Phase 2 Study of DM-CHOC-PEN in Patients with NSCLC with Central Nervous System Involvement
In patients with non–small-cell lung cancer (NSCLC) that involves the central nervous system and who lack genetic rearrangements or tumor targets, DM-CHOC-PEN, a bis-alkylator of DNA, has produced long-term objective responses with manageable toxicities.
DM-CHOC-PEN (4-demethyl-4-cholesteryloxycarbonylpenclomedine) is a poly-chlorinated pyridine cholesteryl carbonate that acts via bis-alkylation of DNA at N7-guanine and N4-cytosine. DM-CHOC-PEN has completed phase 1 and 2 trials, including trials in patients with non–small-cell lung cancer (NSCLC) and central nervous system (CNS) involvement. The primary purpose of the previously reported phase 1/2 DM-CHOC-PEN trials was to assess clinical response, monitor toxicities and safety, and verify the maximum tolerated doses (MTDs) for intravenous (IV) dosing. At the American Association of Cancer Research Annual Meeting 2021, researchers reported responses and toxicities observed with DM-CHOC-PEN in patients with NSCLC who had CNS involvement and whose tumors lacked genetic rearrangements and tumor targets, and/or whose disease had relapsed after treatment with standard therapies.1
DM-CHOC-PEN was administered to adults with cancer, including NSCLC, as a 3-hour IV infusion once every 21 days employing a verified 2-tier MTD schedule: 85.8 mg/m2 for patients with liver involvement and 98.7 mg/m2 for patients with normal liver function.1
So far, a total of 52 adults with cancer have received treatment with DM-CHOC-PEN, including 16 patients with lung cancer. Among these patients, 11 had NSCLC, specifically adenocarcinoma or large-cell carcinomas, that involved the CNS. These tumors lacked genetic rearrangements and had no tumor targets, and/or had failed standard therapies. Seven of the 11 patients with NSCLC involving the CNS also had brain metastases.1
DM-CHOC-PEN was well tolerated. The most common adverse effects included fatigue (17%), nausea (11%), and reversible liver dysfunction (9%). No neurologic, psychological, hematologic, cardiac, or renal toxicities were observed, and there were no drug-associated deaths.1
Eight of 16 patients with NSCLC who received DM-CHOC-PEN had a complete or partial response based on RECIST version 1.1 criteria. Overall survival and progression-free survival based on Kaplan–Meier analyses ranged from 8+ to 70+ months.1
Researchers concluded that DM-CHOC-PEN, a bis-alkylator of DNA, is safe at the dose levels described. It has produced long-term objective responses with manageable toxicities in patients with NSCLC and CNS involvement who lack genetic rearrangements or tumor targets and/or whose disease progressed after standard therapies.1
1. Weiner RS, Morgan LR, Ware M, et al. Phase II clinical trial results for 4-demethyl-4-cholesteryloxycarbonyl-penclomedine (DM-CHOC-PEN) in advanced non-small cell lung cancer (NSCLC) involving the CNS. Presented at: American Association of Cancer Research Annual Meeting 2021; April 10-15, 2021. Abstract CT152.