News Release

DNA alkylation drug may improve outcomes for adolescents and young adults with central nervous system tumors

Reports and Proceedings

American Association for Cancer Research

PHILADELPHIA – In a phase II clinical trial, the drug 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) improved survival for some adolescent and young adult (AYA) patients with cancers involving the central nervous system, according to results presented at the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics, held October 7-10, 2021.

“Adolescents and young adults with central nervous system cancers represent a new group of patients for which we didn’t have a treatment option,” said Lee Roy Morgan, MD, PhD, an adjunct clinical professor of medicine at Tulane University and CEO of DEKK-TEC Inc. “We are excited that we can use DM-CHOC-PEN to treat patients who fall between the cracks because they’re too old to see a pediatrician and too young to see a general oncologist.”

AYAs—defined as individuals aged 15 to 39—are diagnosed with around 200,000 cancer cases per year and face unique physical, social, and financial challenges compared with childhood or older cancer patients. With potentially decades of life remaining, long-term side effects, including toxicity to the kidneys, liver, and reproductive organs, are a significant issue for these patients, so the development of well-tolerated therapeutics is particularly crucial to this community, Morgan explained.

Additionally, about 10 percent of AYA cancers involve the central nervous system as either a primary tumor or a metastasis. The blood-brain barrier prevents many drugs from penetrating these tumors, limiting current therapeutic options to surgery, radiation, and select chemotherapies.

Morgan and colleagues had previously developed DM-CHOC-PEN, which damages DNA by placing alkylating groups on guanine and cytosine bases. It readily crosses the blood-brain barrier and is selectively taken up by a transporter often overexpressed in cancer cells. The tumor-selective nature of DM-CHOC-PEN suggested it may have limited off-target toxicities, a finding that was confirmed in adult studies.

In this trial, the researchers enrolled 19 AYA patients with various types of tumors that either began in or metastasized to the central nervous system. They administered 98.7 mg/m2 DM-CHOC-PEN to patients with normal liver function or 75 mg/m2 to patients with impaired liver function once every 21 days. To date, the researchers have observed complete responses in two patients, partial responses in three patients, and stable disease in one patient. Three patients with responsive disease are still undergoing treatment at 12, 59, and over 72 months.

Morgan and colleagues also evaluated the toxicity of DM-CHOC-PEN in these patients. No severe (grade 3 or higher) toxicities were observed, and no cognitive, liver, hematological, cardiac, renal, or gastrointestinal dysfunction of any grade was noted. Morgan suggested that the lack of toxicities could bode well for its tolerability in combination with other treatments.

“Some of these patients had other tumors outside the nervous system, and their physicians combined DM-CHOC-PEN with another drug. So far, we’ve seen no toxicities, and we just finished a trial showing that it potentiates radiation as well, suggesting that DM-CHOC-PEN could be safely combined with other drugs,” Morgan said.

Additionally, they found that DM-CHOC-PEN has a longer half-life in the plasma of AYA patients than in the plasma of patients over 60; it was detectable for up to 50 days in AYAs but less than 21 days in older individuals, suggesting a prolonged effect in younger patients.

Limitations of this study include the small sample size, as well as the exclusion of patients with abnormal blood counts or debilitating comorbidities.

This study was funded by the National Cancer Institute and the National Institute of General Medical Sciences of the National Institutes of Health. Morgan is the CEO of DEKK-TEC Inc., the developer of DM-CHOC-PEN.


Presentation #: P038       

Title: Early Phase II clinical trial results for 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in adolescents and young adults (AYA) with brain cancers

Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N7 guanine and N4-cytosine that is currently in Phase II trial in AYA subjects with cancer that have CNS involvement. The aims for the trials are to assess clinical responses, monitor toxicities, safety and confirm the MTDs for IV administered DM-CHOC-PEN (IND 68,876) to AYA subjects with cancer involving the CNS. We report here responses and toxicities observed to date in Phases I & II DM-CHOC-PEN clinical trials with AYA subjects that had cancer involving the CNS.

Subjects & Methods: DM-CHOC-PEN was administered as a 3-hr IV infusion once every 21 days to AYA subjects. The dosing schedule was 2-tiered: subjects with liver involvement received 85.8 mg/m2 and subjects with normal liver function received 98.7 mg/m2.

Results: Nineteen (19) AYA subjects with CNS involvement have been treated to date. The common tumor types treated were oligoastrocytoma, astrocytoma, GBM; leukemia (ALL), lymphoma (NHL), melanoma, breast and lung cancers (NSCL). Three (3) AYA patients are currently being followed with diagnoses of breast cancer, astrocytoma, and lung cancer and have had good qualities of life at 12, 59 and 72+ mos. All patients have been followed with lab tests, scans (RECIST 1.1) and virtual exams. The drug was well tolerated. The most common adverse effect was fatigue (17%). No neuro/cognitive, liver dysfunction, hematological, cardiac, renal or GI toxicities were observed. PK modeling revealed that AUCs were parallel for all dose levels. The Cmax for DM-CHOC-PEN and DM-PEN (4-demethylpenclomedine, a metabolite) were 3 and 24 hours, respectively for the AYA subjects; similar to what was seen for older adults. The drug and metabolite were still detectable in plasma and rbcs for 21 to 50 days in the AYA (15 – 39 y/o) group vs. 3 to < 21 days (previously reported for adult subjects (>60 y/o) (AACR #1185, 2013). Differences in PK profiles between AYA and older adult subjects will also be reviewed in depth.

Conclusion: DM-CHOC-PEN is safe for usage and has produced objective responses with manageable toxicities in AYA subjects with cancer involving the CNS. Complete data on subject responses and observed toxicities will be presented. We propose a 3-stage mechanism for drug entry into the CNS and into cancer cells via reversible binding with RBCs and then association with L-glutamine transport into cells.


Supported by NCI/SBIR grants – R43/44CA132257 and R43CA203351 and NIH NIGMS 1 U54 GM104940.

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