Medigene AG: Medigene reports preliminary efficacy and immune monitoring data of Phase I of Phase I/II MDG1011 trial in blood cancers

Planegg/Martinsried (pta023/03.02.2022/12:15 UTC+1)

Medigene AG (Medigene, FSE: MDG1, Prime Standard), a clinical-stage immuno-oncology company focusing on the development of T-cell-based cancer therapies, announces preliminary efficacy and immune monitoring data from the Phase I part of the Phase I/II clinical trial of Medigene's T cell receptor-modified T cell (TCR-T) therapy MDG1011 in patients with advanced-stage blood cancers (ClinicalTrials.gov Identifier: NCT03503968). Data demonstrating safety and tolerability, with no cases of dose-limiting toxicity (DLT) associated with MDG1011, were published in December 2021.

MDG1011 is a TCR-T immunotherapy directed against the tumor antigen PRAME (PReferentially expressed Antigen in MElanoma). Patients with relapsed or refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or multiple myeloma (MM) were included in the open-label, dose-escalation Phase I part of the study that was conducted at nine clinical centers in Germany. Following standard pre-conditioning, patients received MDG1011 as a single intravenous infusion at specified dose levels of 0.5, 1 or 5 million TCR-transduced T cells per kg body weight. The primary study objectives were to evaluate safety, tolerability, and feasibility to manufacture autologous MDG1011 TCR-T cells for heavily pretreated patients. In addition, preliminary signs of clinical efficacy and immune monitoring data were investigated.

Clinical and biological data analysis

MDG1011 contained CD8+ TCR-T cells showing recognition and killing of specific standardized target cells in vitro and was successfully manufactured for 13 patients. The group of patients included ten with AML, two with MM and one with MDS. Four patients succumbed to disease before treatment could be administered, in line with the severity of the underlying condition of study patients. Thus, nine patients received MDG1011 at one of the three specified dose levels.

Patient immune monitoring included detection of PRAME-specific T cells (MDG1011 TCR-T cells) in blood to determine persistence over time and biomarker tracking of PRAME in bone marrow and/or blood (as an indicator for remaining cancer cells) by qPCR.

• One patient with AML treated at the lowest dose experienced complete remission at week 4 after treatment; however, this clinical response was not sustained, and the patient’s disease progressed 8 weeks thereafter. PRAME expression was slightly increased from baseline at week 4 whereas MDG1011 TCR-T cells were below the detection level.
• Two patients with AML, treated at the intermediate and highest dose respectively, experienced transient grade 1 or 2 cytokine release syndrome (CRS) within 3 days of drug administration, providing evidence of biological activity of MDG1011 therapy in vivo. MDG1011 TCR-T cells were still detectable in both patients at week 4.
• One patient with multilineage MDS and myeloproliferative neoplasm (MPN) treated at the highest dose, remained without apparent progression to secondary AML 3 and 6 months after MDG1011 administration and is still monitored. MDG1011 TCR-T cells were found at weeks 4, 8 and 12 and were still present at lower levels at month 6 after treatment. Bone marrow could not be evaluated in this patient. PRAME signals in blood were no longer detected at week 4 but gradually increased thereafter at 2, 3 and 6 months, remaining clearly below the baseline level. In concordance, blast counts both in blood and bone marrow remained well below baseline.
• MDG1011 TCR-T cells were detected in six of eight evaluable patients at one or more time points within four weeks after administration. TCR-T cells were also present in two patients at later time points, albeit at decreased levels.
• The biomarker PRAME was assessed in bone marrow samples from five patients four weeks after MDG1011 administration compared to baseline. PRAME decreases occurred in three AML and one MM patient while a slight increase was noted in another patient with MM. PRAME decreased in blood at week 4 for two patients treated at the highest dose but increased thereafter.

Based on its strategic shift to development of TCR-T immunotherapies for solid cancer, Medigene has announced previously that the Phase II part of this study will only be conducted with or by a partner; based on overall results from the Phase I part.

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