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▎The content team editor of WuXi AppTec today, Roche announced that it will announce the clinical results of a series of innovative therapies for the treatment of different blood diseases at this year's American Society of Hematology (ASH) annual meeting
.
The press release pointed out that these innovative therapies are expected to redefine the standard treatment for a variety of blood diseases
.
Today, WuXi AppTec's content team will share with readers the latest developments in Roche's many bispecific antibodies and antibody-conjugated drugs (ADC)
.
The feature of bispecific antibodies is that they can target two different antigens at the same time.
At present, the most common application is to bring two different cells closer together by binding to specific antigens on the surface of different cells to promote mutual interaction between them.
Role
.
Roche's mosunetuzumab is such a bispecific antibody
.
One end of it binds to the CD20 antigen on the surface of B cells, and the other end binds to the CD3 receptor on the surface of T cells.
It recruits T cells to the vicinity of B cells, activates T cells to kill B cells, and treats many types of cancer caused by B cells.
Blood cancer
.
▲Mosunetuzumab's mechanism of action (picture source: Roche's official website) At the ASH annual meeting, Roche will announce the key clinical trial results of mosunetuzumab in the treatment of patients with relapsed/refractory follicular lymphoma
.
These patients have received at least two pre-treatments, of which 78.
9% of patients developed resistance to anti-CD20 antibody therapy
.
The results described in the ASH summary showed that mosunetuzumab monotherapy showed anticancer activity in most patients
.
The objective response rate (ORR) reached 78.
9%, and the complete response rate (CR) reached 57.
8%
.
The median progression-free survival (PFS) was 17.
9 months
.
In different pre-set patient subgroups, mosunetuzumab also showed consistent anti-cancer activity
.
▲Mosunetuzumab shows anti-cancer activity in most patients (picture source: reference [2]) In terms of safety, cytokine release syndrome (CRS) is the most common adverse event, which occurs in 44% of patients.
Some are grade 1 or 2
.
No patient died due to CRS
.
4.
4% of patients stopped the trial due to adverse events
.
At the R&D Day event held a few days ago, Roche pointed out that based on these positive data, the company will submit a regulatory application for mosunetuzumab before the end of 2021
.
In addition to Mosunetuzumab, another bispecific antibody targeting CD20, glofitamab, developed by the company, has a unique 2:1 structure
.
It contains two protein domains that bind to CD20 and one protein domain that binds to CD3 receptors
.
Roche’s research found that having two protein domains that bind to CD20 enhances the activity of glofitamab, and that it can achieve better results when combined with an approved anti-CD20 monoclonal antibody
.
▲Introduction to Glofitamab (picture source: Roche official website) The clinical trial data described in the ASH summary shows that as a single-agent therapy, glofitamab has achieved an ORR of 81% in early clinical trials for the treatment of patients with relapsed/refractory follicular lymphoma (n =43) and 70% complete metabolic response rate (CMR)
.
If combined with an approved anti-CD20 antibody, the ORR is 100% (n=19) and the CMR is 73.
7%
.
In terms of safety, CRS appeared in 66% of monotherapy patients and 79% of combination therapy patients, most of which were grade 1 or 2
.
Roche believes that these two bispecific therapies have the potential to become "first-in-class" and "best-in-class" therapies for the treatment of follicular lymphoma and diffuse large B-cell lymphoma
.
They have different characteristics, mosunetuzumab is more suitable for use in non-hospital patients, and glofitamab has the potential to bring higher complete relief, allowing doctors and patients to choose according to different needs
.
Image source: Roche official website In addition, cevostamab is a bispecific antibody that targets the FcRH5 receptor
.
FcRH5 receptor is expressed in all myeloma cells, and the expression level in myeloma cells and normal plasma cells is higher than that in normal B cells
.
Cevostamab binds to the CD3 receptor on the surface of T cells, recruiting T cells around multiple myeloma cells, activating them to kill myeloma cells
.
▲Cevostamab profile (picture source: Roche's official website) The latest clinical trial results in the ASH abstract show that as of May 18, 2021, 160 patients with relapsed/refractory multiple myeloma who have received various previous treatments have received different doses of Treatment of cevostamab
.
These patients received an average of 6 pre-treatments, including CAR-T therapy, antibody-conjugated drugs, and B cell maturation antigen (BCMA) targeted therapy and so on
.
The results of the trial showed that among the patients who received cevostamab above the target dose, the ORR of the subgroup of patients who had previously received CAR-T therapy was 36.
7% (4/9), and patients who had received other bispecific therapies The ORR of the subgroup was 33.
3% (3/9), and the ORR of the subgroup of patients who had received ADC or anti-BCMA therapy was 50.
0% (7/14) and 36.
4% (8/22), respectively
.
The estimated median duration of remission is 15.
6 months
.
In addition to bispecific antibodies, the targeted CD79b antibody-conjugated drug Polivy (polatuzumab vedotin) is combined with a treatment program called R-CHP, a pivotal phase 3 clinical trial for the first-line treatment of patients with diffuse large B-cell lymphoma The primary endpoint was reached in mid-, compared with the standard treatment of R-CHOP, the risk of disease progression or death was reduced by 27% (HR=0.
73, 95% CI: 0.
57-0.
95, p<0.
02)
.
Roche pointed out that this is the first treatment plan that significantly improves the progression-free survival outcome of such patients in 20 years compared with standard treatment
.
CD79b protein is specifically expressed in most B cells.
Polivy specifically binds to CD79b on tumor cells to deliver anti-cancer drugs to kill these B cells and minimize damage to normal cells
.
In this clinical trial, 879 patients were treated with Polivy combination therapy or R-CHOP
.
When the median follow-up time was 28.
2 months, the two-year progression-free survival rate of the Polivy combination therapy group was 76.
7%, and that of the R-CHOP group was 70.
2%
.
In terms of overall survival, there was no significant difference between the Polivy combination therapy and the R-CHOP group
.
"Over the past 20 years, we have been committed to deepening our understanding of a variety of benign and malignant hematological diseases in order to better meet the unfinished needs of patients
.
"Roche Chief Medical Officer and Head of Global Product Development Dr.
Levi Garraway said, "The data we announced at the ASH annual meeting will further demonstrate our determination to follow science and develop diverse treatments that improve patient health
.
"References: [1] Roche to present new pivotal data at ASH 2021 from broad and comprehensive portfolio, challenging treatment standards for people with blood disorders.
Retrieved November 23, 2021, from https:// releases/med-cor-2021-11-23.
htm[2] Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study.
Retrieved November 23, 2021, from https://ash.
confex.
com/ash/2021/webprogram/Paper145872.
html[3] Glofitamab Step-up Dosing Induces High Response Rates in Patients (pts) with Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL), Most of Whom Had Failed Prior Bruton's Tyrosine Kinase Inhibitor (BTKi) Therapy.
Retrieved November 23, 2021, from https://ash.
confex.
com/ash/2021/webprogram/Paper148949.
html[4] Cevostamab Monotherapy Continues to Show Clinically Meaningful Activity and Manageable Safety in Patients with Heavily Pre-Treated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study.
Retrieved November 23, 2021, from https://ash.
confex.
com/ash/2021/webprogram/Paper147983.
html[5] Glofitamab As Monotherapy and in Combination with Obinutuzumab Induces High Complete Response Rates in Patients (pts) with Multiple Relapsed or Refractory (R/R) Follicular Lymphoma (FL).
Retrieved November 23, 2021, from https://ash.
confex.
com/ash/2021/webprogram/Paper148778.
html[6] The POLARIX Study: Polatuzumab Vedotin with Rituximab , Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin,Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma.
Retrieved November 23, 2021, from https://ash.
confex.
com/ash/2021/webprogram/Paper154729.
html Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
.
This article is for the purpose of information exchange only.
The opinions expressed in the article do not represent the position of WuXi AppTec, nor does it mean that WuXi AppTec supports or opposes the views in the article
.
This article is not a treatment recommendation either
.
If you need guidance on treatment plans, please go to a regular hospital for treatment
.
.
The press release pointed out that these innovative therapies are expected to redefine the standard treatment for a variety of blood diseases
.
Today, WuXi AppTec's content team will share with readers the latest developments in Roche's many bispecific antibodies and antibody-conjugated drugs (ADC)
.
The feature of bispecific antibodies is that they can target two different antigens at the same time.
At present, the most common application is to bring two different cells closer together by binding to specific antigens on the surface of different cells to promote mutual interaction between them.
Role
.
Roche's mosunetuzumab is such a bispecific antibody
.
One end of it binds to the CD20 antigen on the surface of B cells, and the other end binds to the CD3 receptor on the surface of T cells.
It recruits T cells to the vicinity of B cells, activates T cells to kill B cells, and treats many types of cancer caused by B cells.
Blood cancer
.
▲Mosunetuzumab's mechanism of action (picture source: Roche's official website) At the ASH annual meeting, Roche will announce the key clinical trial results of mosunetuzumab in the treatment of patients with relapsed/refractory follicular lymphoma
.
These patients have received at least two pre-treatments, of which 78.
9% of patients developed resistance to anti-CD20 antibody therapy
.
The results described in the ASH summary showed that mosunetuzumab monotherapy showed anticancer activity in most patients
.
The objective response rate (ORR) reached 78.
9%, and the complete response rate (CR) reached 57.
8%
.
The median progression-free survival (PFS) was 17.
9 months
.
In different pre-set patient subgroups, mosunetuzumab also showed consistent anti-cancer activity
.
▲Mosunetuzumab shows anti-cancer activity in most patients (picture source: reference [2]) In terms of safety, cytokine release syndrome (CRS) is the most common adverse event, which occurs in 44% of patients.
Some are grade 1 or 2
.
No patient died due to CRS
.
4.
4% of patients stopped the trial due to adverse events
.
At the R&D Day event held a few days ago, Roche pointed out that based on these positive data, the company will submit a regulatory application for mosunetuzumab before the end of 2021
.
In addition to Mosunetuzumab, another bispecific antibody targeting CD20, glofitamab, developed by the company, has a unique 2:1 structure
.
It contains two protein domains that bind to CD20 and one protein domain that binds to CD3 receptors
.
Roche’s research found that having two protein domains that bind to CD20 enhances the activity of glofitamab, and that it can achieve better results when combined with an approved anti-CD20 monoclonal antibody
.
▲Introduction to Glofitamab (picture source: Roche official website) The clinical trial data described in the ASH summary shows that as a single-agent therapy, glofitamab has achieved an ORR of 81% in early clinical trials for the treatment of patients with relapsed/refractory follicular lymphoma (n =43) and 70% complete metabolic response rate (CMR)
.
If combined with an approved anti-CD20 antibody, the ORR is 100% (n=19) and the CMR is 73.
7%
.
In terms of safety, CRS appeared in 66% of monotherapy patients and 79% of combination therapy patients, most of which were grade 1 or 2
.
Roche believes that these two bispecific therapies have the potential to become "first-in-class" and "best-in-class" therapies for the treatment of follicular lymphoma and diffuse large B-cell lymphoma
.
They have different characteristics, mosunetuzumab is more suitable for use in non-hospital patients, and glofitamab has the potential to bring higher complete relief, allowing doctors and patients to choose according to different needs
.
Image source: Roche official website In addition, cevostamab is a bispecific antibody that targets the FcRH5 receptor
.
FcRH5 receptor is expressed in all myeloma cells, and the expression level in myeloma cells and normal plasma cells is higher than that in normal B cells
.
Cevostamab binds to the CD3 receptor on the surface of T cells, recruiting T cells around multiple myeloma cells, activating them to kill myeloma cells
.
▲Cevostamab profile (picture source: Roche's official website) The latest clinical trial results in the ASH abstract show that as of May 18, 2021, 160 patients with relapsed/refractory multiple myeloma who have received various previous treatments have received different doses of Treatment of cevostamab
.
These patients received an average of 6 pre-treatments, including CAR-T therapy, antibody-conjugated drugs, and B cell maturation antigen (BCMA) targeted therapy and so on
.
The results of the trial showed that among the patients who received cevostamab above the target dose, the ORR of the subgroup of patients who had previously received CAR-T therapy was 36.
7% (4/9), and patients who had received other bispecific therapies The ORR of the subgroup was 33.
3% (3/9), and the ORR of the subgroup of patients who had received ADC or anti-BCMA therapy was 50.
0% (7/14) and 36.
4% (8/22), respectively
.
The estimated median duration of remission is 15.
6 months
.
In addition to bispecific antibodies, the targeted CD79b antibody-conjugated drug Polivy (polatuzumab vedotin) is combined with a treatment program called R-CHP, a pivotal phase 3 clinical trial for the first-line treatment of patients with diffuse large B-cell lymphoma The primary endpoint was reached in mid-, compared with the standard treatment of R-CHOP, the risk of disease progression or death was reduced by 27% (HR=0.
73, 95% CI: 0.
57-0.
95, p<0.
02)
.
Roche pointed out that this is the first treatment plan that significantly improves the progression-free survival outcome of such patients in 20 years compared with standard treatment
.
CD79b protein is specifically expressed in most B cells.
Polivy specifically binds to CD79b on tumor cells to deliver anti-cancer drugs to kill these B cells and minimize damage to normal cells
.
In this clinical trial, 879 patients were treated with Polivy combination therapy or R-CHOP
.
When the median follow-up time was 28.
2 months, the two-year progression-free survival rate of the Polivy combination therapy group was 76.
7%, and that of the R-CHOP group was 70.
2%
.
In terms of overall survival, there was no significant difference between the Polivy combination therapy and the R-CHOP group
.
"Over the past 20 years, we have been committed to deepening our understanding of a variety of benign and malignant hematological diseases in order to better meet the unfinished needs of patients
.
"Roche Chief Medical Officer and Head of Global Product Development Dr.
Levi Garraway said, "The data we announced at the ASH annual meeting will further demonstrate our determination to follow science and develop diverse treatments that improve patient health
.
"References: [1] Roche to present new pivotal data at ASH 2021 from broad and comprehensive portfolio, challenging treatment standards for people with blood disorders.
Retrieved November 23, 2021, from https:// releases/med-cor-2021-11-23.
htm[2] Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study.
Retrieved November 23, 2021, from https://ash.
confex.
com/ash/2021/webprogram/Paper145872.
html[3] Glofitamab Step-up Dosing Induces High Response Rates in Patients (pts) with Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL), Most of Whom Had Failed Prior Bruton's Tyrosine Kinase Inhibitor (BTKi) Therapy.
Retrieved November 23, 2021, from https://ash.
confex.
com/ash/2021/webprogram/Paper148949.
html[4] Cevostamab Monotherapy Continues to Show Clinically Meaningful Activity and Manageable Safety in Patients with Heavily Pre-Treated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study.
Retrieved November 23, 2021, from https://ash.
confex.
com/ash/2021/webprogram/Paper147983.
html[5] Glofitamab As Monotherapy and in Combination with Obinutuzumab Induces High Complete Response Rates in Patients (pts) with Multiple Relapsed or Refractory (R/R) Follicular Lymphoma (FL).
Retrieved November 23, 2021, from https://ash.
confex.
com/ash/2021/webprogram/Paper148778.
html[6] The POLARIX Study: Polatuzumab Vedotin with Rituximab , Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin,Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma.
Retrieved November 23, 2021, from https://ash.
confex.
com/ash/2021/webprogram/Paper154729.
html Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
.
This article is for the purpose of information exchange only.
The opinions expressed in the article do not represent the position of WuXi AppTec, nor does it mean that WuXi AppTec supports or opposes the views in the article
.
This article is not a treatment recommendation either
.
If you need guidance on treatment plans, please go to a regular hospital for treatment
.
