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.

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.

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.

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. NCT01772004 ; registered 21 January, 2013.

Journal for immunotherapy of cancer. 2019 Oct 24*** epublish ***

Ulka Vaishampayan, Patrick Schöffski, Alain Ravaud, Christian Borel, Julio Peguero, Jorge Chaves, John C Morris, Nuria Kotecki, Martin Smakal, Dongli Zhou, Silke Guenther, Marcis Bajars, James L Gulley

Karmanos Cancer Institute, Wayne State University, 4100 John R. Street, Detroit, MI, 48201, USA. ., General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium., Medical Oncology, Bordeaux University Hospital, Bordeaux, France., Medical Oncology, Centre Paul Strauss, Centre de Recherche, Centres de Lutte Contre le Cancer (CRLCC), Strasbourg, France., Oncology Haematology, Oncology Consultants, Houston, USA., Haematology-Oncology, Northwest Medical Specialties, Lakewood, USA., Internal Medicine, University of Cincinnati, Cincinnati, USA., Centre Oscar Lambret, Lille, France., Horovice Oncology Clinic, Nemocnice Rudolfa a Stefanie Benešov, a. s, Benešov, Czech Republic., Merck Serono Pharmaceutical R&D Co, Beijing, China., Merck KGaA, Darmstadt, Germany., Global Clinical Development, EMD Serono, Billerica, USA., Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA.