Therapy Assessed in Roswell Park Preclinical Study May Facilitate, Simplify Regional Therapy for Melanoma

BUFFALO, N.Y. — Melanoma is the fifth most common cancer in the U.S., and often recurs as multiple small tumors of the extremities. While these small tumors, called “in-transit” disease, can be treated through chemotherapy given directly to the affected limb, the standard for this focused or “regional” treatment has not been improved upon for more than 50 years. Preclinical research at Roswell Park Comprehensive Cancer Center demonstrates that the new anticancer drug CBL0137 is more effective than standard chemotherapy at killing melanoma tumor cells and was well tolerated in laboratory models. The study has been published online ahead of print in Cancer Research, a journal of the American Association for Cancer Research.

CBL0137, the lead compound in a class of small-molecule anticancer agents known as curaxins, modulates several important signaling pathways involved in the development of cancer. Roswell Park scientists Katerina Gurova, MD, PhD, Associate Professor in the Department of Cell Stress Biology, and Andrei Gudkov, PhD, DSci, Senior Vice President of Basic Science and Chair of that department, co-inventors of curaxins, have demonstrated CBL0137’s efficacy in numerous preclinical models of cancer and outlined its unique mechanism of action in previous publications.

The new study describes the results of a series of preclinical studies led by a Roswell Park surgical oncologist, Joseph Skitzki, MD, FACS, in which CBL0137 was delivered intra-arterially and compared with isolated limb perfusion (ILP) using the chemotherapeutic agent melphalan, the current standard regional therapy for in-transit melanoma.

The researchers demonstrated that intra-arterial delivery — which can be administered anywhere a catheter can be placed — took advantage of the drug’s anticancer properties, as it accumulated preferentially in tumors compared with normal tissue. The antitumor effects also were enhanced with the addition of hyperthermia.

“In this preclinical proof-of-concept study, we demonstrated that CBL0137 is more effective than the current standard therapy,” says Dr. Skitzki, the study’s senior author, Associate Professor of Surgical Oncology at Roswell Park. “We also found that unlike current treatment, this novel drug was well tolerated and effective when given by a simple intra-arterial infusion, which would make clinical applications much easier and more comfortable for patients.”

The study’s first author, Minhyung Kim, MD, an Affiliate Member in the Department of Surgical Oncology at Roswell Park, adds, “In this laboratory study, we were able to demonstrate that CBL0137 had several distinct advantages over other therapies, including its rapid accumulation in cancer tissues, simultaneous targeting of multiple cellular pathways critical for tumor cell survival and growth, and less toxicity toward normal cells.”

Roswell Park scientists are actively investigating CBL0137 to assess its effectiveness in cancers of the liver, kidney, brain and sarcoma, in both preclinical and clinical studies.

“Curaxin CBL0137 is one of a series of novel prospective anticancer agents that are being developed with close participation among Cleveland Biolabs Inc., Incuron LLC and Roswell Park,” adds Dr. Gudkov. “The drug’s unique mechanism of action, its efficacy, as demonstrated in a broad range of preclinical tumor models, and low toxicity are, taken together, quite encouraging, and a reflection of the strong capabilities of Roswell Park’s drug discovery and development program.”

This research was supported, in part, by grants from Incuron LLC and by Roswell Park’s Cancer Center Support Grant from the National Cancer Institute (project no. P30CA016056). The study, “Preclinical validation of a single-treatment infusion modality that can eradiate extremity melanomas” appears in the journal Cancer Research and is available at cancerres.aacrjournals.org.

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About Roswell Park:
The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Founded in 1898, Roswell Park is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email AskRoswell@Roswellpark.org. Follow Roswell Park on Facebook and Twitter.

About Incuron LLC:
Incuron LLC is an innovative biopharmaceutical company seeking to develop first-in-class pharmaceuticals designed to address diseases with significant medical need. Curaxin CBL0137 is Incuron’s lead oncology product candidate. Incuron holds worldwide development and commercialization rights to CBL0137. The company conducts business in the United States and in the Russian Federation. To learn more about Incuron LLC, please visit the company’s website at http://www.incuron.com/.

About Curaxin CBL0137:
CBL0137, Incuron LLC’s lead oncology product candidate, is an investigational oncology drug that targets cancer cells by inhibition of the histone chaperone FACT (Facilitates Chromatin Transcription). The interaction of CBL0137 with FACT complex results in simultaneous NF-kB suppression, heat-shock factor 1 suppression and p53 activation. This modulation of three key cellular pathways causes suppression of cancer cell growth. CBL0137 has been shown in preclinical studies to have anti-cancer effects in multiple solid and hematological tumor animal models. The safety, pharmacokinetics and pharmacodynamics of oral and intravenous formulations of CBL0137 are currently being investigated in two ongoing Phase 1 clinical studies in patients with advanced solid tumors. To date, no dose-limiting toxicities have been observed with either oral or intravenous administration through the highest CBL0137 dose levels tested. Incuron LLC holds worldwide development and commercialization rights to CBL0137.