Abstract CT265: A phase 2 multicenter study to evaluate the efficacy of tilsotolimod in combination with nivolumab and ipilimumab for treatment of microsatellite-stable colorectal cancer (ILLUMINATE-206)
Authors: Hani B. Babiker, Heinz-Josef Lenz, Aaron J. Scott, Shah Rahimian, Michael J. Overman
Journal: Cancer Research (2020)

Abstract The checkpoint inhibitors pembrolizumab, nivolumab as monotherapy, and nivolumab in combination with ipilimumab are approved in the US for treatment of patients with previously treated microsatellite instability-high (MSI-high) or mismatch repair-deficient metastatic colorectal cancer (CRC). However, checkpoint inhibitors are not currently approved for treatment of microsatellite-stable (MSS) CRC, and patients do not appear likely to respond to these regimens. Tilsotolimod, an investigational Toll-like receptor 9 (TLR9) agonist, stimulates the innate and adaptive immune systems. In an ongoing phase 1/2 clinical study in patients with advanced melanoma who progressed on or after anti-PD-1 therapy (NCT02644967), intratumoral tilsotolimod in combination with ipilimumab was generally well-tolerated at the recommended phase 2 dose, with durable responses in some patients. Biopsies revealed localized activation of the Type-I interferon pathway, maturation of dendritic cells, and induction of MHC class I antigen presentation. Furthermore, dominant T cell clones are shared between injected and distant, non-injected lesions in responding patients.1 ILLUMINATE-206 (NCT03865082) is a phase 2 multicenter, open-label study of intratumoral tilsotolimod 8 mg in combination with ipilimumab and nivolumab at specified doses and schedules for all 3 agents. ILLUMINATE-206 will comprise multiple cohorts, including patients with immunotherapy-naïve, MSS-CRC who have received at least 2 prior regimens of therapy for advanced or metastatic disease including fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens. Eligible patients are ≥18 years with histologically-confirmed CRC, confirmed MSS status, measurable lesion(s) accessible for injection and RECIST assessment, ECOG performance status 0-1, life expectancy ≥4 months, adequate organ function, no prior TLR or immuno-oncology treatment, and no unstable CNS disease. The primary endpoint is objective response rate based on RECIST v1.1 and duration of response. Safety is a secondary endpoint, and paired blood or biopsy samples may be evaluated for tumor genetics, immune infiltrates, and gene expression. Additional patients may be enrolled in Part 1 after review of the data from the initial safety run-in of 10 patients. Based on data from Part 1, the cohort may be expanded during Part 2. Reference Diab A, et al. Ann Oncol 2018;29(suppl_8):Abstract 1245PD. Citation Format: Hani B. Babiker, Heinz-Josef Lenz, Aaron J. Scott, Shah Rahimian, Michael J. Overman. A phase 2 multicenter study to evaluate the efficacy of tilsotolimod in combination with nivolumab and ipilimumab for treatment of microsatellite-stable colorectal cancer (ILLUMINATE-206) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT265.