Phase II trial of consolidation Pembrolizumab following concurrent chemoradiation in patients (pts) with unresectable or inoperable stage III non-small cell lung cancer (NSCLC): initial safety data from HCRN LUN 14-179.

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Background: A standard of care for pts with inoperable or unresectable stage III NSCLC is concurrent chemoradiation alone, but approximately 80% of pts will develop recurrent or metastatic disease. Pembrolizumab is a monoclonal antibody (mAb) against programmed-death-1 (PD-1) and helps promote a renewed host immune response against malignant cells. Pembrolizumab is FDA-approved for the second line treatment of patients with metastatic NSCLC whose tumors express PD-L1 by an FDA-approved test, and pre-clinical mouse models demonstrate a synergistic effect on tumor cell kill following radiation in combination with PD-1 blockade. Methods: Pts with inoperable or unresectable stage III NSCLC were treated with concurrent chemoradiation (using cisplatin/etoposide, carboplatin/paclitaxel, or cisplatin/pemetrexed); consolidation chemotherapy was permissible. Pts with non-PD 4-8 wks after completing therapy received Pembrolizumab consolidation 200mg IV every 3 weeks until progression or prohibitive toxicity for up to 12 months. The primary endpoint is time to metastatic disease defined as disease progression outside the radiated field. Secondary endpoints include progression free survival, overall survival, and toxicity. An exploratory analysis will correlate these endpoints and PD-L1 expression levels. This abstract reviews the DSMC analysis of the first 10 pts treated on study. Results: As of 1/31/16, 38 of a planned 93 pts have enrolled. Eight of the initial 10 pts remain on treatment with a median of 9 cycles (range 3 to 12) of Pembrolizumab. There have been no treatment-related deaths and no grade 4 toxicities. One pt had grade 3 urinary toxicity. One pt developed grade 1 pneumonitis, and there have been no episodes of esophagitis. Fatigue was the most commonly reported symptom in 5 pts followed by cough in 4 pts (all grade 1-2). Conclusions: This early safety analysis in 10 pts suggests that it is feasible to administer Pembrolizumab 4-8 weeks following the completion of concurrent chemoradiation in pts with stage III NSCLC. Clinical trial information: NCT02343952.