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: Babiker Hani B. , Lenz Heinz-Josef , Scott Aaron J. , Rahimian Shah , Overman Michael J. 
Published: September 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.
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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.