Interim safety analysis of consolidation nivolumab and ipilimumab versus nivolumab alone following concurrent chemoradiation for unresectable stage IIIA/IIIB NSCLC: Big Ten Cancer Research Consortium LUN 16-081.

Abstract

8535 Background: Consolidation PD-1 inhibition after chemoradiation (chemoRT) for unresectable stage IIIA/IIIB NSCLC improves overall survival. The efficacy and safety of combining a CTLA-4 inhibitor with a PD-1 inhibitor in this setting are unknown but may further improve efficacy in this patient population. Methods: In this randomized, multi-center, phase II study, 105 pts with unresectable stage IIIA/IIIB NSCLC will receive chemoRT, then randomize 1:1 to either nivolumab 480mg IV q4 wks (nivo) or nivolumab 3mg/kg IV q2 wks + ipilimumab 1mg/kg IV q6 wks (nivo/ipi), for up to 24 wks. In this interim analysis, we assess the safety of the first 20 patients treated. Results: From 9/2017 to 11/2018, 20 patients were accrued. Characteristics of those treated on the nivo arm (n = 10) were: median age 62 years, stage IIIA/B 7/3; non-squamous/squamous 7/3; and the nivo/ipi arm (n = 10): median age 61 years; stage IIIA/B 6/4; non-squamous/squamous 7/3. Most toxicities were grade 1 or 2 and the most frequently noted grade 2 AEs included fatigue (25%), pneumonia (25%), extremity pain (20%). Adverse events reported in the Nivo only arm included 81 total events with only four grade 3 events and a single grade 4 thromboembolic event. The Nivo/Ipi arm reported 101 total AEs, with only 3 grade 3 events and a single grade 4 toxicity (amylase elevation). With respect to immune-related adverse events (irAEs), in the nivo arm there were two cases of grade 2 pneumonitis and no grade 3/ 4 events. In the nivo/ipi arm, there was one grade 2 pneumonitis, three grade 3 irAEs (pneumonitis, colitis, pancreatitis), and one asympomatic grade 4 amylase elevation. No treatment-related deaths were observed in either arm. Conclusions: There were no unexpected safety signals in the first 20 patients treated on BIG10CRC LUN 16-081. The incidence of grade 3 or higher irAEs was higher in the nivo/ipi arm, as expected, but this was manageable with the use of established guidelines. The study currently remains open to accrual (32 of 105 have been randomized as of 2/8/19). Clinical trial information: NCT03285321.