This is the first clinical study of ALB 109564(a), a tubulin inhibitor, interfering with tubulin polymerization, primarily targeting microtubules that compose the mitotic spindle, resulting in metaphase arrest. The motivation for the development of ALB 109564(a) is to create a molecule that will provide greater anti-tumor activity than other licensed vinca alkaloids, without increasing the level of toxicity often associated with such therapies.~The objectives of the proposed study are: (1) to determine the safety and tolerability, including the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), of ALB 109564(a) administered intravenously every 3 weeks to subjects with advanced, treatment-refractory solid tumors; (2) to evaluate the pharmacokinetics of ALB 109564(a); and (3) to document any observed anti-tumor activity.~The starting dose of 1.2 mg/m2 once every 3 weeks is expected to ensure a safe first-in-human dose and allow increases of 50% with the first several subject cohorts. The first cohort will enroll 3 subjects, and the subsequent 3-subject cohorts will proceed according to a modified Fibonacci scheme. The standard dose increase, in the absence of dose limiting toxicity, will be 50%. However, once 1 subject experiences a DLT, or 2 or more subjects within a cohort experience ≥ Grade 2 drug-related adverse events, all subsequent dose escalations will occur at approximately 25% increments. In the case that the dose escalation increment is decreased to 25% following 2 or more subjects with ≥ Grade 2 drug-related events, the increment can subsequently be reset at 50% if, in the 2 successive cohorts, no DLTs are observed, and no more than 1 subject per cohort experiences a ≥ Grade 2 drug-related AE. DLT and MTD determinations will be made according to the first treatment cycle (single dose plus 3-week follow-up). The MTD will be declared as the highest level at which none of the original 3 subjects or no more than 1 of the expanded 6-subject cohort experiences a DLT. At the MTD level, subjects will be enrolled into two parallel groups: Group A, those with solid tumor of unrestricted tumor type, and Group B, those with primary tumor type of soft tissue sarcoma. Up to a total of 24 subjects will be enrolled at the MTD.~Subjects who tolerate treatment will be eligible to continue receiving treatment to a maximum of 12 cycles on the same 3-week schedule per the Investigator's medical judgment. Subjects whose disease has not progressed after 12 cycles of treatment with ALB 109564(a) may continue receiving treatment on the same 3-week cycle, with the same protocol assessments, contingent upon the Investigator's judgment and the Sponsor's approval.~The actual enrollment of subjects will be determined by the safety experience and the number of dose-escalation cohorts required to achieve the MTD. The projected enrollment is approximately 60 subjects for a total study duration of approximately 2 years.
The purpose of this study is to determine the maximum tolerated dose of ALB 109564(a), a novel tubulin inhibitor, and to assess safety, pharmacokinetics, and anti-tumor activity in subjects with advanced solid tumors.