Abstract 1031P
Background
The ILLUMINATE-101 phase Ib study (NCT03052205) explored the safety, efficacy, and immune effects of intratumoral tilsotolimod, an investigational Toll-like receptor 9 (TLR9) agonist, in multiple solid tumors.
Methods
Adults with cancer not amenable to curative therapies received intratumoral tilsotolimod 8, 16, 23, or 32 mg into a single lesion on Days 1, 8, and 15 of Cycle 1 and Day 1 of each subsequent 3-week cycle, for up to 17 cycles with a primary objective to characterize safety. Additional patients with advanced melanoma were enrolled at the RP2D of 8 mg with the primary objective of efficacy assessment. Blood samples and tumor biopsies of injected lesions were obtained at baseline and 24 hours post treatment for immune analyses.
Results
A total of 54 patients were enrolled. The 38 patients in the dose escalation cohort had a median of 7 prior lines of treatment, 35 had metastatic disease, and the most common cancer types were pancreatic (n=12) and colorectal (n=7). All 16 patients in the melanoma cohort had metastatic disease, and 10 had elevated LDH. Injected lesions were deep and required interventional radiology in 52 of 54 patients. No dose-limiting toxicities were observed. The most common treatment-related adverse events were pyrexia, fatigue, chills, nausea, and vomiting. Biopsies of injected tumors at 24 hours showed increased activation of the Type I IFN pathway, upregulation of MHC class I/II, IFNγ expression, and expression of multiple immune checkpoints (i.e. PD-1, LAG3). Of the 35 evaluable patients in the dose escalation cohort, 12 (34%) achieved a best overall response of stable disease (SD). In the melanoma cohort (N=16), 3 patients had SD, 1 who had a 35% tumor reduction with no confirmatory scan.
Conclusions
Tilsotolimod was generally well tolerated and induced alterations in the tumor microenvironment, including immune checkpoint upregulation, activation of dendritic cells, and induction of Type I IFN signaling. Additional clinical studies of tilsotolimod in combination with checkpoint inhibitors are underway (NCT03445533, NCT03865082, and NCT02644967).
Clinical trial identification
NCT03052205.
Editorial acknowledgement
Legal entity responsible for the study
Idera Pharmaceuticals.
Funding
Idera Pharmaceuticals.
Disclosure
H. Babiker: Advisory/Consultancy: Bayer; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Endocyte; Advisory/Consultancy: Guardant360; Advisory/Consultancy: SIRTeX; Advisory/Consultancy: Tracon. E. Borazanci: Advisory/Consultancy: Ambry Genetics; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Corcept; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Fujifilm; Advisory/Consultancy: Idera Pharmaceuticals; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Minneamrita Therapeutics; Advisory/Consultancy: Mabvax; Advisory/Consultancy: Pharmacyclics; Advisory/Consultancy: Samumed. V. Subbiah: Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: Novartis Oncology; Advisory/Consultancy: Idera Pharmaceuticals; Advisory/Consultancy: Bayer. S. Rahimian: Shareholder/Stockholder/Stock options, Full/Part-time employment: Idera Pharmaceuticals. C. Haymaker, C. Bernatchez: Advisory/Consultancy: Idera Pharmaceuticals. S. Chunduru: Shareholder/Stockholder/Stock options, Full/Part-time employment: Idera Pharmaceuticals. A. Diab: Advisory/Consultancy: Idera Pharmaceuticals; Advisory/Consultancy: Nektar Therapeutics; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy: Array BioPharma. I. Puzanov: Advisory/Consultancy: Amgen. All other authors have declared no conflicts of interest.