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Introduction A follow-up analysis of the Phase Ib/II CARTITUDE-1 trial was published in The Lancet in July 2021
.
CARTITUDE-1 is a registered clinical study (No.
NCT03548207) conducted in the United States and Japan to evaluate the safety and effectiveness of cilta-cel in the treatment of patients with relapsed/refractory multiple myeloma (RRMM)
.
Next, let's take a look at the results of the follow-up analysis of this study
.
Research background After receiving immunomodulators, proteasome inhibitors and anti-CD38 antibody treatment, MM patients eventually relapse or are resistant, leading to poor prognosis
.
Currently, the needs of MM patients for new therapies have not yet been met
.
Ciltacabtagene autotoleucel (also known as cilta-cel) is a CAR-T cell therapy.
Its CAR-T cells are designed to express two single domain antibodies targeting BCMA, and one CD3 with a 4-1BB costimulatory domain.
-ζ signal domain to optimize the activation and proliferation of T cells
.
Research Methods Research Design and Subjects In this single-arm, open-label, phase Ib/II study, RRMM patients from 16 centers in the United States who are ≥18 years old, meet the IMWG diagnostic criteria, and have measured lesions were included
.
Subjects need to meet: ①ECOG score ≤1; ②Have received at least 3 lines of myeloma treatment in the past or have dual resistance to proteasome inhibitors and immunomodulators; ③Have received anti-CD38 antibody treatment
.
Exclude patients who have previously received CAR-T cell targeted therapy or BCMA targeted therapy
.
Another cohort study is underway in Japan
.
The purpose of the Phase Ib trial is to evaluate the safety of cilta-cel treatment and the recommended dose of the Phase II trial; the main purpose of the Phase II trial is to evaluate the efficacy of cilta-cel
.
The baseline data of the patients are listed in Table 1
.
In the test procedure, blood apheresis is performed on the patients as required, and the bridging therapy is allowed after the blood apheresis is completed
.
Cilta-cel is prepared by transducing a lentiviral vector expressing anti-BCMA-CAR (including two BCMA binding domains, a CD3-ζ signal domain, and a 4-1BB costimulatory domain) into T cells, followed by T cells Amplification
.
After the successful preparation of Cilta-cel, the patient first received 3 days intravenous infusion of 300 mg/m² cyclophosphamide and 30 mg/m² fludarabine for lymphatic dissection, and 5-7 days after starting lymphatic dissection, the patient received cilta-cel infusion Note (target dose: 0.
75×106 live CAR-positive T cells/kg [range: 0.
5-1.
0×106/kg])
.
The primary endpoint of the Phase Ib trial is the incidence and severity of adverse events
.
The primary endpoint of the Phase II trial is the overall response rate (ORR)
.
The secondary endpoints of Phase Ib and Phase II trials include strict complete response rate (sCR), complete response rate (CR), and very good partial response rate (VGPR); time to remission; negative rate of minimal residual disease (MRD) ; Progression-free survival (PFS); overall survival (OS); and pharmacokinetic and pharmacodynamic markers
.
Results of the study From July 16, 2018 to October 7, 2019, a total of 113 patients were enrolled in the study, and all patients underwent apheresis (Figure 1)
.
Sixteen (14%) patients did not receive cilta-cel treatment due to disease progression, death, or withdrawal from the study
.
With a median follow-up of 12.
4 months (IQR 10.
6-15.
2), the ORR was 97% (95% CI 91.
2-99.
4), and 65 patients (67%) achieved a strict complete remission (Table 2)
.
The median time to first remission was 1.
0 months (IQR 0 9-1.
0), and 74 of 94 remission patients (79%) had their first remission within 1.
0 months after infusion of cilta-cel
.
The median time to best response was 2.
6 months (1.
0-6.
1)
.
The median time to complete or better remission was 1.
9 months (1.
0-6.
5); among 65 patients who achieved complete or better remission, 40 (62%) patients achieved complete or better remission within 3 months of infusion of cilta-cel Better relief
.
Over time, 70 (72%) of the 97 patients in remission continued their remission and continued to deepen (Figure 2)
.
The median duration of response (DOR) was not reached (95% CI 15.
9-not estimable)
.
The median PFS was not reached (95% CI 16.
8-unestimable) (Figure 3); the 12-month PFS rate was 77% (95% CI 66.
0-84.
3)
.
The 12-month PFS rate of patients who achieved complete or better remission was 85% (72.
0-91.
8), and the 12-month PFS rate of patients who achieved very good partial remission or partial remission was 62% (42.
1-76.
9).
The median PFS was not reached (95% CI 16.
8-unestimable and 5.
4-unestimable, respectively; Figure 3)
.
The 12-month OS rate was 89% (80.
2-93.
5; Figure 3)
.
Of 57 patients with evaluable MRD, 53 (93%) were MRD negative
.
Among 65 patients who achieved strict complete remission, 35 patients (54%) could be assessed for MRD, and 33 patients (94%) were MRD negative
.
The median time to MRD negative was 1.
0 (IQR 0.
9–1.
0) months
.
All 97 patients had adverse events, including grade 3-4 events (Table 3)
.
Hematological adverse events are the most common; grade 3-4 hematological adverse events are neutropenia (92 cases [95%]), anemia (66 cases [68%]), leukopenia (59 cases [61%]) , Thrombocytopenia (58 cases [60%]) and lymphopenia (48 cases [50%])
.
Conclusion This follow-up analysis of the Phase Ib/II CARTITUDE-1 study established a positive risk-benefit analysis data for a single low-dose injection of cilta-cel.
cilta-cel can be used to treat patients with multiple myeloma who have been previously treated.
Produce rapid, deep and lasting relief
.
Research on cilta-cel for other early-stage multiple myeloma patients is ongoing
.
Reference 1.
Berdeja JG, et al.
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.
Lancet.
2021 Jul 24;398(10297):314-324.
Stamp "read the original text" and we will make progress together
.
CARTITUDE-1 is a registered clinical study (No.
NCT03548207) conducted in the United States and Japan to evaluate the safety and effectiveness of cilta-cel in the treatment of patients with relapsed/refractory multiple myeloma (RRMM)
.
Next, let's take a look at the results of the follow-up analysis of this study
.
Research background After receiving immunomodulators, proteasome inhibitors and anti-CD38 antibody treatment, MM patients eventually relapse or are resistant, leading to poor prognosis
.
Currently, the needs of MM patients for new therapies have not yet been met
.
Ciltacabtagene autotoleucel (also known as cilta-cel) is a CAR-T cell therapy.
Its CAR-T cells are designed to express two single domain antibodies targeting BCMA, and one CD3 with a 4-1BB costimulatory domain.
-ζ signal domain to optimize the activation and proliferation of T cells
.
Research Methods Research Design and Subjects In this single-arm, open-label, phase Ib/II study, RRMM patients from 16 centers in the United States who are ≥18 years old, meet the IMWG diagnostic criteria, and have measured lesions were included
.
Subjects need to meet: ①ECOG score ≤1; ②Have received at least 3 lines of myeloma treatment in the past or have dual resistance to proteasome inhibitors and immunomodulators; ③Have received anti-CD38 antibody treatment
.
Exclude patients who have previously received CAR-T cell targeted therapy or BCMA targeted therapy
.
Another cohort study is underway in Japan
.
The purpose of the Phase Ib trial is to evaluate the safety of cilta-cel treatment and the recommended dose of the Phase II trial; the main purpose of the Phase II trial is to evaluate the efficacy of cilta-cel
.
The baseline data of the patients are listed in Table 1
.
In the test procedure, blood apheresis is performed on the patients as required, and the bridging therapy is allowed after the blood apheresis is completed
.
Cilta-cel is prepared by transducing a lentiviral vector expressing anti-BCMA-CAR (including two BCMA binding domains, a CD3-ζ signal domain, and a 4-1BB costimulatory domain) into T cells, followed by T cells Amplification
.
After the successful preparation of Cilta-cel, the patient first received 3 days intravenous infusion of 300 mg/m² cyclophosphamide and 30 mg/m² fludarabine for lymphatic dissection, and 5-7 days after starting lymphatic dissection, the patient received cilta-cel infusion Note (target dose: 0.
75×106 live CAR-positive T cells/kg [range: 0.
5-1.
0×106/kg])
.
The primary endpoint of the Phase Ib trial is the incidence and severity of adverse events
.
The primary endpoint of the Phase II trial is the overall response rate (ORR)
.
The secondary endpoints of Phase Ib and Phase II trials include strict complete response rate (sCR), complete response rate (CR), and very good partial response rate (VGPR); time to remission; negative rate of minimal residual disease (MRD) ; Progression-free survival (PFS); overall survival (OS); and pharmacokinetic and pharmacodynamic markers
.
Results of the study From July 16, 2018 to October 7, 2019, a total of 113 patients were enrolled in the study, and all patients underwent apheresis (Figure 1)
.
Sixteen (14%) patients did not receive cilta-cel treatment due to disease progression, death, or withdrawal from the study
.
With a median follow-up of 12.
4 months (IQR 10.
6-15.
2), the ORR was 97% (95% CI 91.
2-99.
4), and 65 patients (67%) achieved a strict complete remission (Table 2)
.
The median time to first remission was 1.
0 months (IQR 0 9-1.
0), and 74 of 94 remission patients (79%) had their first remission within 1.
0 months after infusion of cilta-cel
.
The median time to best response was 2.
6 months (1.
0-6.
1)
.
The median time to complete or better remission was 1.
9 months (1.
0-6.
5); among 65 patients who achieved complete or better remission, 40 (62%) patients achieved complete or better remission within 3 months of infusion of cilta-cel Better relief
.
Over time, 70 (72%) of the 97 patients in remission continued their remission and continued to deepen (Figure 2)
.
The median duration of response (DOR) was not reached (95% CI 15.
9-not estimable)
.
The median PFS was not reached (95% CI 16.
8-unestimable) (Figure 3); the 12-month PFS rate was 77% (95% CI 66.
0-84.
3)
.
The 12-month PFS rate of patients who achieved complete or better remission was 85% (72.
0-91.
8), and the 12-month PFS rate of patients who achieved very good partial remission or partial remission was 62% (42.
1-76.
9).
The median PFS was not reached (95% CI 16.
8-unestimable and 5.
4-unestimable, respectively; Figure 3)
.
The 12-month OS rate was 89% (80.
2-93.
5; Figure 3)
.
Of 57 patients with evaluable MRD, 53 (93%) were MRD negative
.
Among 65 patients who achieved strict complete remission, 35 patients (54%) could be assessed for MRD, and 33 patients (94%) were MRD negative
.
The median time to MRD negative was 1.
0 (IQR 0.
9–1.
0) months
.
All 97 patients had adverse events, including grade 3-4 events (Table 3)
.
Hematological adverse events are the most common; grade 3-4 hematological adverse events are neutropenia (92 cases [95%]), anemia (66 cases [68%]), leukopenia (59 cases [61%]) , Thrombocytopenia (58 cases [60%]) and lymphopenia (48 cases [50%])
.
Conclusion This follow-up analysis of the Phase Ib/II CARTITUDE-1 study established a positive risk-benefit analysis data for a single low-dose injection of cilta-cel.
cilta-cel can be used to treat patients with multiple myeloma who have been previously treated.
Produce rapid, deep and lasting relief
.
Research on cilta-cel for other early-stage multiple myeloma patients is ongoing
.
Reference 1.
Berdeja JG, et al.
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.
Lancet.
2021 Jul 24;398(10297):314-324.
Stamp "read the original text" and we will make progress together
