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.
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