Trial Title:
A Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Participants With Untreated Locally Advanced Unresectable or Metastatic Renal Cell Carcinoma
NCT ID:
NCT05805501
Condition:
Renal Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Renal Cell
Pembrolizumab
Axitinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tobemstomig
Description:
Participants will receive IV tobemstomig Q3W.
Arm group label:
Arm A (Tobemstomig + Axitinib)
Arm group label:
Arm B (Tobemstomig + Tiragolumab + Axitinib)
Other name:
RO7247669
Intervention type:
Drug
Intervention name:
Tiragolumab
Description:
Participants will receive IV tiragolumab Q3W.
Arm group label:
Arm B (Tobemstomig + Tiragolumab + Axitinib)
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Participants will receive IV pembrolizumab Q3W.
Arm group label:
Control Arm (Pembrolizumab + Axitinib)
Other name:
Keytruda
Intervention type:
Drug
Intervention name:
Axitinib
Description:
Participants will receive axitinib PO BID.
Arm group label:
Arm A (Tobemstomig + Axitinib)
Arm group label:
Arm B (Tobemstomig + Tiragolumab + Axitinib)
Arm group label:
Control Arm (Pembrolizumab + Axitinib)
Other name:
Inlyta
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).
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Alabama at Birmingham; Comprehensive Cancer Center
Address:
City:
Birmingham
Zip:
35294-3300
Country:
United States
Facility:
Name:
UC Irvine Medical Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Facility:
Name:
University of Colorado
Address:
City:
Aurora
Zip:
80045
Country:
United States
Facility:
Name:
Sibley Memorial Hospital
Address:
City:
Washington
Zip:
20016
Country:
United States
Facility:
Name:
Florida Cancer Specialists - Fort Myers (Broadway)
Address:
City:
Fort Myers
Zip:
33901
Country:
United States
Facility:
Name:
EMORY UNIVERSITY; Bone Marrow & Stem Cell Transplant Center
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Facility:
Name:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Skip Viragh Outpatient Cancer Building
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Facility:
Name:
Greco-Hainesworth Centers for Research; ETN (East Tennessee)
Address:
City:
Chattanooga
Zip:
37404
Country:
United States
Facility:
Name:
Thompson Cancer Survival Center
Address:
City:
Knoxville
Zip:
37916-2305
Country:
United States
Facility:
Name:
Sarah Cannon Research Institute / Tennessee Oncology
Address:
City:
Nashville
Zip:
37203
Country:
United States
Facility:
Name:
SCRI Oncology Partners
Address:
City:
Nashville
Zip:
37203
Country:
United States
Facility:
Name:
Vanderbilt University Medical Center; Vanderbilt University
Address:
City:
Nashville
Zip:
37232
Country:
United States
Facility:
Name:
UT Southwestern Medical Center
Address:
City:
Dallas
Zip:
75390-8813
Country:
United States
Facility:
Name:
Sunshine Coast University Hospital; The Adem Crosby Centre
Address:
City:
Birtinya
Zip:
4575
Country:
Australia
Facility:
Name:
ICON Cancer Care Adelaide
Address:
City:
Kurralta Park
Zip:
5037
Country:
Australia
Facility:
Name:
Peking University First Hospital
Address:
City:
Beijing City
Zip:
100034
Country:
China
Facility:
Name:
Beijing Cancer Hospital
Address:
City:
Beijing
Zip:
100142
Country:
China
Facility:
Name:
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
Address:
City:
Nanjing City
Zip:
210008
Country:
China
Facility:
Name:
Tianjin Cancer Hospital
Address:
City:
Tianjin
Zip:
300060
Country:
China
Facility:
Name:
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
Address:
City:
Xi'an
Zip:
710061
Country:
China
Facility:
Name:
Institut Sainte Catherine;Recherche Clinique
Address:
City:
Avignon
Zip:
84918
Country:
France
Facility:
Name:
CHU Besançon - Hôpital Jean Minjoz
Address:
City:
Besançon Cedex
Zip:
25030
Country:
France
Facility:
Name:
CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
Address:
City:
Bordeaux
Zip:
33075
Country:
France
Facility:
Name:
Centre Francois Baclesse; Oncologie
Address:
City:
Caen
Zip:
14076
Country:
France
Facility:
Name:
Centre Leon Berard; Departement Oncologie Medicale
Address:
City:
Lyon
Zip:
69373
Country:
France
Facility:
Name:
Institut Gustave Roussy; Oncologie Medicale
Address:
City:
Villejuif
Zip:
94800
Country:
France
Facility:
Name:
Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie
Address:
City:
Dresden
Zip:
01307
Country:
Germany
Facility:
Name:
Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II
Address:
City:
Hamburg
Zip:
20246
Country:
Germany
Facility:
Name:
Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
Address:
City:
Hannover
Zip:
30625
Country:
Germany
Facility:
Name:
Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik
Address:
City:
München
Zip:
81675
Country:
Germany
Facility:
Name:
Studienpraxis Urologie
Address:
City:
Nürtingen
Zip:
72622
Country:
Germany
Facility:
Name:
Universitätsklinikum Tübingen; Klinik für Urologie
Address:
City:
Tübingen
Zip:
72076
Country:
Germany
Facility:
Name:
Universitätsklinikum Ulm; Klinik für Urologie
Address:
City:
Ulm
Zip:
89081
Country:
Germany
Facility:
Name:
National Cancer Center
Address:
City:
Goyang-si
Zip:
10408
Country:
Korea, Republic of
Facility:
Name:
Chonnam National University Hwasun Hospital
Address:
City:
Jeollanam-do
Zip:
58128
Country:
Korea, Republic of
Facility:
Name:
Severance Hospital, Yonsei University Health System
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Facility:
Name:
Asan Medical Center
Address:
City:
Seoul
Zip:
05505
Country:
Korea, Republic of
Facility:
Name:
Samsung Medical Center
Address:
City:
Seoul
Zip:
06351
Country:
Korea, Republic of
Facility:
Name:
Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny
Address:
City:
Brzozów
Zip:
36-200
Country:
Poland
Facility:
Name:
Centrum Onkologii im. Prof. Franciszka ?ukaszczyka; Ambulatorium Chemioterapii
Address:
City:
Bydgoszcz
Zip:
85-796
Country:
Poland
Facility:
Name:
Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
Address:
City:
Kraków
Zip:
30-688
Country:
Poland
Facility:
Name:
Centrum Onkologii Ziemi LUBELSKIEJ im. Sw Jana z Dukli, I oddz. Chemioterapii
Address:
City:
Lublin
Zip:
20-090
Country:
Poland
Facility:
Name:
Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu; Oddzia? Chemioterapii
Address:
City:
Pozna?
Zip:
60-569
Country:
Poland
Facility:
Name:
Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
Address:
City:
Warszawa
Zip:
04-073
Country:
Poland
Facility:
Name:
Hospital Universitario Reina Sofia; Servicio de Oncologia
Address:
City:
Córdoba
Zip:
14004
Country:
Spain
Facility:
Name:
Hospital Universitari Vall d'Hebron; Oncology
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Facility:
Name:
Hospital de la Santa Creu i Sant Pau
Address:
City:
Barcelona
Zip:
8041
Country:
Spain
Facility:
Name:
Hospital Universitario Ramon y Cajal;Oncology Dept.
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Facility:
Name:
Hospital Universitario Clínico San Carlos; Servicio de Oncologia
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Facility:
Name:
Hospital Universitario 12 de Octubre; Servicio de Oncologia
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Facility:
Name:
Hospital Universitari i Politecnic La Fe; Oncologia
Address:
City:
Valencia
Zip:
46026
Country:
Spain
Facility:
Name:
Barts & London School of Med; Medical Oncology
Address:
City:
London
Zip:
EC1A 7BE
Country:
United Kingdom
Facility:
Name:
Christie Hospital Nhs Trust; Medical Oncology
Address:
City:
Manchester
Zip:
M2O 4BX
Country:
United Kingdom
Facility:
Name:
Nottingham City Hospital; Oncology
Address:
City:
Nottingham
Zip:
NG5 1PB
Country:
United Kingdom
Start date:
April 21, 2023
Completion date:
October 31, 2026
Lead sponsor:
Agency:
Hoffmann-La Roche
Agency class:
Industry
Source:
Hoffmann-La Roche
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05805501
