Leap Therapeutics Presents Positive Data from Phase 1 Study of DKN-01 in Combination with Paclitaxel in Relapsed or Refractory Cancer of the Esophagus or Gastro-esophageal Junction
Cambridge MA – January 21st, 2016 – Leap Therapeutics, a biotechnology company developing novel therapeutics at the leading edge of cancer research, reported its first results of a clinical trial of its lead candidate DKN-01, a monoclonal antibody against the Dickkopf-1 (DKK1) protein. Data from the trial demonstrated meaningful clinical activity in relapsed or refractory cancer of the esophagus or gastro-esophageal junction (GEJ), indications with limited approved therapies. In Part A of the study, the dose escalation phase, three of nine patients achieved a partial response (“PR”) per RECIST v1.1. In the subset of patients with adenocarcinoma who had received one or two prior lines of therapy, three of four patients achieved a PR. The data were presented today by Johanna Bendell, M.D. of the Sarah Cannon Research Institute/Tennessee Oncology, at the ASCO Gastrointestinal Symposium.
“Patients with relapsed or refractory esophageal carcinoma have an extremely poor prognosis,” commented David Ryan, M.D. Massachusetts General Hospital. “The results from the study of DKN-01 in combination with paclitaxel, while early, provide great encouragement, and we look forward to the data from the next phases of this trial.”
SUMMARY RESULTS FROM PART A OF THE P102 STUDY OF DKN-01 IN ESOPHAGEAL CARCINOMA:
Patients were pre-screened for DKK1 expression, with ~90% of tumor biopsy samples staining DKK1 positive via IHC
Nine patients with cancer of the esophagus or GEJ were enrolled in the Part A dose escalation; all were evaluable per the protocol
Patients received either 150 mg or 300 mg twice monthly in combination with weekly infusions of 80 mg/m2 paclitaxel
The combination of DKN-01 and paclitaxel was safe and well tolerated at all doses: no treatment related severe adverse events (SAEs), or treatment emergent adverse events (TEAE) leading to study discontinuation
The most frequently reported DKN-01-related AEs were pyrexia, fatigue, and peripheral neuropathy
Treatment with 300 mg of DKN-01 twice monthly was selected for further study in combination with weekly infusions of 80 mg/m2 paclitaxel
Three patients had PRs and four patients had best responses of Stable Disease, with a total disease control rate of 77.7%
Patients with adenocarcinoma of the esophagus or GEJ with fewer lines of therapy may derive greater benefit (n=4, ORR = 75%, median PFS = 37.3 weeks); this will be explored further
P102 STUDY DESIGN:
P102 is a 4 part (Part A, Part B, Part C and Part D), dose-escalating, open label, multi-center study evaluating the safety, pharmacokinetics, and efficacy of DKN-01 in combination with paclitaxel in adult patients with histologically confirmed recurrent or metastatic esophageal or gastro-esophageal junction cancer with progressive disease requiring therapy.
Study Part A [completed] consists of a standard 3 + 3 dose escalation design to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of DKN-01 in combination with paclitaxel in 2 dosing cohorts (150 and 300 mg) of up to 6 patients per cohort
Study Parts B [ongoing], C and D will enroll up to 20 additional patients each in expansion cohorts in which DKN-01 is administered at 300 mg twice monthly in combination with paclitaxel.
Part B: all patients with esophageal cancer or GEJ
Part C: patients with esophageal or GEJ adenocarcinoma
Part D: patients with recurrent or metastatic esophageal squamous cell cancer
About Esophageal Cancer
Esophageal cancer is an aggressive disease with 17,000 patients diagnosed annually in the US and 400,000 diagnosed worldwide. Over 50% of patients are diagnosed with advanced disease, with an expected overall survival limited to 8-12 months. There are no approved therapies for relapsed or refractory disease, with the patients frequently receiving single-agent chemotherapy (e.g., paclitaxel) as a 2nd-line therapy. While studies with paclitaxel and efficacy outcomes are limited, response rates have historically ranged between 5-15% and progression-free survival of 1-3 months.
DKN-01 is a humanized monoclonal IgG4 monoclonal antibody with neutralizing activity against the Dickkopf-1 protein. DKN-01 is currently being studied in clinical trials in esophageal cancer and cholangiocarcinoma. DKN-01 additionally demonstrated single agent activity in NSCLC in a Phase 1 dose escalation study that was presented at ASCO 2014.
About Leap Therapeutics
Leap Therapeutics’ most advanced clinical candidate, DKN-01, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein. DKN-01 is in clinical trials in patients with gastroesophageal cancer in combination with paclitaxel and in patients with biliary tract cancers in combination with gemcitabine and cisplatin. Leap’s second clinical candidate, TRX518, is a novel, humanized GITR agonist monoclonal antibody designed to enhance the immune system’s anti-tumor response. Leap has signed a Merger Agreement with Macrocure Ltd (Nasdaq:MCUR) that is expected to result in Leap becoming a public company that will trade on The Nasdaq Global Market under the symbol “LPTX.” 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.
FORWARD LOOKING STATEMENTS
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