A Phase II Clinical Trial of Pembrolizumab Efficacy and Safety in Advanced Renal Medullary Carcinoma

Background. Renal medullary carcinoma (RMC) is one of most aggressive renal cell carcinomas and novel therapeutic strategies are therefore needed. Recent comprehensive molecular and immune profiling of RMC tissues revealed a highly inflamed phenotype, suggesting the potential therapeutic role for immune checkpoint therapies. We present the first prospective evaluation of an immune checkpoint inhibitor in a cohort of patients with RMC. Methods. A cohort of patients with locally advanced or metastatic RMC was treated with pembrolizumab 200 mg intravenously every 21 days in a phase II basket trial (ClinicalTrials.gov: NCT02721732). Responses were assessed by irRECIST. Tumor tissues were evaluated for PD-L1 expression and for tumor-infiltrating lymphocyte (TIL) levels. Somatic mutations were assessed by targeted next-generation sequencing. Results. A total of five patients were treated. All patients had advanced disease, with the majority of patients (60%) having metastatic disease at diagnosis. All patients had rapid disease progression despite pembrolizumab treatment, with a median time to progression of 8.7 weeks. One patient (patient 5) experienced sudden clinical progression immediately after treatment initiation and was thus taken off trial less than one week after receiving pembrolizumab. Conclusions. This prospective evaluation showed no evidence of clinical activity for pembrolizumab in patients with RMC, irrespective of PD-L1 or TIL levels.