Conference Coverage

Novel penclomedine shows promise for some AYAs with CNS cancers



A novel penclomedine shows promising safety and efficacy in some adolescent and young adult patients with cancers involving the central nervous system, according to phase 1/2 clinical trial findings.

The trial included 15 patients, aged 15-39 years, with measurable cancer involving the CNS who were treated with the agent 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN).

Two of these patients were “in their 59th month of survival and doing well” as of April, when the data were presented at the AACR virtual meeting I.

One of the patients with long-term survival benefit had non–small cell lung cancer, and one had astrocytoma, Lee Roy Morgan, MD, PhD, chief executive officer of Dekk-Tec Inc., New Orleans, reported during a poster presentation.

Patients with glioblastoma, however, “did not do well,” said Dr. Morgan, an adjunct professor at Tulane University in New Orleans. He noted that none of the five glioblastoma patients experienced a long-term response.


Study subjects were treated with the maximum tolerated dose (MTD) of DM-CHOC-PEN as identified in an earlier study. Patients with liver involvement received 75 mg/m2, and those without liver involvement received up to 98.7 mg/m2. Dosing was by 3-hour intravenous administration once every 21 days as lab tests and subject status allowed.

DM-CHOC-PEN was generally well tolerated. One patient experienced grade 2 vasogenic edema, and another experienced seizures. Both were secondary to tumor swelling, and both resolved with tumor regression.

No grade 3 toxicities occurred at the MTD, and “no renal, hematological, hepatic, or pulmonary toxicities were noted using the MTD in this trial,” Dr. Morgan said.


DM-CHOC-PEN is a polychlorinated pyridine with a cholesteryl carbonate attachment that induces lipophilicity, which potentiates the drug’s penetration of the blood-brain barrier and its entry into the brain and brain cancers, Dr. Morgan explained.

He added that DM-CHOC-PEN is a bis-alkylator that binds to DNA’s cytosine/guanine nucleotides. The agent does not require hepatic activation, it crosses the blood-brain barrier intact, and accumulates in CNS tumors but not normal CNS tissue, he said.

Further, it “is not a substrate for [p-glycoprotein] transport; thus, it doesn’t easily get out of the brain,” Dr. Morgan said. He noted that DM-CHOC-PEN can be used with other agents, such as temozolomide and bis-chloroethylnitrosourea, because of the difference in mechanisms of action.

This study was supported by Louisiana state grants, the National Cancer Institute, the National Institute of General Medical Sciences, and the Small Business Innovation Research program. Dr. Morgan reported having no disclosures, but he is chief executive officer of Dekk-Tec Inc., which is developing DM-CHOC-PEN.

SOURCE: Morgan L et al. AACR 2020, Abstract CT181.

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