Avelumab monotherapy as first-line or second-line treatment in patients with metastatic renal cell carcinoma: phase Ib results from the JAVELIN Solid Tumor trial

Abstract Background Antibodies targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinical activity in the treatment of metastatic renal cell carcinoma (mRCC). This phase Ib cohort of the JAVELIN Solid Tumor trial assessed the efficacy and safety of avelumab (anti–PD-L1) monotherapy in patients with mRCC as either first-line (1 L) or second-line (2 L) treatment. Methods Patients with mRCC with a clear-cell component who were treatment naive (1 L subgroup) or had disease progression after one prior line of therapy (2 L subgroup) received avelumab 10 mg/kg intravenous infusion every 2 weeks. Endpoints included confirmed best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), PD-L1 expression, and safety. Results A total of 62 patients were enrolled in the 1 L subgroup, and 20 patients were enrolled in the 2 L subgroup. In the 1 L and 2 L subgroups, confirmed objective response rates were 16.1 and 10.0%, median DOR was 9.9 months (95% confidence interval [CI], 2.8–not evaluable) and not evaluable (95% CI, 6.9–not evaluable), median PFS was 8.3 months (95% CI, 5.5–9.5) and 5.6 months (95% CI, 2.3–9.6), and median OS was not evaluable (95% CI, not evaluable) and 16.9 months (95% CI, 8.3–not evaluable), respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 51 patients in the 1 L subgroup (82.3%) and 14 patients in the 2 L subgroup (70.0%). Grade ≥ 3 TRAEs occurred in eight patients in the 1 L subgroup (12.9%) and one patient in the 2 L subgroup (5.0%). No treatment-related deaths occurred. Conclusion Avelumab showed clinical activity and a manageable safety profile in both the 1 L and 2 L treatment setting in patients with mRCC. These data support the use of avelumab in combination with other agents in mRCC. Trial registration ClinicalTrials.gov: NCT01772004; registered 21 January, 2013.