Combining Mologen’s TLR9 agonists EnanDIM with an anti-PD-1 immune checkpoint inhibitor may be a promising approach to treat colon cancer patients. The preclinical data was presented at the 2017 Clinical Immuno-Oncology Symposium (ASCO SITC) Feb. 23-25 in Orlando, Florida.
Preclinical data in colon cancer mouse models has shown that the combination has significantly better anti-tumor activity compared to any of the compounds administered as a monotherapy, prolonging the lives of mice.
“We believe that patients can benefit from the combination of these immunotherapeutic approaches due to the fact that their modes of action complement each other,” Dr. Mariola Söhngen, CEO of Mologen AG, said in a news release.
“These new results are an important proof-of-concept for the strategy to combine EnanDIM with checkpoint inhibitors,” Söhngen said. “The same is true for our lead compound lefitolimod – we just recently presented the findings at an important international scientific conference. Consequently, the data open further application possibilities for our TLR9 product family.”
EnanDIM (Enantiomeric, DNA-based, Immunomodulator) is a new generation of immunomudulators that uses a DNA molecule to stimulate the TLR9 receptor in immune cells. It is similar to Mologen’s lefitolimod from the dSLIM family of TRL9 agonists, except that while lefitolimod has a dumbbell-shaped, closed structure, molecules from the EnanDIM family have a linear structure. None of the molecules requires any chemical modification to avoid degradation by enzymes.
Lefitolimod (MGN1703) is currently being evaluated in a Phase 1 trial in combination with the immune checkpoint inhibitor Yervoy (ipilimumab) in up to 60 patients with advanced solid tumors. The study is being conducted by the MD Anderson Cancer Center in Houston, Texas, and its primary aim is to determine the best tolerable dose for the drug in combination with Yervoy.
Lefitolimod is also being investigated in the IMPALA Phase 3 trial (NCT02077868). This randomized, open-label study is designed to assess the safety and effectiveness of lefitolimod as a maintenance therapy following first-line chemotherapy in patients with metastatic colorectal cancer.
The study is estimated to enroll 540 participants who will receive lefitolimod vs. investigator’s choice — treatment break, reduced treatment, or continued treatment in light of chemotherapy toxicity. Its primary measure is overall survival, and secondary measures include progression-free survival, safety, overall response rate, and quality of life.