Medarex announces preliminary data for investigational anti-PD-1 antibody

Medarex, Inc. has announced preliminary data from an ongoing Phase 1 study of MDX-1106 (ONO-4538: development code of Ono Pharmaceutical Co., Ltd.), a fully human anti-PD-1 antibody.

Data presented from patients with recurrent or treatment-refractory cancer in the study included the safety, tolerability and pharmacokinetic profile of single-dose MDX-1106. In addition, preliminary evidence of anti-tumor activity was observed, including one patient with colorectal carcinoma who experienced a confirmed partial response that has been durable for more than 6 months. Tumor regressions (tumor shrinkage that did not meet the criteria for partial response) were also observed in four additional patients, including two patients with melanoma, one patient with non-small cell lung cancer, and one with renal cell carcinoma. These preliminary study results were presented in an oral presentation by investigator Julie Brahmer, M.D., Assistant Professor of Oncology from the Sidney Kimmel Cancer Comprehensive Center at Johns Hopkins University at the annual meeting of the American Society of Clinical Oncology (ASCO) being held in Chicago. (Abstract #3006)

"We are pleased with the safety profile and preliminary evidence of anti- tumor activity from this first human clinical trial of MDX-1106," said Geoffrey M. Nichol, MBChB, Senior Vice President of Product Development at Medarex. "We look forward to the further development of this novel immunotherapy, and plans are underway to initiate a Phase 2 trial of MDX-1106 in cancer this year."

In the single-dose Phase 1 trial, 24 patients initially enrolled in the dose-escalation portion of the trial, and an additional 15 patients are now fully enrolled in the expansion cohort at the highest dose. Eligible patients with recurrent or treatment-refractory solid tumors (including non-small cell lung cancer, renal, colon, melanoma, and hormone-refractory prostate cancer) received single-dose treatment of 0.3, 1, 3 or 10 mg/kg of MDX-1106 and were allowed re-treatment with multiple doses. All doses were well-tolerated with no observed severe immune-related adverse events and no dose-limiting toxicities within the first four weeks following single-dose therapy. Two patients with histories of arthritis that were not disclosed to the investigator prior to enrollment in the trial (history of autoimmune disease requiring treatment is an exclusion criterion for the trial) developed low grade arthritic symptoms that responded to oral corticosteroid treatment. Of the 11 patients that were eligible for re-treatment, one patient with ocular melanoma developed colitis 3 weeks after receiving a fifth dose of 1 mg/kg (over 9 months), and is improving with medical treatment of this immune- related adverse event after discontinuation of MDX-1106 dosing. In the 21 patients who have received 10 mg/kg of MDX-1106, including 3 patients who have received at least 3 doses, no serious immune-related adverse events have been observed.

MDX-1106/ONO-4538 is a novel fully human antibody designed to target and inhibit the function of PD-1 (programmed cell death 1), a receptor expressed on the surface of activated lymphocytes (T-cells) that is involved in the system of negative regulation for the suppression of activated lymphocytes. Preclinical studies suggest that blockade of the PD-1 signaling pathway by MDX-1106/ONO-4538 activates T-cell responses and promotes an immune response to fight tumors and infectious diseases. Medarex and Ono Pharmaceutical are investigating the potential of MDX-1106/ONO-4538 in ongoing Phase 1 trials for the treatment of cancer and hepatitis C.