Dosing of the ninth cohort is underway in a multicenter, phase 1, dose-escalation study assessing the oral administration of CBL0137 in patients with advanced solid tumors that are resistant or refractory to current standard treatment. In parallel, dosing of the seventh cohort is ongoing in a multi-center, phase 1, dose-escalation trial assessing the intravenous administration of CBL0137 in patients with metastatic or unresectable advanced solid cancers and lymphomas. A study of CBL0137 safety and efficacy in hematological malignancies is planned.
A formal interim analysis of the 19 patients enrolled in the first six cohorts of the ongoing oral administration study indicated that the study medication was well tolerated at all investigated dose levels. The observation of drug exposure in plasma documented high oral bioavailability. To date, no dose-limiting toxicities have been observed with either oral or intravenous administration through the highest CBL0137 dose levels tested. Heavily pretreated patients with advanced cancers of the esophagus, colon, breast, cervix, and prostate have had stable disease for periods ranging from 4 to 6 months. Peripheral blood mononuclear cells from evaluable blood samples have shown pharmacodynamic effects consistent with the expected mechanism of action of CBL0137.
Andrei Gudkov, Ph.D., D. Sci., Chief Scientific Officer of CBLI and Senior Vice President of Basic Science of Roswell Park Cancer Institute, commented, "We are delighted with the progress of the CBL0137 development program. CBL0137 represents a unique new drug that addresses nearly universal but difficult-to-target pathways involved in cancer progression and survival. CBL0137 trapping of the chromatin remodeling complex, Facilitates Chromatin Transcription (FACT), in DNA inhibits nuclear factor-kappa-B (NF-kB), a factor essential for survival of tumor cells, while enhancing p53-mediated tumor cell death. CBL0137 has demonstrated preclinical efficacy against broad spectrum of solid tumors and hematological malignancies, including cancers resistant to currently available drugs, and now is showing evidence of pharmacological activity in patients at nontoxic doses."
Langdon Miller, MD, Strategic Medical Advisor to CBLI and Incuron, stated, "The CBLI and Incuron development teams are pleased to be able to translate the very promising CBL0137 preclinical data to the clinic. Dose escalation continues in the ongoing studies of the oral and intravenous formulations of CBL0137 in patients with solid tumors. A successful meeting with the U.S. Food and Drug Administration (FDA) in December 2014 opens the opportunity to initiate an additional Investigational New Drug Application (IND) and move forward in 2015 with a multicenter trial of CBL0137 in patients with hematological cancers."