N-(4-FLUOROPHENYL)-N-(4-((7-METHOXY-6-(METHYLCARBAMOYL)QUINOLIN-4-YL)OXY)PHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE for Clear cell renal cell carcinoma

Inclusion criteria

• {"criterion_text":"- Has a histologically confirmed diagnosis of unresectable locally advanced/metastatic renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features),\n- Is an individual of any sex/gender, from 18 years to 120 years of age inclusive,\n- 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.\n- 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.\n- 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.\n- Has disease recurrence during adjuvant anti- PD-(L)1 therapy or ≤24 months following the last dose of adjuvant anti-PD-(L)1 therapy.\n- 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).\n- Is able to swallow oral medication.\n- Submits an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.\n- Participants receiving bone resorptive therapy(must have therapy initiated at least 2 weeks before allocation/randomization.\n- 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.\n- Has adequate organ function"}

Exclusion criteria

• {"criterion_text":"- Has clinically significant hematuria, hematemesis, or hemoptysis of (>2.5 mL) of red blood, or other history of significant bleeding.\n- Has malabsorption due to prior GI surgery or GI disease.\n- Has moderate to severe hepatic impairment (Child-Pugh B or C).\n- Has received colony-stimulating factors within 28 days prior to intervention allocation/randomization.\n- Has received prior treatment with Hypoxia-Inducible Factor-2α (HIF-2α) and/or Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitor (VEGF/TKI) inhibitors.\n- 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.\n- Is currently receiving strong inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study.\n- Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention.\n- Is currently receiving anticoagulants or platelet inhibitors that cannot be discontinued for the duration of the study,\n- Have been previously allocated/randomized to study intervention in any substudy of protocol MK-3475-U03.\n- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.\n- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention,\n- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.\n- Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.\n- Has active autoimmune disease that has required systemic treatment in the past 2 years.\n- Has an active infection requiring systemic therapy.\n- Has history of human immunodeficiency virus (HIV) infection.\n- Has hepatitis B or hepatitis C virus infection.\n- 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.\n- 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.\n- Has history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis.\n- Has a left ventricular ejection fraction (LVEF) ≤50% or below the institutional (or local laboratory) normal range.\n- Has serious wound, ulcer or bone fracture or has had major surgery within 8 weeks before first dose of study intervention.\n- 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.\n- Has gastrointestinal (GI) disorders, including those associated with a high risk of perforation or fistula formation."}

Primary endpoints

• {"endpoint_text":"- Safety Lead In Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)\n- Safety Lead In Phase: Number of participants who experience one or more adverse events (AEs)\n- Safety Lead In Phase: Number of participants who discontinue study treatment due to an AE\n- Efficacy Phase: Number of participants who experience one or more DLTs\n- Efficacy Phase: Number of participants who experience one or more AEs\n- Efficacy Phase: Number of participants who discontinue study treatment due to an AE\n- Efficacy Phase: Objective Response (OR)","definition_or_measurement_approach":"- Safety Lead In Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs) — counted as participants with ≥1 DLT during lead-in\n- Safety Lead In Phase: Number of participants who experience one or more adverse events (AEs) — counted as participants with ≥1 AE\n- Safety Lead In Phase: Number of participants who discontinue study treatment due to an AE — counted as participants who stop treatment due to AE\n- Efficacy Phase: Number of participants who experience one or more DLTs — counted as participants with ≥1 DLT during efficacy phase\n- Efficacy Phase: Number of participants who experience one or more AEs — counted as participants with ≥1 AE\n- Efficacy Phase: Number of participants who discontinue study treatment due to an AE — counted as participants who stop treatment due to AE\n- Efficacy Phase: Objective Response (OR) — response assessed per RECIST 1.1 (as indicated in objectives)"}

Secondary endpoints

• {"endpoint_text":"- Efficacy Phase: Duration of response (DOR)\n- Efficacy Phase: Progression-free survival (PFS)\n- Efficacy Phase: Overall survival (OS)\n- Efficacy Phase: Clinical benefit rate (CBR)","definition_or_measurement_approach":"- Duration of response (DOR) — per RECIST 1.1\n- Progression-free survival (PFS) — per RECIST 1.1\n- Overall survival (OS) — time to death from any cause\n- Clinical benefit rate (CBR) — per RECIST 1.1"}

France

Earliest CTIS Part Ii Submission Date

12-07-2025

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

262

Number Of Sites

5

Number Of Participants

15

Poland

Earliest CTIS Part Ii Submission Date

19-05-2025

Latest Decision Or Authorization Date

03-04-2026

Processing Time Days

319

Number Of Sites

2

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

21-07-2025

Latest Decision Or Authorization Date

06-04-2026

Processing Time Days

259

Number Of Sites

2

Number Of Participants

8

Primary sponsor

Full Name

Merck Sharp & Dohme LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Parexel International Corp.

Responsibilities

EUB services (call center and medical services)

Name

Pra International

Responsibilities

Independent Central Review of Imaging data

Name

Almac Clinical Technologies LLC

Name

PPD Global Central Labs

Third parties

• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"EUB services (call center and medical services)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pra International","duties_or_roles":"Independent Central Review of Imaging data","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"","organisation_type":"Pharmaceutical company"}