Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with metastatic renal cell carcinoma (mRCC).

Genitourinary (Nonprostate) Cancer
Session Type and Session Title: 
Oral Abstract Session, Genitourinary (Nonprostate) Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 4505)
Daniel C. Cho, Jeffrey Alan Sosman, Mario Sznol, Michael S. Gordon, Antoine Hollebecque, Omid Hamid, David F. McDermott, Jean-Pierre Delord, Ina Park Rhee, Ahmad Mokatrin, Marcin Kowanetz, Roel Peter Funke, Gregg Daniel Fine, Thomas Powles; Beth Israel Deaconess Medical Center, Boston, MA; Vanderbilt University Medical Center, Nashville, TN; Yale University, New Haven, CT; Pinnacle Oncology Hematology, Scottsdale, AZ; Institut Gustave Roussy, Villejuif, France; The Angeles Clinic and Research Institute, Los Angeles, CA; Dana-Farber Cancer Institute, Boston, MA; Institut Claudius Regaud, Toulouse, France; Genentech Inc., South San Francisco, CA; Genentech, Inc., South San Francisco, CA; Barts Cancer Institute, QMUL, Barts Health NHS Trust, London, United Kingdom

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Abstract Disclosures


Background: Human RCC expresses PD-L1 and has been shown to respond to immune-based therapy. 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. Methods: Pts with mRCC received MPDL3280A administered IV q3w at doses between 3-20 mg/kg in a Phase I expansion study. Pts were treated for up to 1 y. Response was assessed by RECIST v1.1. Results: As of Jan 10, 2013, 53 RCC pts were evaluable for safety and treated at doses of 3 (n=2), 10 (n=12), 15 (n=18) and 20 mg/kg (n=21). These pts had a median age of 62 y (range 33-79 y), 100% were PS 0-1 and all had had prior surgery. 83% of pts had received prior systemic therapy; 38% received immunotherapy, 57% received TKIs and 36% received anti-angiogenic therapy. Pts received treatment with MPDL3280A for a median duration of 190 days (range 21-317). The incidence of G3/4 AEs in RCC pts was 43%, regardless of attribution, with hypophosphatemia, fatigue, dyspnea and hyperglycemia (all 4%) being the most common. 13% of G3/4 AEs were attributable to study drug. 1 case of myasthenia gravis was observed in a pt who was retrospectively found to have anti-acetylcholine receptor antibodies prior to starting therapy. No G3-5 pneumonitis or diarrhea was reported. No treatment-related deaths occurred. 39 RCC pts enrolled prior to Jul 1, 2012, were evaluable for efficacy. RECIST responses, including CR, were observed across dose levels, with all responses ongoing at the time of data cutoff. Some RCC pts experienced prolonged SD prior to experiencing RECIST response. The 24-week PFS was 50%. Analysis of biomarker data from mandatory archival tumors demonstrated a correlation between PD-L1 status and efficacy. In addition, response correlated with low IL-17 expression in tumor tissue. Updated data will be presented. Conclusions: MPDL3280A was well tolerated, with no pneumonitis-related deaths. PD-L1–positive status correlates with response to MPDL3280A. Durable responses have been observed in RCC pts treated with MPDL3280A and further study is warranted. Clinical trial information: NCT01375842.