Trial Outcomes & Findings for A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment (NCT NCT04338269)

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.

Participants were randomized in a 1:1 ratio to receive either atezolizumab in combination with cabozantinib or cabozantinib alone.

A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment

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.

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.

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.

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.

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.

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.

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.

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.

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).