Nanopharmaceutics has reached a significant milestone in its oncology pipeline with the completion of patient enrollment in a Phase 2 clinical study evaluating the combination of Triapine with lutetium Lu 177 dotatate for neuroendocrine tumors. The 94-patient randomized controlled trial, sponsored by the National Cancer Institute and conducted through the NCI-funded Experimental Therapeutics Clinical Trials Network, represents a potential advancement in treatment options for patients with metastatic neuroendocrine tumors.
Study Design and Objectives
The Phase 2 trial (NCI protocol 10558, ClinicalTrials.gov Identifier: NCT05724108) is comparing the overall response rate of combination Triapine plus lutetium Lu 177 dotatate (treatment arm 1) versus standard of care lutetium Lu 177 dotatate alone (treatment arm 2) in patients with well-differentiated somatostatin receptor-positive neuroendocrine tumors. The study's primary objective focuses on overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, while secondary objectives include evaluating progression-free survival between the two treatment arms.
The Ohio State University Comprehensive Cancer Center serves as the lead institution for this randomized phase 2 trial, which is being conducted under a Cooperative Research and Development Agreement (CRADA) between NCI and Nanopharmaceutics.
Mechanism of Action and Rationale
Triapine is a synthetic heterocyclic carboxaldehyde thiosemicarbazone with potential antineoplastic activity. As a ribonucleotide reductase inhibitor, also known as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone and 3-AP, Triapine inhibits the enzyme ribonucleotide reductase, resulting in the inhibition of the conversion of ribonucleoside diphosphates to deoxyribonucleotides necessary for DNA synthesis.
Lutetium Lu 177 dotatate is a radioactive drug that binds to somatostatin receptors found on some neuroendocrine tumor cells. The radioconjugate builds up in these cells and delivers targeted radiation that may kill them. It functions as both a radioconjugate and a somatostatin analog.
Clinical Progress and Safety Profile
The Phase 2 trial has successfully passed both the pre-planned interim safety review and interim futility assessment, indicating that the combination therapy demonstrates acceptable safety and continues to show potential efficacy. The study is now awaiting primary endpoint maturity to determine whether adding Triapine improves tumor shrinkage or slows tumor growth compared to standard therapy alone.
This trial builds on previous research demonstrating Triapine's safety profile across multiple clinical studies. The drug has been tested in various cancer types, with recent data from a cervical cancer study showing oral Triapine achieved 59% bioavailability and established a maximum tolerated dose of 100 mg when combined with cisplatin chemoradiation.
Broader Clinical Development Program
The neuroendocrine tumor study represents one component of Nanopharmaceutics' expanding Triapine development program. The company has initiated additional Phase 1 studies combining Triapine with radiation therapy for recurrent glioblastoma and astrocytoma, as well as combination studies with temozolomide for recurrent glioblastoma patients.
The clinical-stage pharmaceutical company is leveraging its expertise in nanoparticle and fine-particle formulations to develop oral, topical, and injectable products across cancer, central nervous system disorders, and infectious diseases. Nanopharmaceutics focuses on formulation development aimed at improving drug absorption and stability, particularly for hard-to-deliver Biopharmaceutics Classification System category II and IV drugs.
