A Phase 1/2 Study of Ipilimumab in Women with Metastatic or Recurrent Hpv-Related Cervical Carcinoma: a Study of the Princess Margaret and Chicago N01 Consortia

Background: Cervical cancer (CC) is the second cause of cancer-related mortality in women worldwide. Response to second-line chemotherapy is infrequent and the poor outcome of patients with advanced disease (median survival 9 months) warrants novel therapeutic strategies that exploit abnormal tumor biology. Based on new evidence that host-dependent immunologic status and HPV-induced immune evasion are responsible for persistent HPV infection, the prime causal factor of CC, immunotherapy is an attractive emerging strategy to target this disease. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule that acts to downregulate the T cell immune response. Trial design: A 2-step multicenter trial was designed to evaluate ipilimumab IV in metastatic or recurrent HPV-related CC (NCT01693783). Eligible patients require measurable disease progression and at least one previous platinum based line of chemotherapy. A safety phase I cohort was planned with ipilimumab 3 mg/kg every 21 days for four cycles in 6 evaluable patients. After demonstration of safety, a phase II trial was planned with ipilimumab 10 mg/kg at the same schedule; followed by four additional cycles maintenance therapy at the same dose every 12 weeks for patients with radiologic confirmed response or stabilization. The primary objective is to assess the safety and the objective response rate at the end of cycle 4. 18 evaluable patients are scheduled and if at least 1 partial response is seen, additional 14 patients will be enrolled. Immune assessment studies are performed on peripheral blood collected prior to and following ipilimumab therapy and on archived and fresh tumour tissue obtained prior to treatment and within the first week of cycle 2. Current status: This trial was activated in September 2012. The phase I cohort is now completed, and 20 patients have been enrolled in the phase II. The majority of the patients were able to have the pre and post treatment biopsy. Previous presentation ASCO. Disclosure: All authors have declared no conflicts of interest.