DETERRED: PD-L1 blockade to evaluate the safety of lung cancer therapy using carboplatin, paclitaxel, and radiation combined with MPDL3280A (atezolizumab).

Abstract

3064 Background: Immune checkpoint blockade in non-small cell lung cancer (NSCLC) may be enhanced when combined with radiation therapy. Atezolizumab (atezo) is a humanized and Fc receptor modified monoclonal antibody that blocks programmed death-ligand-1 (PD-L1) interacting with PD-1 or B7.1 sparing PD-L2, which may result in less pulmonary toxicity. We report the early safety data of combining atezo added sequentially after standard concomitant chemoradiation (CRT) for locally advanced NSCLC (LA-NSCLC). Methods: This is a phase II study in LA-NSCLC assessing the safety and feasibility of adding atezo to CRT in two parts: I) sequentially (N = 10) with CP after completing CRT, or II) concurrently (N = 30) with CRT followed by consolidation atezo with CP. We report on the early toxicity results from part I of the trial. Atezo was given at 1200 mg IV Q3 weeks with consolidation CP for 2 cycles after CRT followed by atezo monotherapy for up to one year. Radiation dose at 60-66 Gy in 30-33 fractions was combined with weekly low dose CP, followed by 2 cycles of full dose CP. Dose limiting toxicities were defined as any adverse events (AEs) ≥ grade 3 within 15 weeks of start of therapy or any immune-related AEs during atezo treatment. Results: From January to December 2016, 10 evaluable patients were enrolled. Seven patients have received consolidation atezo ranging from 1 to 14 doses, with 3 yet to receive atezo after completing CRT. Three patients reported potential immune-related AEs. One patient developed grade 3 arthralgia, and another developed grade 2 radiation-induced pneumonitis, which resolved with steroids. A third patient who experienced grade 3 dyspnea due to COPD exacerbation after 1 dose of atezo discontinued additional therapy. Of the 7 patients who have received atezo, 2 patients developed progression of disease after 6 and 8 doses of atezo. Conclusions: Atezo consolidation with 2 cycles of CP after CRT appears to be feasible and well tolerated with manageable toxicities. Additional data from part I will be reported. Conditions for proceeding after part I are met and part II of the study which adds atezo to CRT followed by atezo-CP consolidation is open for accrual. Clinical trial information: NCT02525757.