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Background: mM is an immunotherapy responsive disease where PD-L1 overexpression is prevalent.MPDL3280A,a human monoclonal antibody containing an engineered Fc-domain designed to optimize efficacy and safety,targets PD-L1,blocking PD-L1 from binding its receptors,including PD-1 and B7.1.Initial antitumor activity observed during dose escalation supported further expansion in mM with MPDL3280A as monotherapy and in combination with targeted therapy.Methods: Pts with mM of any histologic subtype received MPDL3280A administered Ⅳ q3w for up to 1 y.Objective response rate(ORR)was assessed by RECIST v1.1.Reported ORR includes u/cCR and u/cPR.In addition,a separate Ph 1b was initiated to evaluate the safety and efficacy of MPDL3280A with vemurafenib(vem)in pts with BRAF-V600 mutated mM.Results: As of Jan 10,2013,45 mM pts were treated at ≤1(n=4),10(n=10),25(n=20)and 20 mg/kg(n=11)and evaluable for safety.Median pt age was 63 y(range 21-83 y),100%were PS 0-1,91%had prior surgery and 64%received prior systemic therapy.Pts received MPDL3280A treatment for a median duration of 127 days(range 1-282).The incidence of all G3/4 AEs,regardless of attribution,was 33%,including hyperglycemia(7%),elevated ALT(7%)and elevated AST(4%).No G3-5 pneumonitis was reported.No treatment-related deaths occurred on study.35 mM pts who initiated treatment at doses of 1-20 mg/kg and enrolled prior to Jul 1,2012,were evaluable for efficacy.An ORR of 26%(9/35)was observed,with all RECIST responses ongoing or improving.Further,some responding pts experienced tumor shrinkage within days of initial treatment.The 24-week PFS was 35%.Several additional pts had delayed antitumor activity after apparent radiographic progression and were counted as PD for the above analyses.Analysis of mandatory archival tumors showed a correlation between PD-L1 status and efficacy.Further,of three initial pts treated with MPDL3280A and vem,2 experienced tumor shrinkage,including 1 CR.Conclusions: MPDL3280A was well tolerated as monotherapy,and durable ORs were observed.Therefore,further assessment of MPDL3280A as monotherapy and combination therapy is warranted.