Substudy 03C is part of a larger research study that is testing experimental treatments for renal cell carcinoma (RCC). The larger study is the umbrella study (U03).
The goal of substudy 03C is to evaluate the safety and efficacy of experimental combinations of investigational agents in participants with clear cell renal cell carcinoma (ccRCC) who have recurrent disease during or after anti-programmed cell death 1/programmed cell death ligand 1 (PD-\[L\]1) adjuvant therapy.
This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to demonstrate a tolerable safety profile for the combination of investigational agents. There will be no hypothesis testing in this study
Has a histologically confirmed diagnosis of unresectable locally advanced/metastatic renal cell carcinoma (RCC) with clear cell component
Has received no other prior systemic therapy for treatment of advanced/metastatic clear cell renal cell carcinoma (ccRCC) except for adjuvant 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
Is able to swallow oral medication
Has clinically significant hematuria, hematemesis, or hemoptysis of (>2.5 mL) of red blood, or other history of significant bleeding
Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
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
Parallel
Belzutifan
DrugOral Tablet
Zanzalintinib
DrugOral Tablet
Safety Lead In Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)
DLTs are defined as any of a pre-specified list of toxicities if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration, excluding toxicities clearly not related to the drug, such as disease progression, environmental factors, unrelated trauma, etc.
Safety Lead In Phase: 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.
Safety Lead In Phase: Number of participants who discontinue study treatment due to an AE
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.
Efficacy Phase: Number of participants who experience one or more DLTs
DLTs are defined as any of a pre-specified list of toxicities if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration, excluding toxicities clearly not related to the drug, such as disease progression, environmental factors, unrelated trauma, etc.
Efficacy Phase: Duration of response (DOR)
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per 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 BICR will be presented.
Efficacy Phase: Progression-free survival (PFS)
PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by 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 BICR will be presented.
Efficacy Phase: Overall survival (OS)
OS is defined as time from first dose of study treatment to death due to any cause.
Efficacy Phase: Clinical benefit rate (CBR)
CBR is defined as the percentage of participants who have achieved stable disease (SD: Neither sufficient shrinkage to qualify for PR \[at least a 30% decrease in the sum of diameters of target lesions\] nor sufficient increase to qualify for PD) of ≥6 months or confirmed CR (disappearance of all target lesions) or PR 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. The CBR as assessed by BICR will be presented.
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Merck Sharp & Dohme LLC
Lead sponsor
Exelixis
Collaborator
