Carcinoma, Renal Cell
Conditions
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.
Interventions
DRUGAtezolizumab
Atezolizumab 1200 mg will be administered at a fixed dose on Day 1 of each 21-day cycle by IV infusion every 3 weeks.
DRUGCabozantinib
Cabozantinib 60 mg (three 20-mg tablets) administered orally once daily.
Sponsors
Hoffmann-La Roche
Exelixis
Chugai Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm
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 * 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 final dose of atezolizumab and 4 months after final dose of cabozantinib * Severe infection within 4 weeks prior to initiation of study treatment, including, 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 * Pharmacologically uncompensated, symptomatic hypothyroidism * Uncontrolled hypertension defined as sustained blood pressure \>150 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment (all countries except France); sustained BP \> 140 mmHg systolic or \> 90 mmHg diastolic despite optimal antihypertensive treatment (France only) * Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, unstable arrhythmia, or unstable angina) within 3 months prior to initiation of study treatment * 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 * History of congenital QT syndrome * History or presence of an abnormal ECG that is clinically significant in the investigator's opinion * Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g. clopidogrel)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1 | From randomization to the first occurrence of PD according to RECIST v1.1, or death from any cause, whichever occurred first (up to 2 years 5 months) | PFS was defined as the time from randomization to the first occurrence to PD, as determined by the IRF per RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm). Data for participants who did not experience PD or death was censored at the last tumor assessment date. Data for participants with no post-baseline tumor assessments was censored at the randomization date. PFS was estimated using Kaplan-Meier (KM) method. |
| Overall Survival (OS) | From randomization to death due to any cause (up to 2 years 5 months). | OS was defined as the time from randomization to death due to any cause. Data for participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants without post-baseline information were censored at the date of randomization. OS was estimated using KM method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed Objective Response Rate (ORR) (INV-ORR), According to RECIST v1.1 | Up to 2 years 5 months | ORR was defined as the percentage of participants with an objective response i.e. a complete response (CR) or partial response (PR) at two consecutive tumor assessments at least 28 days apart, as determined by the investigator per RECIST v1.1. CR was defined as the disappearance of all target lesions, and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. |
| IRF-assessed ORR (IRF-ORR) According to RECIST v1.1 | Up to 2 years 5 months | ORR was defined as the percentage of participants with an objective response i.e. a CR or PR at two consecutive tumor assessments at least 28 days apart, as determined by the IRF per RECIST v1.1. CR was defined as the disappearance of all target lesions, and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. |
| 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 PD or death from any cause, whichever occurred first (up to 2 years 5 months) | DOR was defined as the time from the first occurrence of an objective response (CR or PR) to PD or death, whichever occurred first, as determined by the investigator per RECIST v1.1. CR was defined as the disappearance of all target lesions, and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. DOR was estimated using KM method. |
| IRF-assessed DOR (IRF-DOR) According to RECIST v1.1 | From the date of first occurrence of a documented objective response to PD or death from any cause, whichever occurred first (up to 2 years 5 months) | DOR was defined as the time from the first occurrence of an objective response (CR or PR) to PD or death, whichever occurred first, as determined by IRF per RECIST v1.1. CR was defined as the disappearance of all target lesions, and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. DOR was estimated using KM method. |
| Number of Participants With Adverse Events (AEs) | Up to approximately 50 months | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Serum Concentration of Atezolizumab | Predose on Day 1 of Cycles 1, 2, 3, 4, 8, 12 and 16; 30 minutes postdose on Cycle 1 Day 1 (1 cycle = 21 days); Treatment discontinuation visit (up to approximately 46 months) | — |
| Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab | Up to approximately 24 months | Participants who received atezolizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). |
| Plasma Concentration of Cabozantinib | Predose on Day 1 of Cycles 2, 3, and 4 (1 cycle = 21 days); Treatment discontinuation visit (up to approximately 48 months) | — |
| PFS Assessed by the Investigators (INV-PFS), According to RECIST v1.1 | From randomization to the first occurrence of PD according to RECIST v1.1, or death from any cause, whichever occurred first (up to 2 years 5 months) | PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. Data for participants who did not experience PD or death was censored at the last tumor assessment date. Data for participants with no post-baseline tumor assessments were censored at the randomization date. PFS was estimated using KM method. |
Countries
Argentina, Australia, Canada, Denmark, France, Germany, Greece, Italy, Japan, Poland, Russia, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 522 participants with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) took part in the study at 135 investigative sites across 15 countries.
Pre-assignment details
Participants were randomized in a 1:1 ratio to receive either atezolizumab in combination with cabozantinib or cabozantinib alone.
Participants by arm
| Arm | Count |
|---|---|
| Cabozantinib (Control) Participants who received treatment until disease progression per RECIST v1.1, unacceptable toxicity, or symptomatic deterioration attributed to disease progression as determined by the investigator. | 259 |
| Atezolizumab + Cabozantinib Participants who received treatment until disease progression per RECIST v1.1, unacceptable toxicity, or symptomatic deterioration attributed to disease progression as determined by the investigator. | 263 |
| Total | 522 |
Baseline characteristics
| Characteristic | Cabozantinib (Control) | Atezolizumab + Cabozantinib | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 115 Participants | 110 Participants | 225 Participants |
| Age, Categorical Between 18 and 65 years | 144 Participants | 153 Participants | 297 Participants |
| Age, Continuous | 61.8 years STANDARD_DEVIATION 10.2 | 61.8 years STANDARD_DEVIATION 9.9 | 61.8 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 23 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 212 Participants | 232 Participants | 444 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 18 Participants | 8 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 23 Participants | 33 Participants | 56 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants | 6 Participants | 22 Participants |
| Race (NIH/OMB) White | 213 Participants | 219 Participants | 432 Participants |
| Sex: Female, Male Female | 62 Participants | 59 Participants | 121 Participants |
| Sex: Female, Male Male | 197 Participants | 204 Participants | 401 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 118 / 259 | 129 / 263 |
| other Total, other adverse events | 251 / 256 | 255 / 262 |
| serious Total, serious adverse events | 95 / 256 | 141 / 262 |
Outcome results
Primary
Overall Survival (OS)
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.
Time frame: From randomization to death due to any cause (up to 2 years 5 months).
Population: The efficacy evaluable population included all patients who received at least one dose of each drug for their assigned treatment regimen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabozantinib (Control) | Overall Survival (OS) | NA Months |
| Atezolizumab + Cabozantinib | Overall Survival (OS) | 25.72 Months |
p-value: 0.690295% CI: [0.7, 1.27]Log Rank
p-value: 0.785395% CI: [0.71, 1.27]Log Rank
Primary
Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1
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.
Time frame: From randomization to the first occurrence of disease progression according to RECIST v1.1 (up to 2 years 5 months).
Population: The efficacy evaluable population included all patients who received at least one dose of each drug for their assigned treatment regimen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabozantinib (Control) | Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1 | 10.81 Months |
| Atezolizumab + Cabozantinib | Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1 | 10.55 Months |
p-value: 0.784495% CI: [0.83, 1.28]Log Rank
Comparison: Cox Proportional Hazards Modelp-value: 0.719595% CI: [0.84, 1.29]Log Rank
Secondary
Independent Review Facility (IRF)-Assessed Duration of Response (DOR) (IRF-DOR) According to RECIST v1.1
Duration of Response (DOR) is defined as the time from the first occurrence of a confirmed objective response (complete response \[CR\] or partial response \[PR\]) to disease progression, or death, whichever occurs first. Data for participants who have not experienced disease progression or death will be censored at the last tumor assessment date. If no tumor assessments were performed after the date of the first occurrence of CR or PR, data for DOR will be censored at the date of the first occurrence of CR or PR.
Time frame: 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)
Population: The DOR evaluable population is defined as participants with measurable disease at baseline who experienced a a confirmed objective response (complete response \[CR\] or partial response \[PR\]).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabozantinib (Control) | Independent Review Facility (IRF)-Assessed Duration of Response (DOR) (IRF-DOR) According to RECIST v1.1 | 14.75 Months |
| Atezolizumab + Cabozantinib | Independent Review Facility (IRF)-Assessed Duration of Response (DOR) (IRF-DOR) According to RECIST v1.1 | 12.65 Months |
p-value: 0.835495% CI: [0.7, 1.54]Log Rank
p-value: 0.815995% CI: [0.71, 1.55]Log Rank
Secondary
Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1
Overall Response Rate (ORR) is defined as the proportion of participants who had an objective response (complete response \[CR\] or partial response \[PR\]) on two consecutive occasions at least 4 weeks apart according to RECIST v1.1. in the ORR evaluable population, defined as patients with measurable disease at baseline.
Time frame: 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).
Population: The ORR evaluable population is defined as participants with measurable disease at baseline. There were discrepancies between the IRF and INV assessments of participants' measurable diseases at baseline, which are reflected in the number of participants analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cabozantinib (Control) | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Not Evaluable | 0.8 Percentage of Participants |
| Cabozantinib (Control) | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Progressive Disease (PD) | 5.1 Percentage of Participants |
| Cabozantinib (Control) | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Complete Response (CR) | 0.8 Percentage of Participants |
| Cabozantinib (Control) | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Missing | 5.5 Percentage of Participants |
| Cabozantinib (Control) | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Partial Response (PR) | 40.2 Percentage of Participants |
| Cabozantinib (Control) | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Responders (CR + PR) | 40.9 Percentage of Participants |
| Cabozantinib (Control) | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Stable Disease (SD) | 47.6 Percentage of Participants |
| Atezolizumab + Cabozantinib | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Responders (CR + PR) | 40.5 Percentage of Participants |
| Atezolizumab + Cabozantinib | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Progressive Disease (PD) | 4.2 Percentage of Participants |
| Atezolizumab + Cabozantinib | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Not Evaluable | 0.8 Percentage of Participants |
| Atezolizumab + Cabozantinib | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Stable Disease (SD) | 50.6 Percentage of Participants |
| Atezolizumab + Cabozantinib | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Missing | 3.9 Percentage of Participants |
| Atezolizumab + Cabozantinib | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Complete Response (CR) | 0 Percentage of Participants |
| Atezolizumab + Cabozantinib | Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1 | Partial Response (PR) | 40.5 Percentage of Participants |
p-value: 0.989395% CI: [0.7, 1.43]Cochran-Mantel-Haenszel
Secondary
Investigator-assessed Duration of Response (DOR) (INV-DOR) According to RECIST v1.1
Duration of Response (DOR) is defined as the time from the first occurrence of a confirmed objective response (complete response \[CR\] or partial response \[PR\]) to disease progression, or death, whichever occurs first. Data for participants who have not experienced disease progression or death will be censored at the last tumor assessment date. If no tumor assessments were performed after the date of the first occurrence of CR or PR, data for DOR will be censored at the date of the first occurrence of CR or PR.
Time frame: 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)
Population: The DOR evaluable population is defined as participants with measurable disease at baseline who experienced a a confirmed objective response (complete response \[CR\] or partial response \[PR\]).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabozantinib (Control) | Investigator-assessed Duration of Response (DOR) (INV-DOR) According to RECIST v1.1 | 12.19 Months |
| Atezolizumab + Cabozantinib | Investigator-assessed Duration of Response (DOR) (INV-DOR) According to RECIST v1.1 | NA Months |
p-value: 0.081695% CI: [0.47, 1.05]Log Rank
p-value: 0.109995% CI: [0.49, 1.08]Log Rank
Secondary
Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1
Overall Response Rate (ORR) is defined as the proportion of participants who had an objective response (complete response \[CR\] or partial response \[PR\]) on two consecutive occasions at least 4 weeks apart according to RECIST v1.1. in the ORR evaluable population, defined as patients with measurable disease at baseline.
Time frame: 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).
Population: The ORR evaluable population is defined as participants with measurable disease at baseline. There were discrepancies between the IRF and INV assessments of participants' measurable diseases at baseline, which are reflected in the number of participants analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cabozantinib (Control) | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Partial Response (PR) | 40.9 Percentage of Participants |
| Cabozantinib (Control) | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Progressive Disease (PD) | 6.6 Percentage of Participants |
| Cabozantinib (Control) | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Complete Response (CR) | 0.8 Percentage of Participants |
| Cabozantinib (Control) | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Not Evaluable | 0 Percentage of Participants |
| Cabozantinib (Control) | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Stable Disease (SD) | 46.3 Percentage of Participants |
| Cabozantinib (Control) | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Missing | 5.4 Percentage of Participants |
| Cabozantinib (Control) | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Responders (CR + PR) | 41.7 Percentage of Participants |
| Atezolizumab + Cabozantinib | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Missing | 3.8 Percentage of Participants |
| Atezolizumab + Cabozantinib | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Responders (CR + PR) | 38.0 Percentage of Participants |
| Atezolizumab + Cabozantinib | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Complete Response (CR) | 1.5 Percentage of Participants |
| Atezolizumab + Cabozantinib | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Partial Response (PR) | 36.5 Percentage of Participants |
| Atezolizumab + Cabozantinib | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Stable Disease (SD) | 48.3 Percentage of Participants |
| Atezolizumab + Cabozantinib | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Progressive Disease (PD) | 9.1 Percentage of Participants |
| Atezolizumab + Cabozantinib | Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1 | Not Evaluable | 0.8 Percentage of Participants |
p-value: 0.430695% CI: [-12.45, 5.1]Cochran-Mantel-Haenszel
Secondary
Progression Free Survival (PFS) as Assessed by Investigators (INV-PFS), According to RECIST v1.1
Progression Free Survival (PFS) is defined as the time from randomization to disease progression, as determined by the Investigators 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.
Time frame: 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).
Population: The efficacy evaluable population included all patients who received at least one dose of each drug for their assigned treatment regimen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabozantinib (Control) | Progression Free Survival (PFS) as Assessed by Investigators (INV-PFS), According to RECIST v1.1 | 10.41 Months |
| Atezolizumab + Cabozantinib | Progression Free Survival (PFS) as Assessed by Investigators (INV-PFS), According to RECIST v1.1 | 10.38 Months |
p-value: 0.803795% CI: [0.83, 1.27]Log Rank
p-value: 0.789495% CI: [0.83, 1.27]Log Rank