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Pembrolizumab Plus Belzutifan With or Without Lenvatinib in Localized Renal Cell Carcinoma (Moonlanding)

18 mai 2026 mis à jour par: Vall d'Hebron Institute of Oncology

A Randomized Phase 2 Trial of Neoadjuvant Pembrolizumab Plus Belzutifan With or Without Lenvatinib in Patients With Localized Renal Cell Carcinoma

This study is designed to evaluate the efficacy of belzutifan in combination with pembrolizumab with or without lenvatinib in the neoadjuvant setting, followed by adjuvant pembrolizumab versus adjuvant pembrolizumab alone, as treatment for participants with intermediate-high and high risk clear cell renal cell carcinoma (ccRCC).

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

150

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

  • Nom: Cristina Suárez, Dr
  • Numéro de téléphone: +34 932543450
  • E-mail: csuarez@vhio.net

Lieux d'étude

  • Espagne
    • Andalusia
      • Córdoba, Andalusia, Espagne, 14004
        • Hospital Universitario Reina Sofia
        • Contact:
          • Mª José Méndez, Dr
          • Numéro de téléphone: +34 957010380
          • E-mail: mjosemv@yahoo.es
        • Chercheur principal:
          • Mª José Méndez, Dr
    • Aragon
      • Zaragoza, Aragon, Espagne, 50009
        • Hospital Clínico Universitario Lozano Blesa
        • Contact:
        • Chercheur principal:
          • Julio Lambea, Dr
    • Cantabria
      • Santander, Cantabria, Espagne, 39008
        • Hospital Universitario Marqués de Valdecilla
        • Contact:
        • Chercheur principal:
          • Ignacio Durán, Dr
    • Catalonia
      • Barcelona, Catalonia, Espagne, 08036
        • Hospital Clinic de Barcelona
        • Contact:
        • Chercheur principal:
          • Oscar Reig, Dr
      • Barcelona, Catalonia, Espagne, 08035
        • Hospital Universitari Vall D Hebron
        • Contact:
          • Cristina Suárez, Dr
          • Numéro de téléphone: +34 932543450
          • E-mail: csuarez@vhio.net
        • Chercheur principal:
          • Cristina Suárez, Dr
      • L'Hospitalet de Llobregat, Catalonia, Espagne, 08908
        • Institut Catala D'oncologia
        • Contact:
        • Chercheur principal:
          • Mayra Lizbeth Orrillo, Dr
      • Sabadell, Catalonia, Espagne, 08208
        • Parc Taulí Hospital Universitari
        • Contact:
        • Chercheur principal:
          • Enrique Gallardo, Dr
    • Galicia
      • Lugo, Galicia, Espagne, 27003
        • Hospital Universitario Lucus Augusti
        • Contact:
        • Chercheur principal:
          • Sergio Vazquez, Dr
      • Ourense, Galicia, Espagne, 32005
        • Complejo Hospitalario Universitario de Ourense
        • Contact:
        • Chercheur principal:
          • Ovidio Fernandez, Dr
    • Madrid
      • Madrid, Madrid, Espagne, 28041
        • Hospital Universitario 12 de Octubre
        • Contact:
        • Chercheur principal:
          • Guillermo de Velasco, Dr
      • Madrid, Madrid, Espagne, 28034
        • Hospital Universitario Ramon y Cajal
        • Contact:
        • Chercheur principal:
          • Javier Molina, Dr
    • Navarre
      • Pamplona, Navarre, Espagne, 31008
        • Hospital Universitario de Navarra
        • Contact:
        • Chercheur principal:
          • Nuria Lainez, Dr
    • Principality of Asturias
      • Oviedo, Principality of Asturias, Espagne, 33011
        • Hospital Universitario Central de Asturias
        • Contact:
        • Chercheur principal:
          • Carlos Alvarez, Dr
    • Valencia
      • Valencia, Valencia, Espagne, 46026
        • Hospital Universitario y Politécnico La Fe
        • Contact:
        • Chercheur principal:
          • Regina Girones, Dr.

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

Inclusion Criteria:

  • Male/female participants who are at least 18 years of age on the day of signing informed consent.

    2. Willing to provide written informed consent. They may also provide consent for Future Biomedical Research; however, the participant may participate in the main trial without participating in the Future Biomedical Research.

    3. Histologically confirmed diagnosis of RCC with a clear cell component with or without sarcomatoid features. Diagnosis is to be made by the investigator and does not require central histology review.

    4. Tumours must be T2 with grade 4, T3, T4, or any T with N1, M0 on radiographic imaging using TNM staging (8th edition)

    1. T2 is defined as a tumour >7cm but limited to the kidney; grade 4 is per the International Society of Urological Pathology (ISUP) grading.
    2. T3 is defined as tumour extension into major veins or perinephric tissues, but not into ipsilateral adrenal gland or beyond Gerota's fascia.
    3. T4 is defined as a tumour involving the ipsilateral adrenal gland or invading beyond Gerota's fascia.

    4. N1 is defined as metastatic involvement of regional lymph nodes. 5. Archival tumour tissue sample or newly obtained core, incisional, or excisional biopsy of a tumour lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.

      6. Have an Eastern Cooperation Oncology Group (ECOG) Performance Status of 0 to 1.

      Evaluation of ECOG is to be performed within 14 days prior to the first dose of study intervention.

      7. Have been considered suitable for curative intent surgery (partial or total nephrectomy), as evaluated by a surgeon. 8. Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg.

      9. Have adequate organ function as defined in the following table (Table 7). Specimens must be collected within 14 days prior to the start of study intervention.

      10.Participants agree to the contraception guidelines outlined in section 5.1.3.2.

      11.Participants who are HBsAg positive are eligible if they have received hepatitis B virus (HBV) anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.

      Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.

      Hepatitis B screening tests are not required unless:

      Known history of HBV infection As mandated by local health authority 12.Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.

      Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.

      Hepatitis C screening tests are not required unless:

      Known history of HCV infection As mandated by local health authority 13.HIV-infected participants must have well-controlled HIV on antiretroviral therapy (ART), defined as:

    1. Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening.
    2. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the lower limit of quantification (LLOQ) (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening
    3. It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.
    4. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the stud

Exclusion Criteria:

  • 1. Has evidence of metastatic disease on screening imaging. 2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).

    3. Has received prior systemic anti-cancer therapy including investigational agents within 3 years prior to randomization.

    4. Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.

Participants with low-risk early-stage prostate cancer either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.

5. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. COVID-19 and influenza vaccinations are allowed provided they are not live vaccines 6. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.

7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug 8. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, and/or lenvatinib, and/or belzutifan.

9. Has active autoimmune disease that has required immunosuppressive systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid).

10.Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease11.Has any of the following:

  1. A pulse oximeter reading <92% at rest, or
  2. Requires intermittent supplemental oxygen, or
  3. Requires chronic supplemental oxygen. 12.Has an active infection requiring systemic intravenous therapy. 13.Has moderate to severe hepatic impairment (Child-Pugh B or C). 14.Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.

Note: Hepatitis B and C screening tests are not required unless:

  1. Known history of HBV and HCV infection
  2. As mandated by local health authority

15.Has urine protein ≥1 g/24 hours.

  1. Note: Participants with proteinuria ≥2+ (≥100 mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.

  2. Note: Urine dipstick is the preferred method for testing urinary protein, however, urinalysis may be used if the use of urine dipsticks is not feasible.

    16.Has had major surgery within 3 weeks prior to first dose of study interventions.

    Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility 17.Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.

    18.Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

    19.Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.

    20.Has had an allogenic tissue/solid organ transplant. 21.Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula22.Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).

    23.Prolongation of QTcF interval to >480 ms. 24.Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.

    25.Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.

    26.Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib 27.Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort)

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation croisée
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Cohort A
Neoadjuvant therapy with Pembrolizumab (400mg q6w) + Lenvatinib (20mg daily for 12w) + Belzutifan (120mg daily for 12w). Followed by nephrectomy and pembrolizumab (400mg q6w for 9 months)
Médicament: Neoadjuvant Pembrolizumab
400mg q6w of Pembrolizumab will be administered before nephrectomy in cohorts A and B
Médicament: Belzutifan
120mg daily for 12w of Belzutifan will be administered before nephrectomy in Cohorts A and B
Médicament: Lenvatinb
20mg daily for 12 weeks of lenvatinib will be administered before nephrectomy in Cohort A
Expérimental: Cohort B
Neoadjuvant therapy with Pembrolizumab (400mg q6w) + Belzutifan (120mg daily for 12w). Followed by nephrectomy and pembrolizumab (400mg q6w for 9 months)
Médicament: Neoadjuvant Pembrolizumab
400mg q6w of Pembrolizumab will be administered before nephrectomy in cohorts A and B
Médicament: Belzutifan
120mg daily for 12w of Belzutifan will be administered before nephrectomy in Cohorts A and B
Comparateur actif: Cohort C
Nephrectomy folloewd by pembrolizumab (400mg q6w for 12 months)
Médicament: Neoadjuvant Pembrolizumab
400mg q6w of Pembrolizumab will be administered before nephrectomy in cohorts A and B

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Response Rate
Délai: At 12 weeks from start of treatment
Radiographic response defined as a decrease of initial tumour size ≥30% from baseline to week 12 CT scan
At 12 weeks from start of treatment

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Vall d'Hebron Institute of Oncology

Les enquêteurs

  • Chercheur principal: Cristina Suárez, Dr, Hospital Vall d'hebrón

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 juin 2026

Achèvement primaire (Estimé)

1 janvier 2028

Achèvement de l'étude (Estimé)

1 juin 2031

Dates d'inscription aux études

Première soumission

11 mai 2026

Première soumission répondant aux critères de contrôle qualité

11 mai 2026

Première publication (Réel)

18 mai 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

20 mai 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

18 mai 2026

Dernière vérification

1 novembre 2025

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • VHIO24002
  • 2024-519673-18-00 (Ctis)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

INDÉCIS

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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