Esophageal Cancer

February 16, 2016

Leap Therapeutics released results of a four part (Part A, Part B, Part C and Part D), dose-escalating, open label, multicenter study evaluating the safety, pharmacokinetics and efficacy of DKN-01 in combination with paclitaxel in adult patients with recurrent or metastatic esophageal or gastro-esophageal junction cancer with progressive disease requiring therapy. 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 150mg or 300mg twice monthly in combination with weekly infusions of 80mg/m2 paclitaxel. The combination of DKN-01 and paclitaxel was safe and well-tolerated at all doses. There were no treatment related severe adverse events (SAEs), or treatment emergent adverse events (TEAE) leading to study discontinuation. Three patients had PRs and four patients had best responses of Stable Disease, with a total disease control rate of 77.7%. Treatment with 300mg of DKN-01 twice monthly was selected for further study in combination with weekly infusions of 80mg/m2 paclitaxel. 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).

February 1, 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. “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.”

February 1, 2010

GenVec reported long term results from a phase II trial of TNFerade for the treatment of esophageal cancer. The dose escalation study enrolled 24 subjects with locally advanced resectable disease. Prior to surgery, TNFerade was administered weekly for five weeks via intratumoral injections in combination with cisplatin, infusional 5-FU, and radiation. Successive dosing cohorts received TNF at 4x108, 4X109, 4x1010, and 4x1011 PU. Five year follow-up was reached in 3 out of 4 groups (4x108 - 4x1010 PU) and showed an overall five-year survival rate of 56% in these three groups combined. The overall survival rate for the entire cohort was 42% and the overall median survival was 47.7 months. At the 4x109 PU dose, a pathological complete response (pCR) was seen in 100% of resected tumors, with a radiographic CR in a fourth subject; all four remained disease-free up to 48 months. At the 4x1010 PU dose, pCR was seen in 25% of resected tumors and the median survival has not yet been reached. The median survival for the 4x108 and 4x1011 PU doses is 47.4 and 30.4 months, respectively.

July 1, 2002

Long-term phase III trial results support the potential of Axcan Pharma's Photofrin photodynamic therapy (PDT) for the prevention of esophageal cancer. The trial included 208 subjects with high-grade dysplasia associated with Barrett's Esophagus. In the long-term analysis, 138 subjects in the Photofrin PDT group and 70 subjects in the comparative group (omeprazole alone) were followed for a minimum two-year period. Results showed that esophageal cancer occurred in 13% of subjects treated with Photofrin PDT, compared to a rate of 27% for omeprazole-treated subjects.