O-027 A pivotal phase 3 trial of MABp1 in advanced colorectal cancer

Abstract

Introduction: The incidence of colorectal cancer (CRC) is associated with economic development and is the second leading cause of cancer in the industrialized world. At least half of patients diagnosed will progress and succumb to the disease. Consequently, a substantial and growing unmet need exists for a therapy to treat patients with advanced CRC.We evaluated a novel anti‐IL‐1 alpha antibody therapy in patients with advanced disease and multiple symptoms known to inversely correlate with overall survival. OR criteria were developed in collaboration with EMA's Scientific Advice Working Group to assess anti‐tumor benefit of therapy based on control of these symptoms. Methods: 309 patients were randomized 2:1 to receive MABp1 plus best supportive care (BSC) versus placebo plus BSC. Patients had metastatic colorectal cancer refractory to standard chemotherapy including oxaliplatin and irinotecan. Inclusion criteria also required a constellation of symptoms/functional impairment (ie. pain, fatigue, anorexia, ECOG 1 or 2), weight loss or elevated systemic inflammation. Objective response criteria used dual‐energy X‐ray absorptiometry and EORTC‐QLQC30 to assess disease control. Secondary endpoints were pharmacodynamics measures also known to correlate with survival. Data was also reported on incidence of Serious Adverse Events (SAEs) and disease progression. Patients were prohibited from receiving any agents that could affect the outcome, including chemotherapy or steroids. Results: Primary endpoint analysis was performed on 102 placebo and 207 MABp1 patients using a non‐parametric statistical test. A 33% treatment response compared to versus 19% for placebo was significant (p = 0.0045). Secondary endpoints were also significant, with improved control of paraneoplastic thrombocytosis and reduced systemic inflammation (IL‐6) in treated patients versus placebo (p = 0.003 and p = 0.004 respectively). Safety and tolerability was excellent as evidenced by a 26% relative risk reduction in the number of SAEs in the treatment arm compared to placebo (p = 0.062). Conclusion: A novel symptom‐based OR a criterion was used successfully to assess efficacy of a new anti‐cancer agent. These findings provide unequivocal evidence that anti‐IL‐1alpha monotherapy can serve as a new treatment for advanced mCRC. [NCT02138422]. For permissions.