medwireNews: Results from the JAVELIN Renal 100 study suggest that avelumab plus axitinib is a tolerable combination, with encouraging antitumor activity in treatment-naïve patients with advanced renal cell carcinoma (RCC).
The phase Ib study, conducted at 14 centers in the USA, UK, and Japan set out to establish the maximum tolerated dose for the anti-PD-L1 monoclonal antibody avelumab when used in combination with the VEGF receptor inhibitor axitinib.
The dose finding phase, which included six patients aged 18 years or older (≥20 years in Japan) with previously untreated advanced RCC, established a maximum tolerated dose of avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily.
During this phase, there was one dose-limiting toxicity of grade 3 proteinuria due to axitinib, which resolved without sequelae.
A further 49 patients underwent treatment during the dose expansion phase, for a median treatment duration of 37 weeks with avelumab and 36 weeks with axitinib.
During a median follow-up period of 52.1 weeks, nearly all patients (96%) had at least one treatment-related adverse event, most commonly diarrhea, hypertension, dysphonia, and fatigue.
More than half (58%) of the patients had a grade 3 or worse treatment-related adverse event, including hypertension in 16 (29%) patients and increased alanine aminotransferase, amylase, and lipase concentrations, and palmar–plantar erythrodysesthesia syndrome in four (7%) patients each.
At the time of analysis, 58% of patients had confirmed objective responses, with 6% achieving a complete response. The disease control rate was 78%, and responses were ongoing in 44%, with the median response duration not yet reached.
Six (11%) patients died before during the study period, five (9%) due to disease progression and one (2%) due to treatment-related autoimmune myocarditis.
Toni Choueiri (Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, Massachusetts, USA) and co-researchers say that the safety profiles and response rates observed in this study were consistent with data from other phase I and II studies of PD-L1 and PD-1 inhibitors combined with angiogenesis inhibitors, including that of axitinib plus pembrolizumab, as previously reported by medwireNews.
They add that a phase III trial comparing avelumab plus axitinib with sunitinib monotherapy is currently underway.
In a comment accompanying the research in The Lancet Oncology, Viktor Grünwald, from Hannover Medical School in Germany, writes: “These antitumour activity findings indicate the potential clinical benefit of targeted-immune combinations and suggest that further studies are warranted to explore whether a first-line targeted-immune combination might overcome the standard of sequential targeted and immune therapies.”
He adds: “With the dawn of immune-immune and targeted-immune combinations, for the first time in a decade, major progress towards improving the median overall survival and possibly delivering cure to some of our patients with metastatic renal-cell carcinoma seems to have been made.”
By Laura Cowen
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