PO53 | PHASE 3 TRIAL EVALUATING THE EFFICACY AND SAFETY OF REGN7508CAT FOR PRIMARY PROPHYLAXIS OF CANCER-ASSOCIATED THROMBOSIS FOR PARTICIPANTS WITH SOLID TUMORS UNDERGOING CANCER TREATMENT (ROXI-CAT-I)

J. Zwicker¹, M. P. O’Brien², M. Carrier³, J. Connors⁴, A. Falanga⁵, A. Manzano⁶, R. Mcbane⁷, Y.Y. Janjigian¹, G. O’Kane⁸, M. Onisko², J. Kaplan², A.P. Kithcart², D.E. Gutstein², A. Khorana⁹, M. F. Walsh² | ¹Memorial Sloan Kettering Cancer Center, New York, USA; ²Regeneron Pharmaceuticals, Inc. , Tarrytown, NY, USA; ³University of Ottawa, Ottawa, ON, Canada; ⁴Harvard Medical School, Boston, MA, USA; ⁵Hospital Papa Giovanni XXIII, Bergamo, Italy; ⁶Hospital Universitario 12 de Octubre, Madrid, Spain; ⁷Mayo Clinic, Rochester, MN, USA; ⁸St. Vincent's University Hospital and School of Medicine, University College Dublin, Dublin, Ireland; ⁹James P. Wilmot Cancer Center and the Department of Medicine, University of Rochester, Rochester, NY, USA

Background. Cancer-associated thrombosis (CAT) negatively impacts the prognosis of patients with cancer by impairing quality of life, delaying treatment, and increasing the frequency and length of hospitalizations. Venous thromboembolism (VTE) risk is elevated in patients with cancer compared with the general population, and even more so with certain cancers (including pancreatic). In primary CAT prophylaxis, activated factor X (FXa)-inhibiting anticoagulants can reduce VTE by ~60% vs. placebo but increase bleeding risk, limiting their use and emphasizing the necessity of anticoagulant approaches with a lower bleeding risk. REGN7508^CAT, a high-affinity human monoclonal antibody targeting FXI, inhibits activation of the intrinsic coagulation pathway, which is expected to provide an antithrombotic effect while preserving hemostasis, potentially offering an optimal approach in primary CAT prophylaxis.

Aim. The ROXI-CAT-I trial will evaluate the effect of REGN7508^CAT vs placebo in the prevention of CAT in participants with solid tumors undergoing cancer treatment. Here we report the study design.

Study design. ROXI-CAT-I is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of REGN7508^CAT in ~860 participants with solid tumors undergoing cancer treatment (Figure). Inclusion criteria include being ≥18 years of age, having histologically confirmed malignant solid tumors, an Eastern Cooperative Oncology Group Performance Status ≤2, a Khorana thromboembolic risk score ≥2 at screening, and being considered medically stable. Participants will be randomized 1:1 to receive either REGN7508^CAT or placebo biweekly. Participants will be categorized based on cancer stage, tumor type, and geographic location. The treatment period will be 169 days, ending 14 days after the final dose. Participants will be followed for an additional 76 days, through Day 245. Primary endpoint: time to first event of centrally adjudicated VTE, or any arterial thromboembolism (ATE), or thromboembolism or ATE-related death through 6 months. Key secondary endpoints: time-to-first event of the centrally adjudicated individual components of the primary efficacy outcome through 6 months. Safety endpoint: time-to-first event of centrally adjudicated ISTH-defined major bleeding or clinically relevant non-major bleeding through 6 months.

Conclusions. Study findings will inform the clinical development of REGN7508^CAT by providing efficacy and safety data in the prevention of CAT.