Roche's CD20xCD3 dual anti-mosunetuzumab obtained FDA breakthrough therapy designation
Recently (July 14), Roche announced that its CD20xCD3 T cell combined with dual-characteristic cancer immunotherapy mosunetuzumab has received FDA Breakthrough Therapy Designation (BTD).
Dr. Levi Garraway, Roche's Chief Medical Officer and Head of Global Product Development, said: "We are very pleased that the FDA has granted mosunetuzumab breakthrough therapy qualification and recognized the early efficacy data of this molecule.
The early efficacy data mentioned here comes from a multi-center phase I/IIb clinical study code-named GO29781 (NCT02500407). At the 2019 ASH Conference, Roche announced the clinical data of the study. The results showed that for patients with refractory/relapsed non-Hodgkin’s lymphoma who had received at least five lines (median) systemic therapy in advance (most of them did not respond to CD20 therapy, some relapsed after receiving CAR-T therapy) In terms of mosunetuzumab, the effect is remarkable.
In terms of objective response rate (ORR), inert NHL was 62.7% (n=42/67), aggressive NHL was 37.1% (n=46/124), and complete response rate (CR) was 43.3% (n =29/67), invasive NHL was 19.4% (n=24/124). In terms of CR persistence, 82.8% (n=24/29) of indolent NHL patients were still in remission within 26 months after initial treatment, and 70.8% (n=17/24) of aggressive NHL patients were in remission after initial treatment16 It was still in remission within months.
In the subgroup who received CAR-T therapy in advance, ORR and CR were 38.9% (n=7/18) and 22.2% (n=4/18), respectively.
In terms of safety, 28.9% of patients had cytokine release syndrome (CRS), of which 20.0% were grade 1 and 1.1% were grade 3. The incidence of grade 3 neurological adverse events was 3.7%.
Mosunetuzumab
Mosunetuzumab is a bispecific antibody under development that can target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual-targeting feature can activate and redirect patient T cells, contact and release cytotoxic proteins to B cells.
The structure of Mosunetuzumab is similar to human natural antibody, with two Fab segments. But unlike natural antibodies, one of the Fab targets CD20, while the other targets CD3. Currently, mosunetuzumab clinical research and development program is underway, its purpose is to explore the molecule as a single or combination therapy for patients with CD20-positive B-cell non-Hodgkin’s lymphoma (including follicular lymphoma, diffuse large B-cell lymphoma and other Blood cancer).
其他相关
目前，罗氏在CD20靶点双抗领域具有明显优势。除了Mosunetuzumab外，罗氏另一款名为Glofitamab的CD20xCD3双特异性抗体更显特别。该抗体具有2：1 TCB结构，包含2个抗CD20的Fab和1个抗CD3的Fab。
该结构的优势在于有助于免疫突触的形成，其抗CD3和抗TAA只间隔一个CH1和CL，既保证了足够的灵活性，又保证整体大小在15nM之内，保证免疫突触的有效形成。免疫突触的形成直接影响CD3/TAA双抗的抗肿瘤活性，生理条件下TCR与MHC-多肽的结合，T细胞与肿瘤细胞的距离大概为15nm。如果CD3/TAA双抗中，TAA过大或者双抗部分过大，容易导致T细胞与肿瘤细胞的距离大于15nm，不利于免疫突触的形成。(详情请点击：罗氏三特异性抗体TriFab-Contorsbody：促进免疫突触形成）
In addition to Roche, Regeneron, IGM Biosciences, Genmab, Xencor and other companies all have CD20xCD3 double antibodies. In China, Cinda and Roche have reached a US$2 billion cooperation that includes TCB double antibodies, while Zai Lab introduced the regenerant CD20xCD3 bispecific antibody REGN1979 for US$190 million.
Research CD20xCD3 double antibody
