A Phase III, Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Atezolizumab Given in Combination With Cabozantinib Versus Cabozantinib Alone in Patients With Inoperable, Locally Advanced, or Metastatic Renal Cell Carcinoma Who Experienced Radiographic Tumor Progression During or After Immune Checkpoint Inhibitor Treatment
Overview
- Phase
- Phase 3
- Intervention
- Atezolizumab
- Conditions
- Carcinoma, Renal Cell
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 522
- Locations
- 125
- Primary Endpoint
- Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy and safety of atezolizumab given in combination with cabozantinib versus cabozantinib alone in participants with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) who experienced radiographic tumor progression during or after Immune Checkpoint Inhibitor (ICI) treatment in the metastatic setting.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed locally advanced or metastatic clear cell or non-clear cell (papillary, chromophobe, and unclassified only) RCC. RCC with sarcomatoid features is allowed. Patients with the chromophobe subtype of non-clear cell RCC must have sarcomatoid differentiation.
- •Radiographic disease progression to prior ICI therapy for RCC. Patients who experienced radiographic tumor progression during or within 6 months after the last dose of adjuvant ICI are also eligible. ICI is defined by anti-PD-L1 or anti-PD1 antibody including atezolizumab, avelumab, pembrolizumab, durvalumab, or nivolumab. Only patients for whom the immediate preceding line of therapy was an ICI are allowed.
- •Measurable disease per RECIST v1.1
- •Evaluable IMDC risk score
- •Archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening, if clinically feasible. Both archival and fresh samples are preferred.
- •KPS score of \>=70
- •Recovery to baseline or Grade \</= 1 NCI CTCAE v5.0 from toxicities related to any prior treatments, unless adverse events are clinically nonsignificant and/or stable in the opinion of the investigator. Grade 2 alopecia is allowed for study participation
- •Adequate hematologic and end-organ function
- •Negative HIV test at screening
- •Negative hepatitis B testing at screening
Exclusion Criteria
- •Treatment with anti-cancer therapy within 14 days prior to initiation of study treatment
- •Patients 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 (mTOR) inhibitor in any setting
- •Symptomatic, untreated, or actively progressing CNS metastases
- •History of leptomeningeal disease
- •Uncontrolled 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, with the exception of malignancies with a negligible risk of metastasis or death
Arms & Interventions
Atezo+Cabo
Participants will receive atezolizumab every 3 weeks on Day 1 of each 21-day cycle (1 cycle=21 days) plus oral tablets of cabozantinib every day.
Intervention: Atezolizumab
Atezo+Cabo
Participants will receive atezolizumab every 3 weeks on Day 1 of each 21-day cycle (1 cycle=21 days) plus oral tablets of cabozantinib every day.
Intervention: Cabozantinib
Cabozantinib
Participants will receive cabozantinib every day.
Intervention: Cabozantinib
Outcomes
Primary Outcomes
Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1
Time Frame: From randomization to the first occurrence of disease progression according to RECIST v1.1 (up to 2 years 5 months).
Progression Free Survival (PFS) is defined as the time from randomization to disease progression, as determined by the Independent Review Facility (IRF) per RECIST v1.1, or death from any cause, whichever occurs first. Data for patients who have not experienced disease progression or death were censored at the last tumor assessment date. Data for patients with no postbaseline tumor assessments were censored at the randomization date.
Overall Survival (OS)
Time Frame: From randomization to death due to any cause (up to 2 years 5 months).
From randomization to death due to any cause. Data for patients who are not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Patients who do not have post-baseline information were censored at the date of randomization.
Secondary Outcomes
- Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1(From randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first) (up to 2 years 5 months).)
- Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1(From randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first) (up to 2 years 5 months).)
- Progression Free Survival (PFS) as Assessed by Investigators (INV-PFS), According to RECIST v1.1(From randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first) (up to 2 years 5 months).)
- Investigator-assessed Duration of Response (DOR) (INV-DOR) According to RECIST v1.1(From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 2 years 5 months))
- Independent Review Facility (IRF)-Assessed Duration of Response (DOR) (IRF-DOR) According to RECIST v1.1(From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 2 years 5 months))