ASCO GU 2023: Cabozantinib in Combination with Atezolizumab in Non-Clear Cell Renal Cell Carcinoma: Extended Follow-up Results of Cohort 10 of the COSMIC-021 Study

( In this abstract, Dr. McGregor presents the extended follow-up results of cohort 10 of the COSMIC-021 study, evaluating the combination of cabozantinib and atezolizumab for patients with non-clear cell RCC.

In the COSMIC-021 phase 1b study (NCT03170960), which evaluated cabozantinib plus atezolizumab in advanced solid tumors, this combination therapy demonstrated encouraging clinical activity in patients with advanced non-clear cell renal cell carcinoma (nccRCC) with a median follow-up of 13 mo.1 Results after extended follow-up (37.2 months) in nccRCC are presented (and have been published).2

Patients with advanced nccRCC and ECOG PS 0/1 who had ≤1 prior VEGFR-targeting tyrosine kinase inhibitor (TKI) were eligible. Prior treatment with TKIs targeting MET or immune checkpoint inhibitors was not allowed. Patients received cabozantinib 40 mg PO QD plus atezolizumab 1200 mg IV Q3W until unacceptable toxicity or progression; dose reductions of cabozantinib (40 mg QD to 20 mg QD, then to 20 mg QOD) were permitted to manage adverse events. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by the investigator; other endpoints included safety, duration of response (DOR), PFS, and OS.

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As of July 2021, 32 patients (2 from dose escalation phase, and 30 from expansion phase of the study) had been enrolled with median follow-up 37.2 months. 5 (16%) patients remaining on study treatment.


ORR by investigator was 31% (all PRs) and disease control rate was 94% (Table); median DOR was 8.1 mo.


Responses were seen across all subgroups and IMDC risk levels – higher response rates were seen for papillary RCC (47%).

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81% of patients had a reduction in tumor size.

Median PFS was 9.3 mo (95% CI 5.5–12.3), and median OS was not reached (95% CI 23.0–NE).

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PFS and OS estimates at 12 mo were 34% and 84%, respectively; 24-mo estimates were 6% and 70%.

Generally, this was a well tolerated combination. Treatment-related AEs occurred in 97% (grade 3/4, 53%); the most common AEs included diarrhea (69%), palmar-plantar erythrodysesthesia (50%), fatigue (44%), dysgeusia (41%), hypertension (31%) and nausea (31%). One grade 5 treatment-related AE of pulmonary hemorrhage occurred. Treatment-related AEs leading to discontinuation of both study treatments occurred in 13% of patients.

Based on the above, the authors conclude that the extended 3-year follow-up of the COSMIC-021 study reinforces the encouraging clinical activity of cabozantinib plus atezolizumab in advanced nccRCC with a manageable safety profile.

Presented by: Bradley Alexander McGregor, MD, Dana-Farber Cancer Institute

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis @tchandra_uromd on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.


  1. Pal SK, McGregor B, Suárez C, Tsao CK, Kelly W, Vaishampayan U, Pagliaro L, Maughan BL, Loriot Y, Castellano D, Srinivas S, McKay RR, Dreicer R, Hutson T, Dubey S, Werneke S, Panneerselvam A, Curran D, Scheffold C, Choueiri TK, Agarwal N. Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study. J Clin Oncol. 2021 Nov 20;39(33):3725-3736. doi: 10.1200/JCO.21.00939. Epub 2021 Sep 7. PMID: 34491815; PMCID: PMC8601305.
  2. Agarwal N, McGregor B, Maughan BL, Dorff TB, Kelly W, Fang B, McKay RR, Singh P, Pagliaro L, Dreicer R, Srinivas S, Loriot Y, Vaishampayan U, Goel S, Curran D, Panneerselvam A, Schwickart M, Choueiri TK, Pal S. Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). Lancet Oncol. 2022 Jul;23(7):899-909. doi: 10.1016/S1470-2045(22)00278-9. Epub 2022 Jun 9. PMID: 35690072.
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Cabozantinib in Combination with Atezolizumab in Non-Clear Cell Renal Cell Carcinoma: Extended Follow-up Results of Cohort 10 of the COSMIC-021 Study - Bradley McGregor