(ChemotherapyAdvisor) – The RNA interference (RNAi) drug TKM-080301 can be safely administered to patients with advanced solid tumors or lymphoma, and some patients show therapeutic benefit, according to authors of a phase 1 open label, dose-escalation study presented at the American Association for Cancer Research (AACR) Annual Meeting 2013, in Washington, DC.

RNAi agents silence expression of specific genes. TKM-080301 targets the polo-like kinase 1 (PLK1) gene, which is involved in tumor cell growth and is highly expressed in several types of cancer, reported Ramesh K. Ramanathan, MD, of the Virginia G. Piper Cancer Center in Scottsdale, AZ, and coauthors.

“Preliminary results from this first-in-human trial indicate TKM-080301 was generally well-tolerated by the majority of patients,” reported Dr. Ramanathan. “Preliminary antitumor efficacy has been observed, supporting PLK1 as a therapeutic target.”

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Preclinical data had showed that by decreasing PLK1 levels in cancer cells, TKM-080301 can kill those cells and halt tumor growth, Dr. Ramanathan said.

In the phase 1 clinical trial, the researchers assigned a total of 23 patients to sequential cohorts of three to six participants, with each cohort receiving escalating doses of TKM-080301 in 30-minute infusions. To date, doses have ranged from 0.15 mg/kg per week to 0.9 mg/kg per week, Dr. Ramanathan reported. A total of 128 doses have been administered to date.

Dose-limiting toxicities were observed among two participants in the 0.9 mg/kg per-week dose cohort. One case of thrombocytopenia was recorded, and another participant with a history of asthma suffered dyspnea and hypoxia, the coauthors reported.

“Mild, transient increases in certain cytokines (e.g., IL-6, IL-8, MCP-1) have been observed at dose levels of 0.75 mg/kg/week or greater and generally correlated with the timing of delayed infusion reactions,” they noted.

The most common drug-related toxicities were mild to moderate delayed infusion related fever, chills, nausea, vomiting, and fatigue, the coauthors reported. Of the 23 patients enrolled, two have received TKM-080301 for more than 6 months (six cycles), and neither has shown any evidence of cumulative toxicity, the team reported. One of these patients has stable colon cancer and the other has durable confirmed partial response (carcinoid tumor).

“RNAi therapies, such as the one used in our study, have the potential to make a significant and broad impact on how we treat cancer because we have the ability to target virtually any protein involved in the disease,” Ramanathan remarked.  Such drugs might one day augment current therapies, he said.

Abstract #LB-289