Background: MEDI4736 (M) is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity. PD-L1 is expressed in NSCLC tumors and may be associated with response to anti-PD-L1 treatment. This ongoing Phase 1/2, multicenter, open-label study (NCT01693562) evaluates the safety and clinical activity of M in patients (pts) with multiple solid tumor types including NSCLC. Methods: M is administered at 10 mg/kg IV every 2 wks (q2w) until unacceptable toxicity, disease progression, or for up to 12 months. Safety evaluations occur prior to each dose (toxicities graded by CTCAE v4.0). Response is based on investigator assessment (RECIST v1.1; includes confirmed/unconfirmed responses) at 6, 12, and 16 wks, then every 8 wks. Retreatment is permitted upon progression after 12 months of therapy. PD-L1 expression within the tumor is assessed using Ventana PD-L1 IHC (SP263). Data included represent a larger population with more mature follow up than previously reported.¹Results: As of 31 Oct 2014, 198 pts (116 non-squamous and 82 squamous histology; mean age 64 [range 26–87]; ECOG PS 0 [24%] or 1 [76%]; 81% current/prior smokers; median 2.5 prior treatments [1–9]) have been treated with M 10 mg/kg q2w (median 6 doses; range 1–23). Drug-related AEs were reported in 48% of pts; most frequently fatigue (14%), decreased appetite (9%), and nausea (8%). Grade ≥ 3 drug-related AEs were reported in 6% of pts. Drug-related AEs led to study discontinuation in 2% of pts. Pneumonitis (Grade 1-2) occurred in 2 (1%) pts. In all, 149 pts were evaluable for response with ≥ 24 wks of follow-up; ORR was 14% (23% in PD-L1+), and DCR at 24 wks was 24%. ORR was higher in squamous (21%) than non-squamous pts (10%). Responses were durable with 76% ongoing (DoR range 0.1+ – 35+ wks). Conclusions: With more mature follow up, the safety profile of M in NSCLC is manageable and consistent with previous reports. Responses are durable; ORR appears to be higher in squamous NSCLC and PD-L1+ pts. A broad development program of M alone and in combination with other treatments is underway in NSCLC.

Antonia S, et al. Poster presented at ESMO 2014, 1325P