Substudy 03C: A Study of Combination Therapies in Participants With Renal Cell Carcinoma With Recurrent Disease During or After Anti-PD-(L)1 Therapy (MK-3475-03C/KEYMAKER-U03)
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
Eligibility
Sex
ALL
Min age
18 Years
Max age
120 Years
Healthy volunteers
No
The main inclusion criteria include but are not limited to the following:
* 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
* Submits an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
* Participants receiving bone resorptive therapy (must have therapy initiated at least 2 weeks before allocation/randomization)
* 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
* Has adequate organ function
The main exclusion criteria include but are not limited to the following:
* 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
* Has serious wound, ulcer or bone fracture or has had major surgery within 8 weeks before first dose of study intervention
* 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
* Has gastrointestinal (GI) disorders, including those associated with a high risk of perforation or fistula formation
* Has malabsorption due to prior GI surgery or GI disease
* Has moderate to severe hepatic impairment
* Has received colony-stimulating factors within 28 days prior to intervention allocation/randomization
* Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
* Is currently receiving strong inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study
* Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
* Is currently receiving anticoagulants or platelet inhibitors that cannot be discontinued for the duration of the study
* Have been previously allocated/randomized to study intervention in any sub study of protocol MK-3475-U03
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
* Has active autoimmune disease that has required systemic treatment in the past 2 years
* Has an active infection requiring systemic therapy
* Has history of human immunodeficiency virus (HIV) infection
* Has hepatitis B or hepatitis C virus infection
Primary outcome measure(s)
Safety Lead In Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs) — Up to approximately 21 days 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) — Up to approximately 74 months 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 — Up to approximately 74 months 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 — Up to approximately 21 days 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: Number of participants who experience one or more AEs — Up to approximately 74 months 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 discontinue study treatment due to an AE — Up to approximately 74 months 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: Objective Response Rate (ORR) — Up to approximately 74 months 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.
Trial sites (32)
Facility
City
Region
Status
UCSF Medical Center at Mission Bay ( Site 5008)
San Francisco
California
Recruiting
Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 5026)
Mineola
New York
Recruiting
Laura and Isaac Perlmutter Cancer Center ( Site 5016)
New York
New York
Recruiting
Memorial Sloan Kettering Cancer Center ( Site 5002)
New York
New York
Recruiting
Duke Cancer Institute ( Site 5015)
Durham
North Carolina
Recruiting
UPMC Cancer Center/Hillman Cancer Center ( Site 5017)
Pittsburgh
Pennsylvania
Recruiting
Vanderbilt University Medical Center ( Site 5004)
Nashville
Tennessee
Recruiting
Centro de Estudios Clínicos SAGA ( Site 6110)
Santiago
Region M. de Santiago
Recruiting
Bradfordhill ( Site 6101)
Santiago
Region M. de Santiago
Recruiting
C.H.U. de Strasbourg Hopital de Hautepierre ( Site 5203)
Strasbourg
Bas-Rhin
Recruiting
Institut Claudius Regaud ( Site 5200)
Toulouse
Haute-Garonne
Recruiting
Centre Eugene Marquis ( Site 5205)
Rennes
Ille-et-Vilaine
Recruiting
Institut De Cancerologie De Lorraine ( Site 5204)
Vandœuvre-lès-Nancy
Meurthe-et-Moselle
Recruiting
Gustave Roussy ( Site 5202)
Villejuif
Île-de-France Region
Recruiting
Rambam Health Care Campus ( Site 5500)
Haifa
Israel
Active Not Recruiting
Rabin Medical Center ( Site 5502)
Petah Tikva
Israel
Active Not Recruiting
Sheba Medical Center ( Site 5501)
Ramat Gan
Israel
Active Not Recruiting
Sourasky Medical Center ( Site 5503)
Tel Aviv
Israel
Active Not Recruiting
Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 6201)
Bydgoszcz
Kuyavian-Pomeranian Voivodeship
Recruiting
Narodowy Instytut Onkologii im. Marii Skłodowskiej Curie ( Site 6203)
Warsaw
Masovian Voivodeship
Recruiting
Uniwersyteckie Centrum Kliniczne ( Site 6202)
Gdansk
Pomeranian Voivodeship
Recruiting
Severance Hospital ( Site 5802)
Seoul
South Korea
Recruiting
Asan Medical Center ( Site 5800)
Seoul
South Korea
Recruiting
Samsung Medical Center ( Site 5801)
Seoul
South Korea
Recruiting
HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 5302)
Madrid
Madrid, Comunidad de
Recruiting
Hospital Universitario Ramon y Cajal ( Site 5301)
Madrid
Madrid, Comunidad de
Recruiting
Hospital Universitari Vall d'Hebron ( Site 5300)
Barcelona
Spain
Recruiting
Western General Hospital ( Site 5402)
Edinburgh
Edinburgh, City of
Recruiting
The Beatson West of Scotland Cancer Centre ( Site 5405)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.
