Leap Therapeutics Announces First Patient Dosed with TRX518 Combination Therapy in Advanced Solid Tumors Trial

CAMBRIDGE, Mass., Jan. 16, 2018 (GLOBE NEWSWIRE) -- Leap Therapeutics, Inc.(Nasdaq:LPTX), a biotechnology company developing targeted and immuno-oncology therapeutics, today announced that the first patient has been dosed in a Phase 1 clinical trial evaluating Leap’s GITR agonist, TRX518, in combination with gemcitabine chemotherapy or in combination with KEYTRUDA® (pembrolizumab) or Opdivo® (nivolumab), anti-PD-1 therapies marketed by Merck (known as MSD outside the United States and Canada) or Bristol-Myers Squibb, respectively.

“TRX518 has demonstrated the ability to reduce immunosuppressive regulatory T cells and to activate tumor-killing T effector cells in clinical and preclinical studies.  The combination of TRX518 with anti-PD-1 immunotherapy has strong scientific rationale and could act synergistically, enabling improved responses without significant additional toxicity.  We look forward to evaluating the safety and efficacy of TRX518 in combination with pembrolizumab or nivolumab,” commented Diwakar Davar, M.D., Assistant Professor of Medicine of the University of Pittsburgh and an investigator on the study.

“There is strong preclinical evidence for synergistic efficacy when combining immune activators targeting GITR with chemotherapy,” commented Cynthia Sirard, M.D., Vice President, Clinical Development of Leap Therapeutics. “This trial represents an important step in our strategy to evaluate the combination activity of TRX518 as a backbone immunotherapy."

The TRX518-003 study is a multipart study evaluating TRX518 as a monotherapy and in combination with gemcitabine, KEYTRUDA® (pembrolizumab), or Opdivo® (nivolumab) in patients with advanced solid tumor malignancies.

The combination arms evaluating TRX518 with gemcitabine includes both dose escalation and dose confirmation cohorts and are designed to evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of the combination. The study will enroll patients who have metastatic or locally advanced, incurable solid malignancies for which gemcitabine is clinically appropriate (e.g., non-small cell lung, breast, ovarian, pancreatic, and renal cancer). The TRX518 + gemcitabine study will enroll approximately 32 patients.

The combination arms evaluating TRX518 with pembrolizumab or nivolumab includes both dose escalation and dose confirmation cohorts and are designed to evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of the combinations. The study will enroll patients who have received treatment with pembrolizumab or nivolumab for ≥4 months with a best response of stable disease and plans to continue treatment in accordance with package insert; or are not currently taking, but eligible for treatment with, pembrolizumab or nivolumab in accordance with the approved indications for each as referenced in the package insert. The TRX518 + PD-1 antagonist study will enroll approximately 64 patients.

About TRX518
TRX518 is a humanized monoclonal antibody with agonist activity targeting glucocorticord-inducible TNF-superfamily receptor (GITR). TRX518 is engineered to enhance immune responses to cancer. TRX518 is being studied in two ongoing repeat-dose clinical trials in patients with advanced solid tumor malignancies. Data from the trials have shown that patients receiving TRX518 monotherapy achieved durable stable disease with signs of pharmacodynamic activity including CD8+ T cell activation and modulation of immunosuppressive regulatory T cells.

About Leap Therapeutics
Leap Therapeutics (NASDAQ:LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's most advanced clinical candidate, DKN-01, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein, a Wnt pathway modulator. DKN-01 is in clinical trials in patients with esophagogastric cancer, biliary tract cancer, and gynecologic cancers, with an emerging focus on patients with defined mutations of the Wnt pathway and in combination with immune checkpoint inhibitors. Leap's second clinical candidate, TRX518, is a humanized GITR agonist monoclonal antibody designed to enhance the immune system's anti-tumor response that is in two advanced solid tumor studies. For more information about Leap Therapeutics, visit http://www.leaptx.com or our public filings with the SEC that are available via EDGAR at http://www.sec.gov.


This press release contains 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 include statements relating to Leap’s expectations with respect to the development and advancement of DKN-01, TRX518, and other programs, including the initiation, timing and design of future studies, enrollment in future studies, business development, and other future expectations, plans and prospects. Leap has attempted to identify forward looking statements by such terminology as ‘‘believes,’’ ‘‘estimates,’’ ‘‘anticipates,’’ ‘‘expects,’’ ‘‘plans,’’ ‘‘projects,’’ ‘‘intends,’’ ‘‘may,’’ ‘‘could,’’ ‘‘might,’’ ‘‘will,’’ ‘‘should,’’ or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Although Leap believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from our expectations. These risks and uncertainties include, but are not limited to: the accuracy of our estimates regarding expenses, future revenues, capital requirements and needs for financing; the ability to complete a financing or form business development relationships to fund our expenses; the outcome, cost, and timing of our product development activities and clinical trials; the uncertain clinical development process, including the risk that clinical trials may not have an effective design or generate positive results; our ability to obtain and maintain regulatory approval of our drug product candidates; our plans to research, develop, and commercialize our drug product candidates; our ability to achieve market acceptance of our drug product candidates; unanticipated costs or delays in research, development, and commercialization efforts; the applicability of clinical study results to actual outcomes; the size and growth potential of the markets for our drug product candidates; our ability to continue obtaining and maintaining intellectual property protection for our drug product candidates; and other risks. Detailed information regarding factors that may cause actual results to differ materially will be included in Leap Therapeutics’ periodic filings with the Securities and Exchange Commission (the "SEC"), including Leap Therapeutics’ Form 10-K that Leap filed with the SEC on February 23, 2018. 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.

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.  OPDIVO® is a registered trademark of Bristol-Myers Squibb Company.  BAVENCIO® is a registered trademark of Pfizer, Inc.



Leap Therapeutics, Inc.:
Douglas E. Onsi
Chief Financial Officer



Argot Partners:
Heather Savelle
Mary Jenkins