Clinical Trials Search at Vanderbilt-Ingram Cancer Center

Inclusion Criteria:

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 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 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