BACKGROUND Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host’s immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non–small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.)

BACKGROUND Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated encouraging overall survival in uncontrolled studies in previously treated patients with advanced renal cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in renal cell carcinoma after prior treatment. METHODS Eight hundred twenty-one patients with advanced clear-cell renal cell carcinoma previously treated with one or two antiangiogenic therapies were randomized (1:1) to receive nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10-mg tablet orally once daily. Primary end point was overall survival. Secondary end points included objective response rate and safety. RESULTS Median (95% confidence interval [CI]) overall survival was 25.0 months (21.8 to not estimable) with nivolumab and 19.6 months (17.6 to 23.1) with everolimus. The hazard ratio for risk of death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.0018), meeting the predefined criterion for superiority (P≤0.0148). Objective response rate was greater with nivolumab (25%) than everolimus (5%; odds ratio 5.98; 95% CI, 3.68 to 9.72; P<0.001). Median (95% CI) progression-free survival was 4.6 months (3.7 to 5.4) with nivolumab and 4.4 months (3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% (nivolumab) and 37% (everolimus) of patients; most common was fatigue (3%) with nivolumab and anemia (8%) with everolimus. CONCLUSIONS Overall survival was longer and fewer grade 3 or 4 adverse events occurred for nivolumab versus everolimus in treatment-experienced patients with advanced renal cell carcinoma. ClinicalTrials.gov Identifier: NCT01668784