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No longer recruiting (closed or complete)Last updated: 20 December 2023

MK-renal: This Phase III trial is evaluating how safe and effective a combination of targeted therapies (belzutifan + lenvatinib) is compared with another targeted therapy (cabozantinib) is in peoplke with advanced renal cell carcinomaAn Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy

Trial purpose

Medical clipboardCancer treatment

Tumor type

Urinary System Cancers Genitourinary

Age

People18+

Trial acronym

MK-renal

Clinical summary

Summary

This is an open-label randomised trial with one Experimental Arm and one Active Comparator Arm. Participants in the Experimental Arm will receive Belzutifan (120mg) and Lenvatinib (20mg) orally once a daily. Participants in the Active Comparator Arm will receive Cabozantinib (60mg) orally once per day.

Conditions

This trial is treating people with renal cell carcinoma

Eligibility

Inclusion

  • Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
  • Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment or neoadjuvant/adjuvant with progression on or within 6 months of last dose.
  • Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.
  • Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.
  • Received no more than 2 prior systemic regimens including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease
  • Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/adjuvant or locally advanced/metastatic RCC.
  • A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib.
  • A female participant is eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm.
  • Adequately controlled blood pressure.
  • Adequate organ function.

Exclusion

  • A pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
  • Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Clinically significant cardiac disease within 6 months of first dose of study intervention.
  • Prolongation of QTc interval to >480 ms.
  • Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable.
  • Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.
  • Moderate to severe hepatic impairment.
  • History of significant bleeding within 3 months before randomization.
  • History of solid organ transplantation.
  • Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
  • Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
  • Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.
  • Received colony-stimulating factors [eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)] within 28 days before randomization.
  • Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor.
  • Prior treatment with lenvatinib.
  • Prior treatment with cabozantinib.
  • Currently participating in a study of an investigational agent or using an investigational device.
  • Active infection requiring systemic therapy.
  • History of human immunodeficiency virus (HIV) infection.
  • History of hepatitis B or known active hepatitis C infection.

Inclusion

  • You are able to swallow medication by mouth.
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • Your cancer has not spread to other parts of the body (localised).
  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Merck

Scientific Title

An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy

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