A completed Phase 1/2 clinical trial has shown encouraging results for Medigene‘s immune cell vaccine — which uses dendritic cells to “educate” T-cells about their targets — in people with acute myeloid leukemia (AML), with the vaccine deemed safe and well-tolerated.
The findings also showed that 80% of participants remained alive over the two-year study period, and 55% were alive and without signs of disease worsening.
“We are pleased with these positive and promising results from the first clinical trial of our DC vaccine. We thank all the patients for participating in the trial and the study team for their efforts and contributions,” Dolores Schendel, CEO and chief scientific officer of Medigene, said in a press release.
“In the future, this novel clinical approach could offer a treatment possibility for AML patients who have insufficient treatment options and face the risk of relapse,” Schendel said. “We are looking forward to providing further updates. More detailed data and analyses will be presented at upcoming scientific conferences.”
AML, a cancer of the blood and bone marrow, is primarily treated with intense chemotherapy, which kills the cancer cells to achieve remission. While some individuals with AML are able to receive additional chemotherapy or a blood stem cell transplant to prevent later relapse, these options can be particularly difficult for patients, and often have low success rates. As the majority of AML patients are over age 60, many also are ineligible for certain treatment options.
With this in mind, the immunotherapy company Medigene developed a vaccine using a type of immune system cell called a dendritic cell, or DC. These DCs are required to activate T-cells — another type of immune cell — against the cancer cells. They do so by essentially “presenting” fragments of cancer proteins at their surface that educate T-cells as to what their targets should be.
For Medigene’s cancer vaccine, the DCs are taken from patients, then engineered to produce and present at their surface two AML proteins. These proteins, WT-1 and PRAME, are known to elicit strong immune responses in patients. Once injected back into the patient, these DCs will direct the T-cells to attack and kill cells producing any of these cancer proteins.
The vaccine is most effectively used for bolstering the immune response, to prevent relapses among patients who are already in remission.
The recently completed, open-label, Phase 1/2 clinical trial (NCT02405338) tested the DC vaccine in 20 people with AML who had achieved a complete remission, with or without full blood recovery, after initial treatment with chemotherapy.
The participants in the trial had AML cells that were at least positive for WT-1, but could be negative for PRAME. They received into-the-skin (intradermal) injections of the vaccine once a week for four weeks, followed by once per month for the following 23 months, or until disease relapse.
The primary goals of the study were to assess the therapy’s safety and tolerability. After two years of treatment, the researchers determined that the vaccine is indeed safe and well-tolerated in patients, with no serious adverse reactions related to the treatment.
The secondary endpoints included measuring the overall survival rate and the proportion of participants who were alive and did not experience any progression in their symptoms. This is referred to as progression-free survival, or PFS. Over the two-year course of treatment, 80% of the participants survived and the PFS rate was 55%.
The researchers noted that half of the 20 patients involved in the trial were older than 60, and therefore would be ineligible for treatment with a stem cell transplant. For this group, overall survival was the same, at 80%, and 50% had no signs of disease progression.
At the study’s one-year mark, the researchers shared interim data specifically measuring an immune response in the patients. This information was presented in a poster, titled “DC Vaccination Induces Antigen Specific Immune Responses in AML Patients: A 1-Year Interim Assessment,” at the 2019 American Society of Hemotology (ASH) Annual Meeting in Orlando, Fla.
At that point, eight of the 20 patients had relapsed, and two of them died due to disease progression. When researchers measured levels of immune activity, they found that six of those eight patients (75%) showed elevated levels of immune system activity, compared with only three of the 12 (25%) in remission. This was a potential indication that the vaccine was stimulating an immune response in these patients, and was therefore operating as intended.
Additionally, a majority of those relapses — five of the eight — occurred within the first 100 days of the study. The researchers believe they may have begun, on a molecular level, prior to the start of the study.
Yngvar Floisand, MD, PhD, head physician of the department of hematology at Oslo University Hospital and a principal investigator of the study, noted that AML progresses rapidly and requires treatment to prevent relapse, particularly among older patients.
“The now final topline results from this Phase I/II clinical trial with patient-derived DCs confirm the previously published promising 12-months interim analysis,” Floisand said. “The clinical outcome is encouraging, not only regarding the excellent safety and tolerability profile, but also for an overall survival when it comes to secondary endpoints.”