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

Renal Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05805501
• Other study ID #: BO43936
• Status: Recruiting
• Phase: Phase 2
• Start date: April 21, 2023
• Est. completion date: March 31, 2026

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BO43936 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: March 31, 2026
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• Tobemstomig
Participants will receive IV tobemstomig Q3W.
• Tiragolumab
Participants will receive IV tiragolumab Q3W.
• Pembrolizumab
Participants will receive IV pembrolizumab Q3W.
• Axitinib
Participants will receive axitinib PO BID.

Locations

Country	Name	City	State
Australia	Sunshine Coast University Hospital; The Adem Crosby Centre	Birtinya	Queensland
Australia	ICON Cancer Care Adelaide	Kurralta Park	South Australia
China	Beijing Cancer Hospital	Beijing
China	Peking University First Hospital	Beijing City
China	Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School	Nanjing City
China	Tianjin Cancer Hospital	Tianjin
China	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an
France	Institut Sainte Catherine;Recherche Clinique	Avignon
France	CHU Besançon - Hôpital Jean Minjoz	Besançon Cedex
France	CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre	Bordeaux
France	Centre Francois Baclesse; Oncologie	Caen
France	Centre Leon Berard; Departement Oncologie Medicale	Lyon
France	Institut Gustave Roussy; Oncologie Medicale	Villejuif
Germany	Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie	Dresden
Germany	Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II	Hamburg
Germany	Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie	Hannover
Germany	Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik	München
Germany	Studienpraxis Urologie	Nürtingen
Germany	Universitätsklinikum Tübingen; Klinik für Urologie	Tübingen
Germany	Universitätsklinikum Ulm; Klinik für Urologie	Ulm
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Poland	Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny	Brzozów
Poland	Centrum Onkologii im. Prof. Franciszka ?ukaszczyka; Ambulatorium Chemioterapii	Bydgoszcz
Poland	Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii	Kraków
Poland	Centrum Onkologii Ziemi LUBELSKIEJ im. Sw Jana z Dukli, I oddz. Chemioterapii	Lublin
Poland	Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu; Oddzia? Chemioterapii	Pozna?
Poland	Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.	Warszawa
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Oncology	Barcelona
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Ramon y Cajal;Oncology Dept.	Madrid
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Universitari i Politecnic La Fe; Oncologia	Valencia
United Kingdom	East Lancashire Hospitals NHS Trust	Burnley
United Kingdom	Colchester General Hospital	Colchester, Essex
United Kingdom	Medway Maritime Hospital	Gillingham
United Kingdom	Barts & London School of Med; Medical Oncology	London
United Kingdom	Royal Marsden Hospital; Dept of Med-Onc	London
United Kingdom	Christie Hospital Nhs Trust; Medical Oncology	Manchester
United Kingdom	Nottingham City Hospital; Oncology	Nottingham
United Kingdom	Plymouth Oncology Centre; Clinical Trials Unit	Plymouth
United Kingdom	Royal Marsden Hospital; Institute of Cancer Research	Sutton
United Kingdom	Singleton Hospital; Cancer Institute	Swansea
United States	EMORY UNIVERSITY; Bone Marrow & Stem Cell Transplant Center	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Skip Viragh Outpatient Cancer Building	Baltimore	Maryland
United States	University of Alabama at Birmingham; Comprehensive Cancer Center	Birmingham	Alabama
United States	Greco-Hainesworth Centers for Research; ETN (East Tennessee)	Chattanooga	Tennessee
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Florida Cancer Specialists - Fort Myers (Broadway)	Fort Myers	Florida
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Sarah Cannon Research Institute / Tennessee Oncology	Nashville	Tennessee
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Vanderbilt University Medical Center; Vanderbilt University	Nashville	Tennessee
United States	UC Irvine Medical Center	Orange	California
United States	Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  China,  France,  Germany,  Korea, Republic of,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)		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)
Secondary	Overall Survival (OS)		From randomization to death from any cause (up to 35 treatment cycles; cycle length = 21 days)
Secondary	Confirmed Objective Response Rate (ORR)		Up to 35 treatment cycles (cycle length = 21 days)
Secondary	Duration of Response (DoR)		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)