Cleveland Biolabs Announces Successful Close of Phase 1 Study of CBL0102

Cleveland BioLabs, Inc. CBLI today announced the achievement of all objectives in a Phase 1 clinical trial of CBL0102, or quinacrine, 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 is the first of a group of compounds identified by CBLI scientists that act 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). CBL0102 is being developed by Incuron, LLC, a joint venture between Bioprocess Capital Ventures and Cleveland BioLabs. 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. Study participants were treated with CBL0102 given orally daily. Patients could continue therapy for eight weeks (or longer if they appeared to be benefiting from therapy). 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.