Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM).

Melanoma/Skin Cancers
Session Type and Session Title: 
Clinical Science Symposium, PD1/PDL1: An Effective Target in Melanoma
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 9010)
Omid Hamid, Jeffrey Alan Sosman, Donald P. Lawrence, Ryan J. Sullivan, Nageatte Ibrahim, Harriet M. Kluger, Peter D. Boasberg, Keith Flaherty, Patrick Hwu, Marcus Ballinger, Ahmad Mokatrin, Marcin Kowanetz, Daniel S. Chen, F. Stephen Hodi; The Angeles Clinic and Research Institute, Los Angeles, CA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Massachusetts General Hospital, Boston, MA; Massachusetts General Hospital Cancer Center, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Yale University, New Haven, CT; The Angeles Clinic and Research Institute, Santa Monica, CA; The University of Texas MD Anderson Cancer Center, Houston, TX; Genentech, Inc., South San Francisco, CA; Genentech Inc., South San Francisco, CA

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Abstract Disclosures


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. Clinical trial information: NCT01375842.