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

NCT ID: NCT05805501

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

199 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-21

Study Completion Date

2026-07-31

Brief Summary

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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

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Conditions

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Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

Tobemstomig

Intervention Type DRUG

Participants will receive IV tobemstomig Q3W.

Axitinib

Intervention Type DRUG

Participants will receive axitinib PO BID.

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.

Group Type EXPERIMENTAL

Tobemstomig

Intervention Type DRUG

Participants will receive IV tobemstomig Q3W.

Tiragolumab

Intervention Type DRUG

Participants will receive IV tiragolumab Q3W.

Axitinib

Intervention Type DRUG

Participants will receive axitinib PO BID.

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.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

Participants will receive IV pembrolizumab Q3W.

Axitinib

Intervention Type DRUG

Participants will receive axitinib PO BID.

Interventions

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Tobemstomig

Participants will receive IV tobemstomig Q3W.

Intervention Type DRUG

Tiragolumab

Participants will receive IV tiragolumab Q3W.

Intervention Type DRUG

Pembrolizumab

Participants will receive IV pembrolizumab Q3W.

Intervention Type DRUG

Axitinib

Participants will receive axitinib PO BID.

Intervention Type DRUG

Other Intervention Names

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RO7247669 Keytruda Inlyta

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-LaRoche

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

UC Irvine Medical Center

Orange, California, United States

Site Status

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Site Status

Peking University First Hospital

Beijing, , China

Site Status

Beijing Cancer Hospital

Beijing, , China

Site Status

Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School

Nanjing, , China

Site Status

Tianjin Cancer Hospital

Tianjin, , China

Site Status

Institut Sainte Catherine

Avignon, , France

Site Status

CHU Besançon - Hôpital Jean Minjoz

Besançon, , France

Site Status

CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre

Bordeaux, , France

Site Status

Centre Francois Baclesse

Caen, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Universitätsklinikum "Carl Gustav Carus"

Dresden, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II

Hamburg, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Klinikum rechts der Isar der TU München

München, , Germany

Site Status

Studienpraxis Urologie

Nürtingen, , Germany

Site Status

Universitätsklinikum Ulm

Ulm, , Germany

Site Status

Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny

Brzozów, , Poland

Site Status

Centrum Onkologii im. Prof. Franciszka ?ukaszczyka

Bydgoszcz, , Poland

Site Status

Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii

Krakow, , Poland

Site Status

Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu

Późna, , Poland

Site Status

National Cancer Center

Goyang-si, , South Korea

Site Status

Chonnam National University Hwasun Hospital

Jeollanam-do, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital Universitario Reina Sofia

Córdoba, Cordoba, Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario Clínico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Site Status

Barts & London School of Med

London, , United Kingdom

Site Status

Christie Hospital Nhs Trust

Manchester, , United Kingdom

Site Status

Countries

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United States Australia China France Germany Poland South Korea Spain United Kingdom

Other Identifiers

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BO43936

Identifier Type: -

Identifier Source: org_study_id