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Updated: May 21, 2026
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Julie R Brahmer1, Scott S Tykodi, Laura Q M Chow
1Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.
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.).
Insights
This study shows that blocking PD-L1 with an antibody can lead to durable tumor regression and disease stabilization in advanced cancers. The treatment demonstrated an objective response rate of 6-17% in patients with various advanced cancers.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Programmed death 1 (PD-1) and its ligand PD-L1 are key in tumor immune evasion.
- Blocking PD-1/PD-L1 interactions can enhance anti-tumor immune responses.
Purpose of the Study:
- To evaluate the safety and efficacy of an anti-PD-L1 antibody in patients with advanced cancers.
- To determine objective response rates and duration of response.
Main Methods:
- A multicenter phase 1 trial administered escalating doses of intravenous anti-PD-L1 antibody every 14 days.
- Treatment cycles lasted 6 weeks, up to 16 cycles or until disease progression/complete response.
- 207 patients with non-small-cell lung cancer, melanoma, and other advanced cancers were enrolled.
Main Results:
- Objective responses (complete or partial) were observed in melanoma (9/52), renal-cell cancer (2/17), non-small-cell lung cancer (5/49), and ovarian cancer (1/17).
- Durable responses lasting over a year were seen in 8/16 patients with follow-up.
- Grade 3 or 4 treatment-related toxic effects occurred in 9% of patients.
Conclusions:
- Antibody-mediated PD-L1 blockade induces durable tumor regression and disease stabilization in advanced cancers.
- The treatment showed efficacy in non-small-cell lung cancer, melanoma, and renal-cell cancer.
- Further investigation into anti-PD-L1 therapy is warranted.
