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, Mass.--(BUSINESS WIRE)--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”

“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 2^nd-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.

About DKN-01

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 is a clinical-stage biopharmaceutical company acquiring and developing novel therapeutics at the leading edge of cancer research. Leap’s portfolio includes two antibodies that target pathways involved in cancer cell signaling and immuno-oncology. Leap’s lead clinical candidate, DKN-01, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein, and is currently being studied in Phase 1/2 clinical trials in esophageal cancer and cholangiocarcinoma. Leap’s second clinical candidate, TRX518, is a novel, humanized anti-GITR (glucocorticoid-induced tumor necrosis factor receptor) monoclonal antibody designed to enhance the immune system’s anti-tumor response. TRX518 was the first anti-GITR agonist in clinical trials. Led by a proven management team, Leap is dedicated to building and developing a pipeline of therapeutics that has the potential to change the practice of cancer medicine. For more information of Leap Therapeutics, visit http://www.leaptx.com.