(P 553) A PHASE 1/2A OPEN-LABEL, DOSE-ESCALATION/DOSE EXPANSION SAFETY, TOLERABILITY AND PHARMACOKINETIC STUDY OF IMX-110 IN PATIENTS WITH ADVANCED SOLID TUMORS

Objective:

Background: IMX-110 (DOX/CUR Micelles) is a PEG-PE polymeric micelle encapsulating a Stat3/NF-kB/poly-kinase inhibitor, curcuminoid complex (CUR), and low-dose topoisomerase inhibitor, doxorubicin (DOX).

Objectives: Primary: To determine the safety of IMX-110 administered intravenously in patients with advanced solid tumors; and to determine the maximum tolerated dose (MTD) and RP2D of IMX-110. Secondary: To determine the plasma PK profile of IMX-110 in treatment cycle 1; and to determine the efficacy of IMX-110 as assessed by ORR, DCR, PFS, DOR and OS. Exploratory: To assess the pharmacodynamic activity of IMX-110 with appropriate biomarkers.

Methods:

Methods: Ten to 30 previously treated patients with advanced solid tumors will be enrolled in the Phase 1b component. Starting at 0.67 mg/m2 doxorubicin in IMX-110, the study has employed an accelerated dose escalation followed by the standard “cohort of three” design. The maximum tolerated dose based on doxorubicin (DOX-based) is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. Phase 2 (n=40): Patients in the expansion phase will receive IMX-110 at the RP2D and may continue treatment until disease progression or unacceptable toxicity occurs. Statistical considerations: NIH CTCAE v5.0 and RECIST v1.1 will be used. There are three analysis populations: Safety, Efficacy in Evaluable Population and PK. Safety: All enrolled patients who receive any quantity of study treatment will be included in the Safety Population. Efficacy: All subjects who receive at least one full cycle of study treatment and have a follow-up RECIST assessment. PK: All subjects who receive study treatment and have sufficient plasma concentration for analysis of the PK parameters. Safety analysis: Incidence, severity and causality of AE and serious adverse events will be reported. Efficacy analysis: Summary tables presenting the number and proportion of responders and non-responders, together with the two-sided 95% Pearson-Clopper confidence intervals for response rates will be presented. The time to event endpoints, including DOR, PFS and OS will be analyzed by survival analysis method. In addition, the graphs of Kaplan-Meier estimates of survival functions will be presented. Descriptive statistics will be provided from available data from plasma (mandatory) and tissue (optional) samples collected and stored for biomarker analysis pre- and post-treatment. Nineteen patients have been dosed to date. Currently, Cohort 9 is being dosed.

Results: N/A This abstract is submitted under Trials in Progress

Conclusion: N/A This abstract is submitted under Trials in Progress