Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1/Phase 2
Merck Sharp & Dohme LLC (Voir sur ClinicalTrials)
juillet 2025
octobre 2031
14 octobre 2026
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
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Laurence ALBIGES | 13/10/2026 23:35:34 | Contacter | ||
Critères
Tous
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
- 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