Clinical trials

Blood-cancer clinical-trial CD-TCR-001 investigates TCR-T-Immunotherapy with MDG1011

End of March 2018, Medigene announced the start of the Phase I/II clinical trial CD-TCR-001 (NCT03503968) with TCR-T cell immunotherapy MDG1011 for the treatment of various types of blood cancer. MDG1011 is Medigene’s first clinical TCR-T immunotherapy product candidate and the trial with MDG1011 is the first clinical trial with a TCR-T therapy in Germany.

What is the research-subject investigated in this clinical trial?

In Phase I of the trial, approximately 12 blood cancer patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or multiple myeloma (MM) are to be treated. In total (Phase I and Phase II) roughly 92 patients should be included in the trial.

Which patients with blood-cancer can participate?

Patients are first tested for suitable Human Leukocyte Antigen (HLA) status and then whether their tumor cells are positive for the expression of the PRAME antigen. Only if these basic requirements are met, among other inclusion criteria, can the respective patient be enrolled into the clinical trial. As a first step, an apheresis is performed to isolate the patient’s own T cells. These are then equipped with Medigene’s specific PRAME TCRs and subsequently expanded. After comprehensive quality testing of the T cell therapy product the patient undergoes a preparative chemotherapy and a one-time infusion of MDG1011. In the early stages of this clinical development, Medigene expects a production time of about six weeks from the beginning of an apheresis process until completion of the cell product. 

Where is the clinical trial being conducted?

For this “first-in-country” and “first-in-human” TCR-therapy trial in Germany, Medigene has trained and activated three study centers to conduct this personalized cell therapy. The university hospitals in Regensburg, Erlangen and Würzburg actively screen suitable patients and enroll them in the trial.

In addition to the currently active study centers at the university hospitals, two more study centers started in recent months at the university clinics of Freiburg and Heidelberg. 

Also see TCR Modified T Cells MDG1011 in High Risk Myeloid and Lymphoid Neoplasms 

Contact at Medigene for clinical trials: klinische.studien(at) oder Tel: +49 89 2000 3329 90

CD-FDC-001: DC vaccine trial

March 2015, Medigene started CD-FDC-001, a clinical phase I/II trial with its DC vaccine for the treatment of acute myeloid leukemia (AML) at Oslo University Hospital (NCT02405338). This trial will treat 20 patients with AML positive for the vaccine-specific antigens. In the first half of 2016, the Phase II part of this trial was started after a positive recommendation of the Data and Safety Monitoring Board (DSMB). At the end of 2017, all necessary 20 patients have been enroled into the trial.

This is an open-label trial for patients who have completed intensive induction chemotherapy and if possible consolidation therapy that brings them into remission.

The primary objective is to test feasibility and safety. Secondary objectives are overall survival, relapse rate, time to progression and induction of immune responses. 

In April 2018, Medigene and researchers from Oslo University Hospital presented a poster on the generation of dendritic cell vaccines for Medigene’s ongoing Phase I/II clinical trial with AML patients. The results clearly demonstrate the feasibility and robustness of Medigene’s production protocol for clinical grade TLR7/8-polarized fast mature DCs from critically ill and heavily pretreated AML patients, allowing for long-term vaccination of trial subjects in the ongoing trial.

In December 2018, Medigene published topline data from a period of one year of vaccination of all patients that represents an interim dataset after half of the treatment period.

The vaccinations were well tolerated with no serious adverse events (SAEs) related to the treat-ment. The most common adverse events (AEs) were injection site related, accounting for 35% of all AEs and mild in nature (Grade 1).

After a 12-months treatment period, the overall survival was 89% (18 of 20 patients, 95% confi-dence interval: 61 to 97%) and the progression free survival was 60% (12 of 20 patients, 95% confidence interval: 36 to 78%). Most relapses, 5 out of 8, occurred within the first 80 days after the start of the vaccination, out of which the 2 deaths were in patients with relapses on days 45 and 64, which could point to a starting relapse upon entering the study. 

Patients will be vaccinated for two years or until progression. Final trial data is expected at the end of 2019.

Also see DC Vaccination for Post-remission Therapy in AML

Contact at Medigene for clinical trials: klinische.studien(at) oder Tel: +49 89 2000 3329 90

Further studies utilizing Medigene’s DC vaccine technology include two ongoing clinical investigator-initiated trials: a clinical Phase I/II trial in AML at the Ludwigs-Maximilians-University Hospital of Munich Großhadern and a clinical Phase II trial in prostate cancer at Oslo University Hospital. Moreover, a compassionate use program is being conducted at the Department of Cellular Therapy at Oslo University Hospital. Medigene is concentrating on the further development of the DC vaccines in hematological malignancies.