A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)

Merck Sharp & Dohme (MSD)

Status and phase: Begins enrollment this month; Phase 3

Conditions: Carcinoma, Renal Cell

Treatments: Drug: Placebo; Drug: Zanzalintinib; Drug: Belzutifan

Study type: Interventional

Funder types: Industry

Identifiers

NCT07489495

2024-516993-31-00 (Registry Identifier)

LS-034 (Other Identifier)

MK-6482-034 (Other Identifier)

6482-034

LITESPARK-034 (Other Identifier)

U1111-1311-4692 (Registry Identifier)

Details and patient eligibility

About

Researchers are looking for new ways to treat advanced renal cell carcinoma (RCC).

A standard (usual) treatment for certain people with RCC is belzutifan (a study medicine), which is a targeted therapy. Targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. Researchers want to learn if adding another targeted therapy called zanzalintinib (another study medicine) can treat more people with advanced RCC than belzutifan alone.

The goal of this study is to learn if people who receive belzutifan and zanzalintinib live longer overall and without the cancer getting worse compared to people who receive belzutifan and placebo.

Enrollment: 758 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

The main inclusion criteria include but are not limited to the following:

• Has a histologically confirmed diagnosis of unresectable, advanced renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV RCC per American Joint Committee on Cancer (8th Edition)
• Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
• Has received no more than 3 prior systemic regimens for RCC, including only 1 prior anti-Programmed Cell Death-1/Programmed Cell Death 1 Ligand 1 therapy

Exclusion criteria

For exclusion criteria: The main exclusion criteria include but are not limited to the following:

• Has any of the following: a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
• Has deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization
• Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram
• Has had major surgery within 8 weeks before randomization
• Has current pneumonitis/interstitial lung disease
• Has a history of human immunodeficiency virus infection
• Has Hepatitis B or Hepatitis C virus infection
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has a history of solid organ transplant
• Has not adequately recovered from major surgery or has ongoing surgical complications

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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758 participants in 2 patient groups

Belzutifan + Zanzalintinib

Experimental group

Description:

Participants will receive 120 mg belzutifan orally and 60 mg zanzalintinib once daily for approximately 24 months.

Treatment:

Drug: Zanzalintinib

Drug: Belzutifan

Belzutifan + Placebo

Active Comparator group

Description:

Participants will receive 120 mg belzutifan orally and zanzalintinib-matching placebo once daily for approximately 24 months.

Treatment:

Drug: Belzutifan

Drug: Placebo