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

• ClinicalTrials.gov Identifier: NCT05805501
• Recruitment Status: Recruiting
• First Posted: April 10, 2023
• Last Update Posted: May 8, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: March 28, 2023
• First Posted Date: April 10, 2023
• Last Update Posted Date: May 8, 2024
• Actual Study Start Date: April 21, 2023
• Estimated Primary Completion Date: September 30, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 28, 2023): Progression-Free Survival (PFS) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 35 treatment cycles; cycle length = 21 days) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 28, 2023)

• Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to 35 treatment cycles; cycle length = 21 days) ]
• Confirmed Objective Response Rate (ORR) [ Time Frame: Up to 35 treatment cycles (cycle length = 21 days) ]
• Duration of Response (DoR) [ Time Frame: From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 35 treatment cycles; cycle length = 21 days) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Participants With Untreated Locally Advanced Unresectable or Metastatic Renal Cell Carcinoma
• Official Title: A Randomized Open Label Phase II Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic Renal Cell Carcinoma
• Brief Summary: This study will evaluate the efficacy, safety, and pharmacokinetics of tobemstomig (also known as 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Renal Cell Carcinoma

Intervention

• Drug: Tobemstomig
  Participants will receive IV tobemstomig Q3W.
  Other Name: RO7247669
• Drug: Tiragolumab
  Participants will receive IV tiragolumab Q3W.
• Drug: Pembrolizumab
  Participants will receive IV pembrolizumab Q3W.
  Other Name: Keytruda
• Drug: Axitinib
  Participants will receive axitinib PO BID.
  Other Name: Inlyta

Study Arms

• Experimental: Arm A (Tobemstomig + 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).
  Interventions:

  • Drug: Tobemstomig
  • Drug: Axitinib
• Experimental: Arm B (Tobemstomig + Tiragolumab + 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.
  Interventions:

  • Drug: Tobemstomig
  • Drug: Tiragolumab
  • Drug: Axitinib
• Active Comparator: Control Arm (Pembrolizumab + Axitinib)
  Participants will receive IV pembrolizumab Q3W on Day 1 of each 21-day cycle. Participants will also receive axitinib PO BID.
  Interventions:

  • Drug: Pembrolizumab
  • Drug: Axitinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 28, 2023): 210
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2026
• Estimated Primary Completion Date: September 30, 2024 (Final data collection date for primary outcome measure)

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 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: BO43936 https://forpatients.roche.com/; 888-662-6728; global-roche-genentech-trials@gene.com

• Listed Location Countries: Australia, China, France, Germany, Korea, Republic of, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05805501
• Other Study ID Numbers: BO43936
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-LaRoche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2024