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In this 2021 ASH annual meeting, a number of research data on the application of the CD20×CD3 bispecific antibody Mosunetuzumab (Mosun) in lymphoma patients were announced.
Yimaitong invited Professor Cao Junning from Fudan University Cancer Hospital to interpret and comment , Focus on the frontier progress of blood diseases, and share the academic feast
.
[Oral 127] Mosun monotherapy is effective and well-tolerated in patients with relapsed/refractory (3L+R/R) follicular lymphoma (FL) who have previously received ≥2 lines of treatment.
This phase I/II clinical study (NCT02500407) The enrolled patients were 3L+R/R FL patients with the Eastern Cooperative Oncology Group (ECOG) Health Status (PS) score ≤1
.
After the patients were enrolled in the group, 21 days (D) as a cycle (C) intravenous injection (IV) Mosun, and the dose was increased in the C1 phase (C1D1: 1mg, C1D8: 2mg, C1D15: 60mg), and the subsequent cycle dosing schedule C2D1: 60mg, C3-C17D1: 30mg
.
If the patient achieves complete remission (CR) after 8 cycles of treatment, the treatment is stopped
.
Other patients with partial remission or stable disease will continue to be treated for a total of 17 cycles unless there is disease progression (PD) or uncontrollable toxicity
.
A total of 90 patients were enrolled in the study, 76.
7% of whom had stage III or IV disease, and the median number of previous treatment lines was 3
.
78.
9% of patients did not respond to previous anti-CD20 (aCD20) antibody treatment, and 53.
3% of patients did not respond to previous treatment with aCD20 antibody and alkylating agent (double refractory)
.
52.
2% of patients developed PD (POD24) within 24 months after the start of the initial treatment
.
As of August 27, 2021, the median follow-up time was 18.
3 months, and the primary study endpoint CR rate reached 60% (assessed by an independent review agency), which was significantly higher than the previous control CR rate (14%) referenced during the study design
.
The best objective response rate (ORR) reached 80%, and the CR rate and ORR were basically the same in each subgroup (as shown in Table 1)
.
After the first response, the 12-month event-free survival (EFS) of all patients was 62%, and the EFS of CR patients was 76%
.
Table 1 The CR rate and ORR median progression-free survival (PFS) of 3L+R/R FL patients treated with Mosun monotherapy was 17.
9 months (as shown in Figure 1)
.
Figure 1 In terms of the safety of Mosun monotherapy for PFS in patients with 3L+R/R FL, the most common adverse event (AE) is cytokine release syndrome (CRS), with an incidence of 44.
4%, mainly in the C1 stage, most CRS is grade 1-2, and it is resolved after treatment with tocilizumab or corticosteroids (as shown in Figure 2)
.
There were no treatment-related AEs that caused the patient's death
.
Figure 2 The occurrence of CRS in 3L+R/R FL patients treated with Mosun monotherapy [Oral 129] Mosun combined with lenalidomide regimen is safe and controllable for patients with R/R FL who have previously received ≥1 line therapy, and the effect is good.
This stage Ib The patients enrolled in the study (NCT04246086) were R/R FL patients who had previously received ≥1 line therapy
.
The patients received 12 cycles of combined therapy with Mosun and lenalidomide after enrollment.
The specific dosing schedule is shown in Figure 3
.
As of September 13, 2021, a total of 29 patients were enrolled with ECOG PS≤2, the median number of previous treatment lines was 1, and the POD24 ratio was 10.
3%
.
Figure 3 The safety of the Mosun and lenalidomide combination treatment regimen can be assessed at the time the data is cut off.
All patients have had at least one AE.
44.
8% of the patients had serious AEs of grade 3-4, and grade 5 was not observed.
(Fatal) AE, no AE that caused Mosun's drug discontinuation occurred
.
CRS is the most common AE, with an incidence rate of 27.
6% and both grades 1-2.
The median time of occurrence is 1 day after the first administration, and the median duration is 3 days.
All CRS events have been resolved (e.
g.
Shown in Figure 4)
.
Figure 4 The occurrence of CRS in patients with the combined Mosun and lenalidomide regimen.
The curative effect of 13 patients can be evaluated at the time of data cutoff.
The ORR is 89.
7% and the CR rate is 65.
5%.
The ORR and CMR rates of the overall population and patients with high-risk diseases are relatively high.
High
.
(As shown in Figure 5) Figure 5 The ORR of patients with Mosun and lenalidomide combined regimen.
The above research data supports the initiation of the randomized controlled phase III study of the Mosun+lenalidomide combination regimen and the rituximab+lenalidomide combination regimen
.
[Poster 3573] Mosun subcutaneous injection (SC) in the treatment of R/RB cell non-Hodgkin's lymphoma (B-NHL) is safe and effective An ongoing phase I/II study, 66 cases have been enrolled in the past R/R B-NHL patients with ≥1 line of treatment were treated with Mosun SC using a dose-escalation regimen
.
In terms of safety, no dose-limiting toxicity was observed during the dose escalation period, and no treatment-related AEs that led to the patient's discontinuation or death occurred
.
It was observed that the incidence of CRS was lower in the 5/45/45mg administration dose, and the target dose was reached earlier
.
In terms of efficacy, the efficacy of a total of 62 patients can be evaluated at the time of the data cut-off.
Among them, the ORR of the indolent NHL patients reached 81.
8% (9/11), and the CR rate reached 63.
6% (7/11), and it continued until the data cut-off.
Complete relief
.
Compared with IV, there is no significant difference in the PK characteristics of patients after SC administration (as shown in Figure 6).
The increase rate of IL-6 and IFN-γ in plasma is slower, and the incidence and severity of CRS are lower.
The specific situation is shown in Figure 7
.
In addition, the SC administration method can effectively improve the convenience of patients using Mosun and the work efficiency of medical workers
.
Figure 6 The concentration-time curve of Mosun SC vs IV predicted by the population PK model Figure 7 The occurrence of CRS in the 5/15/45 mg cohort and the 5/45/45 mg cohort >>> Expert comment on Professor Cao Junning Mosun as a kind of CD20 ×CD3 bispecific antibody, one end 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, which can recruit T cells to the vicinity of B cells, activate T cells to kill B cells, and thereby treat more A blood tumor caused by the malignant transformation of B cells
.
In a multi-center phase I/II study, Mosun single-drug fixed-course regimen treated 3L+R/R FL patients, including POD24 and dual refractory patients.
Most patients achieved a high remission rate (ORR: 80%, CR: 60%), and maintained for ≥12 months
.
In addition, Mosun has controllable safety, and the C1 dose escalation program can effectively alleviate CRS
.
The above research results show that Mosun is a new therapy with great potential for the treatment of 3L+R/R FL patients
.
In view of the immunomodulatory activity of lenalidomide, it has a potential synergistic effect when used in combination with Mosun
.
The Phase Ib study evaluated the safety and effectiveness of the lenalidomide + Mosun combination regimen
.
Preliminary research data show that for patients with R/R FL who have previously received ≥1 line therapy, the lenalidomide + Mosun combination regimen has controllable safety and preliminary observation of anti-lymphoma activity.
These data support further research Development
.
In the process of using Mosun and other T cell-mediated tumor therapy, CRS is a common AE, and effective measures need to be taken to reduce its incidence and severity
.
The C1 dose escalation program is an effective strategy to alleviate CRS, and SC administration also suggests that it may reduce the risk of CRS
.
The development of Mosun subcutaneous formulations is expected to further improve the occurrence of CRS, become a more convenient treatment for patients, and bring more clinical benefits to patients with lymphoma
.
Professor Junning Cao, Deputy Chief Physician, Lymphoma Specialist, Department of Oncology, Fudan University Cancer Hospital, Deputy Chief Physician, Lymphoma Multidisciplinary Deputy Chief Expert, Chairman, Lymphoma Professional Committee, Shanghai Anti-Cancer Association, Standing Committee, Lymphoma Professional Committee, Chinese Anti-Cancer Association, Chinese Society of Clinical Oncology Member of the Standing Committee of the Lymphoma Alliance Member of the Chinese Society of Clinical Oncology Vice-Chairman, Lymphoma Professional Committee of China Association for Geriatric Health Care, Vice-Chairman, Member of the Expert Committee of Quality and Efficacy Consistency Evaluation of Generic Drugs of the State Food and Drug Administration Reference: [1] L.
Elizabeth Budde, et al.
2021ASH.
Oral 127.
[ 2] Franck Morschhauser, et al.
2021ASH.
Oral 129.
[3] Nancy L.
Bartlett, et al.
2021ASH.
Poster 3573.
Wonderful review 1.
ASH's new "Strength" | Multi-tumor species, cutting-edge, Ortuzumab Monoclonal Antibody Research Progress Express 2.
ASH New "Strength" | Professor Zhu Jun, Huang Huiqiang: All-out efforts to "recover", Glofitamab data in the field of relapsed and refractory aggressive lymphomas are brilliant 3.
ASH New "Strength" I Ma Jun, Song Yuqin Professor: The results of the global Phase III POLARIX study lead the LBA list, opening up a new pattern for the first-line DLBCL treatment! 4.
ASH's new "Strength" | Professor Li Jianyong: Otuzumab fixed course of treatment leads the future treatment direction of CLL 5.
ASH's new "Strength" | Professor Wu Runhui: HAVEN 6 study announced the heavy results, building dreams of light and medium blood "0 bleeding" new life stamp "read the original text" for patients with friendly disease A, let's make progress together
Yimaitong invited Professor Cao Junning from Fudan University Cancer Hospital to interpret and comment , Focus on the frontier progress of blood diseases, and share the academic feast
.
[Oral 127] Mosun monotherapy is effective and well-tolerated in patients with relapsed/refractory (3L+R/R) follicular lymphoma (FL) who have previously received ≥2 lines of treatment.
This phase I/II clinical study (NCT02500407) The enrolled patients were 3L+R/R FL patients with the Eastern Cooperative Oncology Group (ECOG) Health Status (PS) score ≤1
.
After the patients were enrolled in the group, 21 days (D) as a cycle (C) intravenous injection (IV) Mosun, and the dose was increased in the C1 phase (C1D1: 1mg, C1D8: 2mg, C1D15: 60mg), and the subsequent cycle dosing schedule C2D1: 60mg, C3-C17D1: 30mg
.
If the patient achieves complete remission (CR) after 8 cycles of treatment, the treatment is stopped
.
Other patients with partial remission or stable disease will continue to be treated for a total of 17 cycles unless there is disease progression (PD) or uncontrollable toxicity
.
A total of 90 patients were enrolled in the study, 76.
7% of whom had stage III or IV disease, and the median number of previous treatment lines was 3
.
78.
9% of patients did not respond to previous anti-CD20 (aCD20) antibody treatment, and 53.
3% of patients did not respond to previous treatment with aCD20 antibody and alkylating agent (double refractory)
.
52.
2% of patients developed PD (POD24) within 24 months after the start of the initial treatment
.
As of August 27, 2021, the median follow-up time was 18.
3 months, and the primary study endpoint CR rate reached 60% (assessed by an independent review agency), which was significantly higher than the previous control CR rate (14%) referenced during the study design
.
The best objective response rate (ORR) reached 80%, and the CR rate and ORR were basically the same in each subgroup (as shown in Table 1)
.
After the first response, the 12-month event-free survival (EFS) of all patients was 62%, and the EFS of CR patients was 76%
.
Table 1 The CR rate and ORR median progression-free survival (PFS) of 3L+R/R FL patients treated with Mosun monotherapy was 17.
9 months (as shown in Figure 1)
.
Figure 1 In terms of the safety of Mosun monotherapy for PFS in patients with 3L+R/R FL, the most common adverse event (AE) is cytokine release syndrome (CRS), with an incidence of 44.
4%, mainly in the C1 stage, most CRS is grade 1-2, and it is resolved after treatment with tocilizumab or corticosteroids (as shown in Figure 2)
.
There were no treatment-related AEs that caused the patient's death
.
Figure 2 The occurrence of CRS in 3L+R/R FL patients treated with Mosun monotherapy [Oral 129] Mosun combined with lenalidomide regimen is safe and controllable for patients with R/R FL who have previously received ≥1 line therapy, and the effect is good.
This stage Ib The patients enrolled in the study (NCT04246086) were R/R FL patients who had previously received ≥1 line therapy
.
The patients received 12 cycles of combined therapy with Mosun and lenalidomide after enrollment.
The specific dosing schedule is shown in Figure 3
.
As of September 13, 2021, a total of 29 patients were enrolled with ECOG PS≤2, the median number of previous treatment lines was 1, and the POD24 ratio was 10.
3%
.
Figure 3 The safety of the Mosun and lenalidomide combination treatment regimen can be assessed at the time the data is cut off.
All patients have had at least one AE.
44.
8% of the patients had serious AEs of grade 3-4, and grade 5 was not observed.
(Fatal) AE, no AE that caused Mosun's drug discontinuation occurred
.
CRS is the most common AE, with an incidence rate of 27.
6% and both grades 1-2.
The median time of occurrence is 1 day after the first administration, and the median duration is 3 days.
All CRS events have been resolved (e.
g.
Shown in Figure 4)
.
Figure 4 The occurrence of CRS in patients with the combined Mosun and lenalidomide regimen.
The curative effect of 13 patients can be evaluated at the time of data cutoff.
The ORR is 89.
7% and the CR rate is 65.
5%.
The ORR and CMR rates of the overall population and patients with high-risk diseases are relatively high.
High
.
(As shown in Figure 5) Figure 5 The ORR of patients with Mosun and lenalidomide combined regimen.
The above research data supports the initiation of the randomized controlled phase III study of the Mosun+lenalidomide combination regimen and the rituximab+lenalidomide combination regimen
.
[Poster 3573] Mosun subcutaneous injection (SC) in the treatment of R/RB cell non-Hodgkin's lymphoma (B-NHL) is safe and effective An ongoing phase I/II study, 66 cases have been enrolled in the past R/R B-NHL patients with ≥1 line of treatment were treated with Mosun SC using a dose-escalation regimen
.
In terms of safety, no dose-limiting toxicity was observed during the dose escalation period, and no treatment-related AEs that led to the patient's discontinuation or death occurred
.
It was observed that the incidence of CRS was lower in the 5/45/45mg administration dose, and the target dose was reached earlier
.
In terms of efficacy, the efficacy of a total of 62 patients can be evaluated at the time of the data cut-off.
Among them, the ORR of the indolent NHL patients reached 81.
8% (9/11), and the CR rate reached 63.
6% (7/11), and it continued until the data cut-off.
Complete relief
.
Compared with IV, there is no significant difference in the PK characteristics of patients after SC administration (as shown in Figure 6).
The increase rate of IL-6 and IFN-γ in plasma is slower, and the incidence and severity of CRS are lower.
The specific situation is shown in Figure 7
.
In addition, the SC administration method can effectively improve the convenience of patients using Mosun and the work efficiency of medical workers
.
Figure 6 The concentration-time curve of Mosun SC vs IV predicted by the population PK model Figure 7 The occurrence of CRS in the 5/15/45 mg cohort and the 5/45/45 mg cohort >>> Expert comment on Professor Cao Junning Mosun as a kind of CD20 ×CD3 bispecific antibody, one end 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, which can recruit T cells to the vicinity of B cells, activate T cells to kill B cells, and thereby treat more A blood tumor caused by the malignant transformation of B cells
.
In a multi-center phase I/II study, Mosun single-drug fixed-course regimen treated 3L+R/R FL patients, including POD24 and dual refractory patients.
Most patients achieved a high remission rate (ORR: 80%, CR: 60%), and maintained for ≥12 months
.
In addition, Mosun has controllable safety, and the C1 dose escalation program can effectively alleviate CRS
.
The above research results show that Mosun is a new therapy with great potential for the treatment of 3L+R/R FL patients
.
In view of the immunomodulatory activity of lenalidomide, it has a potential synergistic effect when used in combination with Mosun
.
The Phase Ib study evaluated the safety and effectiveness of the lenalidomide + Mosun combination regimen
.
Preliminary research data show that for patients with R/R FL who have previously received ≥1 line therapy, the lenalidomide + Mosun combination regimen has controllable safety and preliminary observation of anti-lymphoma activity.
These data support further research Development
.
In the process of using Mosun and other T cell-mediated tumor therapy, CRS is a common AE, and effective measures need to be taken to reduce its incidence and severity
.
The C1 dose escalation program is an effective strategy to alleviate CRS, and SC administration also suggests that it may reduce the risk of CRS
.
The development of Mosun subcutaneous formulations is expected to further improve the occurrence of CRS, become a more convenient treatment for patients, and bring more clinical benefits to patients with lymphoma
.
Professor Junning Cao, Deputy Chief Physician, Lymphoma Specialist, Department of Oncology, Fudan University Cancer Hospital, Deputy Chief Physician, Lymphoma Multidisciplinary Deputy Chief Expert, Chairman, Lymphoma Professional Committee, Shanghai Anti-Cancer Association, Standing Committee, Lymphoma Professional Committee, Chinese Anti-Cancer Association, Chinese Society of Clinical Oncology Member of the Standing Committee of the Lymphoma Alliance Member of the Chinese Society of Clinical Oncology Vice-Chairman, Lymphoma Professional Committee of China Association for Geriatric Health Care, Vice-Chairman, Member of the Expert Committee of Quality and Efficacy Consistency Evaluation of Generic Drugs of the State Food and Drug Administration Reference: [1] L.
Elizabeth Budde, et al.
2021ASH.
Oral 127.
[ 2] Franck Morschhauser, et al.
2021ASH.
Oral 129.
[3] Nancy L.
Bartlett, et al.
2021ASH.
Poster 3573.
Wonderful review 1.
ASH's new "Strength" | Multi-tumor species, cutting-edge, Ortuzumab Monoclonal Antibody Research Progress Express 2.
ASH New "Strength" | Professor Zhu Jun, Huang Huiqiang: All-out efforts to "recover", Glofitamab data in the field of relapsed and refractory aggressive lymphomas are brilliant 3.
ASH New "Strength" I Ma Jun, Song Yuqin Professor: The results of the global Phase III POLARIX study lead the LBA list, opening up a new pattern for the first-line DLBCL treatment! 4.
ASH's new "Strength" | Professor Li Jianyong: Otuzumab fixed course of treatment leads the future treatment direction of CLL 5.
ASH's new "Strength" | Professor Wu Runhui: HAVEN 6 study announced the heavy results, building dreams of light and medium blood "0 bleeding" new life stamp "read the original text" for patients with friendly disease A, let's make progress together
