UCDCC#270: Avelumab and Stereotactic Ablative Radiotherapy in Non-responding and Progressing NSCLC Patients

Lung cancer is the leading cause of cancer deaths worldwide. More than half of lung cancer patients present with metastatic disease at diagnosis, with a median survival of only 10-12 months. In recent years the development of more efficacious therapies for metastatic non-small cell lung cancer (NSCLC) based upon an improved understanding of the underlying tumor biology has resulted in an improvement in median overall survival by several months. However, survival remains poor for most patients and there remains an urgent unmet need for novel treatment strategies to improve survival for these patients. Avelumab is a fully human anti-PD-L1 IgG1 monoclonal antibody. In phase I studies, avelumab was well-tolerated at a dose of 10 mg/kg IV Q2 weeks with the most frequently observed treatment related adverse events including fatigue, infusion-related reactions, nausea, chills, diarrhea, and pyrexia. However, many patients will not respond to checkpoint inhibition, and developing strategies to further improve the efficacy and extend the benefit of these treatments to non-responding and progressing patients is an area of substantial need. Among NSCLC patients, approximately 80% of patients will not respond to a checkpoint inhibitor as monotherapy. Combinatorial strategies may increase response rates. Radiotherapy is an intriguing partner therapy, with preclinical and clinical studies confirming the immunomodulatory effects of radiotherapy. There is particularly interest in the use of radiotherapy in patients who have failed a checkpoint inhibitor as monotherapy as this approach will isolate the effects of radiation in enhancing response rates. Stereotactic ablative radiotherapy (SAR) (also known as stereotactic body radiotherapy or SBRT) has emerged as a potentially curative treatment option for patients with early stage, medically inoperable non-small cell lung cancer and as a safe and effective local treatment for metastatic lesions. The investigators hypothesize that local radiotherapy can augment the systemic effects of avelumab in NSCLC patients previously refractory to a checkpoint inhibitor previously used as standard-of-care treatment. This proposal seeks to gain insight into the clinical and biological efficacy of this combination.