480P - Phase Ii, Multicenter, Open-Label, Proof of Concept Study of Tasquinimod in Patients with Advanced Hepatocellular (Hcc), Ovarian (Oc), Renal Cell (Rcc) and Gastric (Gc) Carcinomas

Abstract

ABSTRACT Aim: Tumor immunosuppression and angiogenesis play a role in disease progression in HCC, OC, RCC and GC. Tasquinimod is a novel, small molecule compound that targets the tumor microenvironment by binding to S100A9, modulating accumulation and function of regulatory myeloid cells (myeloid derived suppressor cells [MDSCs] and tumor associated macrophages [TAMs]). Tasquinimod is an immunomodulator, antiangiogenic and antimetastatic agent. Antiangiogenic effects may be partly explained by action on MDSCs and TAMs, and through interaction with histone deacetylase-4, reducing the hypoxic response and down regulating HIF1a genes. Tasquinimod significantly improves median PFS (7.6 v 3.3 months) in patients with metastatic hormone resistant prostate cancer1 and is currently in late stage development in this indication. Its unique mode of action makes tasquinimod an attractive compound to be evaluated in other tumors. The primary objective was to determine the clinical activity of tasquinimod in advanced HCC pre-treated with sorafenib, platinum-resistant OC, RCC pre-treated with VEGF inhibitor and GC pre-treated with platinum therapy. Methods: The study design has been previously reported2. The primary endpoint was the PFS rate at a predefined time for each cohort. Secondary objectives included PFS, response rate, OS, safety, pharmacokinetics and biomarkers. Results: Cohort Pts PFS rate*, % Median PFS, w (95% CI) Pts with stable disease*, N (%) Median OS, w (95% CI) OC 55 24w: 7 8 (8-17) 27 (49) NR (31-NR) RCC 38 16w: 13 15 (8-17) 18 (47) 33 (26-41) GC 21 12w: 10 6 (5-7) 5 (24) 22 (14-33) HCC** 45 N/A *Central reading; **Ongoing; NA, not assessed; NR, not reached The most frequent treatment-emergent adverse events (all grade incidence >15%) were nausea (44%), vomiting (34%), constipation (32%), abdominal pain (32%), diarrhea (22%), fatigue (47%), decreased appetite (40%), back pain (27%), cough (22%), peripheral edema (20%), and insomnia (18%). Conclusions: The data did not support further development of tasquinimod mono therapy in heavily pretreated patients with OC, RCC and GC. Pharmacokinetic and biomarkers analyses are ongoing.HCC cohort is continuing with results expected 2015. Pili R et al, J Clin Oncol. 2011; 29:4022-8. Escudier B et al, J Clin Oncol. 2013;31(abstract TPS2622). Disclosure: R. Plummer: Ipsen funding to institution for present study; I.B. Vergote: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Eisai, Eli Lilly, GE, GSK, Ipsen, Janssen, Menarini, MSD, Novartis, Novo Nordisk, Pfizer, Quintiles, Roche, Sanofi, Sandoz, Shering-Plough, Vifor, Wyett; R.J. Jones: Ipsen research funding GSK research funding, speaker honoraria, advisory board Pfizer research funding, speaker honoraria, advisory board Novartis research funding, speaker honoraria, advisory board Roche research funding; E. Van Cutsem: Ipsen funding to institution for present study; S. Faivre: Ipsen: research funding, advisory board; C. Descot: Ipsen employee; N. Germann: Ipsen employee. All other authors have declared no conflicts of interest.