Date: 2014-02-03
Type of information:
phase: 1-2
Announcement: presentation of results4in a poster at the 2014 Genitourinary Cancers Symposium.
Company: Mologen (Germany)
Product: MGN1601
Action
mechanism: The tumor therapy with MGN1601 is a therapeutic vaccination to fight advanced renal cancer and to prevent their recurrence after operation and medical treatment.
MGN1601 is a cell-based cancer therapy based on genetically modified tumor cells. A cell bank established by Mologen AG from human renal cancer cells in accordance with pharmaceutical regulations forms the basis. These cancer cells from the cell bank, foreign (allogeneic) to the patient, are “genetically modified” with additional genetic information with the help of four different MIDGE® vectors developed by Mologen and are combined with the DNA immunomodulator dSLIM®, also developed by Mologen, as an adjuvant.
The active principle of the cell-based gene therapy involves induction of a cross-reaction of the patient’s immune system against their own cancer cells after the immune system has learned what cancer cells typically look like via its response to the genetically-modified foreign cancer cells.
Disease: renal cancer
Therapeutic area: Cancer - Oncology
Country: Germany
Trial
details: The primary goal of the ASET study is to investigate the safety and compatibility of the medicament. In addition, efficacy data will be collected that contains the clinical, immunological and radiological parameters of the patients. The process developed by Mologen for cell-based gene therapy to treat renal cancer is a therapeutic inoculation (vaccination) to treat advanced kidney tumors and to prevent their reoccurrence after operation and medicinal treatment. The therapy is based on human renal cancer cells. To this end, Mologen has developed a unique renal cancer cell line. These cancer cells, foreign to the patient (allogeneic), are “gene-modified“ with the help of MIDGE® DNA vectors with additional genetic information and combined with Mologen’s own DNA immunomodulator dSLIM® as an adjuvant. .
The clinical study is led by Dr. med. Steffen Weikert, deputy clinic director of the clinic for urology at the Charité Universitätsmedizin Berlin, who is an expert in the field of renal cancer
Within the framework of the ASET study, patients receive a total of eight treatments with MGN1601 over a period of twelve weeks. The patients are examined after completion of the treatment phase. If the patients have at least responded to the treatment with stabilization of the originally progressing cancer disease after twelve weeks, they can be treated further within an extension phase. In this extension phase, the patients receive up to five further treatments distributed over two years at increasing intervals. As reported, patient recruitment was finalized ahead of schedule after acceptance of 19 patients into the study, since it had already been possible to achieve the primary goal of the study, namely to verify the safety and tolerability of the compound.
Latest
news: * On February 3, 2014, final results from the phase I/II clinical study with MGN1601 (ASET trial) have been presented in a poster at the 2014 Genitourinary Cancers Symposium. The trial evaluated safety and tolerability of MGN1601 in 19 heavily pretreated patients with advanced renal cancer which had no other treatment options. The monotherapy with tumor cell-based cancer vaccine MGN1601 was well tolerated and safe. Furthermore, treatment with MGN1601 resulted in promising median overall survival data in a subgroup of patients. One patient achieved a long term partial response and another patient up to 60 weeks with disease control. Putative predictive biomarkers were identified from pre-treatment characteristics, which were associated with longer overall survival. Those may allow identifying patients more likely to benefit from this innovative vaccination approach with MGN1601.
In total 19 patients were included into the study and received at least one MGN1601 injection (ITT population). 10 patients completed the study per protocol (PP population). 9 patients discontinued the study early without completing the planned treatment phase due to the worsening of their tumor disease (non-PP population).
During the study 109 adverse events (AE) were documented. Only 10 (9.2%) AE were assessed having a relationship to MGN1601: 8 AE were mild (grade 1) and 2 AE moderate (grade 2). Mainly administration site reactions and skin disorders were observed. 16 serious adverse events (SAE) have been reported of which none was assessed as drug related.
Overall, 2 patients of the PP population achieved disease control after 12 treatment weeks and continued treatment in the extension phase of the trial. One patient had tumor progression after further 60 weeks, the other completed all 5 vaccinations of the extension phase with an objective tumor response and was still in tumor remission after more than 132 weeks of treatment (12 weeks treatment phase + 120 weeks extension phase). The median overall survival (OS) was 24.8 weeks in the ITT population and 115.3 weeks in the PP population.
All 19 patients of the ITT population were included in the biomarker evaluation. The analysis of pre-treatment characteristics showed that MSKCC score and neutrophil-lymphocyte ratios (NLR) amongst others may have some predictive value for longer overall survival. In addition the findings from the evaluation of T-cell responses in subgroups of patients showed first evidence of cytotoxic antitumor immune response after MGN1601 vaccination and significant improvement of the cellular immune function during the course of the treatment.
Alfredo Zurlo, M.D., Chief Medical Officer of MOLOGEN AG comments, "Our cancer vaccine MGN1601 demonstrated in this phase I/II trial a very favorable safety and tolerability profile. Furthermore the promising overall survival observed in a subgroup of these late stage renal cancer patients exceeded our expectations. We eagerly want to further evaluate these promising data in a larger, controlled clinical trial. Thus, we are very much looking forward to the next stage of clinical testing of MGN1601.”
* On September 30, 2013, Mologen has announced that it has performed the final analysis of the clinical trial phase I/II with cancer vaccine MGN1601. The study evaluated safety and tolerability of MGN1601 in 19 advanced renal cancer patients which had no other treatment options. The data confirm the preliminary findings presented at last year’s "ESMO 2012 Congress". The primary endpoints safety and tolerability were met.A subgroup of patients showed a promising benefit from the treatment with MGN1601, and some of them are still alive with follow-up ongoing. Such response patterns are comparable to the observations from other cancer immune therapies.
* On March 30, 2012, Mologen has announced that data have been presented at the annual meeting of the American Association for Cancer Research. In a further evaluation of the phase I/II renal cancer study with MGN1601, the company has analyzed the survival times of patients enrolled in the study and the first data of the accompanying immunological tests. The result show that patients that were able to completely finish the twelve-week therapy scheme scheduled in the study protocol with the study drug MGN1601 (PP group) have an unexpectedly clear survival benefit in comparison with patients that had to terminate their study therapy early (non-PP group). Thus far, the ten patients in the PP group already survived more than ten months on average. Since only one patient in this group has died by now, this parameter will continue to improve.
In the non-PP group, the median survival time is a little over two months; all nine patients had died at the latest after six months. With regard to historical clinical data and statistical models, a median survival time of five to seven months was expected. Hence, this was clearly exceeded in this study. Furthermore it is very remarkable that for two patients who are currently being treated in the extension phase of the study at fixed intervals, the disease has not progressed in over ten months.
With the evaluation of immunological data it was possible to prove that those patients that completed the entire planned three-month treatment cycle with MGN1601 in accordance with the study protocol have generated a clear immune response. The strength of the immune response increased with continued treatment. With these results, the mechanism of action demonstrated in preclinical studies could also be confirmed in patients.
Concurrently to the evaluation of the study, Mologen has also applied for scientific advice at the Paul-Ehrlich-Institut, to discuss, amongst others, questions relating to the design of future clinical studies. Subsequent clinical studies with MGN1601 will then be applied for.
* On August 29, 2011, Mologen has published the first results from the phase I/II clinical trial with the cell-based renal cancer therapy MGN1601. The primary goal of this study is the investigation of safety and tolerability of the medicament. According to the investigators safety and tolerability has to be assessed as very positive up to now. The tolerability of MGN1601 proved to be very good without exception. No adverse events that could be classified as serious were observed. Only in singular cases did patients report fatigue or mild fever; signs that might rather indicate activation of the immune system. In addition, the first efficacy data have been collected using clinical, immunological and radiological patient parameters. Two patients have responded in part very well to the cell-based cancer therapy MGN1601. In one case, progress of the renal cancer was halted and in the case of the other patient, the size of the metastases was reduced by more than 50 %. At the same time the state of health of the patients is a challenge: the trial only accepts patients whose tumor growth could not be halted with medicaments that are currently available. The patients are initially treated with MGN1601 over a time period of three months. Those patients who respond to the treatment with MGN1601 are treated further during an extension phase. The clinical trial will be conducted at three study centers in Berlin, Hanover and Bonn.
* On January 17, 2011, Mologen has announced that within the scope of the Phase I/II clinical studies started in December with the renal cancer medication MGN1601, patients may be admitted and treated. Previously, the patients had to be treated one after the other with an additional observation time afterwards. The treatment with the cancer medication is excellently tolerated and has shown no side effects up to now. The medication completely fulfills the expectations in regard to safety and tolerability.The underlying test plan which was approved by the authorities and the ethics commission provided for a week-long postponement of the acceptance of the first three patients in the clinical study in order to immediately record all effects which were not known up to now and to avoid them with additional patients.Since no side effects and intolerances occurred after the first applications, all of the additional patients can now be accepted into the study and treated without additional waiting periods as planned. This means an acceleration of this clinical study phase I/II with the renal cancer medication MGN1601 (ASET-Study). With these further Mologen products, an innovative cell-based gene therapy for the treatment of advanced renal cancer is in an important test phase.
