Safety and Activity of Durvalumab + Tremelimumab in Immunotherapy (Imt)-Pretreated Advanced NSCLC Patients.

9041 Background: The combination of anti-PD-L1 antibody durvalumab (D) with anti-CTLA-4 antibody tremelimumab (T) showed antitumor activity and manageable tolerability in IMT-naïve patients with advanced NSCLC in the dose-escalation part of a phase 1b study. Here we report safety and clinical activity in one of 3 expansion cohorts. Methods: Eligible patients had received up to 3 prior lines of therapy, including prior anti-PD-1 or anti-PD-L1 monotherapy to which they did not respond ("refractory") or responded and then progressed ("relapsed"). Patients had no subsequent systemic therapy until start of study treatment, and had not had any toxicity leading to discontinuation of prior IMT. Patients received D IV 20 mg/kg Q4W for up to 12 months and T IV 1 mg/kg Q4W with the first 4 cycles of D. Results: As of 27 Nov 2017, 78 patients received therapy and were followed for a median of 18.4 (0.7–28.0) months. 80% had non-squamous histology, 19% were KRAS mutant and 3% were EGFR mutant. 94% had received ≥2 lines of prior therapy, including 5 patients with 2 prior IMT. Median time to progression on prior IMT was 7.0 months in relapsed and 2.6 months in refractory patients. Treatment-related AEs were reported in 72% of patients; the most common were fatigue (26%), diarrhea (23%), and nausea (14%). Grade 3/4 treatment-related AEs occurred in 28% of patients, with diarrhea (6%) being most common. 5 patients (6%) discontinued due to a treatment-related AE, (diarrhea in 4%) and no treatment-related deaths occurred. Clinical outcomes are summarized in the Table. DCR24 was 21.8% (95% CI, 13.2–32.6); for these 17 patients, median duration of exposure was 9.5 months, compared with 6.1 months on prior IMT. Conclusions: D+T had a manageable safety profile in IMT-pretreated patients with prolonged stable disease or better seen in some patients. Clinical trial information: NCT02000947. IMT-relapsed n = 40 IMT-refractory n = 38 Total N = 78 Confirmed ORR (CR + PR) n (%) 2 (5.0) 2 (5.3) 4 (5.1) (95% CI) (0.6–16.9) (0.6–17.7) (1.4–12.6) DCR at 24 wks n (%) 9 (22.5) 8 (21.1) 17 (21.8) (95% CI) (10.8–38.5) (9.6–37.3) (13.2–32.6) PFS Median, mo 2.5 1.7 1.8 (95% CI) (1.6–3.5) (1.6–1.8) (1.6–2.5) OS Median, mo 8.5 8.3 8.4 (95% CI) (4.0–14.3) (6.0–10.4) (6.2–10.4) 12-mo rate (%) 37.5 30.1 34.1