Informations générales (source: ClinicalTrials.gov)
A Randomized Open Label Phase II Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic Renal Cell Carcinoma
Interventional
Phase 2
Hoffmann-La Roche (Voir sur ClinicalTrials)
avril 2023
octobre 2025
02 septembre 2025
This study will evaluate the safety of tobemstomig (RO7247669) in combination with
axitinib alone or with tiragolumab (anti-TIGIT) and axitinib as compared to pembrolizumab
and axitinib in participants with previously untreated, unresectable locally advanced or
metastatic clear-cell renal cell carcinoma (ccRCC).
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 | 14/06/2024 09:34:24 | Contacter | ||
Critères
Tous
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- International Metastatic RCC Database Consortium (IMDC) risk intermediate (score of
1 or 2) or poor (score of 3-6)
- Measurable disease with at least one measurable lesion
- Histologically confirmed ccRCC with or without sarcomatoid features
- Negative for HIV, hepatitis B, or hepatitis C virus (HCV)
Exclusion Criteria:
- Pregnant or breastfeeding, or intention of becoming pregnant during the study or
within 90 days after the final dose of tiragolumab, 4 months after the final dose of
tobemstomig (RO7249669) and pembrolizumab, or for 1 week after the final dose of
axitinib, whichever occurs last
- Inability to swallow a tablet or malabsorption syndrome
- Prior treatment for localized and/or metastatic RCC with systemic RCC-directed
therapy, including T-cell costimulating or immune checkpoint blockade therapies
- Ongoing use or anticipated need for treatment with a strong CYP3A4/5 inhibitor or
inducer
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to
initiation of study treatment, or anticipation of need for a major surgical
procedure during the study
- Uncontrolled or symptomatic hypercalcemia or symptomatic hypercalcemia requiring
continued use of bisphosphonate therapy or denosumab
- Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases
- History of leptomeningeal disease
- Uncontrolled tumor-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)
- Moderate to severe hepatic impairment (Child-Pugh B or C)
- Uncontrolled hypertension
- Prior history of hypertensive crisis or hypertensive encephalopathy
- Significant cardiovascular/cerebrovascular disease within 3 months (12 months for UK
participants) prior to randomization
- History of clinically significant ventricular dysrhythmias or risk factors for
ventricular dysrhythmias
- History of congenital QT syndrome
- Resting heart rate (HR) > 100 bpm (or clinically significant tachycardia)
- Stroke (including transient ischemic attack), myocardial infarction, or other
symptomatic ischemic event, or thromboembolic event (e.g., deep venous thrombosis
[DVT], pulmonary embolism [PE]) within 3 months (12 months for UK participants)
before randomization
- Significant vascular disease (e.g., aortic aneurysm or arterial dissection requiring
surgical repair or recent peripheral arterial thrombosis) within 6 months prior to
Day 1 of Cycle 1
- Tumors invading pulmonary blood vessels, cavitating pulmonary lesions or known
endobronchial disease
- Tumor invading the gastrointestinal (GI) tract, including abdominal or
tracheoesophageal fistulas
- Evidence of abdominal free air not explained by paracentesis or recent surgical
procedure
- Active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic
or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric
outlet obstruction
- Intra-abdominal abscess within 6 months before initiation of study treatment
- Clinical signs or symptoms of GI obstruction or requirement for routine parenteral
hydration, parenteral nutrition, or tube feeding
- Evidence of bleeding diathesis or significant coagulopathy
- Grade ≥ 3 hemorrhage or bleeding event within 28 days prior to initiation of study
treatment
- Clinically significant hematuria, hematemesis, hemoptysis of > 0.5 teaspoon (2.5 mL)
of red blood, coagulopathy, or other history of significant bleeding (e.g.,
pulmonary hemorrhage) within 3 months before initiation of study treatment
- Active or history of autoimmune disease or immune deficiency
- Treatment with systemic immunosuppressive medication within 2 weeks prior to
initiation of study treatment, or anticipation of need for systemic
immunosuppressive medication during study treatment
- Prior allogeneic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan
- History of another primary malignancy other than RCC within 2 years prior to
screening, with the exception of malignancies with a negligible risk of metastasis
or death (e.g., 5-year OS rate > 90%)
- Administration of a live, attenuated vaccine within 4 weeks before randomization or
anticipation that such a live, attenuated vaccine will be required during the study
- Active tuberculosis (TB)
- Severe infection within 4 weeks prior to initiation of study treatment
- Participants with active Epstein-Barr virus (EBV) infection or known or suspected
chronic active EBV infection at screening
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment
- Known hypersensitivity to Chinese hamster *ovary cell products or to any component
of tobemstomig, tiragolumab, pembrolizumab, or axitinib