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A clinical study of combination therapies in people with kidney cancer (MK-3475-03C)
EU CTIS ID: 2024-516437-12-00
What this study is testing
1. Safety Lead-in Phase: To assess the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) if applicable, of treatment combinations that have not been evaluated in a separate study 2. Efficacy Phase: To assess the safety and tolerability based on the proportion of participants with adverse events (AEs). 3. Efficacy Phase: To evaluate objective response (OR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Has a histologically confirmed diagnosis of unresectable locally advanced/metastatic renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features),
- Is an individual of any sex/gender, from 18 years to 120 years of age inclusive,
- A participant assigned male sex at birth, capable of producing sperm, continues contraception at least 7 days after the last dose of Belzutifan, and at least 96 days after the last dose of Zanzalintinib. Refrains from donating sperm and abstains from penile-vaginal intercourse and remains abstinent, or uses external condom or contraceptives consistent with local regulations.
- A participant assigned female sex at birth is not breast feeding at least 96 days after the last dose of study intervention. A participant of childbearing potential (POCBP) is not pregnant and has a negative highly sensitive pregnancy test before the first dose of study intervention. A POCBP uses a highly effective contraceptive method, and continues using contraception at least 30 days after the last dose of Belzutifan, and at least 186 days after the last dose of Zanzalintinib.
- Has received no other prior systemic therapy for treatment of advanced/metastatic clear cell RCC (ccRCC) except for adjuvant anti- programmed cell death 1/programmed cell death ligand 1 (PD-(L)1) therapy.
- Has disease recurrence during adjuvant anti- PD-(L)1 therapy or ≤24 months following the last dose of adjuvant anti-PD-(L)1 therapy.
You likely can't join if
- Has clinically significant hematuria, hematemesis, or hemoptysis of (>2.5 mL) of red blood, or other history of significant bleeding.
- Has malabsorption due to prior GI surgery or GI disease.
- Has moderate to severe hepatic impairment (Child-Pugh B or C).
- Has received colony-stimulating factors within 28 days prior to intervention allocation/randomization.
- Has received prior treatment with Hypoxia-Inducible Factor-2α (HIF-2α) and/or Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitor (VEGF/TKI) inhibitors.
- Ha recibido radioterapia previa dentro de las 2 semanas del comienzo de la intervención del estudio o tiene toxicidades relacionadas con la radiación que requieren corticoesteroides.
See the full eligibility criteria
Who can join
- Has a histologically confirmed diagnosis of unresectable locally advanced/metastatic renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features),
- Is an individual of any sex/gender, from 18 years to 120 years of age inclusive,
- A participant assigned male sex at birth, capable of producing sperm, continues contraception at least 7 days after the last dose of Belzutifan, and at least 96 days after the last dose of Zanzalintinib. Refrains from donating sperm and abstains from penile-vaginal intercourse and remains abstinent, or uses external condom or contraceptives consistent with local regulations.
- A participant assigned female sex at birth is not breast feeding at least 96 days after the last dose of study intervention. A participant of childbearing potential (POCBP) is not pregnant and has a negative highly sensitive pregnancy test before the first dose of study intervention. A POCBP uses a highly effective contraceptive method, and continues using contraception at least 30 days after the last dose of Belzutifan, and at least 186 days after the last dose of Zanzalintinib.
- Has received no other prior systemic therapy for treatment of advanced/metastatic clear cell RCC (ccRCC) except for adjuvant anti- programmed cell death 1/programmed cell death ligand 1 (PD-(L)1) therapy.
- Has disease recurrence during adjuvant anti- PD-(L)1 therapy or ≤24 months following the last dose of adjuvant anti-PD-(L)1 therapy.
- Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigator and verified by blinded independent central review (BICR).
- Is able to swallow oral medication.
- Submits an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
- Participants receiving bone resorptive therapy(must have therapy initiated at least 2 weeks before allocation/randomization.
- Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤140/90 mm Hg with no change in antihypertensive medications within 1 week before allocation/randomization.
- Has adequate organ function
What rules you out
- Has clinically significant hematuria, hematemesis, or hemoptysis of (>2.5 mL) of red blood, or other history of significant bleeding.
- Has malabsorption due to prior GI surgery or GI disease.
- Has moderate to severe hepatic impairment (Child-Pugh B or C).
- Has received colony-stimulating factors within 28 days prior to intervention allocation/randomization.
- Has received prior treatment with Hypoxia-Inducible Factor-2α (HIF-2α) and/or Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitor (VEGF/TKI) inhibitors.
- Ha recibido radioterapia previa dentro de las 2 semanas del comienzo de la intervención del estudio o tiene toxicidades relacionadas con la radiación que requieren corticoesteroides.
- Is currently receiving strong inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study.
- Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention.
- Is currently receiving anticoagulants or platelet inhibitors that cannot be discontinued for the duration of the study,
- Have been previously allocated/randomized to study intervention in any substudy of protocol MK-3475-U03.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention,
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.
- Has active autoimmune disease that has required systemic treatment in the past 2 years.
- Has an active infection requiring systemic therapy.
- Has history of human immunodeficiency virus (HIV) infection.
- Has hepatitis B or hepatitis C virus infection.
- Has deep vein thrombosis within 3 months before allocation/randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before allocation/randomization.
- Has deep vein thrombosis within 3 months before allocation/randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before allocation/randomization.
- Has history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis.
- Has a left ventricular ejection fraction (LVEF) ≤50% or below the institutional (or local laboratory) normal range.
- Has serious wound, ulcer or bone fracture or has had major surgery within 8 weeks before first dose of study intervention.
- Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage in the last 4 weeks before allocation/randomization.
- Has gastrointestinal (GI) disorders, including those associated with a high risk of perforation or fistula formation.
The study team makes the final eligibility decision.
Where it's taking place
- United Kingdom
- United States
- Chile
- Israel
- Korea, Republic of
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United Kingdom; United States; Chile; Israel; Korea, Republic of. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.