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

Phase 2
Active, not recruiting
Conditions
Renal Cell Carcinoma
Interventions
Registration Number
NCT06307431
Lead Sponsor
Merck Sharp & Dohme LLC
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
272
Inclusion Criteria
  • 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.
Exclusion Criteria
  • 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 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intismeran autogene + PembrolizumabIntismeran autogeneParticipants 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.
Intismeran autogene + PembrolizumabPembrolizumabParticipants 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.
Placebo + PembrolizumabPembrolizumabParticipants 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.
Placebo + PembrolizumabPlaceboParticipants 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.
Primary Outcome Measures
NameTimeMethod
Disease-Free Survival (DFS)up to ~43 months

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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Who Experience an Adverse Event (AE)up to ~15 months

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants that experience at least one AE will be reported.

Overall Survival (OS)up to ~96 months

OS is defined as the time from randomization to death due to any cause.

Percentage of Participants Who Discontinue Study Treatment Due to an AEup to ~12 months

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants who discontinue study treatment due to an AE will be reported.

Distant Metastasis-free survival (DMFS)up to ~ 43 months

DMFS is defined as the time from randomization to the first diagnosis of a distant metastasis, or death due to any cause, whichever occurs first. Distant metastasis refers to cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes.

Trial Locations

Locations (63)

Westmead Hospital ( Site 1501)

🇦🇺

Westmead, New South Wales, Australia

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

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Duarte, California, United States

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

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Los Angeles, California, United States

UCSF Medical Center at Mission Bay ( Site 0108)

🇺🇸

San Francisco, California, United States

CHU Besançon ( Site 0302)

🇫🇷

Besançon, Doubs, France

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

🇺🇸

New Haven, Connecticut, United States

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

🇺🇸

Boston, Massachusetts, United States

Dana-Farber Cancer Institute-GU ( Site 0101)

🇺🇸

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center ( Site 0100)

🇺🇸

New York, New York, United States

Duke Cancer Institute ( Site 0106)

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Durham, North Carolina, United States

Abramson Cancer Center ( Site 0107)

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Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center ( Site 0111)

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Philadelphia, Pennsylvania, United States

UT Southwestern Medical Center ( Site 0110)

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Dallas, Texas, United States

Hospital Británico de Buenos Aires-Oncology ( Site 1106)

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Ciudad autónoma de Buenos Aires, Buenos Aires, Argentina

Asociación de Beneficencia Hospital Sirio Libanés ( Site 1110)

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Buenos Aires, Caba, Argentina

Instituto Alexander Fleming-Alexander Fleming ( Site 1101)

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Ciudad Autónoma de Buenos Aires, Caba, Argentina

Centro Privado de RMI Rio Cuarto ( Site 1104)

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Río Cuarto, Cordoba, Argentina

Fundacion Estudios Clinicos ( Site 1111)

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Rosario, Santa Fe, Argentina

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

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Macquarie University, New South Wales, Australia

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

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Brisbane, Queensland, Australia

Fiona Stanley Hospital-Medical Oncology ( Site 1503)

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Murdoch, Western Australia, Australia

BC Cancer Vancouver ( Site 0005)

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Vancouver, British Columbia, Canada

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

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Québec, Quebec, Canada

Bradfordhill-Clinical Area ( Site 1201)

🇨🇱

Santiago., Region M. De Santiago, Chile

FALP-UIDO ( Site 1202)

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Santiago, Region M. De Santiago, Chile

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

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Santiago, Region M. De Santiago, Chile

ONCOCENTRO APYS-ACEREY ( Site 1200)

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Viña del Mar, Valparaiso, Chile

Institut Claudius Regaud ( Site 0303)

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Toulouse, Haute-Garonne, France

Gustave Roussy ( Site 0304)

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Villejuif, Ile-de-France, France

CENTRE LEON BERARD ( Site 0305)

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Lyon Cedex08, Rhone-Alpes, France

Hôpital Européen Georges Pompidou ( Site 0300)

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Paris, France

Klinikum Stuttgart - Katharinenhospital ( Site 0400)

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Stuttgart, Baden-Wurttemberg, Germany

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

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Munich, Bayern, Germany

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

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Dresden, Sachsen, Germany

Universitätsklinikum Jena ( Site 0402)

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Jena, Thuringen, Germany

Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0401)

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Berlin, Germany

Asklepios Altona-Department of Urology ( Site 0410)

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Hamburg, Germany

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

🇮🇹

Roma, Lazio, Italy

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

🇮🇹

Milan, Lombardia, Italy

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

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Firenze, Toscana, Italy

Azienda Ospedaliero Universitaria di Parma ( Site 0503)

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Parma, Italy

Seoul National University Hospital ( Site 1600)

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Seoul, Korea, Republic of

Severance Hospital, Yonsei University Health System ( Site 1603)

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Seoul, Korea, Republic of

Asan Medical Center ( Site 1602)

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Seoul, Korea, Republic of

Samsung Medical Center ( Site 1601)

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Seoul, Korea, Republic of

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

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Bydgoszcz, Kujawsko-pomorskie, Poland

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

🇵🇱

Warszawa, Mazowieckie, Poland

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

🇵🇱

Koszalin, Zachodniopomorskie, Poland

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

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Madrid, Madrid, Comunidad De, Spain

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

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Barcelona, Spain

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

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Sevilla, Spain

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

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Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan

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

🇨🇳

Taichung, Taiwan

Taichung Veterans General Hospital ( Site 1704)

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Taichung, Taiwan

Taipei Veterans General Hospital ( Site 1703)

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Taipei, Taiwan

Hacettepe Universite Hastaneleri-oncology hospital ( Site 0901)

🇹🇷

Ankara, Turkey

Ankara Universitesi Tip Fakultesi Hastanesi-Oncology ( Site 0902)

🇹🇷

Ankara, Turkey

Ege Universitesi Hastanesi-Medical Oncology ( Site 0903)

🇹🇷

Izmir, Turkey

Addenbrooke's Hospital ( Site 1004)

🇬🇧

Cambridge, Cambridgeshire, United Kingdom

Gartnavel General Hospital-Clinical Trials Unit ( Site 1002)

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Glasgow, Glasgow City, United Kingdom

St Bartholomew's Hospital ( Site 1000)

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London, London, City Of, United Kingdom

Western General Hospital ( Site 1003)

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Edinburgh, Midlothian, United Kingdom

The Christie NHS Foundation Trust ( Site 1001)

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Manchester, United Kingdom

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