NPI-2358 is well tolerated and stabilizes disease in patients with solid tumors and lymphoma
SAN ANTONIO – The Institute for Drug Development, a division of The Cancer Therapy & Research Center at The University of Texas Health Science Center at San Antonio, announced the results of a new phase I clinical study on NPI-2358, a targeted anti-cancer agent designed to rapidly disrupt blood flow to the tumor mass, causing tumor death. The novel agent destabilizes the cells in the blood vessels leading to the tumor, resulting in a toxic effect on the cancer cells, leaving the healthy cells unharmed. The data was presented today during the Annual Meeting of the American Association for Cancer Research (AACR) in San Diego, Calif.
Results presented show the novel anti-cancer agent NPI-2358 to be well tolerated by patients with solid tumors and lymphoma. Minimal side effects included intermittent nausea, fever, tumor pain and temporary hypertension, demonstrating a successful drug effect on stabilizing the tumor growth.
The study, “Phase I Dose Escalation Trial with DCE-MRI Imaging of the Novel Vascular Disrupting Agent NPI-2358,” was authored by Dr. Monica Mita and her colleagues at the Institute for Drug Development, Virtual Scopics Inc., Northwestern Medical Specialties, Karmanos Cancer Institute and Nereus Pharmaceuticals.
”This vascular disrupting agent produces a rapid and selective shutdown of the established tumor vasculature. Other compounds with the same mechanism of action are also currently in clinical development and demonstrated clinical benefit as single agents and also in combination with chemotherapy agents,” said lead author Monica Mita, M.D., principal investigator at The Institute for Drug Development. “NPI-2358 is well tolerated and demonstrated promising results in patients with advanced solid tumors. Clinical studies with NPI-2358 as a single agent and in combination are ongoing.”
NPI-2358 underwent preclinical testing at The Institute for Drug Development. This research demonstrated that the agent strengthens the effects of many other chemotherapy agents. The preclinical data suggested that the blood flow to the tumor continued to be reduced 24 hours after dosage.
In the Phase I clinical study, 25 patients with a solid tumor malignancy or lymphoma received NPI-2358 at 6-30 mg/m2 administered weekly for 15 or 30 minutes by intravenous infusion on days 1, 8 and 15 on a 28-day cycle. A trend toward tumor blood flow decrease was demonstrated in patients evaluated above 13.5 mg/m2. Tumor pain was reported in multiple patients. Together these findings, in addition to temporary hypertension, fever and nausea, which occurred in multiple patients, suggest NPI-2358 is affecting tumor blood flow and has biological activity at and above 13.5 mg/m2. The recommended phase II dose was established at 30 mg/m2. No responses have been reported, although seven patients have had stable disease with pancreatic cancer, melanoma, adrenocortical carcinoma, anal squamous cell carcinoma, liposarcoma, hemangiopericytoma and colorectal carcinoma.
Preclinical data, indications of drug effect and toxicity profile support the initiation of a phase II program.
The Cancer Therapy & Research Center at The University of Texas Health Science Center at San Antonio, located in San Antonio, Texas, is one of the nation’s leading academic research and treatment centers, serving more than 4.4 million people in the high-growth corridor of Central and South Texas including Austin, San Antonio, Laredo and the Rio Grande Valley. CTRC is one of a few elite cancer centers in the country to be named a National Cancer Institute-designated (NCI) Cancer Center, and is one of only three in Texas. CTRC handles more than 120,000 patient visits each year and is a world leader in developing new drugs to treat cancer. The CTRC Institute for Drug Development (IDD) is internationally recognized for conducting the largest oncology Phase I clinical drug trials program in the world, and has participated in the clinical and/or preclinical development of many of the cancer drugs approved by the U.S. Food & Drug Administration. For more information, visit www.ctrc.uthscsa.edu.
American Association for Cancer Research
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 27,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is the only journal worldwide dedicated exclusively to cancer prevention from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.