EP1.04-23 Ongoing Phase II Trial of Anti-PD1 Therapy in Combination with CIMAvax-EGF in Patients with Advanced NSCLC or Squamous Cell Head and Neck Cancer

Abstract

CIMAvax-EGF (CE) is a novel EGF-depleting immunotherapy consisting of human recombinant EGF conjugated to recombinant P64k derived from Neisseria meningitidis, that elicits an anti-EGF antibody response, resulting in reduction of circulating EGF levels. A randomized phase III study of CIMAvax-EGF administered after first-line platinum-based chemotherapy as switch maintenance therapy, in patients with advanced NSCLC, demonstrated improved overall survival versus best supportive care alone, particularly in patients with high baseline serum EGF levels. A recently completed phase I trial combining CE with nivolumab (N), an anti-PD1 immune checkpoint inhibitor, as second-line therapy for advanced NSCLC, demonstrated the combination is safe and induces a higher frequency of good anti-EGF antibody responses compared to the historical experience with CE alone (Figure 1). In addition, promising efficacy was observed in patients with PD-L1 low (< 1%) tumors. These results led to the initiation of this multi-arm phase II trial. CIMAvax-EGF (2.4 mg IM every 2 weeks x 4 doses, then every 4 weeks thereafter) in combination with Nivolumab (240mg IV every 2 weeks) is being evaluated in this multi-arm phase II study (NCT02955290) as second-line therapy in patients with advanced NSCLC (cohort A), advanced/recurrent head and neck squamous cell cancer (cohort B) and is also being tested as first-line therapy in combination with pembrolizumab (200 mg IV every 4 weeks) in patients with advanced NSCLC with PD-L1 ≥50% (cohort C). The primary and secondary endpoints are to evaluate 12-month OS and PFS in cohorts A and B, and to evaluate objective response rate, PFS and 12-month OS in cohort C. Exploratory objectives include characterizing tissue-based immune and EGFR signaling as well as serum EGF levels, anti-EGF antibody levels and other blood-based biomarkers in relation to clinical outcomes. A total of 10 patients have been enrolled to this ongoing study with a planned enrollment of up to 127 patients. An update on accrual along with interim safety, efficacy and correlative data will be presented. To date, the combination of CIMAvax-EGF with anti-PD1 therapy has been safe and well tolerated. Enrollment to the phase II portion of this study is ongoing at Roswell Park and is in the process of being expanded to additional U.S. sites.