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

 BACKGROUND

The fixed die 1 (PD-1) protein, T-cell receptor coinhibitory, and one of the ligands, PD-L1, plays an important role in the ability of tumor cells to evade the host immune system. Blockade of the interaction between PD-1 and PD-L1 enhance immune function in vitro and mediate antitumor activity in preclinical models.

METHOD

In the multicenter Phase 1 trial, we are given an intravenous anti-PD-L1 antibody (in increasing doses ranging from 0.3 to 10 mg per kilogram of body weight) for patients with advanced cancer were selected. Anti-PD-L1 antibody was given every 14 days in 6-week cycles 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 lung cancer non-small cell, 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 - has received an anti-PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2-111). Grade 3 or 4 toxic effects that the investigator considered related to treatment occurred in 9% of patients. Among patients with a response that can be evaluated, objective response (complete response or partial) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal cell cancer, 5 out of 49 lung cancer non-small cell, and 1 of 17 ovarian cancer. The response lasts for 1 year or more in 8 of 16 patients with at least 1 year of follow-up.

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CONCLUSION

blockade antibody-mediated PD-L1 induced regression of durable tumor (rate of objective response of 6 to 17%) and stabilization of prolonged illness (rates 12 to 41% at 24 weeks) in patients with advanced cancer, including non-small cell lung cancer -paru, melanoma and renal cell cancer. (Funded by Bristol-Myers Squibb and others ;. ClinicalTrials.gov number, NCT00729664).