A phase III study of xilonix in refractory colorectal cancer patients with weight loss.

Abstract

685 Background: Xilonix, an anti-interleukin-1α true human monoclonal antibody is being assessed as cancer therapy to improve overall survival (OS) in advanced colorectal cancer (CRC) patients. Methods: An open label multicenter randomized comparator controlled study to evaluate efficacy and safety of Xilonix in CRC complicated with cachexia. Eligible patients had metastatic CRC, failed oxaliplatin or irinotecan based chemotherapy, and lost ≥5% total body weight in the previous 6 months (m). Patients were 1:1 randomized to Xilonix (3.75 mg/kg intravenously every two weeks) or megestrol acetate (MA, oral 800 mg daily) until progression. Primary endpoint was OS. Secondary endpoints included assessment of patient well-being using the EORTC QLQ-C30 questionnaire. Platelets support tumor growth and metastasis and platelet counts increase during cancer progression. IL-1α on platelets may be a target of Xilonix and thus platelet count was a key pharmacodynamic measure. Results: 40 patients were enrolled between March 2013 and July 2014, at which time the study was halted to revise inclusion criteria to reduce screen failures. An eligibility violation excluded 1 Xilonix patient from analysis (Xilonix n=19, MA n=20). MA treatment arm had a 39% shorter median OS (2.0 versus 2.8 months) and a trend in increased risk of death (hazard ratio 2.17, p=0.17). Physical and role function worsened in patients receiving megesterol (median change of -13.3 (p=0.02), -16.7 (p=0.02) respectively), whereas in Xilonix treated patients these functions did not decline during therapy (median change 0, p=0.88 and 0, p=0.69, respectively). Xilonix patients had treatment-related reduction in platelets compared to the MA group (median -60,000/mm3, vs 10,000/mm3, p=0.03). No infusion reactions, no discontinuations due to adverse events (AEs) and no related SAEs were reported for Xilonix. Conclusions: The trend in OS for Xilonix patients was encouraging and consistent with improved function and intended pharmacodynamic activity. An amended Phase III protocol has been developed to simplify enrollment for an ongoing study of Xilonix in an advanced CRC population. (NCT01767857) Clinical trial information: NCT01767857.