ABI-011 is a novel, albumin-bound formulation of a potent thiocolchicine analog, IDN 5404, with a mean particle size of approximately 100 nanometers (nm). The active drug, IDN 5404, is related to the colchicine family of tubulin-binding compounds that have been found to have vascular-disrupting activity in vivo. Studies are ongoing to determine whether IDN 5404 has vascular-disrupting activity. As a dimer, IDN 5404 has an additional activity as an inhibitor of topoisomerase I, a critical enzyme in deoxyribonucleic acid (DNA) repair mechanisms. Although the active compound has limited solubility, IDN 5404 formulated as ABI-011 is soluble in saline, facilitating IV dosing and delivery of the active agent to tumors and the tumor vasculature.~The primary objective of study CA601.2 is to determine the MTD or RP2D of ABI-011 when administered by IV infusion on Days 1, 8, and 15, followed by a week of rest, in patients with advanced solid tumor malignancies or lymphomas. The MTD will be determined using a standard 3+3 design. The secondary objectives are to evaluate the safety and toxicity profile, to evaluate the plasma PK (elimination rate constant, elimination half-life, volume of distribution, maximum serum concentration (Cmax), time to maximum concentration (tmax), and area under the time-concentration curve to time infinity (AUCinf), to assess the biological activity and pharmacodynamics, and to make a preliminary assessment of tumor response in patients with advanced solid tumors or lymphomas. The exploratory objectives are to determine the genomic and proteomic profile of patients' tumors to identify gene mutations, gene amplifications, levels of protein expression, and pinpoint oncoproteins. Correlations between genomic/proteomic profiles and efficacy outcomes will be assessed and principal metabolites of ABI-011 will be determined, if possible.~Approximately 45-60 patients will be treated to determine DLTs, the MTD, and/or RP2D of ABI-011. Once the RP2D is identified, expansion of this cohort (up to 10 patients) will occur.~Patients with cytologically or histologically confirmed solid tumor malignancies or lymphoma for which no curative standard approved therapy is available with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 will be included. In the dose-escalation phase of the study, patients can have measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, criteria. In the dose-expansion phase of the study, only patients with measurable disease will be enrolled. No anti-cancer therapies (inclusive of investigational therapies) are allowed 5 half-lives/4 weeks (whichever is longer) prior to study drug administration (6 weeks for nitrosoureas or mitomycin C).~ABI-011 will be administered via IV infusion for 30 minutes weekly on Days 1, 8, and 15 of a 28-Day cycle. The starting dose will be 2 mg/m2. Patients will be allowed to continue treatment until they experience progressive disease or unacceptable toxicity, withdraw consent, or their physician feels it is no longer in their best interest to continue on treatment.
The primary objective of study CA601.2 is to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ABI-011 when administered by intravenous (IV) infusion on Days 1, 8, and 15, followed by a week of rest, in patients with advanced solid tumor malignancies or lymphomas. The MTD will be determined using a standard 3+3 design. The secondary objectives are to evaluate the safety and toxicity profile, to evaluate the plasma pharmacokinetics (PK), to assess the biological activity and pharmacodynamics, and to make a preliminary assessment of tumor response in patients with advanced solid tumors or lymphomas. The exploratory objectives are to determine the genomic and proteomic profile of patients' tumors to identify gene mutations, gene amplifications, levels of protein expression, and pinpoint oncoproteins. Correlations between genomic/proteomic profiles and efficacy outcomes will be assessed and principal metabolites of ABI-011 will be determined, if possible.~Approximately 45-60 patients will be treated to determine dose limiting toxicities (DLTs), the MTD, and/or RP2D of ABI-011. Once the RP2D is identified, expansion of this cohort (up to 10 patients) will occur.