A Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Participants With Untreated Locally Advanced Unresectable or Metastatic Renal Cell Carcinoma

Roche

Status and phase

Active, not recruiting

Phase 2

Conditions

Renal Cell Carcinoma

Treatments

Drug: Tobemstomig

Drug: Tiragolumab

Drug: Pembrolizumab

Drug: Axitinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT05805501

BO43936

Details and patient eligibility

About

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).

Enrollment

199 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

199 participants in 3 patient groups

Arm A (Tobemstomig + Axitinib)

Experimental group

Description:

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).

Treatment:

Drug: Axitinib

Drug: Tobemstomig

Arm B (Tobemstomig + Tiragolumab + Axitinib)

Experimental group

Description:

Participants will receive IV tobemstomig followed by IV tiragolumab Q3W on Day 1 of 21-day cycle. Participants will also receive axitinib PO BID.

Treatment:

Drug: Axitinib

Drug: Tiragolumab

Drug: Tobemstomig

Control Arm (Pembrolizumab + Axitinib)