Abstract 2882
Background
Tilsotolimod, a synthetic toll-like receptor 9 (TLR9) agonist, modulates the tumor immune microenvironment and has antitumor activity as monotherapy in preclinical models. In the ILLUMINATE-204 phase I/II study of tilsotolimod in combination with ipilimumab in patients with refractory melanoma, increased antitumor immune activity was observed in injected and uninjected tumors at 24 hours following tilsotolimod treatment. The ILLUMINATE-101 phase Ib study explored the safety, efficacy, and immune effects of tilsotolimod monotherapy in multiple solid tumors.
Methods
Adults with histologically or cytologically confirmed diagnosis of cancer not amenable to curative therapies received intratumoral tilsotolimod in doses escalating from 8 mg to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11. Additional patients with advanced melanoma were enrolled into an expansion cohort at the 8-mg dose, the recommended phase II dose established for melanoma. Objectives included characterizing safety and efficacy, and immunological assessment. Blood samples and tumor biopsies of injected and distal lesions were obtained at baseline and 24 hours post treatment for immune analyses.
Results
As of May 6 2019, 54 patients have been enrolled, including 38 patients into the dose evaluation portion and 16 patients into the melanoma expansion cohort. No dose-limiting toxicities were observed. The most common treatment-related adverse events were fever, fatigue, and chills. Within 24 hours, fresh tumor biopsies showed increased gene expression for multiple immune checkpoint pathways, increased IFN gamma levels, activation of the type 1 IFN pathway, and upregulation of MHC class I and II, compared to pretreatment biopsies. Of 43 evaluable patients, 15 (35%) had a RECIST v1.1 disease assessment of stable disease (duration 1.2 to 11.1 months, 1 patient ongoing).
Conclusions
Tilsotolimod was well tolerated and induced robust alterations in the tumor microenvironment, including immune checkpoint upregulation, activation of dendritic cells, and induction of Type 1 IFN signaling. A phase II study of tilsotolimod in combination with nivolumab and ipilimumab has been initiated for the treatment of multiple solid tumors (ILLUMINATE-206; NCT03865082).
Clinical trial identification
NCT03052205.
Editorial acknowledgement
Ted Everson, Idera Pharmaceuticals, Inc.
Legal entity responsible for the study
Idera Pharmaceuticals, Inc.
Funding
Idera Pharmaceuticals, Inc.
Disclosure
H. Babiker: Advisory / Consultancy: Endocyte; Advisory / Consultancy: Celgene. V. Subbiah: Advisory / Consultancy: Idera Pharmaceuticals; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bayer; Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy: Loxo Oncology. S. Rahimian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Idera Pharmaceuticals. C. Haymaker: Research grant / Funding (institution): Idera Pharmaceuticals. C. Bernatchez: Research grant / Funding (institution): Idera Pharmaceuticals. G. Bindra: Shareholder / Stockholder / Stock options, Full / Part-time employment: Idera Pharmaceuticals. I. Iverson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Idera Pharmaceuticals. S. Chunduru: Shareholder / Stockholder / Stock options, Full / Part-time employment: Idera Pharmaceuticals. A. Diab: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy: Nektar Therapeutics; Honoraria (self): Bristol-Myers Squibb; Advisory / Consultancy: Jounce Therapeutics; Honoraria (self): Novartis; Advisory / Consultancy: Idera. All other authors have declared no conflicts of interest.
Resources from the same session
3988 - Basal NK activity and early Treg function inhibition predicts Nivolumab responsiveness in metastatic renal cancer patients (REVOLUTION) trial.
Presenter: Sara Santagata
Session: Poster Display session 3
Resources:
Abstract
2142 - Low NK Cell Abundance Correlates with High Expression of PD-1 in CD8+ T Cells
Presenter: Moon Hee Lee
Session: Poster Display session 3
Resources:
Abstract
5501 - Tobacco smoking is associated with the immune suppressive microenvironment in head and neck squamous cell carcinoma (HNSCC)
Presenter: Christine Chung
Session: Poster Display session 3
Resources:
Abstract
5726 - Evaluation of Antibody-Dependent Cell Cytotoxicity (ADCC) in lung cancer cell lines treated with combined anti-EGFR and anti-PD-L1 therapy.
Presenter: Francesca Sparano
Session: Poster Display session 3
Resources:
Abstract
2534 - Radiomic Signatures for Identification of Tumors Sensitive to Nivolumab or Docetaxel in Squamous Non-Small Cell Lung Cancer (sqNSCLC)
Presenter: Laurent Dercle
Session: Poster Display session 3
Resources:
Abstract
3366 - Analysis of gut microbiota in advanced non-small cell lung cancer (NSCLC) patients treated with immune-checkpoints blockers
Presenter: FEIYU ZHANG
Session: Poster Display session 3
Resources:
Abstract
2089 - Pathogenesis of Myocarditis Following Treatment with Immune Checkpoint Inhibitors in a Cynomolgus Monkey Model
Presenter: Changhua Ji
Session: Poster Display session 3
Resources:
Abstract
4463 - Effects of dietary restriction in cancer patients receiving irinotecan
Presenter: Ruben Van Eerden
Session: Poster Display session 3
Resources:
Abstract
4841 - Investigating the Link between Burn Injury and Tumorigenesis
Presenter: Lucy Barrett
Session: Poster Display session 3
Resources:
Abstract
4619 - Prognostic value of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratio in male breast cancer patients
Presenter: Joanna Huszno
Session: Poster Display session 3
Resources:
Abstract