The human monoclonal antibody MPDL3280A is directed against the immune checkpoint receptor programmed death-1 (PD-1) ligand 1(PD-L1), disrupting PD-L1 binding to its receptors PD-1 and B7.1. A phase 1 study evaluated the safety and efficacy of MPDL3280A in several cancer types, including melanoma and metastatic renal-cell carcinoma (mRCC). McDermott and colleagues reported the long-term follow-up and immune correlative data for the cohort of patients with mRCC, who were treated with MPDL3280A intravenously every 3 weeks, at doses of 3 to 20 mg/kg for ?1 year (McDermott D, et al. ESMO 2014: Abstract 809O). The 69 enrolled patients received MPDL3280A for a median duration of 239 days (range, 21-834 days). Of the 62 patients evaluable for efficacy, the overall response rate (ORR) was 15%; the median duration of response was 54 weeks. The 24-week progression-free survival rate was 51% (95% confidence interval, 38-63). Responses to MPDL3280A correlated with the intensity of PD-L1 expression, with PD-L1–positive patients (defined by immunohistochemistry 1/2/3 level staining) achieving a 20% ORR, whereas patients with PD-L1–negative disease achieved an ORR of 10%. Of the 69 enrolled patients in this study, 80% had a treatment-related adverse event (AE), the majority of which were grade 1 or 2. The incidence of grade 3 treatment-related AEs was 16%, including anemia (4%), dehydration (3%), fatigue (3%), and hypophosphatemia (3%); there were no reports of grade 4 treatment-related AEs or deaths. The results from a cohort with 10 patients with mRCC from another phase 1 study of MPDL3280A, in combination with bevacizumab, were also presented. In this study, 1 MPDL3280A-related grade 3 AE of neutropenia was reported; no grade 4 AEs or deaths were attributed to MPDL3280A. Objective responses were achieved by 4 patients, and 5 patients achieved disease stabilization. Of the 10 patients in this cohort, 9 are still receiving the study treatment. Taken together, the results from these 2 studies suggest that MPDL3280A is well-tolerated and demonstrates antitumor activity alone, as well as in combination with bevacizumab. There results also provide preliminary indications that responses to MPDL3280A may correlate with PD-L1 positivity.
