A Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Participants With Untreated Locally Advanced Unresectable or Metastatic Renal Cell Carcinoma
Tobemstomig: Participants will receive IV tobemstomig Q3W.
Tiragolumab: Participants will receive IV tiragolumab Q3W.
Pembrolizumab: Participants will receive IV pembrolizumab Q3W.
Axitinib: Participants will receive axitinib PO BID.
Study 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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Incidence and Severity of Adverse Events (AEs) — Up to a maximum of 2 years
Trial sites (43)
Facility
City
Region
Status
University of Alabama at Birmingham
Birmingham
Alabama
UC Irvine Medical Center
Orange
California
Emory University
Atlanta
Georgia
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore
Maryland
SCRI Oncology Partners
Nashville
Tennessee
Vanderbilt University Medical Center
Nashville
Tennessee
UT Southwestern Medical Center
Dallas
Texas
Sunshine Coast University Hospital
Birtinya
Queensland
Peking University First Hospital
Beijing
China
Beijing Cancer Hospital
Beijing
China
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
Nanjing
China
Tianjin Cancer Hospital
Tianjin
China
Institut Sainte Catherine
Avignon
France
CHU Besançon - Hôpital Jean Minjoz
Besançon
France
CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
Bordeaux
France
Centre Francois Baclesse
Caen
France
Centre Leon Berard
Lyon
France
Institut Gustave Roussy
Villejuif
France
Universitätsklinikum "Carl Gustav Carus"
Dresden
Germany
Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II
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.
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