Pivotal phase III data of Bavencio + Inlyta for renal cell carcinoma is published in NEJM.- Merck KGaA + Pfizer

Merck KGaA and Pfizer Inc. announced the publication of results from an interim analysis of the pivotal JAVELIN Renal 101 trial online in the New England Journal of Medicine. The combination of Bavencio (avelumab) and Inlyta (axitinib) significantly extended median progression-free survival (PFS) by more than five months compared with Sutent (sunitinib) as a first-line treatment for patients with advanced renal cell carcinoma (RCC), irrespective of PD-L1 expression (HR: 0.69 [95% CI: 0.56�0.84]; Bavencio + Inlyta: 13.8 months [95% CI: 11.1-NE]; Sutent: 8.4 months [95% CI: 6.9-11.1]; p<0.001). further the objective response rate orr was doubled with bavencio inlyta versus sutent in this population 51.4 95 ci: 46.6-56.1 vs. 25.7 95 ci: 21.7-30.0. the study is continuing for the other primary endpoint of overall survival os.>

Additional data presented at the 2019 Genitourinary Cancers Symposium reinforce the consistency of the PFS and ORR results across patient subgroups, including patients with favorable, intermediate and poor prognoses as well as those with PD-L1-positive or negative tumors. In subgroup analyses, approximately two-thirds of patients with favorable risk (66% of patients using the Memorial Sloan Kettering Cancer Center risk model and 68% with the International Metastatic Renal Cell Carcinoma Database Consortium risk model) achieved a complete or partial response with Bavencio + Inlyta. Median PFS for these patients is not yet estimable. Bavencio + Inlyta also extended median PFS2, defined as the time from randomization to disease progression on next-line therapy (HR: 0.56 [95% CI: 0.42-0.74]; NE [95% CI: 19.9-NE] vs. 18.4 months [95% CI: 15.7-23.6]) and increased median duration of response by more than four months (95% CI: 2.9-5.1) in the overall population.

Adverse events of grade 3 or higher during treatment (treatment-emergent adverse events [TEAEs]) occurred in 71.2% of patients in the Bavencio + Inlyta arm and 71.5% in the Sutent arm); grade 3 or higher TEAEs that occurred in more than 5% of patients receiving the combination were hypertension (25.6%), diarrhea (6.7%), increased alanine aminotransferase level (6.0%) and hand�foot syndrome (5.8%). In the combination arm, 9.0% of patients experienced grade 3 or higher immune-related adverse events. Grade 5 events occurred in three patients in the Bavencio + Inlyta arm (myocarditis, necrotizing pancreatitis, sudden death; n=1 each); and in one patient in the Sutent arm (intestinal perforation). There were fewer discontinuations due to adverse events that occurred during treatment with Bavencio + In;yta, compared with Sutent (7.6% vs. 13.4%).

Comment:On February 11, 2019, the alliance announced that the US Food and Drug Administration (FDA) accepted for Priority Review the supplemental Biologics License Application (sBLA) for BAVENCIO in combination with INLYTA for patients with advanced RCC. The application has been given a target action date in June 2019. A supplemental application for BAVENCIO+INLYTA in unresectable or metastatic RCC was submitted in Japan on January 30, 2019.

See- Motzer RJ, Rini B, Albiges L, et al. "Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma". NEJM. February 16, 2019.Published online ahead of print.