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Tekmira Releases Phase I Cancer Drug Data, Plans Phase II Trial in Neuroendocrine Tumors

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Tekmira Pharmaceuticals this week released data from an ongoing phase I clinical trial of its RNAi-based cancer drug TKM-PLK1, showing that the drug is safe and offering hints of efficacy.

Notably, two patients have received the drug for at least six months with no evidence of cumulative toxicity. Meantime, three patients achieved stable disease, including one patient with metastatic appendiceal carcinoid cancer, another with metastatic colorectal cancer, and a third with metastatic adrenocortical carcinoma, Tekmira said.

In addition, another patient with progressive, metastatic appendiceal carcinoid cancer had a “durable partial tumor response” continuing for more than 10 months, the company said.

This kind of cancer generally has a “very poor prognosis and is difficult to treat,” Mark Gilbert, an oncologist and Tekmira scientific advisor, said during a conference call held to discuss the phase I data. “In fact, the average response rates of neuroendocrine tumors such as his are typically less than 15 percent, even with combination chemotherapies.”

Encouragingly, the patient’s response occurred within the first two cycles of treatment and lasted through 10 cycles, he added. Despite withdrawing from treatment due to complications unrelated to his disease, the patient remains alive — 14 months after enrolling in the TKM-PLK1 study.

“A durable response and early reduction in tumor burden in this disease setting with a disseminated neuroendocrine tumor was truly unexpected,” Gilbert said.

In light of the findings, which were presented at this year’s American Association for Cancer Research annual meeting, Tekmira said that it intends to initiate a phase II trial of TKM-PLK1 in gastrointestinal carcinoid, or neuroendocrine, tumors later this year.

TKM-PLK1 comprises siRNAs against polo-like kinase 1, a serine/threonine kinase key to cell progression and which is over-expressed in a number of cancer types. It is formulated with Tekmira’s proprietary lipid nanoparticle technology.

In the phase I trial, sequential cohorts of three to six patients with advanced solid tumors or lymphoma received TKM-PLK1 as a 30-minute intravenous infusion on days one, eight, and 15 of a 28-day cycle, according to Tekmira.

A total of 24 patients were treated, receiving a combined total of 152 doses of the drug at levels ranging from 0.15 to 0.9 mg/kg per week.

The most common drug-related adverse events have been mild-to-moderate infusion-related reactions with delayed onset, fever, chills, nausea, vomiting, and fatigue, according to the AACR data. Additionally, mild transient cytokine increases were observed at dose levels at or below 0.75 mg/kg per week and generally correlated with the timing of delayed infusion reactions.

These increases peaked at six hours and were normalized by 24 hours, Gilbert said. Further, the adverse events “resolved quickly with standard treatment and without symptom recurrence or late sequelae.

“In essence, they were highly predictable,” he said.

No dose-dependent changes in liver function tests were observed. However, dose-limiting toxicities occurred at the highest dose, including grade III hypoxia/dyspnea in one patient with a history of asthma and transient grade III thrombocytopenia in another patient.

As a result, dosing in an ongoing 10-patient expansion arm of the study, which is expected to conclude this year, has been set at 0.75 mg/kg per week. This dose will also be tested in the planned phase II trial.

Gilbert said that Tekmira views neuroendocrine cancer as a “high-value” indication given the lack of therapies on the market or in development.

“Neuroendocrine tumor patients often receive a drug known as octreotide, a parental drug that mimics somatostatin and relieves some of the symptoms of neuroendocrine tumors and has been shown to prolong progression-free survival,” he said. “But it doesn’t reduce tumor burden.”

Other than this drug, there is no other US Food and Drug Administration-approved treatment for this cancer, Gilbert noted. “Further, there is no specific treatment in late-stage development in this disease setting either.”

Tekmira President and CEO Mark Murray said during the call that the company would provide additional details about the upcoming phase II trial in the coming months, as well as the other indications the company is considering for TKM-PLK1.

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