[HTML][HTML] Safety and activity of anti–PD-L1 antibody in patients with advanced cancer

JR Brahmer, SS Tykodi, LQM Chow… - … England Journal of …, 2012 - Mass Medical Soc
JR Brahmer, SS Tykodi, LQM Chow, WJ Hwu, SL Topalian, P Hwu, CG Drake, LH Camacho
New England Journal of Medicine, 2012Mass Medical Soc
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 …
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.)
The New England Journal Of Medicine