Avelumab, an anti PD L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study
PurposeAgents targeting programmed death receptor 1 (PD 1) or its ligand (PD L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC) The aim of this study was to assess the activity of avelumab, a PD L1 inhibitor, in patients with MBC.MethodsIn a phase 1 trial (JAVELIN Solid Tumor; NCT01772004) patients with MBC refractory to or progressing after standard of care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI CTCAE v4.0. Membrane PD L1 expression was assessed by immunohistochemistry (Dako PD L1 IHC 73 10 pharmDx).ResultsA total of 168 patients with MBC, including 58 patients with triple negative breast cancer (TNBC) were treated with avelumab for 2 50 weeks and followed for 6 15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade 3 treatment related AEs occurred in 13.7% of patients, including two treatment related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD L1+ versus PD L1 tumor associated immune cells in the overall population (16.7% vs. 1.6% and in the TNBC subgroup (22.2% vs. 2.6%.ConclusionAvelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD L1 expression in tumor associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.
Breast Cancer Research and Treatment