a study of immune checkpoint inhibitor combinations with axitinib in participants with untreated locally advanced unresectable or metastatic renal cell carcinoma

Conditions: Renal Cell Carcinoma

Summary: 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).


Eligibility criteria:
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 (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