Phase 1 Study of Bpm 31510 (UBIDECARANONE) in Advanced Solid Tumors: Updated Analysis of a Novel Treatment with Promising Activity

ABSTRACT Background BPM is a novel small molecule that targets aerobic glycolytic pathway, re-capitulates BCL-2 mediated apoptosis and disrupts tumor angiogenesis. Methods A standard 3 + 3, dose-escalation study was designed with primary objectives of dose finding (MTD), toxicity and pharmacokinetic correlates (PK). Secondary objectives included response, response duration and clinical benefit. Results 42 patients with advanced solid tumors (refractory to standard therapy) were enrolled in 8 dose cohorts (5.6 mg/kg to 104.3 mg/kg). The trial is still ongoing as the MTD has yet to be reached. 31 (74%) patients completed at least one cycle and are considered evaluable for efficacy and toxicity. Median number of treatment cycles administered were 2 (range, 1-7) with median duration of 14 weeks (4-52 weeks). Of the 31 evaluable patients, 23 had grade I and 14 patients grade II elevation of INR without any significant clinical bleeding. Normalization of INR was observed in all the patients with vitamin K supplementation. Nine patients (29.0%) experienced mild headache during the first week of therapy, relieved with acetaminophen. There was no grade 3/4 treatment related toxicity. The pharmacokinetics of BPM was noted to be linear. The values for t1/2 ranged from 2.18 to 13.3 hr, with little or no dependence of t1/2 on dose. Objective tumor responses were noted at the dose of 58.6mg/kg with 1 complete response (myxoid liposarcoma) and 1 minor response (fibrosarcoma). With a median follow up of 14 weeks (4-52 weeks) clinical stabilization was observed in 61% of the patients. Conclusions Interim data from this phase I study indicate that BPM is well tolerated with no dose limiting toxicity to date. There was no grade III/IV toxicity. Grade I/II toxicity included elevation of INR (without significant clinical bleeding) and mild headache. One patient had partial and one patient had minor response with stabilization of the disease in the majority. The current trial is in progress and there is strong rationale for further development of this unique compound which lacks the toxicity associated with chemotherapy. Disclosure S.P. Chawla: I am an adviser to Berg Pharma LLC, Natick, MA; USA. A. Hendifar: I am an adviser to Berg Pharma LLC, Natick, MA; USA. V.S. Chua: I am an adviser to Berg Pharma LLC, Natick, MA; USA. D. Quon: I am an adviser to Berg Pharma LLC, Natick, MA; USA. Y. Lavinski: I am an employee of Berg Pharma LLC, Natick, MA; USA. J. McCook: I am an employee of Berg Pharma LLC, Natick, MA; USA. R. Sarangarajan: I am an employee of Berg Pharma LLC, Natick, MA; USA. P. Song: I am an employee of Berg Pharma LLC, Natick, MA; USA. N. Narain: I am an employee of Berg Pharma LLC, Natick, MA; USA. All other authors have declared no conflicts of interest.