COSMIC-021 Expansion Cohort Sheds Light on Efficacy of Cabozantinib, Atezolizumab for aUC

The COSMIC-021 study began in 2017 to analyze the effects of cabozantinib alone or in combination with atezolizumab in patients with advanced solid tumors. New results from the study’s expansion cohorts demonstrate the efficacy of the treatment combination in patients with advanced urothelial carcinoma (UC).

The phase Ib study enrolled patients with inoperable locally advanced or metastatic UC into one of four cohorts: first-line cisplatin-eligible, first-line cisplatin-ineligible, previous platinum-containing chemotherapy, or previous immune checkpoint inhibitor (ICI)-treated.

From March 2018 to November 2021, 121 patients underwent study treatment, 31 in the previous ICI-treated cohort and 30 in each of the other cohorts. Patients were administered oral cabozantinib 40 mg once daily and intravenous atezolizumab 1,200 mg once every 3 weeks.

The primary endpoint was objective response rate (ORR), determined by the investigator based on RECIST v1.1 criteria every 6 weeks for 12 months and every 12 weeks thereafter; the secondary endpoint was safety.

The ORR (95% CI) was 30% (15 to 49) for cisplatin-eligible, 20% (8 to 39) for cisplatin-ineligible, 27% (12 to 46) for previous chemotherapy-treated, and 10% (2 to 26) for previous ICI-treated cohorts. The median progression-free survival rate (95% CI) was 5.5 (1.6 to 11.6), 5.6 (3.1 to 11.1), 5.4 (1.6 to 7.6), and 3.0 (1.8 to 5.5) months, respectively.

Grade 3 or 4 treatment-related adverse events (TRAEs) were experienced by 43%, 67%, 57%, and 45% of patients, respectively. TRAEs resulted in discontinuation of all treatment components in 17%, 13%, 3%, and 19% of patients, respectively, and no grade 5 TRAEs were reported in any cohort.

Cabozantinib, in combination with atezolizumab, provides beneficial clinical activity in patients with advanced UC; activity in patients with previous ICI-treated UC was modest.