Car-t cell therapy killer! CD19 targeting a new type of FC optimized immunoenhancer monoclonal antibody tafasitamab has a strong therapeutic effect on B cell tumor!

December 28, 2019 / BIOON / -- morphasys is a clinical German biopharmaceutical company dedicated to developing innovative and differentiated therapies for critical patients It is worth mentioning that, just yesterday, tremfya (Chinese trade name: tenoya, general name: guselkumab, gussechiumab), a proprietary antibody technology product of morphasys, was approved by China Drug Administration (nmpa) to be marketed in the mainland It is a product of Johnson & Johnson for adults with moderate and severe plaque psoriasis suitable for systematic treatment Recently, morphosy company announced that the first phase IB study to evaluate tafasitamab (mor208) in the first-line treatment of diffuse large B-cell lymphoma (DLBCL) has been completed Tafasitamab is a new humanized monoclonal antibody targeting at CD19, which is a clear biomarker of B cell malignancies This phase IB study is an open label, randomized, multicenter study in newly diagnosed, untreated adult patients with DLBCL The safety and initial efficacy of tafasitamab + R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, prednisone) and tafasitamab + lenalidomide + R-CHOP are being evaluated The primary end point of the study was the incidence and severity of treatment emergent adverse events (teaes), and the key secondary end points included objective response rate (ORR) and pet negative complete response rate (CR) at the end of the treatment Dr Malte Peters, chief development officer of morphasys, said: "this is a good opportunity for us to extend the clinical development of tafasitamab to the first-line DLBCL treatment Based on the encouraging results we have seen in recurrent and refractory (R / R) DLBCL, we are looking forward to exploring the potential of tafasitamab combined with R-CHOP, tafasitamab combined with lenalidomide and R-CHOP in newly diagnosed DLBCL patients This phase IB study will lay the foundation for the follow-up phase III study of first-line treatment of DLBCL DLBCL is a very aggressive and challenging disease We hope to improve the current R-CHOP treatment standard by adding tafasitamab and lenalidomide, and provide a potential new treatment option for these critical patients " CD19: CD19, the most popular target in the field of immunooncology, is a very important B cell biomarker, which is widely expressed on B cells and can enhance the signal transmission of B cell receptor (BCR), which is very important for B cell survival Therefore, CD19 is an ideal target for the treatment of a variety of B-cell malignancies In recent two years, CD19 has surpassed PD-1 and PD-L1 to become the most popular target of immunooncology and cell therapy Top 15 immune oncology target Tafasitamab is a humanized FC enhanced monoclonal antibody targeting CD19 The Fc domain of tafasitamab is modified (containing two amino acids instead of s239d and i332e) By increasing the affinity for the activated FC γ riiia on the effector cells, it can significantly enhance the antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell phagocytosis (ADCP), so as to improve the tumor The key mechanism of cell killing In preclinical model studies, tafasitamab has been shown to induce direct apoptosis of cancer cells by binding to CD19 At present, tafasitamab is being developed for two kinds of B-cell malignant tumors, including DLBCL and CLL Globally, DLBCL is the most common type of non Hodgkin's lymphoma (NHL) in adults, accounting for 40% of all cases; CLL is the most common type of leukemia in adults In terms of regulation, FDA awarded tafasitama breakthrough drug qualification (BTD) in October 2017, and lenalidomide is not suitable for the treatment of relapsed or refractory (R / R) DLBCL patients with high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) In 2014, FDA granted tafasitamab the fast track qualification (FTD) for R / R DLBCL treatment Also in 2014, FDA and EMA awarded tafasitamab the orphan drug qualification to treat DLBCL and CLL / SLL (small cell lymphoma) At present, morphasys company is carrying out a number of combination therapy research: (1) phase II l-mind research, to evaluate the R / R of tafasitamab combined with lenalidomide that has received at least one but not more than three kinds of systemic therapy and does not meet the requirements of HDC and ASCT DLBCL patients; (2) key phase II / III study b-mind to evaluate the efficacy of tafasitamab combined with bendamoxetine in the treatment of R / r not eligible for HDC and ASCT DLBCL patients, the phase III part of the study passed the invalid analysis in November this year According to IDMC recommendation, the enrolled patients will be expanded from the current 330 cases to 450 cases, and it is expected that the top line results will be obtained in Q1 2022; (3) in the phase II study cosmos, tafasitamab combined with idelalisib or venetoclax will be evaluated to treat R / R CLL / SLL patients who have previously received Btk inhibitors (such as ibrutinib) Tafasitamab in the treatment of B-cell malignant tumors -- DLBCL shows strong efficacy In May this year, the l-mind study reached the main end point: the overall response rate (ORR) of tafasitamab + lenalidomide was 60%, and the complete response rate (CR) was 43%; the median progression free survival period (PFS) was 12.1 months when the median follow-up was 17.3 months; the remission was persistent, and the median duration of remission (DOR) was 21.7 months At a median follow-up of 19.6 months, the median overall survival (OS) was not reached (95% CI: 18.3 months NR), and the 12-month survival rate was 73.3% At the end of October this year, real world data research r-mind reached the main end point: compared with the single drug treatment of lenalidomide, tafasitamab + lenalidomide combination therapy has clinical advantages In this study, 490 patients with R / R DLBCL who were not eligible for transplantation in the United States and the European real world received lenalidomide monotherapy were collected 76 of them matched with 80 patients in the l-mind study in 1:1 important baseline characteristics The data showed that tafasitamab + lenalidomide combination therapy had statistically significant advantages (67.1% vs 34.2%, P < 0.0001) in the primary end point orr compared with lenalidomide monotherapy, and also had consistent advantages in all secondary end points, including Cr (39.5% vs 11.8%, P < 0.0001), OS (not reaching vs 9.3 months, P < 0.0008) Based on the results of l-mind study, morphasys has started rolling submission of biological product license application (BLA) of tafasitamab combined with lenalidomide for R / R DLBCL to the US FDA, and expects to complete the submission of marketing authorization application (MAA) in the EU by the middle of 2020 At present, the company has completed the deployment of marketing team in the U.S market, which is ready for the commercialization of tafasitamab in the U.S in 2020 In Europe, tafasitamab is expected to be available in 2021 "Car-t killer": tafasitamab will challenge two CD19 car-t therapies already on the market Some analysts pointed out that tafasitamab will directly challenge two anti-CD19 car-t therapies on the market for R / R DLBCL - Novartis kymariah and Geely's yescarta Car-t therapy is different from conventional small molecule or biological therapy It is a living T cell therapy product Both kymriah and yescarta treatment processes need to separate patients' T cells, and carry out gene modification in vitro to make T cells express a chimeric antigen receptor (car) aimed at CD19 After that, the modified T cells will be sent back to patients to find the cancer cells expressing CD19, so as to play a therapeutic role In terms of efficacy, tafasitamab was comparable with kymriah and yescarta In terms of medication, kymriah and yescarta need to be prepared separately for each patient, which takes a certain time Tafasitamab is an industrial ready to use monoclonal antibody, which can be used at any time In terms of treatment cost, kymriah and yescarta both price hundreds of thousands of dollars, while tafasitamab can control very low Some analysts compare tafasitamab to "car-t cell therapy killer" If the drug is successfully launched, it will have a huge impact on kymriah and yescarta Source: MorphoSys