2020 ASH Double Resistance . . Regeneration, Roche, Johnson and Johnson, Pfizer and other dual anti-therapy will be on display

According to a summary of THESH's annual meeting, several dual-specific antibodies from companies such as Regeneron, Roche, Johnson and Johnson, Janssen and Pfizer will make their debuts at the conference.
this paper, we have selected some of the most interesting bisexual antibodies in the study therapy to see what new research advances they have made in treating relapsed/re treatable blood cancers.
1, Odronextamab (REGN1979) Inc.: Regenerative Meta Target: CD20 x CD3 Adaptation: Resuscidable B-cell non-Hodgkin's lymphoma Odronextamab is a CD20 x CD3 dual-specific antibody produced by Regeneratives through its unique Veloci-Bi dual-specific antibody platform.
this technology platform is capable of producing full-length dual-specific antibodies similar to natural antibodies, which can not only be manufactured using standard antibody production techniques, but also have pharmacological properties similar to antibodies.
REGN1979 is designed to kill cancer cells by binding to B-cell tumor proteins (CD20) and immune system T-cells (CD3).
annual meeting, researchers will release updated data on the relapse/difficult-to-treat B-cell non-Hodgkin's lymphoma (B-NHL).
Updated data from ongoing dose increment and early dose expansion studies show that odronextamab shows good single-drug anti-tumor activity in highly incurable B-NHL patients, long-lasting total remission (CR) rates, including CAR-T therapy, are observed in inert and invasive B-NHL patients, and odronextamab has acceptable safety and tolerability.
, researchers are also conducting a global Phase 2 clinical study to further evaluate the efficacy of odronextamab for relapse/difficult-to-treat B-NHL.
It is worth mentioning that in April 2020, Reding Pharmaceuticals and Regenerative Dollars reached a regional strategic partnership to obtain the development and exclusive commercialization rights of odronextamab's oncology-related oncology in Greater China (Chinese mainland, Hong Kong, Macau and Taiwan).
september, odronextamab was approved in China to conduct clinical trials in B-NHL patients.
2, Mosunetuzumab Company: Roche Target: CD20 x CD3 Adaptation: Diffuse Large B Cell Lymphoma Although the R-CHOP program (lyxi monoantigens and cyclophosphamides, dorobi stars, changchun neo-alkalis, and peronisson) were effective in the first-line treatment of diffuse large B-cell lymphoma (DLBCL), 35% to 40% of patients who received R-CHOP treatment eventually died of the disease.
, there is an urgent need for improved clinical treatment.
Mosunetuzumab is a dual-specific antibody developed by Roche's genentech that binds to T cells, guiding T cells to eliminate malignant B cells by binding to CD3 on T cells and CD20 on B cells.
conference, the researchers reported data from the study data on the mosunetuzumab plus CHOP (M-CHOP program) in patients with relapsed/recurring (R/R) non-Hodgkin's lymphoma (NHL) and newly diagnosed DLBCL (GO40515 study).
as of June 3, 2020, a total of 43 patients were treated with M-CHOP.
results showed that the overall efficiency (ORR) was 86% in R/R NHL patients treated with M-CHOP, with 71% of patients achieving CR.
36 DLBCL patients, 27 started treatment at least three months before the data deadline, with a ORR of 96% and a CR rate of 85%.
: Preliminary data show that mosunetuzumab, in combined with CHOP, has high response rates and manageable safety for R/R NHL patients and previously untreated DLBCL patients.
3, IGM-2323 Company: IGM Biosciences Target: CD20 x CD3 Adaptation: Advanced B Cell Malignant Tumor IgM-2323 is a new dual-specific antibody based on the structure of the five-pletamer IgM developed by IGM Biosciences, with a recombinant J chain fused with anti-CD3 scfv.
its structure has 10 CD20 high affinity binding domains and one CD3 high affinity binding domain.
In preclinical studies, IGM-2323 has been shown to bind irreversibly to cd20-expressed cells and deplete them in a single nuclear cell (PBMC) culture with limited cytokine secretion.
At this conference, researchers will present data from the first dose increment phase 1 trial in the human body to assess the safety, tolerance, biomarkers, and initial anti-tumor activity of ICM-2323 in adult B-cell malignancies.
as of June 12, 2020, eight patients had been treated at four dose levels.
results show that IgM-2323 has improved safety and tolerance at higher doses, and that IgM-2323 may have novel mechanisms of effect compared to other antibodies that bind to T cells.
4, Teclistamab (JNJ-64007957) Company: Janssen Target: BCMA x CD3 Adaptation: Recurrence/Refractive Multiple Myeloma Teclistamab is a targeted B-cell antigen (BCMA) and T-cell expression of CD3 receptors of the bisceptive antibody, which can raise T cells near tumor cells and activate T-cells to attack tumor cells.
preclinical studies have shown that teclistamab kills cell line and myeloma cells from patients with multiple myeloma (MM).
researchers will present the latest results of a phase 1 study of teclistamab in multiple myeloma at the current ASH conference.
as of 20 July 2020, 84 patients had received teclistamab intravenous treatment and 44 patients had received teclistamab intraskinal injection.
study data show that patients had ORR of 63.8%, of which 51% achieved very good partial remission (VGPR) and 9 patients achieved complete remission.
the study determined a phase 2 clinical recommended dose (RP2D) for subdern injection administration groups of 1500 μg/kg.
Of the 48 patients who responded in both intravenous and intraskinal injections, the medium time for the first reaction was 1 month, and the duration of the meso-reaction had not yet been reached, with 38 patients who responded remaining effective during treatment from 1.6 to 21.3 plus months.
80% (4/5) of patients in the intravenous group and 2 patients with subsulctic injections achieved MRD-negative in patients with CR's minimum residual lesions (MRD).
study concluded that teclistamab had manageable safety in both intravenous and subsurface injection groups, including low-level cytokine release syndrome (CRS), low severe infection and neurotoxicity rates, and long-lasting reactions were observed in both groups.
results will support phase 2 single-drug trials and future joint studies.
5, REGN5458 Company: Regenerative Target: BCMA x CD3 Adaptation: Recurring/Reassociative Multiple Myeloma REGN5458 is a dual-specific antibody developed by Regeneratives based on its VelocImmune and VelociBi technology platforms.
Veloclmmune is a new generation of genetically modified mice with an humanized B-cell immune system that produces optimized all-humanized antibodies.
VelociBi platform produces full-length dual-specific antibodies similar to natural antibodies with pharmacological properties similar to all-humanized antibodies.
reGEN5458 can be combined with BCMA and CD3 to target MM cells with T-cell effect function through BCMA.
At this session, researchers will present updated data from phase 1 trials of REGEN5458 single-drug therapy recurrence/difficult MM patients who have previously received more than ≥3 lines of treatment, including protease inhibitors, immunomodulants, and anti-CD38 monoantigens.
as of June 15, 2020, 45 patients had been treated with REN5458.
study data showed that ORR was 35.6 per cent (the highest dose level was 60 per cent) for all dose level groups, of which 81.3 per cent had at least a very good partial response; 43.8% of respondents had a duration of efficacy (DoR) of 4 months, 18.8% of DOR of 8 months, and ORR of patients with myeloma had 16.7%.
study, updated data show that REN5458 has acceptable safety and long-lasting efficacy in patients with relapsed/recurring MM.
6, PF-06863135 Company: Pfizer Target: BCMA x CD3 Adaptation: Recurring/Refractic Multiple Myeloma PF-06863135 is a dual-specific antibody developed by Pfizer that can target both BCMA and CD3.
this session, researchers will release the latest research data on PF-06863135 for patients with relapsed/refrased MM.
as of April 15, 2020, 18 patients had received PF-06863135 subsotrapic injections (doses of 80 μg/kg, 130?g/kg, These patients have previously been treated with anti-CD38 monoantigens, and 4 of these patients have also been treated with antibody combination drugs or CAR-T therapy targeted at BCMA.
by the data cut-off date, the dose increase was still ongoing, but the maximum to-dosage (MTD) was not reached.
test data showed that the objective remission rate was 33% in all subsuplific injection dose groups and 75% in two high dose groups (215 mg/kg and 360 μg/kg).
2 patients achieved good remission.
7 patients had the best stable response.
exposure to PF-06863135 increased proportionally with the increase in dose.
, subdern injections produced a lower maximum concentration (Cmax) dose and a longer absorption period than intravenous administers, with a medium Cmax time of 3-7 days.
study concluded that the adverse events of PF-06863135 subsotrol injections were generally controllable, with the majority of patients reporting CRS levels 1-2;
7, TNB-383B Company: Teneobio/AbbVie Target: BCMA x CD3 Adaptation: Recurrence/Refrogenic Multiple Myeloma TNB-383B is a twin-specific antibody developed by Teneobio to target both BCMA and CD3, with the aim of guiding its immune system to target and kill tumor tumors that express BCMA antigens.
February 2019, AbbVie and TeneoOne, a subsidiary of TeneoOne, will work together to develop and promote TNB-383B.
session, researchers released data from the first human clinical trial of TNB-383B.
This is a phase 1 study of dose increment and dose expansion in patients with relapsed/refractic multiple myeloma, and they have received at least 3 treatment options, including protease inhibitors, immunomodulation drugs, and anti-CD38 monoclonal antibodies.
objective of the study was to determine the safety/tolerance and clinical pharmacological effects of TNB-383B and to determine MTD/RP2D.
as of July 13, 2020, 38 subjects had taken TNB-383B (0.025-40mg).
: The maximum to-dosage of TNB-383B is 40 mg, eliminating the need for step-by-step/batch dosing.
a preliminary ORR of 52% (12/23) was observed at a dose of ≥5.4 mg, and a better remission and lasting (up to 24 weeks) reaction was observed despite being given every 3 weeks.
In addition to the above-mentioned drugs, there are several dual-specific antibody data presented at this conference, including Roche's FcRH5 x CD3 dual resistance, Johnson and Johnson's GPRC5D x CD3 dual resistance, Affimed's CD30 x CD16A dual resistance, etc., limited to space, this article is no longer described.
look forward to the smooth progress of these twin-specific antibody follow-up studies, as soon as possible for the recurrence / difficult treatment of blood cancer patients to bring new treatment options.
: Summary of the 62nd Annual Meeting of the American Society of Hematology (ASH). Retrieved Nov 09, 2020, from the official websites and public information of the companies Source: Pharmaceutical Mission Hills