Hanmi Pharmaceuticals and Collaborative Partner Kinex Pharmaceuticals Announce Preliminary Results from a Phase I Clinical Study (HM-OTE-103) with Oratecan® in Patients with Advanced Cancer

BUFFALO, N.Y., Oct. 15, 2014 /PRNewswire/ -- Hanmi Pharmaceuticals and Collaborative Partner Kinex Pharmaceuticals announce today preliminary results from a Phase I Clinical Study of Oratecan - an oral form of the approved intravenously administered cancer drug irinotecan, with HM30181, a potent and selective, P-glycoprotein inhibitor of the gastro-intestinal tract. Irinotecan is a type 1 DNA topoisomerase inhibitor, marketed under the trade name Camptosar. It is approved for the treatment of colon cancer.

Two previous Phase I clinical studies of Oratecan determined the maximum tolerated dose (MTD) when administered as monotherapy. The MTD was 20 mg/m² where Oratecan was dosed on days 1-5 during a 21 day cycle; the MTD was 10 mg/m² when Oratecan was dosed on days 1-5 and 8-12 during a 21 day cycle.

Study HM-OTE-103, entitled "A Phase I Clinical Trial to Determine the Maximum Tolerated Dose and to Assess the Safety of Oratecan in Combination with Capecitabine in Patients with Advanced Solid Cancer" was conducted at two clinical sites in South Korea.  The primary objective of this study was to determine the MTD of Oratecan when given in combination with Capecitabine during a 21 day cycle. A total of 21 patients were enrolled in the study and were included in the safety analysis set. In the first part of this study, the Capecitabine dose was fixed at 800 mg/m² twice-daily for 14 days.  Oratecan was dosed on days 1 through 5 at 10, 15 or 20 mg/m². The second part of the study included a standard dose of Capecitabine (1000 mg/m²) twice daily in combination therapy and Oratecan was dosed at 15 mg/m². The MTD of this study was 15mg/m² of irinotecan (as Oratecan) and 1000mg/m² twice daily of capecitabine.

Pharmacokinetic analysis during this study indicated that exposure to Irinotecan and its active metabolite SN38 (administered orally as Oratecan) increased proportionately with dose. Efficacy evaluation was performed on 18 subjects who received at least one dose of Oratecan and capecitabine. Two subjects (11.1%) had a partial response (PR), 8 subjects (44.4%) had stable disease (SD), and 8 subjects (44.4%) had progressive disease (PD) as their best overall response.

"We are pleased that this study validated the utility of the Orascovery platform with a second drug, irinotecan, on top of its application previously demonstrated for paclitaxel, with its combination named Oraxol. Although the study was designed to determine the MTD, we were delighted to observe that a high percentage of the patients showed SD with some patients showing PR, proving the concept of platform technology," said Dr. Jeewoong Son, Chief Medical Officer at Hanmi Pharmaceuticals.

"Study HM-OTE-103 provides Hanmi and Kinex with important clinical data that will help to guide the further development of Oratecan," said Dr. Rudolf Kwan, Chief Medical Officer at Kinex Pharmaceuticals. "Based on our understanding of the data that has been generated in South Korea by Hanmi, we have designed a clinical study in the U.S. that will refine the dosing strategy to allow for optimal oral delivery of Irinotecan," commented Dr. Kwan.  That study is expected to initiate at 3 U.S. clinical sites during the fourth quarter of 2014.

"The convenience of an oral formulation of Irinotecan means a lot to patients can avoid lengthy infusions.  Oral drugs may also provide an opportunity for long term maintenance therapy," said Dr. Wing Kai Chan, Kinex Vice President for Clinical Operations, Asia Pacific.

Kinex received allowance of its IND submission for Oratecan from the US FDA on May 2, 2014. Oratecan and Oraxol (oral paclitaxel in combination with HM30181) are part of the Orascovery Platform and are being developed globally by Kinex and its partners Hanmi Pharmaceuticals, PharmaEssentia, and Zenith Technologies.

Additional Orascovery-based drug candidates are being developed in collaboration with Hanmi Pharmaceuticals and some of the projects received research funding support from the Innovation and Technology Commission (ITC) of the Government of the Hong Kong Special Administrative Region through Kinex Pharmaceuticals (HK) Limited* and the support of the Department of Applied Biology and Chemical Technology of the Hong Kong Polytechnic University.

*Any opinions, findings, conclusions or recommendations expressed in this material do not reflect the views of the Government of the Hong Kong Special Administrative Region, the Innovation and Technology Commission or the Small Entrepreneur Research Assistance Programme Project Assessment Panel.

SOURCE Kinex Pharmaceuticals

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