CAMBRIDGE, Mass.--(BUSINESS WIRE)--Leap Therapeutics, a company developing immuno-oncology therapeutics, reported results of a Phase 1 clinical trial of TRX518, an aglycosylated monoclonal agonist antibody targeting glucocorticoid-induced TNFR-related (GITR) protein. The Phase 1 trial demonstrated that a single dose of TRX518 in patients with advanced solid tumors was safe and well-tolerated. There were no autoimmune treatment-related adverse events. Saturation of TRX518 on GITR on T cells in peripheral blood was observed, and exposures demonstrating efficacy in preclinical models were safely reached. Henry Koon, M.D., of the University Hospitals, presented the data at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO).
“The safety and pharmacokinetic results from this clinical study have allowed us to further develop the drug in a repeat-dose study. We look forward to the exploring the activity of TRX518 as a single-agent and in combinations,” commented Dr. Koon.
Leap is enrolling patients in two clinical studies in patients with advanced solid tumors to assess the safety, pharmacokinetics, pharmacodynamics, and efficacy of TRX518 when dosed at various dose levels and frequencies.
“GITR is emerging as an important target in regulating anti-tumor immune responses. Preclinical studies have shown that agonist anti-GITR antibodies can modulate inhibitory and stimulatory signals, which may potentiate anti-cancer immune responses,” commented Jedd Wolchok, M.D., Ph.D., Chief of Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center and the principal investigator in Leap’s TRX518 study.
TRX518 is a humanized aglycosyl IgG1 monoclonal antibody with agonist activity targeting GITR. TRX518 has been shown to bind and activate GITR through bivalent binding to the receptor. TRX518 was engineered to remove Fc-receptor interactions to prevent complement-mediated cytolysis and antibody-mediated depletion of leukocytes expressing GITR. TRX518 surrogate antibodies have been effective in preclinical animal models, prolonging survival or enhancing immune responses when combined with chemotherapeutics and checkpoint inhibitors.
About Leap Therapeutics
Leap Therapeutics is an immuno-oncology company with two clinical stage programs. Leap’s most advanced clinical candidate, DKN-01, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein. DKN-01 is in Phase 1/2 clinical trials in esophageal cancer and cholangiocarcinoma. Leap’s second clinical candidate, TRX518, is a novel, humanized anti-GITR monoclonal antibody designed to enhance the immune system’s anti-tumor response. For more information of Leap Therapeutics, visit http://www.leaptx.com.
FORWARD LOOKING STATEMENTS:
Some of the statements in this release are forward looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. These statements relate to future events of Leap’s pre-clinical and clinical development of DKN-01, TRX518 and other programs, future expectations, plans and prospects. Although Leap believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. Leap has attempted to identify forward looking statements by terminology including ‘‘believes,’’ ‘‘estimates,’’ ‘‘anticipates,’’ ‘‘expects,’’ ‘‘plans,’’ ‘‘projects,’’ ‘‘intends,’’ ‘‘potential,’’ ‘‘may,’’ ‘‘could,’’ ‘‘might,’’ ‘‘will,’’ ‘‘should,’’ ‘‘approximately’’ or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors. Any forward looking statements contained in this release speak only as of its date. We undertake no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.