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Updated: Jun 12, 2026
Magnetic Fluorescent Bead-Based Dual-Reporter Flow Analysis of PDL1-Vaxx Peptide Vaccine-Induced Antibody Blockade of the PD-1/PD-L1 Interaction
Published on: July 7, 2023
Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical
Julie R Brahmer1, Charles G Drake, Ira Wollner
1Johns Hopkins University School of Medicine, and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Purpose:
Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates.
Patients And Methods:
Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non-small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti-PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy.
Results:
Anti-PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti-PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells > or = 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment.
Conclusion:
Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.
Insights
Blocking programmed death-1 (PD-1) with anti-PD-1 antibody therapy is safe and shows antitumor activity in patients with advanced cancers. Further research into dosing and combinations is recommended.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Programmed death-1 (PD-1) is an inhibitory receptor on T cells that can suppress antitumor immunity.
- Understanding PD-1's role is crucial for developing novel cancer therapies.
Purpose of the Study:
- To evaluate the safety and tolerability of anti-PD-1 blockade in patients with refractory solid tumors.
- To preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates of anti-PD-1 therapy.
Main Methods:
- A phase I dose-escalation study of anti-PD-1 (MDX-1106) in 39 patients with advanced melanoma, CRC, prostate cancer, NSCLC, or RCC.
- Dose cohorts ranged from 0.3 to 10 mg/kg, with an expansion cohort at 10 mg/kg. Patients with clinical benefit could receive repeated therapy.
Main Results:
- Anti-PD-1 was well tolerated, with one serious adverse event (inflammatory colitis).
- Observed responses included one complete response (CRC) and two partial responses (melanoma, RCC), plus tumor regressions in two other patients.
- Pharmacodynamics showed sustained PD-1 occupancy on T cells for over 2 months, and B7-H1 expression correlated with response.
Conclusions:
- Intermittent anti-PD-1 antibody dosing is safe and demonstrates antitumor activity in advanced cancers.
- Further investigation into alternative dosing schedules and combination therapies is warranted.
