A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)

Phase 3RecruitingNCT07227402

Merck Sharp & Dohme LLC904 enrolled

Overview

Researchers are looking for more ways to treat advanced renal cell carcinoma (RCC) that is recurrent. Researchers want to learn if recurrent advanced renal cell carcinoma (RCC) responds (gets smaller or goes away) after treatment with belzutifan (MK-6482) and zanzalintinib compared to cabozantinib. The goal of this study is to learn if: People who take belzutifan and zanzalintinib live longer overall and without the cancer getting worse than people who take cabozantinib.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

904

Conditions

Renal Cell Carcinoma

Interventions

BelzutifanDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has a histologically confirmed diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) i.e., Stage IV renal cell cancer per American Joint Committee on Cancer (AJCC) (8th Edition) * Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) * Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy * Has received no other prior systemic therapy for their RCC except for their adjuvant anti-PD-1/L1 therapy Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * 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, new-onset angina, pulmonary embolism, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability * Had 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 or has not adequately recovered from major surgery or has ongoing surgical complications * Has current pneumonitis/interstitial lung disease * Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage within 4 weeks prior to randomization * Has a gastrointestinal disorder including those associated with a high risk of perforation or fistula formation * Has a serious active nonhealing wound/ulcer/bone fracture * Has a requirement for hemodialysis or peritoneal dialysis * Has history of human immunodeficiency virus infection * Has hepatitis B or hepatitis C virus * Has pharmacologically uncompensated, symptomatic hypothyroidism * Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

Locations (127)

Alaska Oncology and Hematology ( Site 0133)

Anchorage, Alaska, United States

RECRUITING

Providence Medical Foundation ( Site 0141)

Fullerton, California, United States

RECRUITING

USC Norris Comprehensive Cancer Center ( Site 0126)

Los Angeles, California, United States

RECRUITING

Cedars-Sinai Medical Center ( Site 0112)

Los Angeles, California, United States

Outcomes

Primary Outcomes

Progression Free Survival (PFS)

PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented.

Time frame: Up to approximately 73 months

Overall Survival (OS)

OS is defined as the time from randomization to death due to any cause.

Time frame: Up to approximately 73 months

Secondary Outcomes

Objective Response Rate (ORR)

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

Time frame: Up to approximately 73 months

Duration of Response (DOR)

For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.

Time frame: Up to approximately 73 months

Number of Participants Who Experience One or More Adverse Events (AEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported.

Time frame: Up to approximately 73 months

Number of Participants Who Discontinue Study Treatment due to an AE

Time frame: Up to approximately 73 months

Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Global Health/Health-Related Quality of Life (HRQoL) Items 29 and 30 Combined Score

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent), then summed. Summed raw scores are standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome.