Incuron, LLC Announces the Successful Completion of a Phase 1 Study of CBL0102

15.01.2012

Incuron, LLC Announces the Successful Completion of a Phase 1 Study of CBL0102

Incuron, a joint subsidiary of the Bioprocess Capital Ventures closed-end investment fund and Cleveland BioLabs, Inc. (NASDAQ:CBLI) announced the achievement of all objectives in a Phase 1 clinical trial of CBL0102 an orally administered small molecule. The study was performed in patients with advanced cancers for which no standard care exists or which had become resistant to conventional therapies. All patients had tumors involving the liver.

CBL0102 or quinacrine is the first of a compound group, which has the mechanism of action by blocking activity of the chromatin remodeling complex, FACT (Facilitates Chromatin Transcription), resulting in simultaneous modulation of several signal transduction pathways (p53, PI3K/AKT/mTOR, NF-kappaB and heat shock response) that are commonly deregulated in cancer (Guo et al., 2009 and Gurova et al., 2005).

The primary objective of the study was to evaluate for a maximum tolerated dose and dose-limiting toxicities of CBL0102 in patients with advanced cancers. Secondary objectives were to characterize the drug's safety and to profile its pharmacokinetics. The study also assessed for preliminary evidence of CBL0102 antitumor activity. In particular, the study was designed to explore potential effects related to CBL0102's high relative biodistribution into the liver and therefore included only patients with primary or metastatic liver cancers. Patients were enrolled to receive sequentially higher starting doses of CBL0102 in seven cohorts. The study therapy was performed till signs of dose limiting toxicity or tumor progression occurred.

A total of 32 patients enrolled. Participants had cancers of breast, gastric, hepatic, pancreatic, and colorectal origin. The study successfully achieved both the primary and secondary objectives. CBL0102 was generally well-tolerated and a recommended Phase 2 dose of 400 mg/day was established. The most common adverse events were skin discoloration due to drug accumulation in skin, fatigue, upper abdominal pain, mild to moderate gastrointestinal disorders, and hepatic transaminase elevations, with most events being low grade. The analysis of pharmacokinetics showed that plasma exposures rose with increasing dose and that steady state had been achieved by 15 days of therapy. Liver biopsies were performed in two patients after four weeks of therapy and confirmed much higher liver concentrations of CBL0102 than were present in plasma.

By eight weeks of therapy, a partial tumor regression was recorded in one breast cancer patient, who experienced a 46% reduction in target lesion maximum dimensions. Disease stabilization was observed in four other patients (patients with breast cancer, hepatocellular carcinoma, salivary gland cancer, and rectal cancer). In the patient with hepatocellular carcinoma, long-term stabilization was observed for a period of 7.5 months, during which the patient remained on continuous CBL0102 treatment.  

Professor S.A. Tyulyandin, MD, D.Sci., Deputy Director of Clinical Oncology and Director of Clinical Pharmacology and Chemotherapy at the Russian Oncological Scientific Center in Moscow, a leading Russian oncology center was the national coordinator for the study. Dr. Tyulyandin commented, "I believe the favorable tolerability, pharmacological properties and initial signs of efficacy observed in several advanced cancer patients in the trial warrant serious consideration of advancing the development of CBL0102."

Andrey Leonov, Ph.D., Chief Executive Officer of Incuron stated, "We are very encouraged by the outcome of this trial. We are looking to partner CBL0102 for further potential development, as well as support investigator-initiated trials. Moreover, the information derived from this trial of CBL0102 supports the development of our optimized proprietary FACT inhibitor, CBL0137, which is currently being evaluated in the United States and in Russia in ongoing Phase 1 trials assessing both oral and intravenous administration."

A Phase 1/2 study evaluating the safety and efficacy of combination treatment with erlotinib and CBL0102 in Stage IIIB-IV non-small cell lung cancer was recently initiated by the Case Comprehensive Cancer Center in cooperation with the National Cancer Institute (http://clinicaltrials.gov/ct2/show/NCT01839955?term=quinacrine&rank=1).

CBL0102 was granted Orphan Drug status by the U.S. Food and Drug Administration for the treatment of hepatocellular carcinoma in October 2012.

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