ALM201 is a novel 23-amino acid peptide derived from FKPB-L, a human endogenous protein with inherent anti-angiogenic activity. Pre-clinically, ALM201 potently inhibits cell migration, invasion and neo-vessel formation without effects on cell cycle or proliferation.
We enrolled pts with solid tumours using a single patient (10 - 40mg) then 3 + 3 (80 - 300mg) dose escalation design. ALM201 was administered subcutaneously (S.C.) once daily on days 1-5, 8-12, and 15-19 every 21 days. All pts continued until disease progression (PD) or dose-limiting toxicity (DLT). Primary objectives were to determine the safety, tolerability and recommended phase II dose (RP2D) of ALM201. Secondary objectives were to determine the pharmacokinetics (PK) and anti-tumour activity. Plasma and urine samples were analysed by a validated LC-MS/MS method.
We report interim data in 18 evaluable pts enrolled in 8 dose levels. Cancers included ovarian (5), colorectal (4), NSCLC (2), endometrial (1), gallbladder (1), cervical (1), urachal (1), renal (1), pancreatic (1) and mesothelioma (1). Doses of 10 - 300mg were well tolerated. No DLTs were observed. The only toxicity was grade 1 injection site skin reaction. Median treatment duration was 11.1 weeks (range 3-18 wks). Two patients had stable disease for up to 6 cycles prior to progression. Maximal plasma concentrations were typically observed 1.5h (0.75-4h) after dosing indicating fairly rapid absorption. Above 40mg, plasma concentrations were consistently seen up to 6h after dosing (assay LLOQ = 100ng/mL). Where the terminal phase could be defined, half-lives
Monotherapy ALM201 administered S.C. demonstrated a very good safety profile and acceptable PK in patients with advanced solid tumors. The RP2D analysis is currently ongoing.
Clinical trial identification
EudraCT No: 2014-001175-31
Legal entity responsible for the study
Almac Discovery and Invest Northern Ireland
R. Kennedy: Employee at Almac Diagnostics & Almac Group. A. Cranston: Employee at Almac Discovery. All other authors have declared no conflicts of interest.