Renal cell carcinoma (RCC) MedDRA version: 21.0 Level: LLT Classification code 10038395 Term: Renal carcinoma System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10038400 Term: Renal carcinoma stage IV System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10050076 Term: Metastatic renal carcinoma System Organ Class: 100000004864
Conditions
Sponsors
F. Hoffman-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age >= 18 years • Histologically confirmed locally advanced or metastatic clear cell or non-clear cell RCC (papillary, chromophobe and unclassified only). RCC with sarcomatoid features is allowed. Patients with the chromophobe subtype of non-clear cell RCC must have sarcomatoid differentiation • Radiographic disease progression during or following treatment with immune checkpoint inhibitors (ICI) for locally advanced or metastatic RCC either in first- or second-line treatment. Patients who experienced radiographic tumor progression during or within 6 months after the last dose of adjuvant ICI are also eligible. Patients must have received at least 2 cycles of ICI treatment . ICI must have been used in the immediate preceding line of therapy. ICI is defined by anti?PD-L1 or anti?PD1 antibody including atezolizumab, avelumab, pembrolizumab, durvalumab or nivolumab. Ipilimumab monotherapy is not considered an anti?PD L1 or anti?PD1 therapy. • Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 • Evaluable International Metastatic Renal Cell Carcinoma Database Consortium risk scores • Representative pretreatment tumor specimen for exploratory biomarker research: archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening, if clinically feasible. Both archival and fresh samples are preferred. • Karnofsky Performance Status score of >= 70 • Recovery to baseline or Grade =65 years) yes F.1.3.1 Number of subjects for this age range 225
Exclusion criteria
Exclusion criteria: • Treatment with anti-cancer therapy within 14 days prior to initiation of study treatment • Patients who received cabozantinib at any time prior to screening • Patients who received more than one ICI treatment in the locally advanced or metastatic setting • Patients who received more than two prior lines of therapy in the locally advanced or metastatic setting • Patients who have received a mammalian target of rapamycin inhibitor in any setting • Symptomatic, untreated, or actively progressing CNS metastases • History of leptomeningeal disease • Uncontrolled tumor-related pain or pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab • History of malignancy other than renal carcinoma within 5 years prior to screening • Radiotherapy for RCC within 14 days prior to Day 1 of Cycle 1 • Active tuberculosis • 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 • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab and 4 months after the final dose of cabozantinib • Severe infection within 4 weeks prior to initiation of study treatment,but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia or any active infection that, in the opinion of the investigator, could impact patient safety • Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives prior to initiation of study treatment • 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 • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment • Prior allogeneic stem cell or solid organ transplantation • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications • Current treatment with anti-viral therapy for HBV or HCV • Active or history of autoimmune disease or immune deficiency • Pharmacologically uncompensated, symptomatic hypothyroidism • Malabsorption syndrome • Uncontrolled hypertension • Tumors invading the GI-tract, active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel disease • Stroke, myocardial infarction, or other symptomatic ischemic event, or thromboembolic event within 6 months before first dose randomization • Significant cardiovascular disease within 3 months prior to initiation of study treatment • History of clinically significant ventricular dysrhythmias or risk factors for ventricular dysrhythmias or congenital QT syndrome • History or presence of an abnormal ECG that is clinically significant • Concomitant anticoagulation with coumarin agents, direct thrombin inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of atezolizumab in combination with cabozantinib (i.e. atezolizumab + cabozantinib arm) compared with cabozantinib alone (cabozantinib arm) in the intent-to-treat population;Secondary Objective: • To evaluate the efficacy of atezolizumab in combination with cabozantinib compared with cabozantinib alone in the intent-to-treat population • To evaluate the safety of atezolizumab in combination with cabozantinib compared with cabozantinib alone in the intent-to-treat population • To characterize the pharmacokinetics profile of atezolizumab and cabozantinib administered in combination • To evaluate the immune response to atezolizumab (for atezolizumab+ cabozantinib arm) ;Primary end point(s): 1. Progression-free survival as assessed by Independent Review Facility (IRF) 2. Overall survival ;Timepoint(s) of evaluation of this end point: 1. Approximately 55 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1-4. Approximately 55 months 5-6. From baseline (Day-28 to -1) to 55 months 7. Day 1 of Cycle 1-4, 8, 12, 16 and at treatment discontinuation visit (for atezolizumab+ cabozantinib arm) 8. Day 1 of Cycle 2-4, and at treatment discontinuation visit 9. Day 1 of Cycle 1-4, 8, 12, 16 and at treatment discontinuation visit (for atezolizumab+ cabozantinib arm) ;Secondary end point(s): 1. Progression-free survival as assessed by investigators 2. Investigator- and IRF-assessed objective response rate 3. Investigator- and IRF-assessed duration of objective response 4. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 5. Change from baseline in targeted vital signs 6. Change from baseline in targeted clinical laboratory test results 7. Atezolizumab concentrations at specified timepoints (for atezolizumab+ cabozantinib arm) 8. Cabozantinib concentrations at specified timepoints 9. Prevalence of anti-drug antibodies (ADAs) to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study (for atezolizumab+ cabozantinib arm) | — |
Countries
Argentina, Australia, Canada, Denmark, France, Germany, Greece, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed