Combining IMO-2125 and an anti-CTLA-4 antibody induces long-term systemic anti-cancer immune responses in mice that outperform those seen with either of the treatments alone, according to recent preclinical results presented at the Third Annual CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, in Frankfurt, Germany.
The poster presentation,“Intratumoral IMO-2125 Treatment in Combination with Anti-CTLA4 mAB Induces Durable Anti-Tumor Reponses Associated with Tumor-Specific Memory in Preclinical Studies,” was made by Daqing Wang, PhD, principal investigator and group leader at Idera Pharmaceuticals.
Developed by Idera, IMO-2125 was made to activate a protein called toll-like receptor (TLR9). The molecule is found at the surface of dendritic and B-cells, and its activation boosts immune signaling cascades that trigger the activity of cancer-fighting T-cells.
IMO-2125 has received orphan drug designation from the U.S. Food and Drug Administration in June 2017, for the treatment of melanoma.
In the study, mice were injected with two solid tumors on opposite flanks. Then they were randomized to receive a saline solution, IMO-2125 monotherapy (injected directly into one of the tumors), a CTLA-4 antibody, or a combination of both.
The data presented at the conference revealed that intratumoral injections of IMO-2125, in combination with an anti-CTLA-4 antibody, promoted the regression of tumors better than either drug alone. Importantly, the effect was seen not only in the tumor receiving IMO-2125, but also in the distant tumor.
The effect, called abscopal effect, happens when immune cells from the treated tumor are primed to recognize the cancer cells and travel the body to eradicate signs of cancer in distant places.
Importantly, this created a sustained immune response, as mice challenged with cancer cells a second time were able to eliminate any traces of cancer without additional treatment.
Currently, IMO-2125 is being assessed in metastatic melanoma patients in combination with the CTLA-4 antibody, Yervoy (ipilimumab), or the PD-1 antibody, Keytruda (pembrolizumab).
“These findings further support our current clinical trials which are designed to demonstrate that the combination of intratumoral IMO-2125 and Ipilimumab provides an opportunity to break the resistance to anti-PD-1 therapy and lead to durable effect in this patient population, one that clearly represents a significant unmet need in immuno-oncology,” Joanna Horobin, CB, ChB, and chief medical officer at Idera, said in a press release.
Results from the first 18 patients enrolled in the Yervoy arm of the Phase 1/2 study (NCT02644967) have shown that intratumoral injection IMO-2125 plus Yervoy is well tolerated, and actively promotes anti-tumor immune responses.
The data was presented during the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain. The study was titled “A Phase 1-2 Trial of Intratumoral IMO-2125 (IMO) in Combination with Checkpoint Inhibitors (CPI) in PD-(L)1-refractory Melanoma.”
IMO-2125 also is being tested in patients with other refractory solid tumors, in an U.S.-based Phase 1 trial (NCT03052205). Those interested in participating in the trial may contact the company by email ([email protected]) or phone (617) 679-5500.