A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants With RCC (KEYMAKER-U03): Substudy 03C in Participants With Recurrent Disease During or After Anti-PD-(L)1 Adjuvant Therapy
Summary
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
Arms & interventions
- DrugBelzutifan
Oral Tablet
- DrugZanzalintinib
Oral Tablet
Outcome measures
Primary
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.
Time frame: Up to approximately 21 days
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.
Time frame: Up to approximately 74 months
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.
Time frame: Up to approximately 74 months
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.
Time frame: Up to approximately 21 days
Efficacy Phase: Number of participants who experience one or more 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.
Time frame: Up to approximately 74 months
Efficacy 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.
Time frame: Up to approximately 74 months
Efficacy Phase: 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 74 months
Secondary
Efficacy Phase: Duration of response (DOR)
Time frame: Up to approximately 74 months
Efficacy Phase: Progression-free survival (PFS)
Time frame: Up to approximately 74 months
Efficacy Phase: Overall survival (OS)
Time frame: Up to approximately 74 months
Efficacy Phase: Clinical benefit rate (CBR)
Time frame: Up to approximately 74 months
Eligibility criteria
Study locations (7)
UCSF Medical Center at Mission Bay ( Site 5008)
San Francisco, California, 94158
Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 5026)
Mineola, New York, 11501
Laura and Isaac Perlmutter Cancer Center ( Site 5016)
New York, New York, 10016
Memorial Sloan Kettering Cancer Center ( Site 5002)
New York, New York, 10065
Duke Cancer Institute ( Site 5015)
Durham, North Carolina, 27710
UPMC Cancer Center/Hillman Cancer Center ( Site 5017)
Pittsburgh, Pennsylvania, 15232
Vanderbilt University Medical Center ( Site 5004)
Nashville, Tennessee, 37232