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

Julie R. Brahmer, Scott S. Tykodi, Laura Q.M. Chow, Wen Jen Hwu, Suzanne L. Topalian, Patrick Hwu, Charles G. Drake, Luis H. Camacho, John Kauh, Kunle Odunsi, Henry C. Pitot, Omid Hamid, Shailender Bhatia, Renato Martins, Keith Eaton, Shuming Chen, Theresa M. Salay, Suresh Alaparthy, Joseph F. Grosso, Alan J. KormanSusan M. Parker, Shruti Agrawal, Stacie M. Goldberg, Drew M. Pardoll, Ashok Gupta, Jon M. Wigginton

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4279 Scopus citations

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.)

Original languageEnglish (US)
Pages (from-to)2455-2465
Number of pages11
JournalNew England Journal of Medicine
Volume366
Issue number26
DOIs
StatePublished - Jun 28 2012

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ASJC Scopus subject areas

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Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W. J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., Pitot, H. C., Hamid, O., Bhatia, S., Martins, R., Eaton, K., Chen, S., Salay, T. M., Alaparthy, S., Grosso, J. F., ... Wigginton, J. M. (2012). Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. New England Journal of Medicine, 366(26), 2455-2465. https://doi.org/10.1056/NEJMoa1200694