Clinical activity and biomarkers of MEDI4736, an anti-PD-L1 antibody, in patients with NSCLC.

8021^ Background: Lung cancer is the leading cause of cancer death in both men and women. PD-L1 is upregulated in NSCLC and may be associated with a poor prognosis. MEDI4736 is a human IgG1 antibody which binds specifically to PD-L1 preventing binding to PD-1 and CD80. Methods: An ongoing phase 1, multicenter, open-label study (NCT01693562) is evaluating the safety and efficacy of MEDI4736 administered IV every 2 wks (q2w) or every 3 wks (q3w) using a 3+3 dose escalation followed by expansion cohorts. NSCLC pts were assigned to expansion cohorts by histology and line of therapy (including treatment- naïve pts). Retreatment was permitted for progression after 12 mos of therapy. Response is assessed by immune-related response criteria (irRC) in escalation and RECIST v1. 1 in expansion. Results: As of Jan 17, 2014, 13 NSCLC pts in dose escalation (median age 65 yrs; 40-76), all PS 0-1, with a median of 4 prior treatments, received a median of 7 doses (1-25) of MEDI4736 across 6 cohorts (0. 1 – 10 mg/kg q2w; 15 mg/kg q3w). Treatment-related AEs occurred in 43% of pts, all of which were Grade 1-2; none led to discontinuation of study drug. No pneumonitis or colitis was reported in dose escalation. Of 13 pts, 3 PRs were observed, with 2 additional pts achieving tumor shrinkage not meeting PR per irRC (46% and 48% decreases). Tumor shrinkage was reported as early as first assessment (6 wks) and benefit was durable; 4/13 pts remain on study (10+, 10+, 11. 1+, 14. 9+ mos) as of the data cutoff. Expansion cohorts opened Sep 2013; 43 pts (including treatment-naïve pts) have been dosed, with the opportunity to enroll > 300 NSCLC pts in total. Preliminary clinical activity has been observed with acceptable safety, no ≥ grade 3 pneumonitis, and no apparent differences in toxicity between treatment-naïve vs pretreated pts. Assessment of clinical activity by PD-L1 expression, underlying mutation, smoking history, and line of therapy patient-reported outcomes is ongoing. Conclusions: The preliminary safety and durable clinical efficacy profile of MEDI4736 in NSCLC supports continued clinical development; AEs are manageable, even in highly pretreated pts. Recruitment continues and development of MEDI4736 in NSCLC as monotherapy and in combination is ongoing. Clinical trial information: NCT01693562.