Safety results from a phase 1b dose-finding and dose expansion study for the avelumab plus axitinib combination in untreated (treatment-naive) renal cell carcinoma (RCC) patients were published in the journal Lancet Oncology recently. Headline results from this study were previously reported at the American Society of Clinical Oncology (ASCO) annual meeting in June last year (2017), and the combination has been designated a breakthrough therapy by the FDA earlier this year.
The study was conducted at 14 centres in the US, UK, and Japan to identify the best dose of each drug (dose-finding) to use in the next part of the study to assess effectiveness (dose expansion) in people with metastatic RCC. The study primarily monitored the safety profile and the side effects in patients following treatment.
Six patients were recruited in the dose-finding phase and then 49 patients were enrolled in the dose expansion phase. The results of dose-finding phase revealed a dose of 10 mg/kg for avelumab administered by infusion every two weeks, together with 5 mg axitinib tablets twice a day. 58% of patients had a reduction in the size of their tumours.
However, 58% of the patients also exhibited very severe side effects (grade 3 or worse), with increased blood pressure being the most common side effect, and 2% of patients had treatment-related myocarditis. The safety of these drugs is currently being assessed in a phase 3 study to compare the combination with other anti-angiogenic drugs.
In this study, the safety profile of the avelumab plus axitinib combination seemed comparable to the safety profiles of each treatment alone. There is, therefore, no increased risk associated with combining these two drug treatments. The effectiveness of the avelumab plus axitinib combination is promising, and ongoing phase 3 studies will confirm this effectiveness in the treatment of metastatic RCC.