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
- Interventions
- Registration Number
- NCT05805501
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 199
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (Tobemstomig + Axitinib) Tobemstomig Participants will receive intravenous (IV) tobemstomig every three weeks (Q3W) on Day 1 of each 21-day cycle. Participants will also receive oral (PO) axitinib twice daily (BID). Arm A (Tobemstomig + Axitinib) Axitinib Participants will receive intravenous (IV) tobemstomig every three weeks (Q3W) on Day 1 of each 21-day cycle. Participants will also receive oral (PO) axitinib twice daily (BID). Arm B (Tobemstomig + Tiragolumab + Axitinib) Tobemstomig Participants will receive IV tobemstomig followed by IV tiragolumab Q3W on Day 1 of 21-day cycle. Participants will also receive axitinib PO BID. Arm B (Tobemstomig + Tiragolumab + Axitinib) Tiragolumab Participants will receive IV tobemstomig followed by IV tiragolumab Q3W on Day 1 of 21-day cycle. Participants will also receive axitinib PO BID. Arm B (Tobemstomig + Tiragolumab + Axitinib) Axitinib Participants will receive IV tobemstomig followed by IV tiragolumab Q3W on Day 1 of 21-day cycle. Participants will also receive axitinib PO BID. Control Arm (Pembrolizumab + Axitinib) Pembrolizumab Participants will receive IV pembrolizumab Q3W on Day 1 of each 21-day cycle. Participants will also receive axitinib PO BID. Control Arm (Pembrolizumab + Axitinib) Axitinib Participants will receive IV pembrolizumab Q3W on Day 1 of each 21-day cycle. Participants will also receive axitinib PO BID.
- Primary Outcome Measures
Name Time Method Incidence and Severity of Adverse Events (AEs) Up to a maximum of 2 years
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (47)
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
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
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Klinikum rechts der Isar der TU München
🇩🇪München, Germany
Studienpraxis Urologie
🇩🇪Nürtingen, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Sunshine Coast University Hospital
🇦🇺Birtinya, Queensland, Australia
Peking University First Hospital
🇨🇳Beijing City, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing City, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Institut Sainte Catherine
🇫🇷Avignon, France
CHU Besançon - Hôpital Jean Minjoz
🇫🇷Besançon Cedex, France
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Jeollanam-do, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny
🇵🇱Brzozów, Poland
Centrum Onkologii im. Prof. Franciszka ?ukaszczyka
🇵🇱Bydgoszcz, Poland
Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
🇵🇱Kraków, Poland
Centrum Onkologii Ziemi LUBELSKIEJ im. Sw Jana z Dukli, I oddz. Chemioterapii
🇵🇱Lublin, Poland
Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu
🇵🇱Pozna?, Poland
Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
🇵🇱Warszawa, Poland
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Cordoba, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Barts & London School of Med
🇬🇧London, United Kingdom
Christie Hospital Nhs Trust
🇬🇧Manchester, United Kingdom