In a small phase II trial, patients with stable disease after first-line therapy for metastatic colorectal cancer showed unexpectedly long progression-free survival when given maintenance treatment with MGN1703 immunotherapy.
In the IMPACT trial, a small international randomized phase II trial of MGN1703 immunotherapy as maintenance therapy for metastatic colorectal cancer, patients with stable disease after first-line chemotherapy showed unexpectedly long progression-free survival (PFS) of up to 30 months.
“As single-agent maintenance, MGN1703 seems to be attractive because it's not toxic and seems to be able to support a long-term outcome,” says principal investigator Hans-Joachim Schmoll, MD, PhD, of Martin Luther University in Halle, Germany. Schmoll presented the findings at the European Society of Medical Oncology 15th World Congress on Gastrointestinal Cancer, in Barcelona, Spain, on July 5.
The final analysis of the IMPACT study data included 59 patients with stable disease after 4.5 to 6 months on chemotherapy. Patients taking MGN1703 alone for maintenance had a 55% reduced risk of progression compared with those taking placebo. While overall survival data are not yet mature, the survival rate was 63% at 17 months. Four patients are still taking the drug without progression after 15 to 30 months.
Developed by Mologen of Berlin, Germany, MGN1703 acts as an immunostimulating TLR-9 agonist. The drug triggers dendritic and B cells to release a cytokine cascade that signals downstream innate and adaptive immune cells to act against tumor cells. “Several biomarkers show that the TLR-9 agonist is working as it should work, inducing a cytokine storm and the activation of the other immune cells,” says Schmoll.
He and his colleagues found that patients with an elevated pretreatment fraction of natural killer T cells (exceeding 3% of the immune cell population) benefitted most from the drug. “The proportion of natural killer T cells is obviously predictive, at least in this very small group analyzed, so it might be a predictive marker for those who will benefit from TLR-9 agonists,” he says.
Because the drug is not tumor-specific, it may show similar effects in other types of cancer, Schmoll suggests. Further, MGN1703 may be effective in combination with other immunotherapies, such as anti-PDL1 drugs, which block a tumor cell's ability to deactivate T cells and evade the immune system's natural ability to destroy them. “This is a hypothesis for the future,” he emphasizes.
Schmoll and his colleagues are launching a new trial of similar design to validate these findings in a larger population.