Tilsotolimod Exploits the TLR9 Pathway to Promote Antigen Presentation and Type 1 IFN Signaling in Solid Tumors: A Multicenter International Phase I/II Trial (ILLUMINATE-101)

Hani Babiker*, Erkut Borazenci, Vivek Subbiah, Sanjiv Agarwala, Alain Algazi, Jacob Schachter, Michael Lotem, Corinne Maurice-Dror, Daniel Hendler, Shah Rahimian, Hans Minderman, Cara Haymaker, Daruka Mahadevan, Chantale Bernatchez, Ravi Murthy, Rolf Hultsch, Nadia Kaplan, Gregory Woodhead, Charles Hennemeyer, Srinivas ChunduruPeter M. Anderson, Adi Diab, Igor Puzanov

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Purpose: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated antitumor activity in preclinical models. The ILLUMINATE-101 phase I study explored the safety, dose, efficacy, and immune effects of intratumoral (it) tilsotolimod monotherapy in multiple solid tumors. Patients and Methods: Patients with a diagnosis of refractory cancer not amenable to curative therapies received tilsotolimod in doses escalating from 8 to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11. Additional patients with advanced malignant melanoma were enrolled into an expansion cohort at the 8 mg dose. Objectives included characterizing the safety, establishing the dose, efficacy, and immunologic assessment. Blood samples and tumor biopsies of injected and noninjected lesions were obtained at baseline and 24 hours after treatment for immune analyses. Results: Thirty-eight and 16 patients were enrolled into the dose escalation and melanoma expansion cohorts, respectively. Deep visceral injections were conducted in 91% of patients. No dose-limiting toxicities (DLT) or grade 4 treatment-related adverse events were observed. Biopsies 24 hours after treatment demonstrated an increased IFN pathway signature and dendritic cell maturation. Immunologic profiling revealed upregulation of IFN-signaling genes and modulation of genes for checkpoint proteins. In the dose escalation cohort, 12 (34%) of 35 evaluable patients achieved a best overall response rate (ORR) of stable disease (SD), whereas 3 (19%) of 16 evaluable patients in the melanoma cohort achieved stable disease. Conclusions: Overall, tilsotolimod monotherapy was generally well tolerated and induced rapid, robust alterations in the tumor microenvironment.

Original languageEnglish
Pages (from-to)5079-5087
Number of pages9
JournalClinical Cancer Research
Issue number23
StatePublished - 1 Dec 2022
Externally publishedYes


FundersFunder number
National Institutes of HealthR01CA242845
University of Texas MD Anderson Cancer Center


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