A Proof of Principle Study of Pembrolizumab With SBRT in TKI mRCC Patients

This study is designed as a phase-II proof of concept trial to investigate if a treatment strategy where stereotactic body radiation therapy (SBRT) is given with pembrolizumab is sufficiently active to warrant further investigation in randomized phase II or III studies. Metastatic renal cell cancer (mRCC) patients with PD-1 expressing immune cells are more likely to have larger more aggressive tumours and reduced survival and renal tumours that express PD-L1 are more aggressive with poorer outcome. Blocking this receptor/ligand interaction with monoclonal antibodies can restore the activity of tumour specific T-cells within the tumour with durable responses documented in early clinical trials in several tumour types including renal cell carcinoma. The study drug pembrolizumab is designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. SBRT will be given to the 1-3 most clinically significant lesions at the time of progression on pembrolizumab or at the 2nd course of pembrolizumab treatment in an effort to improve the activity of pembrolizumab. A total of 35 patients refractory to the approved first line therapy with a targeted drug (Sunitinib or Pazopanib) or untreated RCC patients with sarcomatoid differentiation will be enrolled on study. This group of patient has a poor outcome on any other 2nd line therapy and urgently need novel therapy.