Choueiri TK, et al. - The initial results for the combination of avelumab (an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1) and axitinib (a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma) in treatment-naive patients with advanced renal-cell carcinoma were reported herein. In this patient population, the combination avelumab plus axitinib displayed a seeming manageable safety profile, which was consistent with that of each drug alone. Also, the preliminary data on antitumour activity are encouraging.

• An ongoing open-label, multicentre, dose-finding, and dose-expansion, phase 1b study viz, the JAVELIN Renal 100 study, has been performed in 14 centres in the USA, UK, and Japan, including eligible patients ie, those aged 18 years or older (≥20 years in Japan) and had histologically or cytologically confirmed advanced renal-cell carcinoma with clear-cell component, life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 1 or less, received no previous systemic treatment for advanced renal cell carcinoma, and had a resected primary tumour.
• 5 mg axitinib orally twice daily for 7 days, followed by combination therapy with 10 mg/kg avelumab intravenously every 2 weeks and 5 mg axitinib orally twice daily was given to patients enrolled into the dose-finding phase.
• Enrollment of ten additional patients to the dose-expansion phase was done based on the pharmacokinetic data from the dose-finding phase, and these patients were assigned to this regimen.
• The other patients in the dose-expansion phase started taking combination therapy directly.
• Dose-limiting toxicities in the first 4 weeks (two cycles) of treatment with avelumab plus axitinib was the primary endpoint.
• Also, all patients who received at least one dose of avelumab or axitinib were assessed via safety and antitumour activity analyses.

• The enrollment of 6 patients into the dose-finding phase and 49 into the dose-expansion phase of the study was done between Oct 30, 2015, and Sept 30, 2016.
• Researchers noted one dose-limiting toxicity of grade 3 proteinuria due to axitinib among the six patients treated during the dose-finding phase.
• They also found that at the cutoff date (April 13, 2017), six (100%, 95% CI 54–100) of six patients in the dose-finding phase and 26 (53%, 38–68) of 49 patients in the dose-expansion phase had confirmed objective responses (32 [58%, 44–71] of all 55 patients).
• Grade 3 or worse treatment-related adverse events were reported in 32 (58%) of 55 patients.
• Among those, the most frequent being hypertension detected in 16 (29%) patients and increased concentrations of alanine aminotransferase, amylase, and lipase, and palmar-plantar erythrodysaesthesia syndrome in four (7%) patients each.
• Death of 6 (11%) of 55 patients was reported before data cutoff, five (9%) were ascribed to disease progression and one (2%) to treatment-related autoimmune myocarditis.
• Additionally, findings demonstrated that at the end of the dose-finding phase, the maximum tolerated dose established for the combination was avelumab 10 mg/kg every 2 weeks and axitinib 5 mg twice daily.