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
4900 - Molecular profiling and prognostic significance of TP53 mutations in Diffuse Large B Cell Lymphoma: identifying a high-risk subgroup
Presenter: Yuan-Kai Shi
Session: Poster Display session 3
Resources:
Abstract
3809 - Differential expression of various miRNAs in Pediatric Cytogenetically Normal Acute Myeloid Leukemia (CN-AML)
Presenter: Vikas Gaur
Session: Poster Display session 3
Resources:
Abstract
4750 - Circulating tumour cells in head and neck and non-small cell lung cancer
Presenter: Kenneth O'Byrne
Session: Poster Display session 3
Resources:
Abstract
3704 - OX40/OX40L protein expression in Non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers
Presenter: Xiaoshen Zhang
Session: Poster Display session 3
Resources:
Abstract
2235 - Effect of Serum Survivin on Survival among Non-Small Cell Lung Cancer Patients; NCI Experience
Presenter: Reham Rashed
Session: Poster Display session 3
Resources:
Abstract
2788 - Enhanced performance of prognostic estimation from TCGA RNAseq data using transfer learning.
Presenter: Helene Vanacker
Session: Poster Display session 3
Resources:
Abstract
4689 - Analysis of Circulating Tumor DNA for Early Relapse Detection in Stage III Colorectal Cancer After Adjuvant Chemotherapy
Presenter: Samuel Jacobs
Session: Poster Display session 3
Resources:
Abstract
1454 - Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites
Presenter: Hye Sook Han
Session: Poster Display session 3
Resources:
Abstract
5574 - Results from TRIO030, a Pre-Surgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide
Presenter: Hsiao-Wang Chen
Session: Poster Display session 3
Resources:
Abstract
1787 - JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in gastric cancer
Presenter: Yasushi Sato
Session: Poster Display session 3
Resources:
Abstract