 sites · Protocol V940-005

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ongoing, recruitment ended
Participants planned 237
Countries 6
Sites 27

Muscle-invasive Urothelial Carcinoma

1. Adjuvant Cohort: To compare V940 plus pembrolizumab to placebo plus pembrolizumab with respect to DFS. 2. Perioperative Cohort: To evaluate the safety and tolerability of V940 plus pembrolizumab plus EV

Key facts

Sponsor
Merck Sharp & Dohme LLC
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
16 Apr 2024 → ongoing
Decision date (initial)
2024-03-28
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Moderna · Merck Sharp & Dohme LLC

External identifiers

EU CT number
2023-505658-17-00
WHO UTN
U1111-1292-1952

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacodynamic, Efficacy, Pharmacokinetic

1. Adjuvant Cohort: To compare V940 plus pembrolizumab to placebo plus pembrolizumab with respect to DFS.
2. Perioperative Cohort: To evaluate the safety and tolerability of V940 plus pembrolizumab plus EV

Secondary objectives 5

  1. Adjuvant Cohort: To evaluate OS in participants treated with V940 plus pembrolizumab and placebo plus pembrolizumab
  2. Adjuvant Cohort: To evaluate DMFS as assessed by investigator in participants treated with V940 plus pembrolizumab and placebo plus pembrolizumab
  3. Adjuvant Cohort: To evaluate the safety and tolerability of V940 plus pembrolizumab
  4. Perioperative Cohort: To evaluate pCR as assessed by the local pathologist in participants treated with V940 plus pembrolizumab plus EV
  5. Perioperative Cohort: To evaluate pDS as assessed by the investigator in participants treated with V940 plus pembrolizumab plus EV

Conditions and MedDRA coding

Muscle-invasive Urothelial Carcinoma

VersionLevelCodeTermSystem organ class
20.0 LLT 10064467 Urothelial carcinoma 10029104

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

  1. Has a histological diagnosis of UC
  2. Must provide blood samples per protocol, to enable V940 production, and circulating tumor Deoxyribonucleic acid (ctDNA) testing
  3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before randomization
  4. Must provide a formalin-fixed paraffin-embedded (FFPE) tumor tissue sample for next generation sequencing (NGS)
  5. Adjuvant Cohort: Has muscle-invasive urothelial carcinoma (MIUC)
  6. Adjuvant Cohort: Has high-risk pathologic disease after radical resection
  7. Adjuvant Cohort: For participants who have not received cisplatin-based neoadjuvant chemotherapy, are ineligible to receive cisplatin according to protocol pre-defined criteria
  8. Perioperative Cohort: Has muscle-invasive bladder cancer (MIBC)
  9. Perioperative Cohort: Is deemed eligible for radical cystectomy (RC) and pelvic lymph node dissection (PLND) and agrees to undergo curative intent standard RC and PLND and neoadjuvant and adjuvant treatment per protocol
  10. Perioperative Cohort: Is ineligible to receive cisplatin according to protocol pre-defined criteria

Exclusion criteria 12

  1. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  2. Has known additional malignancy that is progressing or has required active treatment ≤3 years prior to study randomization
  3. Has current pneumonitis/interstitial lung disease
  4. Has active infection requiring systemic therapy
  5. Has active hepatitis B and hepatitis C virus infection
  6. Adjuvant Cohort: Has received prior systemic anticancer therapy
  7. Adjuvant Cohort: Has received prior neoadjuvant therapy, with the exception of neoadjuvant cisplatin-based chemotherapy for MIUC
  8. Adjuvant Cohort: Has severe hypersensitivity to either V940 or pembrolizumab (MK-3475) and/or any of their excipients
  9. Perioperative Cohort: Has received any prior systemic treatment, cancer vaccine treatment, chemoradiation, and/or radiation therapy treatment for MIBC
  10. Perioperative Cohort: Has severe hypersensitivity to either V940, pembrolizumab, or enfortumab vedotin (EV) and/or any of their excipients
  11. Perioperative Cohort: Has ongoing sensory or motor neuropathy
  12. Perioperative Cohort: Has active keratitis or corneal ulcerations

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

  1. Adjuvant Cohort: Disease-Free Survival (DFS)
  2. Perioperative Cohort: Number of Participants Who Experience an Adverse Event (AE)
  3. Perioperative Cohort: Number of Participants Who Discontinue Study Treatment Due to AE

Secondary endpoints 6

  1. Adjuvant Cohort: Overall-Survival (OS)
  2. Adjuvant Cohort: Distant Metastasis-Free Survival (DMFS)
  3. Adjuvant Cohort: Number of Participants Who Experience an AE
  4. Adjuvant Cohort: Number of Participants Who Discontinue Study Treatment Due to an AE
  5. Perioperative Cohort: Pathologic Complete Response (pCR) Rate
  6. Perioperative Cohort: Pathologic Downstaging (pDS) Rate

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

—

SCP56433228 · ATC

Route of administration
INTRAVENOUS INFUSION
Max daily dose
125 mg milligram(s)
Max total dose
2250 mg milligram(s)
Max treatment duration
27 Week(s)
Authorisation status
Authorised
ATC code
L01FX13 — ENFORTUMAB VEDOTIN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

KEYTRUDA 25 mg/mL concentrate for solution for infusion

PRD4323105 · Product

Active substance
Pembrolizumab
Substance synonyms
Lambrolizumab, MK-3475, SCH-900475, ABP 234
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
400 mg milligram(s)
Max total dose
3600 mg milligram(s)
Max treatment duration
54 Week(s)
Authorisation status
Authorised
ATC code
L01FF02 — -
Marketing authorisation
EU/1/15/1024/002
MA holder
MERCK SHARP & DOHME B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

mRNA-4157

PRD10340373 · Product

Active substance
MRNA-4157
Pharmaceutical form
DISPERSION FOR INJECTION
Route of administration
INTRAMUSCULAR INJECTION
Max daily dose
1 mg milligram(s)
Max total dose
9 mg milligram(s)
Max treatment duration
27 Week(s)
Authorisation status
Not Authorised
MA holder
MODERNATX, INC.
Paediatric formulation
No
Orphan designation
No

Placebo 1

Placebo to V940

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

290 Total trials 92 Recruiting 184 Ended
Commercial
Sponsor organisation
Merck Sharp & Dohme LLC
Address
126 East Lincoln Avenue
City
Rahway
Postcode
07065-4607
Country
United States

Scientific contact point

Organisation
Merck Sharp & Dohme LLC
Contact name
Abhi Bavle

Public contact point

Organisation
Merck Sharp & Dohme LLC
Contact name
Abhi Bavle

Third parties 8

OrganisationCity, countryDuties
Bioclinica Inc.
ORG-100033079
 Princeton, United States Other
Personalis Inc.
ORG-100043141
 Fremont, United States Laboratory analysis
Q Squared Solutions LLC.
ORL-000008178
 Valencia, United States Laboratory analysis
Fortrea Inc.
ORG-100012602
 Durham, United States Other
Pharmaceutical Product Development LLC
ORG-100016999
 Highland Heights, United States Laboratory analysis
Parexel International Corp.
ORG-100007310
 Auburndale, United States Other
Almac
ORG-100013160
 Souderton, United States Interactive response technologies (IRT)
Natera Inc.
ORG-100045860
 Austin, United States Laboratory analysis

Locations

6 EU/EEA countries · 27 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruitment ended 14 5
Germany Ongoing, recruitment ended 11 5
Italy Ongoing, recruitment ended 25 5
Poland Ongoing, recruitment ended 16 5
Spain Ongoing, recruitment ended 17 5
Sweden Ongoing, recruitment ended 7 2
Rest of world
United Kingdom, Korea, Republic of, Canada, Turkey, Peru, Colombia, Chile, New Zealand, United States, Australia
 — 147 —

Investigational sites

France

5 sites · Ongoing, recruitment ended
Institut De Cancerologie De L Ouest
Oncologie, 15 Rue Andre Boquel, 49100, Angers
Assistance Publique Hopitaux De Paris
Oncologie médicale, 1 Avenue Claude Vellefaux, 75010, Paris
Institut Gustave Roussy
Innovation Thérapeutique et des Essais Précoces, 114 Rue Edouard Vaillant, 94800, Villejuif
Centre Hospitalier Universitaire De Lille
Urologie, Andrologie, Transplantation rénale, Rue Michel Polonovski, 59037, Lille Cedex
Institut Universitaire Du Cancer Toulouse-Oncopole
Oncologie médical, 1 Avenue Irene Joliot Curie, 31059, Toulouse Cedex 9

Germany

5 sites · Ongoing, recruitment ended
Universitaetsklinikum Regensburg AöR
Klinik fuer Urologie, Landshuter Strasse 65, Kasernenviertel, Regensburg
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
Klinik und Poliklinik fure Urologie, Fetscherstrasse 74, Johannstadt-Nord, Dresden
Universitaetsklinikum Halle (Saale) AöR
Universitaetsklinik und Poliklinik fuer Urologie, Ernst-Grube-Strasse 40, Kroellwitz, Halle Saale
Charite Universitaetsmedizin Berlin KöR
Klinik fuer Urologie, Chariteplatz 1, Mitte, Berlin
Klinikum rechts der Isar der TU Muenchen AöR
Urologische Klinik und Poliklinik, Ismaninger Strasse 22, Au-Haidhausen, Munich

Italy

5 sites · Ongoing, recruitment ended
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Oncologia Medica, Largo Francesco Vito 1, 00168, Rome
Ospedale San Raffaele S.r.l.
Oncologia Medica, Via Olgettina 60, 20132, Milan
Fondazione IRCCS Istituto Nazionale Dei Tumori
Oncologia Medica, Via Giacomo Venezian 1, 20133, Milan
IRCCS Ospedale Policlinico San Martino
Oncologia Medica 1, Largo Rosanna Benzi 10, 16132, Genoa
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
Oncologia Medica, Via Antonio Cardarelli 9, 80131, Naples

Poland

5 sites · Ongoing, recruitment ended
Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Kielcach
Klinika Onkologii Klinicznej, Ul. Prezydenta Stefana Artwinskiego 3, 25-734, Kielce
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Klinika Nowotworów Układu Moczowego, Ul. Wilhelma Konrada Roentgena 5, 02-781, Warsaw
Szpital Wojewodzki Im. Mikolaja Kopernika W Koszalinie
Oddział Onkologii Klinicznej z Pododdziałem Chemioterapii Jednodniowej., Ul. Tytusa Chalubinskiego 7, 75-581, Koszalin
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Ambulatorium Chemioterapii, Ul. Izabeli Romanowskiej 2, 85-796, Bydgoszcz
Clinical Research Center Sp. z o.o. Medic-R sp.k.
N/A, Ul. Feliksa Nowowiejskiego 5, 61-731, Poznan

Spain

5 sites · Ongoing, recruitment ended
University Hospital Virgen Del Rocio S.L.
Medical oncology, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Universitario Quironsalud Madrid
Oncology, Calle De Diego De Velazquez 1, 28223, Pozuelo De Alarcon
Institut Catala D'oncologia
Oncology, Carretera Canyet S/n, 08916, Badalona
Hospital Universitario Ramon Y Cajal
Oncology, Carretera Del Colmenar Viejo Km 9 100, Por El Pardo, Madrid
Hospital Universitari Vall D Hebron
Oncology, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona

Sweden

2 sites · Ongoing, recruitment ended
Karolinska University Hospital
Urologisk onkologi, Eugeniavagen 3, 171 64, Solna
Uppsala University Hospital
Oncology, Akademiska Sjukhuset, 751 85, Uppsala

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2024-04-29 2024-05-21 2025-11-03
Germany 2024-05-08 2024-06-18 2026-02-05
Italy 2024-05-10 2024-06-03 2025-10-03
Poland 2024-04-18 2024-04-18 2025-10-23
Spain 2024-04-16 2024-04-30 2025-11-03
Sweden 2024-05-07 2024-06-27 2026-02-05

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2023-505658-17_SM05_for pub 03R
Recruitment arrangements (for publication) K1_Recruitment Arrangements and IC Procedure_DEU_EN_SM04_for pub 2.0
Recruitment arrangements (for publication) K1_Recruitment Arrangements and IC Procedure_ESP_ES_for pub 13SEP2023R
Recruitment arrangements (for publication) K1_Recruitment Arrangements and IC Procedure_FRA_FR_for pub 12FEB2024
Recruitment arrangements (for publication) K1_Recruitment Arrangements and IC Procedure_ITA_EN_SM04_for pub 2.0
Recruitment arrangements (for publication) K1_Recruitment Arrangements and IC Procedure_POL_PL_for pub 1.0
Recruitment arrangements (for publication) K1_Recruitment Arrangements and IC Procedure_SWE_SV_for pub 1.0
Recruitment arrangements (for publication) K1_Recruitment Arrangements_FRA_EN_for pub outofscope
Recruitment arrangements (for publication) K1_Recruitment Doc Advertisment_AC_DEU_DE_SM04_for pub 00.1
Recruitment arrangements (for publication) K1_Recruitment Doc Advertisment_PVG_DEU_DE_SM04_for pub 00.1
Recruitment arrangements (for publication) K1_Recruitment Doc Advertisment_TYC_DEU_DE_SM04_for pub 00.1
Recruitment arrangements (for publication) K2_Recruitment Doc Patient Brochure_DEU_DE_for pub 00.1
Recruitment arrangements (for publication) K2_Recruitment Doc Patient Brochure_FRA_FR_for pub 00.1
Recruitment arrangements (for publication) K2_Recruitment Doc Patient Brochure_SWE_SV_for pub 00.1
Subject information and informed consent form (for publication) L1_ICF Main consent_Adjuvant Cohort_DEU_DE_SM06_for pub AM02v2.02R
Subject information and informed consent form (for publication) L1_ICF Main consent_Perioperative Cohort_DEU_DE_SM06_for pub AM01v1.02R
Subject information and informed consent form (for publication) L1_ICF_Main consent perioperative_SWE_SV_SM06_for pub AM01 v1.02
Subject information and informed consent form (for publication) L1_ICF_Main consent_Adjuvant Cohort_ITA_IT_SM06_for pub AM02v2.02
Subject information and informed consent form (for publication) L1_ICF_Main consent_Adjuvant Cohort_POL_PL_SM06_for pub 2.02R
Subject information and informed consent form (for publication) L1_ICF_Main consent_ESP_ES_SM06_for pub AM02v2.02R
Subject information and informed consent form (for publication) L1_ICF_Main consent_FRA_FR_SM06_for pub AM02v2.01R
Subject information and informed consent form (for publication) L1_ICF_Main consent_Perioperative Cohort_POL_PL_SM05_for pub 1.00R
Subject information and informed consent form (for publication) L1_ICF_Main consent_SWE_SV_SM06_for pub AM02 v2.02
Subject information and informed consent form (for publication) L1_ICF_Main data privacy_ITA_IT_SM04_for pub 26NOV2024
Subject information and informed consent form (for publication) L1_ICF_Optional Crossborder_DEU_DE_SM04_for pub 0.01R
Subject information and informed consent form (for publication) L1_ICF_Optional_DILI sample_ITA_IT_SM04_for pub 26NOV2024
Subject information and informed consent form (for publication) L1_ICF_Optional_Greenphire adults_SWE_SV_SM04_for pub AM01v1.00
Subject information and informed consent form (for publication) L1_ICF_Optional_Pregnancy Follow up_ESP_ES_SM04_for pub 0.00
Subject information and informed consent form (for publication) L1_ICF_Optional_Pregnant Partner_ESP_ES_SM04_for pub 0.00
Subject information and informed consent form (for publication) L1_Patient Information Leaflet_Keytruda 01DEC2023
Summary of Product Characteristics (SmPC) (for publication) E2_ SmPC RSI_ENFORTUMAB VEDOTIN Astellas Pharma Ltd_SM06_for pub 23SEP2025
Synopsis of the protocol (for publication) D1_PPLS_2023-505658-17_DEU_EN_SM04_for pub 2.0
Synopsis of the protocol (for publication) D1_PPLS_2023-505658-17_ESP_ES_SM04_for pub 2.0
Synopsis of the protocol (for publication) D1_PPLS_2023-505658-17_FRA_FR_SM04_for pub 2.0
Synopsis of the protocol (for publication) D1_PPLS_2023-505658-17_ITA_IT_SM04_for pub 2.0
Synopsis of the protocol (for publication) D1_PPLS_2023-505658-17_POL_PL_SM04_for pub 2.0
Synopsis of the protocol (for publication) D1_PPLS_2023-505658-17_SM04_for pub 2.0
Synopsis of the protocol (for publication) D1_PPLS_2023-505658-17_SWE_SV_SM04_for pub 2.0

Application history

12 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-11-13 Sweden Acceptable
2024-03-28
 2024-03-28
2 SUBSTANTIAL MODIFICATION SM-1 2024-04-04 Acceptable 2024-04-26
3 SUBSTANTIAL MODIFICATION SM-2 2024-04-15 Acceptable 2024-05-21
4 SUBSTANTIAL MODIFICATION SM-3 2024-05-30 Sweden Acceptable
2024-08-19
 2024-08-20
5 NON SUBSTANTIAL MODIFICATION NSM-1 2024-09-17 Sweden Acceptable
2024-08-19
 2024-09-17
6 SUBSTANTIAL MODIFICATION SM-4 2024-12-19 Sweden Acceptable
2025-04-09
 2025-04-11
7 NON SUBSTANTIAL MODIFICATION NSM-2 2025-04-17 Acceptable
2025-04-09
 2025-04-17
8 NON SUBSTANTIAL MODIFICATION NSM-3 2025-06-09 Acceptable
2025-04-09
 2025-06-09
9 SUBSTANTIAL MODIFICATION SM-5 2025-07-07 Sweden Acceptable
2025-09-29
 2025-09-30
10 NON SUBSTANTIAL MODIFICATION NSM-4 2025-10-06 Sweden Acceptable
2025-09-29
 2025-10-06
11 SUBSTANTIAL MODIFICATION SM-6 2026-01-07 Sweden Acceptable
2026-03-19
 2026-03-19
12 NON SUBSTANTIAL MODIFICATION NSM-5 2026-05-21 Sweden Acceptable
2026-03-19
 2026-05-21

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