Dataset Information

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.

ABSTRACT:

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.).

SUBMITTER: Brahmer JR

PROVIDER: S-EPMC3563263 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.

Brahmer Julie R JR Tykodi Scott S SS Chow Laura Q M LQ Hwu Wen-Jen WJ Topalian Suzanne L SL Hwu Patrick P Drake Charles G CG Camacho Luis H LH Kauh John J Odunsi Kunle K Pitot Henry C HC Hamid Omid O Bhatia Shailender S Martins Renato R Eaton Keith K Chen Shuming S Salay Theresa M TM Alaparthy Suresh S Grosso Joseph F JF Korman Alan J AJ Parker Susan M SM Agrawal Shruti S Goldberg Stacie M SM Pardoll Drew M DM Gupta Ashok A Wigginton Jon M JM

The New England journal of medicine 20120602 26

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 22658128

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Dataset Information

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.

Background

Methods

Results

Conclusions

Publications

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.

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