Abstract A113: ATI-1123, a novel human albumin-stabilized docetaxel liposomal formulation: Final results of a phase I study in patients with advanced solid malignancies.
Authors: Mita Alain C. , Senzer Neil N. , Vemulapalli Sushma , Sarantopoulos John , Mahalingam Devalingam , Mita Monica M. , Hart Jessica , Gallegos Nicole S. , Anderson Gavin , Charles John , Kosuba Ahmed , Rogers Jon M. , Nemunaitis John J. 
Published: June 2012

Abstract
Background: ATI-1123 is a novel liposomal docetaxel (D) formulation utilizing human serum albumin that facilitates tumor targeting. It was hypothesized that liposomal D formulations may reduce hypersensitivity reactions, eliminate premedication requirements, have a broader therapeutic index, and enhance systemic D exposure. This study assessed the safety, tolerability, pharmacokinetics (PK) and antitumor activity of ATI-1123 in patients (pts) with advanced solid tumors.
Methods: Eligible pts had progressive disease after standard therapy, measurable disease (RECIST), ECOG ≤ 2, and adequate organ function. Dosing (1 hr infusion) began at 15 mg/m2 using an accelerated titration design, followed by a modified Fibonacci schema to MTD. Dosing was continued until disease progression or unacceptable toxicities. Plasma was analyzed for encapsulated/non-encapsulated D using a validated assay. PK was determined by model independent methods.
Results: 29 pts were enrolled, median age 60 yr, (range 35–81); 48% male; 6 (20.7%) NSCLC; 6 (20.7%) pancreas; 5 (17.2%) prostate; 3 (10.4%) ovary; cervix 2 (6.8%); 7 (24.2%) other. Nine out of 29 pts (31%) received prior D. Doses studied (mg/m2) were 15 (2 pts), 30 (1 pt), 60 (2 pts), 75 (8 pts), 90 (10 pts) and 110 (6 pts). MTD was 90 mg/m2. At 110 mg/m2, 2 pts experienced DLTs (Gr 3 mucositis; Gr 3 neutropenic fever) and the 90 mg/m2 cohort was expanded to 10 pts. Since 3 patients at 90 mg/m2 developed reversible, uncomplicated grade 4 neutropenia, an intermediate dose level of 75 mg/m2 was explored (8 pts) with no DLT. Five (26%) pts had hypersensitivity reactions in cycle 1, all Gr 2, managed with prolonged infusion time and/or premedication. One reaction required ATI-1123 discontinuation. No unexpected toxicities were noted compared to standard D. PR was seen in 1 NSCLC pt, and SD was noted in 22 of 29 pts (75.9%; pancreatic, 6; NSCLC, 5; prostate, 5; other, 6). Two prostate cancer pts had robust PSA response (&gt;95% reduction) following multiple treatment cycles. PK results demonstrated linear and dose proportional PK. ATI-1123 appears to enhance the drug exposure compared to standard D, as demonstrated by Cmax and AUC0–24 ratios which were 1.60–3.32 and 1.80–4.11 fold higher, respectively, and by D clearance which was 1.68–4.10 fold lower with ATI-1123.
Conclusions: ATI-1123 is a novel albumin-stabilized liposomal D formulation which demonstrated acceptable tolerability, a favorable PK profile and antitumor activity that warrant exploration in larger Phase 2 trials.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A113.