Margenza significantly reduces the risk of disease progress/death and re-introduces medicine to China

In December 2020, the FDA approved Margenza, a combination chemotherapy program for adult patients who have received two or more anti-HER2 treatments, at least one of which is used to treat metastasis-positive HER2-positive breast cancer.
MacroGenics expects Margenza to go public in the US in March 2021.
It's worth noting that Margenza is the first HER2 targeted therapy to significantly improve progressive survival (PFS) in a head-to-head Phase 3 clinical trial compared to Roche's ace biologic agent Herceptin (Herceptin, generic name: trastuzumab, tratojutatin monoantigen), which is approved to market as a new treatment option for her2-positive metastasis breast cancer patients.
Margenza is the first product regulatoryly approved in the MacroGenics pipeline, and its active pharmaceutical ingredient is Margetuximab, a new Fc domain optimization immuno-enhanced monoclonal antibody developed using MacroGenics' proprietary Fc optimization technology platform that targets blocking her2 proteins.
margetuximab has HER2 binding and proliferative effects similar to crayto-bead monoantigens, while its engineered Fc domain enhances immune system participation.
the end of November 2018, Reding Pharmaceuticals entered into a strategic partnership with MaclorGenics to develop and commercialize three immuno-oncology products in Greater China, including margetuximab.
SOPHIA is a head-to-head, randomized, open labeling study that is evaluating the efficacy and safety of margetuximab plus chemotherapy in relation to the treatment of HER2-positive metastasis breast cancer patients with curtojudan-plus chemotherapy.
Patients in the
group must have received at least 2 HER2 targeted therapies in the treatment of metastasis diseases, or at least one HER2 targeted therapy to treat metastasis diseases, with no more than 3 therapies in total for metastasis diseases.
the study included 536 patients who had previously been treated with Herceptin (Herceptin, craturbation monoantigen) and Perjeta (perturbation, patojutin monoanti) and about 90 percent of patients who had also been treated with Kadcyla (ado-curtoju monoantin).
the study, these patients were randomly assigned to 2 treatment groups at a 1:1 ratio and received an intravenous infusion of 15 mg/kg dose of margetuximab (n=266) or intravenous infusion of 6 mg every 3 weeks /kg (or load dose of 8 mg/kg) quercturt bead monoantigen (n-270) and one of the four chemotherapy drugs (Capetabin, Erebrin, Gissithamin, Changchun Ruibin, dose at standard dose) was treated.
results showed that the study reached the primary endpoint of progress-free survival (PFS): a significant 24% reduction in disease progressity or risk of death in the margetuximab plus chemotherapy group compared to the quertoju monoanti-chemotherapy group (middle PFS: 5.8 months vs 4.9 months;HR=0.76;95%CI:0.59-0.98;p=0.033).
about 85 percent of the patients in the study group carried CD16A (Fc-RIIIa) 158F allebetic gene, which was associated with a reduced clinical response to curtojuumam and other antibody therapies.
In this pre-designated exploratory subgroup, the risk of disease progression or death in the margetuximab plus chemotherapy group was reduced by 32% compared to the quertoju monoanti-chemotherapy group (medium PFS: 6.9 months vs 5.1 months; HR=0.68; 95% CI:0.52-0.90; p=0.005).
total remission rate (ORR) for the first two secondary endpoints, the margetuximab plus chemotherapy group was 22% (95% CI: 17.3-27.7%) and the qurtoju monoanti-chemotherapy group was 16% (95% CI:11.8-21.0%).
second Interim Total Lifetime (OS) analysis, released at the San Antonio Breast Cancer Symposium (SABCS) in December 2019, was conducted after 270 events in September 2019 (click to view).
in the intentional therapy (ITT) group, the mid-OS in the margetuximab plus chemotherapy group was extended by 1.8 months (21.6 months vs. 19.8 months, HR-0.885; 95%CI:0.693-1.130, p-0.326) compared to the curtoju single-anti-chemotherapy group.
a pre-specified exploratory goal of the study was to assess the effect of CD16A allied gene variants on margetuximab activity, and the results showed that in patients with CD16A 158F allied genes, the margetuximab plus chemotherapy group was compared to the crater bead monoantigen and chemotherapy group. The mid-OS was extended by 4.3 months (23.7 months vs 19.4 months, HR=0.793; 95% CI:0.607-1.035, p=0.087).
in about 15% of patients with CD16A 158V allegant gene purification, the cratur bead monoantigen performed better than the margetuximab group.
final OS analysis is expected in the second half of 2021.
study, the safety of margetuximab plus chemotherapy was compared with that of curt bead monoanti-chemotherapy.
the margetuximab group was more common (13% vs 3%)," mostly level 1 or 2, than infusion-related reactions in the crater bead monoantigroup, and was associated with first-time drug use.
human skin growth factor inhibitor 2 (HER2) is a protein present on the surface of certain cancer cells that promotes tumor growth and is associated with invasive diseases and poor prognostofic conditions.
about 15-20% of breast cancer cases are HER2-positive.
monoclonal antibody (mAb) targeting HER2 has greatly improved the prognosis of HER2-positive breast cancer patients and is now the standard treatment for early and late breast cancer.
, however, there is currently no approved HER2 targeted therapy for metastasis breast cancer patients who receive these medications.
For patients with relapse or incurability, continuous HER2 blocking is recommended, but there is no approved treatment outside of third-line and beyond-third-line therapy, and standard care is not developed after the progressation of the disease with curto-bead monoanti, patojuumab memtanine (T-DM1).
In addition to exploring the potential of margetuximab in breast cancer, MacroGenics is also working with Mercator to use margetuximab in combination with PD-1 oncology immunotherapy Keytruda to treat HER2-positive gastroesophageal cancer patients by simultaneously mobilizing congenital and adaptive immunotherapy.
2020, the two sides announced the results of the Margetuximab-Keytruda Treatment of HER2-Positive Advanced Gastroesophageal Adenocarcinoma (GEA) Phase II Study (CP-MGAH22-0, NCT02689284) Data show that the medium follow-up period was 19.9 months: (1) objective mitigation rate (ORR) was 18%, disease control rate (DCR) was 53%, medium progression-free lifetime (PFS) was 2.7 months, and the medium total Lifetime (OS) was 12.5 months; (2) ORR was 44%, DCR was 72%, and PFS median were in double-positive subgroups with HER2 high expression (HER2 IHC3 positive) and PD-L1 positive 4.8 months, with a median OS of 20.5 months, (3) ORR was 60% in three-positive subgroups with HER2 amplification (HER2amp)/HER2 IHC3-positive/PD-L1-positive. DcR is 80%.
is consistent with previous studies on margetuximab in other tumor types, in which an analysis of samples of treated GEA patients showed anti-HER2-specific T-cell immune enhancement, suggesting the potential for participation in congenital and adaptive immune responses.
original source: MacroGenics Announces Publications of SOPHIA Trial Results for MARGENZA? in JAMA Oncology