Clinical trial NCT05805501: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-04-10
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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 (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 outcomes:
measure: Incidence and Severity of Adverse Events (AEs)
timeFrame: Up to a maximum of 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Beijing City
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Nanjing City
country: China
facility: Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Besançon Cedex
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
city: Caen
country: France
facility: Centre Francois Baclesse
city: Lyon
country: France
facility: Centre Leon Berard
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus"
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München
city: Nürtingen
country: Germany
facility: Studienpraxis Urologie
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Brzozów
country: Poland
facility: Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka ?ukaszczyka
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi LUBELSKIEJ im. Sw Jana z Dukli, I oddz. Chemioterapii
city: Pozna?
country: Poland
facility: Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu
city: Warszawa
country: Poland
facility: Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Cordoba
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: London
country: United Kingdom
facility: Barts & London School of Med
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust
Study officials:
affiliation: Hoffmann-LaRoche
name: Clinical Trials
role: STUDY_DIRECTOR
References: