On July 19, 2016 Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading hepatitis B virus (HBV) therapeutic solutions company, reported topline results from the completed Phase I/II TKM-PLK1 clinical study in patients with advanced Hepatocellular Carcinoma (HCC). Arbutus intends to explore partnership opportunities to enable further study of TKM-PLK-1 in HCC (Press release, Arbutus Biopharma, JUL 19, 2016, View Source [SID:1234513962]). Schedule your 30 min Free 1stOncology Demo! Arbutus today reported the following topline results from the Phase I/II study of TKM-PLK1 in HCC:
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TKM-PLK1 was well-tolerated at all dose levels;
51% of subjects showed overall stable disease (SD) according to RECIST criteria;
22% of subjects showed an overall partial response (PR) according to Choi response criteria;
Tumor density reduction of up to 59% was observed;
"We are encouraged by the results from the TKM-PLK1 clinical trial in HCC patients and believe it supports further evaluation of this candidate as a potential treatment for HCC," said Dr. Mark Kowalski, Arbutus’ Chief Medical Officer. "The observed radiographic tumor density changes are consistent with tumor necrosis in a significant proportion of subjects, warranting further study of TKM-PLK1 for HCC, alone and in combination with other therapies."
"We are very pleased to report the positive results of this study of TKM-PLK1 in HCC, which we view as further validation of our capability to develop promising product candidates using our proprietary LNP delivery technology," said Dr. Mark J. Murray, Arbutus’ President and CEO. "Given Arbutus’ focus on HBV, we look forward to finding the right partner to advance the development of TKM-PLK1 for HCC and maximize the value of this asset for our shareholders."
Trial Design
The Phase I/II TKM-PLK1 HCC clinical study was an open-label, multi-center, study in patients with advanced HCC conducted in the US, Asia, and Canada. The trial was designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of the product. TKM-PLK1 was administered weekly with each four-week cycle consisting of three once-weekly doses followed by a rest week. The study included a total of 43 subjects (12 subjects in the dose escalation arm, followed by 31 subjects in the expansion cohort). The HCC efficacy endpoint of the study was tumor response rate.
About TKM-PLK1
TKM-PLK1 (TKM-080301) is a lipid nanoparticle (LNP) encapsulated small interfering RNA (siRNA) directed against polo-like kinase 1 (PLK1), a protein involved in tumor cell proliferation and a validated oncology target. Inhibition of PLK1 expression prevents the tumor cell from completing cell division, resulting in cell cycle arrest and death of the cancer cell. TKM-PLK1 has been evaluated in clinical trials with patients who have HCC, gastrointestinal neuroendocrine tumors (GI-NET), and adrenocortical carcinoma (ACC).