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A Novel Combination of Cabozantinib Plus Atezolizumab Demonstrates Encouraging Activity and Acceptable Tolerability in Advanced RCC

Findings from the COSMIC-021 study
21 Sep 2021
Anticancer agents & Biologic therapy;  Cancer Immunology and Immunotherapy;  Genitourinary cancers

In the COSMIC-021 study, cabozantinib plus atezolizumab demonstrated encouraging clinical activity in patients with advanced renal cell carcinoma (RCC). Robust clinical activity was observed across dose levels and histologic subtypes. The safety profile with the combination was tolerable with dose modification and comparable to previous reports. The findings are published by Dr. Sumanta K. Pal of the Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center in Duarte, CA, USA and colleagues on 7 September 2021 in the Journal of Clinical Oncology (JCO).

COSMIC-021 is evaluating the combination of cabozantinib plus atezolizumab in patients with various advanced solid tumours, including clear cell and non–clear cell RCC. Cabozantinib plus atezolizumab showed encouraging antitumour activity in patients with clear cell RCC in the dose-escalation stage of COSMIC-021 and in expansion cohorts of other solid tumours. In the latest article published in the JCO, the study team reports the results for all patients with advanced clear cell RCC and non-clear cell RCC enrolled in the study.

This phase Ib study enrolled adult patients with advanced RCC. A dose-escalation stage was followed by expansion cohorts. For cohort expansion, prior systemic therapy was not permitted for clear cell RCC, but it was allowed for non-clear cell RCC. Patients received oral cabozantinib 40 mg once a day (clear cell RCC and non-clear cell RCC) or 60 mg once a day (clear cell RCC only) plus 1,200 mg of atezolizumab intravenously, once every 3 weeks. The study primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. The secondary endpoint was safety.

In total, 102 patients were enrolled. Median follow-up was 25.8, 15.3, and 13.3 months for the 40 mg clear cell RCC, 60 mg clear cell RCC and non-clear cell RCC groups, respectively.

The ORR was 53% (80% confidence interval [CI] 41 to 65) in the 40 mg clear cell RCC group and 58% (80% CI 46 to 70) in the 60 mg clear cell RCC group, with complete response of 3% and 11%, respectively. Median progression-free survival (mPFS) which was exploratory endpoint was 19.5 and 15.1 months. In non-clear cell RCC group, ORR was 31% (80% CI 20 to 44), all partial responses; mPFS was 9.5 months.

Grade 3 or 4 treatment-related adverse events (TRAEs) were reported by 71% of patients in the 40 mg clear cell RCC group, 67% in the 60 mg clear cell RCC group, and 38% in the non-clear cell RCC group. TRAEs leading to discontinuation of both agents occurred in 15%, 6%, and 3% of patients, respectively. There were no grade 5 TRAEs.

The authors concluded that they observed encouraging antitumour activity with the combination of cabozantinib plus atezolizumab across clear cell RCC and non-clear cell RCC histologies, with a tolerable safety profile. Side effects were managed with dose modifications and supportive care measures.

Further evaluation of cabozantinib plus atezolizumab in RCC is ongoing in the phase III CONTACT-03 study, which is evaluating cabozantinib plus atezolizumab compared with cabozantinib alone in patients with clear cell RCC and non-clear cell RCC who received prior immune checkpoint inhibitor as a first- or second-line treatment.

Reference

Pal SK, McGregor B, Suárez, et al. Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study. JCO; Published online 7 September 2021. DOI:10.1200/JCO.21.00939

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