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).
其他相關
目前，羅氏在CD20靶點雙抗領域具有明顯優勢。除了Mosunetuzumab外，羅氏另一款名為Glofitamab的CD20xCD3雙特異性抗體更顯特別。該抗體具有2：1 TCB結構，包含2個抗CD20的Fab和1個抗CD3的Fab。
該結構的優勢在于有助于免疫突觸的形成，其抗CD3和抗TAA只間隔一個CH1和CL，既保證了足夠的靈活性，又保證整體大小在15nM之內，保證免疫突觸的有效形成。免疫突觸的形成直接影響CD3/TAA雙抗的抗腫瘤活性，生理條件下TCR與MHC-多肽的結合，T細胞與腫瘤細胞的距離大概為15nm。如果CD3/TAA雙抗中，TAA過大或者雙抗部分過大，容易導致T細胞與腫瘤細胞的距離大于15nm，不利于免疫突觸的形成。(詳情請點擊：羅氏三特異性抗體TriFab-Contorsbody：促進免疫突觸形成）
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
