The combination of avelumab and cabozantinib has shown preliminary clinical activity and an acceptable safety profile in previously untreated metastatic clear cell renal cell carcinoma (RCC), according to study results published in The Oncologist.

Researchers found that the recommended dose of cabozantinib is 40 mg daily, when combined with avelumab at 10 mg/kg every 2 weeks.

In this phase 1 dose-escalation trial ( Identifier: NCT03200587), researchers sought to determine the safety and recommended phase 2 dose of the combination. Their secondary objective was to determine preliminary clinical activity, including objective response rate and disease control rate.

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The study included 12 patients with untreated metastatic clear cell RCC. Patients were assigned to receive avelumab at 10 mg/kg every 2 weeks plus cabozantinib at 20 mg daily (n=3), 40 mg daily (n=3), or 60 mg daily (n=6). 

The median treatment duration was 19 months, and the median follow-up was 27.6 months.

The most common grade 3 or higher adverse events (AEs) were thromboembolic events (41.6%), diarrhea (25%), and hypertension (25%). There were no dose-limiting toxicities or treatment-related deaths. 

Half of the patients did require dose reductions of cabozantinib, including 5 of 6 patients treated with 60 mg and 1 patient treated with 40 mg. This led the researchers to conclude that the recommended phase 2 dose of cabozantinib is 40 mg daily when combined with avelumab.

The researchers also found that the combination demonstrated antitumor activity. The objective response rate was 50%. This included 1 complete response and 5 partial responses. The disease control rate was 92%.

The median progression-free survival was 11.3 months. Five patients continued with the regimen beyond progression.

The researchers noted that this combination is unlikely to be developed further in the setting of metastatic clear cell RCC because multiple other combinations of cabozantinib plus immune checkpoint inhibitors have either reached advanced phases of development or have already received regulatory approval.

Nevertheless, the researchers concluded that the recommended phase 2 dose of cabozantinib plus avelumab “was found to be safe and demonstrated tolerable AEs with preliminary evidence of antitumor activity.”

Disclosures: This research was supported by Exelixis and EMD Serono, Inc., an affiliate of Merck KGaA, as part of an alliance between Merck and Pfizer. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Li H, Sahu KK, Brundage J, et al. Phase I trial of combination therapy with avelumab and cabozantinib in patients with newly diagnosed metastatic clear cell renal cell carcinoma. Oncologist. Published online March 23, 2023. doi:10.1093/oncolo/oyad019