Date: 2016-04-19
Type of
information: Presentation of results at a congress
phase:
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: Idera Pharmaceuticals (USA - CA)
Product: IMO-2125 in combination with an inhibitor of the immunosuppressive enzyme, indoleamine-pyrrole 2,3-dioxygenase (IDO1)
Action
mechanism:
- TLR9 agonist/oligonucleotide/enzyme inhibitor/IDO1 inhibitor. Idera's TLR9 agonist, IMO-2125 is a synthetic oligonucleotide-based agonist of Toll-like receptor 9. It has been shown to activate dendritic cells and induce interferon. Idera selected IMO-2125 to advance into clinical development in combination with checkpoint inhibitors based on this immunological profile.
- IDO1 inhibitor. IDO1 (indoleamine-2,3-dioxygenase 1) is a rate-limiting enzyme in the pathway that metabolises tryptophan. Overexpression of this enzyme has been detected in a variety of cancers, including glioma, melanoma, lung, ovarian and colorectal cancers, and is associated with poor prognosis and survival.
Disease:
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On April 19, 2016, Idera Pharmaceuticals announced new preclinical data demonstrating enhanced systemic anti-tumor activity in preclinical cancer models with intra-tumoral administration of IMO-2125 in combination with an inhibitor of the immunosuppressive enzyme, indoleamine-pyrrole 2,3-dioxygenase (IDO1). These data are being presented at the AACR Annual Meeting 2016 in New Orleans.
In the presentation, entitled "Creating the tumor microenvironment for effective immunotherapy: Anti-tumor activity of intra-tumoral IMO-2125, a TLR9 agonist is further enhanced by inhibition of indoleamine-pyrrole 2,3-dioxygenase (IDO)," Idera scientists presented data further supporting the hypothesis that intra-tumoral IMO-2125 changes the tumor microenvironment by increasing tumor-infiltrating lymphocytes (TILs) and generating a favorable tumor microenvironment. Changes in IDO checkpoint inhibitor expression were also observed.
In the current studies, IMO-2125 (alone and in combination with an IDO-1 inhibitor) increased TIL infiltration and decreased the growth of treated and distant tumors, providing evidence of an enhanced systemic antitumor immune response compared to either agent given alone.
In the study the company evaluated the antitumor activity of i.t. IMO-2125 in combination with an IDO1 inhibitor in a murine syngeneic colon carcinoma CT26 model. There was a statistically significant decrease in the growth of both local and distant tumors which was greater for combination therapy than for either IMO-2125 or IDO-1 alone (for lung metastases: combination vs IMO-2125: P = 0.0393; combination vs IDO-1 inhibitor: P = 0.0128).
These results and previous observations with IMO plus anti-CTLA4 and IMO plus PD-1 demonstrate that combination immunotherapy with IMO-2125 has the potential to improve clinical outcomes over currently available anti-CTLA4 and PD-1 inhibitors, and now IDO-1 inhibitors. These presentations are all currently available on Idera's website at http://www.iderapharma.com/our-science/key-presentations-and-publications.
In partnership with the MD Anderson Cancer Center , the company is currently conducting a Phase 1/2 clinical trial of intra-tumoral IMO-2125 in combination with ipilimumab (CTLA4) for the treatment of pembrolizumab (PD1) treated refractory metastatic melanoma patients. The study has also recently been amended to include an arm studying the combination of IMO-2125 and PD1 in the same patient population.
Is
general: Yes
