Background: Durvalumab (D) is a human IgG1 monoclonal antibody (mAb) that blocks PD-L1 binding to programmed cell death-1 (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 D in patients (pts) with multiple solid tumor types including NSCLC.

Methods: D is administered at 10 mg/kg IV every 2 weeks (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 disease progression after 12 months of therapy. PD-L1 expression within the pre-treatment tumor is assessed using Ventana PD-L1 immunohistochemistry (IHC) (SP263).

Results: As of February 27, 2015, 228 pts (126 non-squamous and 102 squamous histology; mean age 64 [range 26 – 87]; Eastern Cooperative Oncology Group Performance Status 0 [25%] or 1 [74%]; 83% current/prior smokers; 0 [12%], 1 [29%], or ≥2 [56%] prior lines of therapy) have been treated with D 10 mg/kg q2w (median 6 doses; range 1 – 27). Drug-related adverse events (AEs) were reported in 50% of pts; most frequently fatigue (15%), decreased appetite (9%), and nausea (8%). Grade ≥3 drug-related AEs were reported in 8% of pts. Drug-related AEs led to study discontinuation in 5% of pts with no treatment-related deaths. Pneumonitis occurred in 3 (1%) pts; none were Grade ≥3. In all, 200 pts were evaluable for response with ≥12 wks of follow-up; objective response rate (ORR) was 16% (27% in PD-L1+), and disease control rate at 12 wks was 42%. ORR was higher in squamous (21%) than non-squamous pts (13%). Responses were durable with 66% ongoing (duration of response range 0.1+ – 54.4+ wks). Data from translational studies will be presented.

Conclusions: With longer follow-up, the safety profile of D in NSCLC is manageable and consistent with our previous reports. Responses are durable; ORR appears to be higher in squamous NSCLC and PD-L1+ pts. A broad development program of D alone and in combination with other treatments in NSCLC is underway.

Citation Format: Scott Antonia, Naiyer Rizvi, Julie Brahmer, Sai-Hong Ou, Samir N. Khleif, Wen-Jen Hwu, Martin Gutierrez, Patrick Schoffski, Omid Hamid, Jared Weiss, Jose Lutzky, Michele Maio, John Nemunaitis, Dirk Jaeger, Ani Balmanoukian, Marlon C. Rebelatto, Keith E. Steele, Xiaoping Jin, Paul B. Robbins, John A. Blake-Haskins, Neil H. Segal. Safety and clinical activity of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 (PD-L1) antibody, in patients with non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A047.