ProLynx Launches Phase I/II Trial of PLX038 for Rare CNS Tumors at NCI

ProLynx Inc. has initiated a Phase I/II clinical trial for a novel drug, PLX038, which is designed to target primary central nervous system (CNS) tumors characterized by MYC or MYCN amplifications. This first-of-its-kind treatment involves a pegylated version of SN-38, a potent topoisomerase 1 inhibitor and the active metabolite of irinotecan and sacituzumab govitecan. The drug is engineered to provide a sustained release of SN-38, which is crucial for both safety and effectiveness.

MYC genes are known to regulate genes that control cell division, and their overexpression is associated with the development of various cancers. Amplifications of MYC and MYCN are particularly prevalent in several types of CNS tumors, including medulloblastomas and ependymomas. These tumors are known for their aggressive nature and resistance to conventional treatments. The topoisomerase enzymes, which are abundant in MYC or MYCN-induced tumors, are the targets of topoisomerase inhibitors like PLX038.

The clinical trial, led by investigators from the National Institutes of Health's NCI, will evaluate the safety and efficacy of PLX038 in treating these challenging CNS tumors. The Phase I portion of the trial will determine the optimal dosage for Phase II, which will then involve three distinct patient cohorts: those with newly diagnosed MYCN-amplified ependymoma, those with recurrent ependymoma or medulloblastoma with MYCN or MYC amplification, and patients with other types of recurrent primary CNS tumors with MYC or MYCN amplifications.

In a unique approach, the Phase II trial will also include on-treatment tumor biopsies to explore biomarkers that may predict response and resistance to the drug. The expression levels of SLFN11, MYC, MYCN, and various topoisomerase enzymes will be examined to identify patients who are most likely to benefit from PLX038.

Furthermore, in collaboration with The Office of Patient-Centered Outcomes (OPCORe), the trial will gather patient-reported outcomes to assess the therapy's impact on patients' lives, including its toxicity, symptom severity, and effects on daily activities and physical functioning.

ProLynx's co-founder, Daniel V. Santi, expressed enthusiasm for the potential of PLX038 to offer new hope to patients with rare CNS cancers. He highlighted the clinical activity of conventional short-acting topoisomerase 1 inhibitors in certain CNS tumors and expressed optimism that the long-acting nature of PLX038 could enhance its efficacy and safety.

More details about the trial can be found on clinicaltrials.gov with the identifier number NCT06161519. Patients interested in participating in the trial can reach out through various channels, including a toll-free number, the NCI website, and email.

ProLynx, a biotechnology firm based in San Francisco, is dedicated to developing innovative systems that enhance the pharmacokinetics and efficacy of essential drugs.