Abstract CT113: Safety and activity of second-line durvalumab + tremelimumab in non-squamous advanced NSCLC
Authors: Chaft Jamie , Cho Byoung Chul , Ahn Myung-Ju , Moulec Sylvestre Le , Cho Eun Kyung , Papadimitrakopoulou Vassiliki , Garon Edward , Lee Sylvia , Aix Santiago Ponce , Ma Patrick C. , Otterson Gregory , Narwal Rajesh , Gao Guozhi , McDevitt Jennifer , Englert Judson , Antonia Scott 
Published: August 2018

Abstract
Background: The anti-PD-L1 antibody durvalumab (D) has shown manageable safety and encouraging clinical activity in patients with advanced NSCLC. Combination of D with anti-CTLA-4 antibody tremelimumab (T) may amplify T-cell responses against tumors through non-redundant immune checkpoint blockade and provide synergistic antitumor activity. We previously reported that D+T showed antitumor activity and manageable tolerability in the dose-escalation part of a phase 1b study (NCT02000947) of patients with advanced NSCLC. Here we present safety, clinical activity, and long-term follow-up for one of 3 expansion cohorts.
Methods: Immunotherapy-naive patients with non-squamous NSCLC who progressed after 1 prior platinum-based therapy, ECOG PS 0-1, received D IV 20 mg/kg every 4 weeks (Q4W) for up to 12 months and T IV 1 mg/kg Q4W with the first 4 cycles of D. Tumor PD-L1 expression (fresh biopsy or archival sample within 3 mo) was assessed with the Ventana PD-L1 (SP263) assay, PD-L1 cutoff: ≥25% of tumor cells with membrane staining.
Results: As of 20 Oct 2017, 213 patients (71% ECOG PS 1) received therapy and were followed for a median of 13.3 (0.5-21.0) mo. Treatment-related adverse events (AEs) were reported in 76% of patients; the most common were fatigue (19%), pruritus (17%), diarrhea (15%), decreased appetite (14%), and rash (14%). 14 patients (7%) had a treatment-related AE leading to discontinuation, with colitis (1%), diarrhea (1%), and pneumonitis (1%) reported in more than 1 patient. Grade 3/4 treatment-related AEs occurred in 23% of patients; the most common were increased lipase (5%), colitis (3%), and increased amylase (3%). There was 1 treatment-related death (multifactorial hypoxia). The 12-month OS rate was 53.8% (95% CI, 46.4-60.6). The Table shows antitumor activity and survival by PD-L1 status.
Conclusions: Second-line D+T had a manageable safety profile in patients with non-squamous NSCLC. Clinical activity was seen in both PD-L1 ≥25% and &lt;25% groups, with encouraging OS.
Response and survivalPD-L1 ≥25% n=57PD-L1 &lt;25% n=136Totala N=213CR1 (1.8)01 (0.5)PR19 (33.3)16 (11.8)39 (18.3)SD17 (29.8)55 (40.4)77 (36.2)PD16 (28.1)52 (38.2)77 (36.2)Confirmed ORR (CR + PR)n (%)20 (35.1)16 (11.8)40 (18.8)95% CI22.9-48.96.9-18.413.8-24.7DORMedian, weeks51.7NR51.795% CI25.1-NE24.3-NE40.3-NEPFSMedian, months7.13.33.595% CI3.4-9.21.7-3.51.8-4.0OS rate12-month OS, %71.647.353.895% CI57.3-81.938.2-55.946.4-60.6Note: Investigator-assessed antitumor activity according to RECIST v1.1. NE, not estimable. a20 patients had unknown PD-L1 expression
Citation Format: Jamie Chaft, Byoung Chul Cho, Myung-Ju Ahn, Sylvestre Le Moulec, Eun Kyung Cho, Vassiliki Papadimitrakopoulou, Edward Garon, Sylvia Lee, Santiago Ponce Aix, Patrick C. Ma, Gregory Otterson, Rajesh Narwal, Guozhi Gao, Jennifer McDevitt, Judson Englert, Scott Antonia. Safety and activity of second-line durvalumab + tremelimumab in non-squamous advanced NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT113.