Merck KGaA and Pfizer Inc. announced positive top-line results from the pivotal phase III JAVELIN Renal 101 study evaluating Bavencio (avelumab) in combination with Inlyta (axitinib), compared with Sutent (sunitinib) as initial therapy for patients with advanced renal cell carcinoma.
As part of a planned interim analysis, an independent Data Monitoring Committee confirmed that the trial showed a statistically significant improvement in progression-free survival by central review for patients treated with the combination whose tumors had programmed death ligand-1 positive expression greater than 1 percent (the primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (the secondary objective).
According to the statistical analysis plan, if PFS was statistically significant in the PD-L1+ subgroup, then PFS in the entire study population was to be analyzed for statistical significance. JAVELIN Renal 101 will continue as planned to the final analysis for the other primary endpoint of overall survival.
No new safety signals were observed, and adverse events for Bavencio, Inlyta, and Sutent in this trial were consistent with the known safety profiles for all three medicines. The alliance intends to pursue a regulatory submission in the U.S. based on these interim results, and these results will be discussed with global health authorities. A detailed analysis will also be submitted for presentation at an upcoming medical congress.
In Dec. 2017, the FDA granted Breakthrough Therapy Designation for Bavencio in combination with Inlyta for treatment-naïve patients with advanced RCC. Despite available therapies, the outlook for patients with advanced RCC remains poor. About 20 to 30 percent of patients are first diagnosed at the metastatic stage. The five-year survival rate for patients with metastatic RCC is approximately 12 percent.
JAVELIN Renal 101 is a global Phase III, multicenter, randomized (1:1) study investigating the efficacy and safety of Bavencio in combination with Inlyta as a first-line treatment option compared with SUTENT monotherapy in 886 patients with advanced RCC across all risk groups.
The primary objectives are to demonstrate that Bavencio in combination with Inlyta is superior to Sutent monotherapy in prolonging PFS or OS in patients with PD-L1+ tumors. Bavencio was administered at 10 mg/kg IV every two weeks in combination with Inlyta at 5 mg orally twice daily; Sutent was administered at 50 mg orally once daily, four weeks on/two weeks off.
The combination of Bavencio and Inlyta is under clinical investigation for advanced RCC, and there is no guarantee this combination will be approved for advanced RCC by any health authority worldwide.
In the US, INLYTA is approved as monotherapy for the treatment of advanced RCC after failure of one prior systemic therapy. Inlyta is also approved by the European Medicines Agency for use in the EU in adult patients with advanced RCC after failure of prior treatment with Sutent or a cytokine.
