Phase I Study of Anti-Programmed Death-1 Treatment Shows Promise in Refractory Solid Tumors

Researchers at Johns Hopkins University, led by J.R. Brahmer, have published a study in the Journal of Clinical Oncology detailing the safety and efficacy of a new treatment that blocks the PD-1 immune checkpoint in patients with refractory solid tumors. The study, which involved 39 patients with various types of cancer, found that the treatment was well-tolerated and showed evidence of antitumor activity, including one complete response and two partial responses.

Key Takeaways:

• The study was conducted in 39 patients with advanced metastatic melanoma, colorectal cancer, castrate-resistant prostate cancer, non-small-cell lung cancer, or renal cell carcinoma.
• Patients 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.
• Anti-PD-1 was well-tolerated, with only one serious adverse event (inflammatory colitis) observed in a patient with melanoma.
• Pharmacodynamics indicated a sustained mean occupancy of 70% of PD-1 molecules on circulating T cells for at least 2 months following infusion, regardless of dose.
• Tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment.
• The researchers concluded that exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.

Statistics:

• 39 patients participated in the study, representing various types of cancer, including melanoma, colorectal cancer, castrate-resistant prostate cancer, non-small-cell lung cancer, and renal cell carcinoma.
• Patients received a single intravenous infusion of anti-PD-1 (MDX-1106) at doses ranging from 0.3 to 10 mg/kg.
• One serious adverse event (inflammatory colitis) was observed in a patient with melanoma.
• A sustained mean occupancy of 70% of PD-1 molecules on circulating T cells was observed for at least 2 months following infusion, regardless of dose.
• Nine patients examined showed tumor cell surface B7-H1 expression.

Sources:

• Brahmer, J. R., et al. "Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates." Journal of Clinical Oncology, vol. 28, no. 19, 2010, pp. 3167-75.
• Johns Hopkins University, Sidney Kimmel Cancer Center.