Oncoceutics, Inc. announced today that the first patient has been treated in a Phase II clinical trial of ONC201 for patients with recurrent or metastatic neuroendocrine tumors at the Cleveland Clinic. The selection of neuroendocrine tumors for a clinical trial was driven by the discovery in 2016 that ONC201 is a direct antagonist of the D2 dopamine receptor (DRD2). This receptor is highly up-regulated in neuroendocrine cancers.
This trial, which is being led by Peter Anderson, MD, PhD, a pediatric oncologist at the Cleveland Clinic, will enroll up to 24 patients with a variety of neuroendocrine tumors, including patients with desmoplastic small round cell tumors and pheochromocytoma-paraganglioma (PC-PG).
Analysis of samples in The Cancer Genome Atlas (TCGA) and tumor tissue from patients reveal that DRD2 was highly overexpressed in PC-PG relative to normal tissue or any other type of cancer. A large portion of PC-PG also had low expression of a dopamine receptor family member that opposed DRD2 signaling, indicating that many PC-PG patients may have a biomarker signature that predicts for enhanced responsiveness to ONC201.
“We are thrilled to be initiating this clinical trial in an indication where DRD2 appears to play an important role,” said Martin Stogniew, PhD, Chief Development Officer at Oncoceutics. “The support of our collaborators including Weill Cornell Medical College, Dr. El-Deiry at Fox Chase Cancer Center, the Wellcome Trust Sanger Institute, and others, has allowed Oncoceutics to bring ONC201 to these patients in an area of significant unmet medical need rapidly after the discovery of DRD2 as the binding target for ONC201.”
The ONC201 trial is designed to measure anti-hypertensive reduction as a secondary endpoint in the PC-PG patients, and may provide an opportunity to demonstrate a clinical benefit in a relatively rapid time frame. Shrinkage of the tumor may lead to a reduction in the hormones produced by PC-PG, therefore allowing reduced dosing of the anti-hypertensive medications required to control their effects. The FDA has recognized that reducing these specific medications represents a clinically meaningful benefit for patients and has allowed the reduction in anti-hypertensive medications to be an approvable endpoint.
“When I originally learned about ONC201’s unique target and low toxicity, I was immediately interested in bringing the drug to my patients with neuroendocrine tumors,” said Dr. Anderson. “I look forward to exploring the effect of ONC201 on tumor volume and biomarker production for these patients who have few treatment options for their cancer.”
Oncoceutics, Inc. is a clinical-stage drug discovery and development company with a novel class of compounds that selectively target G protein-coupled receptors for oncology. The first lead compound to result from this program is ONC201, an orally active DRD2 small molecule antagonist that is well-tolerated and effective against advanced cancers. The company recently completed a successful Phase I study in solid tumors and has begun additional Phase I/II and Phase II clinical programs in both solid and hematological malignancies. Oncoceutics and collaborative groups have received significant grants over the last two years, from institutions such as the National Cancer Institute, the U.S. Food and Drug Administration, the Pennsylvania Department of Health, and The Musella Foundation. In addition, outside interest in the company’s portfolio has resulted in several R&D alliance agreements and collaborations between Oncoceutics and leading cancer research institutions, including The University of Texas MD Anderson Cancer Center, the NIH/NCI, Harvard and the Fox Chase Cancer Center. The company has established a robust intellectual property position, including several issued patents.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.