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Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with metastatic renal cell carcinoma (mRCC).
J Clin Oncol 31, 2013 (suppl; abstr 4505)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
Abstracts by D. C. Cho:
A phase I study of the combination of sorafenib (Sor) and bortezomib (Bor) in patients (pts) with metastatic melanoma (MM).
A phase I, dose-escalation, safety, pharmacokinetic, pharmacodynamic study of thioureidobutyronitrile, a novel p53 targeted therapy, in patients with advanced solid tumors.
Presentations by D. C. Cho:
Meeting: 2012 Genitourinary Cancers Symposium
Session: Oral Abstract Session C: Renal Cancer (Oral Abstract Session)
A phase I dose-escalation study of the Hsp90 inhibitor ganetespib (STA-9090) administered twice weekly in patients with solid tumors: Updated report.Session: Developmental Therapeutics - Experimental Therapeutics (General Poster Session)
Meeting: 2010 Genitourinary Cancers Symposium
Session: Translational Science Session - Renal Cancer (Translational Research Session)