Activity of Combined Immune Checkpoint and VEGF Inhibition as First-Line Therapy in Advanced Clear Cell RCC


Key Points

  • Objective response was observed in 58% of patients.
  • Median duration of response was not reached.

In the dose-finding, dose-expansion phase Ib JAVELIN Renal 100 trial reported in The Lancet Oncology, Choueiri et al identified the maximum tolerated dose of the immune checkpoint inhibitor avelumab (Bavencio) in combination with the vascular endothelial growth factor inhibitor axitinib (Inlyta). The researchers found high levels of activity for the combination in first-line treatment of resected advanced clear cell renal cell carcinoma (RCC).

Study Details

In the ongoing study, between October 2015 and September 2016, 6 patients were enrolled into a dose-finding phase and 49 into a dose-expansion phase at 14 sites in the United States, United Kingdom, and Japan.

Patients in the dose-finding phase received 5 mg of oral axitinib twice daily for 7 days followed by combination therapy with 10 mg/kg of intravenous avelumab every 2 weeks and 5 mg of axitinib twice daily. In the dose-expansion phase, 10 patients received this regimen, with the remainder starting treatment with the combination without axitinib lead-in.


One dose-limiting toxicity—grade 3 proteinuria associated with axitinib—was reported among the six patients during the dose-finding phase. At the end of the dose-finding phase, the maximum tolerated dose established for the combination was avelumab at 10 mg/kg every 2 weeks and axitinib at 5 mg twice daily.

Among all patients, 58% had grade ≥ 3 treatment-related adverse events, with the most common being hypertension (29%), increased concentrations of ALT, amylase, and lipase, and palmar-plantar erythrodysesthesia syndrome (7% each). One patient died from treatment-related autoimmune myocarditis. Overall, 36% of patients had serious adverse events, which were considered treatment-related in 22%.

Response Rates

The median follow-up for all patients was 52.1 weeks. At data cutoff in April 2017, 32 (58%) of all 55 patients had an objective response, including 6 (100%) of 6 patients in the dose-finding phase and 26 (53%) of 49 in the dose-expansion phase. The disease control rate was 78%. At data cutoff, 24 patients had ongoing responses; the median duration of response was not reached. The median time to achieve objective response was 6.8 weeks.

The investigators concluded, “The safety profile of the combination avelumab plus axitinib in treatment-naive patients with advanced renal cell carcinoma seemed to be manageable and consistent with that of each drug alone, and the preliminary data on antitumour activity are encouraging. A phase III trial is assessing avelumab and axitinib compared with sunitinib monotherapy.”

The study was funded by Pfizer and Merck.

Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and Brigham and Women’s Hospital, is the corresponding author for The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.