A Study of Adjuvant Intismeran Autogene (V940) and Pembrolizumab in Renal Cell Carcinoma (V940-004).

NCT06307431 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: V940-0042023-505177-32-00U1111-1291-1851
• Study Type: interventional
• Target: 272
• Locations: 14 countries
• Sites: 63

Brief Summary

The primary objective of the study is to compare intismeran autogene plus pembrolizumab to placebo plus pembrolizumab in participants with renal cell carcinoma (RCC) with respect to disease-free survival (DFS) as assessed by the investigator. The primary hypothesis is that intismeran autogene plus pembrolizumab is superior to placebo plus pembrolizumab with respect to DFS.

Conditions

Renal Cell Carcinoma

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1(PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (1)

• Disease-Free Survival (DFS)

  DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, or occurrence of distant kidney cancer metastasis(es), or death due to any cause, whichever occurs first.

  up to ~43 months

Secondary Outcomes (4)

• Overall Survival (OS)

  up to ~96 months

• Distant Metastasis-free survival (DMFS)

  up to ~ 43 months

• Percentage of Participants Who Experience an Adverse Event (AE)

  up to ~15 months

• Percentage of Participants Who Discontinue Study Treatment Due to an AE

  up to ~12 months

Study Arms (2)

Intismeran autogene + Pembrolizumab

EXPERIMENTAL

Participants will receive intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks (Q3W) for up to 9 doses plus Pembrolizumab 400 mg via an intravenous (IV) infusion every 6 weeks (Q6W) for 9 cycles (up to \~54 weeks). Each cycle is 6 weeks.

Biological: Intismeran autogene; Biological: Pembrolizumab

Placebo + Pembrolizumab

ACTIVE COMPARATOR

Participants will receive placebo as an IM injection Q3W for up to 9 doses plus Pembrolizumab 400 mg via an IV infusion Q6W for 9 cycles (up to \~54 weeks). Each cycle is 6 weeks.

Biological: Pembrolizumab; Biological: Placebo

Interventions

Intismeran autogene BIOLOGICAL

IM injection

Also known as: mRNA-4157, V940

Intismeran autogene + Pembrolizumab

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Intismeran autogene + Pembrolizumab; Placebo + Pembrolizumab

Placebo BIOLOGICAL

IM injection

Placebo + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has histologically or cytologically confirmed diagnosis of renal cell carcinoma (RCC) with clear cell or papillary histology.
• Has intermediate-high-risk, high-risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node metastasis and tumor grading:
• Intermediate-high-risk RCC: pT2 Gr4, N0, M0; pT3 Gr3/4, N0, M0
• High-risk RCC: pT4, N0, M0; pT any stage, N1, M0
• M1 NED RCC participants who present not only with the primary kidney tumor, but also solid, isolated, soft tissue metastases that can be completely resected at 1 of the following: the time of nephrectomy (synchronous), or ≤2 years from nephrectomy (metachronous)
• Has undergone complete resection of the primary tumor (partial or radical nephrectomy) and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants.
• Must have undergone a nephrectomy and/or metastasectomy ≤12 weeks prior to randomization and recovered from surgery and any post-operative complications before randomization.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization.

You may not qualify if:

• Has had a major surgery other than nephrectomy plus resection of preexisting metastases for M1 NED participants, within 4 weeks prior to randomization.
• Has residual thrombus post nephrectomy in the vena renalis or vena cava.
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
• Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Received prior treatment with a cancer vaccine.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has a history of brain or bone metastatic lesions.
• Has severe hypersensitivity to study medication or any of the substances used to prepare the study medication.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• History of allogeneic tissue/solid organ transplant
• Has not adequately recovered from major surgery or has ongoing surgical complications

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• ModernaTX, Inc.: collaborator

Study Sites (63)

City of Hope Comprehensive Cancer Center-Medical Oncology ( Site 0104)

Duarte, California, 91010, United States

Location

UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro

Los Angeles, California, 90095, United States

Location

UCSF Medical Center at Mission Bay ( Site 0108)

San Francisco, California, 94158, United States

Location

Yale-New Haven Hospital-Yale Cancer Center ( Site 0102)

New Haven, Connecticut, 06510, United States

Location

Beth Israel Deaconess Medical Center-Cancer Clinical Trials Office ( Site 0109)

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute-GU ( Site 0101)

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center ( Site 0100)

New York, New York, 10065, United States

Location

Duke Cancer Institute ( Site 0106)

Durham, North Carolina, 27710, United States

Location

Abramson Cancer Center ( Site 0107)

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center ( Site 0111)

Philadelphia, Pennsylvania, 19111, United States

Location

UT Southwestern Medical Center ( Site 0110)

Dallas, Texas, 75390, United States

Location

Hospital Británico de Buenos Aires-Oncology ( Site 1106)

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1280AEB, Argentina

Location

Instituto Alexander Fleming-Alexander Fleming ( Site 1101)

Buenos Aires, Buenos Aires F.D., 1426ANZ, Argentina

Location

Asociación de Beneficencia Hospital Sirio Libanés ( Site 1110)

Buenos Aires, Buenos Aires F.D., C1419AHN, Argentina

Location

Centro Privado de RMI Rio Cuarto ( Site 1104)

Río Cuarto, Córdoba Province, X5800ALB, Argentina

Location

Fundacion Estudios Clinicos ( Site 1111)

Rosario, Santa Fe Province, S2000CEJ, Argentina

Location

Macquarie University-MQ Health Clinical Trials Unit ( Site 1502)

Macquarie University, New South Wales, 2109, Australia

Location

Westmead Hospital ( Site 1501)

Westmead, New South Wales, 2145, Australia

Location

Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si

Brisbane, Queensland, 4029, Australia

Location

Fiona Stanley Hospital-Medical Oncology ( Site 1503)

Murdoch, Western Australia, 6150, Australia

Location

BC Cancer Vancouver ( Site 0005)

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CHU de Quebec - Université Laval - Hotel Dieu de Quebec ( Site 0008)

Québec, Quebec, G1R 2J6, Canada

Location

FALP-UIDO ( Site 1202)

Santiago, Region M. de Santiago, 7500921, Chile

Location

Pontificia Universidad Catolica de Chile-Centro del Cáncer ( Site 1205)

Santiago, Region M. de Santiago, 8330073, Chile

Location

Bradfordhill-Clinical Area ( Site 1201)

Santiago, Region M. de Santiago, 8420383, Chile

Location

ONCOCENTRO APYS-ACEREY ( Site 1200)

Viña del Mar, Región de Valparaíso, 2520598, Chile

Location

CENTRE LEON BERARD ( Site 0305)

Lyon Cedex08, Auvergne-Rhône-Alpes, 69373, France

Location

CHU Besançon ( Site 0302)

Besançon, Doubs, 25030, France

Location

Institut Claudius Regaud ( Site 0303)

Toulouse, Haute-Garonne, 31059, France

Location

Hôpital Européen Georges Pompidou ( Site 0300)

Paris, 75015, France

Location

Gustave Roussy ( Site 0304)

Villejuif, Île-de-France Region, 94805, France

Location

Klinikum Stuttgart - Katharinenhospital ( Site 0400)

Stuttgart, Baden-Wurttemberg, 70174, Germany

Location

klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Sit

Munich, Bavaria, 81675, Germany

Location

Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Urologie ( Site 0405)

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Jena ( Site 0402)

Jena, Thuringia, 07747, Germany

Location

Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0401)

Berlin, 10117, Germany

Location

Asklepios Altona-Department of Urology ( Site 0410)

Hamburg, 22763, Germany

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 0501)

Rome, Lazio, 00168, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0500)

Milan, Lombardy, 20133, Italy

Location

Azienda Ospedaliera Universitaria Careggi-SOD ONCOLOGIA MEDICA ( Site 0504)

Florence, Tuscany, 50134, Italy

Location

Azienda Ospedaliero Universitaria di Parma ( Site 0503)

Parma, 43126, Italy

Location

Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 0701)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Moczowego ( S

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0702)

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

Location

Seoul National University Hospital ( Site 1600)

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System ( Site 1603)

Seoul, 03722, South Korea

Location

Asan Medical Center ( Site 1602)

Seoul, 05505, South Korea

Location

Samsung Medical Center ( Site 1601)

Seoul, 06351, South Korea

Location

Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 0801)

Madrid, Madrid, Comunidad de, 28034, Spain

Location

Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0800)

Barcelona, 08035, Spain

Location

HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Medical Oncology ( Site 0802)

Seville, 41013, Spain

Location

Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 1701)

Kaohsiung Niao Sung Dist, Kaohsiung, 83301, Taiwan

Location

China Medical University Hospital-Department of Urology ( Site 1702)

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital ( Site 1704)

Taichung, 40705, Taiwan

Location

Taipei Veterans General Hospital ( Site 1703)

Taipei, 112, Taiwan

Location

Hacettepe Universite Hastaneleri-oncology hospital ( Site 0901)

Ankara, 06230, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi Hastanesi-Oncology ( Site 0902)

Ankara, Turkey (Türkiye)

Location

Ege Universitesi Hastanesi-Medical Oncology ( Site 0903)

Izmir, 35100, Turkey (Türkiye)

Location

Addenbrooke's Hospital ( Site 1004)

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

Location

Gartnavel General Hospital-Clinical Trials Unit ( Site 1002)

Glasgow, Glasgow City, G12 0YN, United Kingdom

Location

St Bartholomew's Hospital ( Site 1000)

London, London, City of, EC1A 7BE, United Kingdom

Location

Western General Hospital ( Site 1003)

Edinburgh, Midlothian, EH4 2XU, United Kingdom

Location

The Christie NHS Foundation Trust ( Site 1001)

Manchester, m20 4bx, United Kingdom

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Renal Cell; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2024
• First Posted: March 12, 2024
• Study Start: April 10, 2024
• Primary Completion (Estimated): January 8, 2028
• Study Completion (Estimated): June 8, 2032
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (11); AR (5); CA (2); CL (4); IT (4); DE (6); PL (3); FR (5); KR (4); TU (3); GB (5); AU (4); TW (4); ES (3)