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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, activity, and immune correlates of anti-PD-1 antibody in cancer
Suzanne L Topalian1, F Stephen Hodi, Julie R Brahmer
1Department of Surgery, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA. stopali1@jhmi.edu
Background:
Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1.
Methods:
We enrolled patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred.
Results:
A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non-small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non-small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1-PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1-negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1-positive tumors had an objective response (P=0.006).
Conclusions:
Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00730639.).
Insights
This study shows that blocking programmed death 1 (PD-1) with an antibody can lead to objective responses in patients with advanced cancers like melanoma and non-small-cell lung cancer. Preliminary data suggest PD-1 ligand (PD-L1) expression on tumors may predict response to this immunotherapy.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Programmed death 1 (PD-1) is an inhibitory receptor on T cells that can be blocked to overcome immune resistance.
- BMS-936558 is an antibody designed to specifically block the PD-1 pathway.
Purpose of the Study:
- To assess the antitumor activity of BMS-936558, an anti-PD-1 antibody.
- To evaluate the safety profile of anti-PD-1 therapy in patients with advanced cancers.
Main Methods:
- Patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, renal-cell, or colorectal cancer received anti-PD-1 antibody.
- Treatment involved doses ranging from 0.1 to 10.0 mg/kg every 2 weeks for up to 12 cycles.
- Response was assessed every 8 weeks; immunohistochemical analysis of PD-L1 expression was performed on pretreatment tumor specimens.
Main Results:
- Objective responses were observed in patients with non-small-cell lung cancer (18%), melanoma (28%), and renal-cell cancer (27%).
- Responses were durable, with 20 of 31 responses lasting 1 year or more.
- Patients with PD-L1-positive tumors had a significantly higher objective response rate (36%) compared to those with PD-L1-negative tumors (0%).
Conclusions:
- Anti-PD-1 antibody therapy demonstrated objective responses in approximately 18-28% of patients with non-small-cell lung cancer, melanoma, or renal-cell cancer.
- The observed adverse event profile appears manageable and does not preclude its clinical use.
- Preliminary findings indicate a potential correlation between tumor cell PD-L1 expression and objective response to anti-PD-1 therapy.
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