Diclofenac for the Treatment of Patients With Metastatic Non-small Cell Lung Cancer on Single Agent Immunotherapy

PRIMARY OBJECTIVE: I. To evaluate the clinical benefit rate of concomitant diclofenac potassium (diclofenac) and single agent checkpoint blockade. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of concomitant diclofenac and single agent checkpoint blockade. II. To evaluate the efficacy of concomitant diclofenac and single agent checkpoint blockade in NSCLC. EXPLORATORY OBJECTIVES: I. To evaluate the change in immunophenotype in circulating CD8 T cells following initiation of diclofenac oral therapy in patients who show early sings of progression on single agent immunotherapy for advanced lung cancer. II. To investigate the role of PD-L1 expression status in response to the addition of diclofenac daily oral therapy in patients who show early sings of progression on single agent immunotherapy for advanced lung cancer. III. To evaluate the role of serum lactic acid levels in determining dose exposure to diclofenac. IV. To evaluate the change in circulating immune parameters (CD4 T cells and B cells) with the addition of diclofenac to single agent immunotherapy. V. To evaluate the role of the tumor microenvironment at the time of diagnosis on efficacy. OUTLINE: Patients receive diclofenac orally (PO) twice daily (BID) and standard of care immunotherapy with pembrolizumab, atezolizumab, nivolumab or cemiplimab on day 1 of each cycle. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and computed tomography (CT), positron emission tomography (PET), or magnetic resonance imaging (MRI) on study. After completion of study treatment, patients are followed up every 12 weeks for up to 1 year.