Bispecific antibody! Merus, a partner of pioneer pharmaceutical industry, announced the strong therapeutic effect data of HER2 / 3 antibody mcla-128 on NRG1 fusion cancer!

October 28, 2019 / BIOON / -- merus, partner of Simcere, recently announced the preliminary clinical data of NRG1 fusion cancer patients who received the treatment of dual antibody candidate drug mcla-128 through early access program (EAP) at the aacr-nci-eortc molecular target and cancer treatment international conference held in Boston Mcla-128 is an antibody dependent cell-mediated cytotoxic (ADCC) - enhanced biloopic ® targeting the HER3 signaling pathway This is a bispecific antibody, which binds to HER2, which is expressed in a large number of tumor cells, and effectively blocks the growth of tumor cells stimulated by HER3 Mcla-128 overcomes the inherent and acquired resistance of tumor cells to HER2 targeted therapy through two mechanisms: 1) blocking the growth and survival pathways to prevent tumor expansion; 2) recruiting and enhancing immune response cells to eliminate tumor NRG1 gene encodes neuregulin (also known as Heregulin), the ligand of HER3 NRG1 and partner gene fusion is a rare carcinogenic gene event, which occurs in some lung cancer and other cancer patients, and is related to the activation of HER2 / HER3 heterodimer and the growth of cancer cells In the preclinical study, merus observed that mcla-128 can effectively inhibit the formation of HER2 / HER3 heterodimer, thus blocking the growth of tumor cells in NRG1 fusion model At this meeting, researchers from memorial Sloan Caitlin Cancer Center (MSKCC) provided a summary and preliminary data on three NRG1 fusion cancer patients who received intravenous injection of 750mg mcla-128 once every two weeks NRG1 gene fusion in these patients was determined by RNA based sequencing The EAP project was evaluated at MSKCC All three patients showed tumor reduction, symptom improvement and long-term remission At present, the three patients are still receiving treatment Images of pancreatic ductal adenocarcinoma (PDAC) EAP patients at 1:8 weeks showed a 44% reduction in tumor diameter, which was further improved to 54% in the subsequent 5-month confirmatory scan (RECIST v1.1 assessed as partial remission [PR]) Positron emission tomography (PET) showed no evidence of metabolically active tumors, and the related serum biomarkers (CA19-9) showed improvement in the first 4 weeks Moreover, within weeks of the first administration, the patient's symptoms, including fatigue and weight loss, improved After more than seven months of treatment, the patient is still receiving treatment In PDAC EAP patients, the diameter of tumor was reduced by 22% at 2:7 weeks, and 25% at 5 months later on confirmatory scan (RECIST v1.1 was evaluated as stable disease [SD]); PET images showed no sign of metabolic active tumor The abdominal pain caused by tumor was improved after treatment After more than seven months of treatment, the patient is still receiving treatment The imaging examination of EAP patients with NSCLC at 3:8 weeks showed a 33% reduction in tumor diameter, which was further improved to 41% in the subsequent 5-month confirmatory scan (RECIST v1.1 was evaluated as PR), and brain metastasis also improved Prior to mcla-128, patients received six therapies, including the tyrosine kinase inhibitor afatinib After about five months of treatment, the patient is still receiving treatment Alison Schram, a medical oncologist at MSKCC's early drug development service and researcher of three patients, said: "these initial data are an important proof of concept and confirm the prospect of NRG1 fusion targeted with mcla-128 It is worth noting that two of them have pancreatic cancer, which is a disease with poor prognosis and limited treatment options The mechanism of action of mcla-128 solves the specific molecular abnormality of cancer with NRG1 fusion by binding with HER2 and blocking the interaction between NRG1 fusion oncoprotein and HER3, which may make mcla-128 particularly suitable for targeting this unique carcinogenic driver " Mcla-128 is still well tolerated in 1 / 2 phase clinical trials, which is consistent with previous reports As of January 2019, 117 patients treated with single drug mcla-128 were given weekly to once every three weeks Most of the reported adverse events were mild to moderate (AE) The incidence of level 3 and level 4 adverse events was 37% and 3%, respectively The incidence of suspected drug-related Level 3 adverse events was about 4%, and there was no suspected drug-related level 4 event One patient developed a grade 5 allergic reaction So far, the safety of mcla-128 in NRG1 fusion cancer patients is consistent with previous reports in all patients treated with mcla-128 Merus is a clinical stage immune tumor company, with the development and innovation of a full-length human bispecific antibody treatment drug technology platform biconics ® Biclonics ®, based on full-length immunoglobulin IgG, uses industry standard methods to produce double antibodies, and in preclinical studies, it was found that the double antibodies prepared by this platform have similar characteristics with conventional monoclonal antibodies, such as long half-life and low immunogenicity In January 2018, Xiansheng pharmaceutical entered into strategic cooperation with merus, and obtained the exclusive authorization of merus to develop and commercialize three kinds of bispecific antibodies in China by using merus's proprietary biconics ® technology platform According to the terms of the agreement, merus led the research and discovery, and Xiansheng was responsible for the ind application research, clinical development, registration application and commercialization of the cooperative products in China As a key strategic element of this cooperation, Xiansheng will complete the ind application research and clinical sample production in China, which will be used to support the registration application and early clinical development of merus in other regions of the world According to the agreement, merus will receive the down payment, milestone payment and sales commission in the China region; Xiansheng is also entitled to the sales commission outside China Additional financial details are not disclosed At present, mcla-128 is the candidate drug of bispecific antibody with the fastest development in merus It is in phase II clinical treatment for metastatic breast cancer and phase I / II clinical treatment for NRG1 solid tumor Mcla-117 is the second candidate of bispecific antibody for merus, and it is in phase I clinical practice in patients with acute myeloid leukemia Merus also has a series of bispecific antibody candidate drugs, including: mcla-158, which is in phase I clinical, can be combined with cancer stem cells and potentially used in the treatment of colorectal cancer and other solid tumors; mcla-145, which is in phase I clinical, can be combined with PD-L1 and another undisclosed immune regulation target Original source: merus bispecific antibiotic mcla-128 shows encouragingearly clinical activity in patients with cancer harboring NRG1 gene fusion