Acute Lymphoblastic Leukemia
Conditions
Keywords
Blinatumomab, AMG 404, Leukemia
Brief summary
The primary objective of this phase 1b study is to evaluate the safety and tolerability of blinatumomab and AMG 404 in combination in adults with R/R B-ALL and to estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG 404 when combined with continuous intravenous infusion (cIV) blinatumomab.
Interventions
DRUGBlinatumomab
Blinatumomab will be administered as a continuous intravenous infusion (cIV).
DRUGAMG 404
AMG 404 will be administered as an intravenous infusion (IV).
DRUGDexamethasone Premedication
Dexamethasone will be administered orally or intravenously prior to blinatumomab treatment, as needed.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years at enrollment. * Greater than or equal to 5% blasts in the bone marrow. * Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2. * Negative pregnancy test in women of childbearing potential.
Exclusion criteria
* Cancer chemotherapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy) within 14 days prior to study Day 1. * Known hypersensitivity to blinatumomab or AMG 404 or to any component of the product formulation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days | Investigators determined whether an adverse event (AE) qualified as a DLT per pre-specified protocol defined criteria. An AE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. |
| Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | Median (min, max) overall duration from first dose until 30 days after last dose is: 83.4 (40.2, 274.1) days | A TEAE was defined as any AE starting on or after first dose of blinatumomab or AMG 404. The investigator used clinical judgment to assess causal relationship. A serious AE (SAE) was defined as any AE that: * results in death, * immediately life-threatening, * requires in-patient hospitalization or prolongation of existing hospitalization, * results in persistent or significant disability/incapacity, * is a congenital anomaly/birth defect, and/or * other medically important serious AE. AEs of interest (EOIs) for blinatumomab included capillary leak syndrome, cytokine release syndrome, decreased immunoglobulins, elevated liver enzyme, embolic and thrombotic events, immunogenicity, infections, infusion reactions without considering duration, leukoencephalopathy, progressive multifocal leukoencephalopathy, neurologic events, neutropenia and febrile neutropenia, pancreatitis, and tumor lysis syndrome. EOIs for AMG 404 included non-infectious diarrhea and hemorrhages. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles | Up to approximately 274 days | Duration of CR was calculated from the date CR was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR to event/censor date, divided by 30.5. Median time to event and 95% CI was summarized using the Kaplan-Meier (KM) method. |
| Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles | Up to approximately 274 days | Duration of CR/CRh was calculated from the date CR/CRh was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR/CRh to event/censor date, divided by 30.5. Median time to event and 95% CI was summarized using the KM method. |
| Steady-state Concentrations (Css) of Blinatumomab | Cohort 1: C1D1 and D8 (predose, 2 to 24 h postdose), and D11, D18 and D29; C2D1 (predose, 2 to 24 h postdose) and D29. Cohort 2a: C1D3 and D10 (predose, 2 to 48 h postdose), and D29, D30 and D31; C2D1 (predose, 2 to 24 h postdose), D13 and D29 | Pharmacokinetic (PK) parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol. |
| Maximum Observed Concentration (Cmax) of AMG 404 | Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion) | PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol. |
| Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh) | Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days | Hematological remissions were defined by the following criteria: CR: * Less than 5% blasts in the bone marrow (BM) * No evidence of disease * Full recovery of peripheral blood (PB) counts: * Platelets \> 100 000/μl * Absolute neutrophil count (ANC) \> 1000/μl CR with only CRh: * Less than 5% blasts in the BM * No evidence of disease * Partial recovery of PB counts: * Platelets \> 50 000/μl and * ANC \> 500/μl Percentage of participants with CR/CRh were summarized along with corresponding 95% exact confidence interval (CI) using the Clopper-Pearson method. |
| Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404 | Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion) | PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol. |
| Number of Participants With Incidences of Anti-Blinatumomab Antibodies | Up to approximately 274 days | Only samples testing positive for anti-blinatumomab binding antibodies were to be tested for neutralizing antibodies (NAbs) as pre-specified in the protocol. |
| Number of Participants With Incidences of Anti-AMG 404 Antibodies | Up to approximately 274 days | Only samples testing positive for anti-AMG 404 binding antibodies were to be tested for NAbs as pre-specified in the protocol. |
| Time to Cmax (Tmax) of AMG 404 | Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion) | PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol. |
| Percentage of Participants Who Achieved CR | Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days | Hematological remissions were defined by the following criteria: CR: * Less than 5% blasts in the BM * No evidence of disease * Full recovery of PB counts: * Platelets \> 100 000/μl * ANC \> 1000/μl Percentage of participants with CR were summarized along with corresponding 95% exact CI using the Clopper-Pearson method. |
Countries
Australia, Austria, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 22 centers in Australia, Austria, France, Germany, Italy, Netherlands, Spain, United Kingdom, and the United States between 02 October 2020 to 24 January 2023.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) Blinatumomab cIV was administered at 9 μg/day on Days 1 to 7, then at 28 μg/day thereafter. Each cycle consisted of 42 days and included a 14-day blinatumomab treatment-free interval between Days 29 and 42. The treatment-free interval could be prolonged by up to 7 days if deemed necessary by the investigator. AMG 404 was administered IV at 240 mg, starting on C1D11 and dosed Q4W thereafter. Participants could receive up to 5 cycles. | 8 |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) Blinatumomab cIV was administered at 9 μg/day on Days 3 to 9, then at 28 μg/day thereafter. Cycle 1 consisted of 44 days and included a 14-day blinatumomab treatment-free interval between Days 31 and 44. Each cycle thereafter consisted of 42 days and included a 14-day blinatumomab treatment-free interval between Days 29 and 42. The treatment-free interval could be prolonged by up to 7 days if deemed necessary by the investigator. AMG 404 was administered IV at 480 mg, starting on C1D1 and dosed Q4W thereafter. Participants could receive up to 5 cycles. | 9 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 3 |
| Overall Study | Decision by Sponsor | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal of Consent From Study | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: Blinatumomab + AMG 404 (240 mg) | Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 8 Participants | 14 Participants |
| Age, Continuous | 52.9 Years STANDARD_DEVIATION 18 | 39.3 Years STANDARD_DEVIATION 15.7 | 45.7 Years STANDARD_DEVIATION 17.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 5 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 8 | 3 / 8 |
| other Total, other adverse events | 8 / 8 | 8 / 8 |
| serious Total, serious adverse events | 6 / 8 | 7 / 8 |
Outcome results
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Investigators determined whether an adverse event (AE) qualified as a DLT per pre-specified protocol defined criteria. An AE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment.
Time frame: Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days
Population: DLT Analysis Set: included DLT-evaluable participants in the Safety Analysis Set. A participant was DLT-evaluable if the participant had completed DLT-evaluable period which begins with the first AMG 404 dose and includes 28 days after the second AMG 404 dose is administered or experienced a DLT any time during the DLT-evaluable period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
Primary
Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs)
A TEAE was defined as any AE starting on or after first dose of blinatumomab or AMG 404. The investigator used clinical judgment to assess causal relationship. A serious AE (SAE) was defined as any AE that: * results in death, * immediately life-threatening, * requires in-patient hospitalization or prolongation of existing hospitalization, * results in persistent or significant disability/incapacity, * is a congenital anomaly/birth defect, and/or * other medically important serious AE. AEs of interest (EOIs) for blinatumomab included capillary leak syndrome, cytokine release syndrome, decreased immunoglobulins, elevated liver enzyme, embolic and thrombotic events, immunogenicity, infections, infusion reactions without considering duration, leukoencephalopathy, progressive multifocal leukoencephalopathy, neurologic events, neutropenia and febrile neutropenia, pancreatitis, and tumor lysis syndrome. EOIs for AMG 404 included non-infectious diarrhea and hemorrhages.
Time frame: Median (min, max) overall duration from first dose until 30 days after last dose is: 83.4 (40.2, 274.1) days
Population: Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | Serious TEAEs | 6 Participants |
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | AMG 404-related TEAEs | 3 Participants |
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | Blinatumomab-related TEAEs | 8 Participants |
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | EOIs | 8 Participants |
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | TEAEs | 8 Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | EOIs | 8 Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | TEAEs | 8 Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | Serious TEAEs | 7 Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | Blinatumomab-related TEAEs | 6 Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs) | AMG 404-related TEAEs | 4 Participants |
Secondary
Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404
PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Time frame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Population: PK Analysis Set: Defined as all participants in the Safety Analysis Set who have at least 1 PK sample collected. Includes only participants with available data at each timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404 | 750 day·mg/mL | Standard Deviation 269 |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404 | 1920 day·mg/mL | Standard Deviation 660 |
Secondary
Maximum Observed Concentration (Cmax) of AMG 404
PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Time frame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Population: PK Analysis Set: Defined as all participants in the Safety Analysis Set who have at least 1 PK sample collected. Includes only participants with available data at each timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Maximum Observed Concentration (Cmax) of AMG 404 | 70.2 mg/mL | Standard Deviation 18.7 |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Maximum Observed Concentration (Cmax) of AMG 404 | 175 mg/mL | Standard Deviation 53.5 |
Secondary
Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles
Duration of CR/CRh was calculated from the date CR/CRh was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR/CRh to event/censor date, divided by 30.5. Median time to event and 95% CI was summarized using the KM method.
Time frame: Up to approximately 274 days
Population: Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404. Includes only participants who achieved CR/CRh within the first 2 cycles of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles | NA Months |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles | NA Months |
Secondary
Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles
Duration of CR was calculated from the date CR was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR to event/censor date, divided by 30.5. Median time to event and 95% CI was summarized using the Kaplan-Meier (KM) method.
Time frame: Up to approximately 274 days
Population: Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404. Includes only participants who achieved CR within the first 2 cycles of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles | NA Months |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles | NA Months |
Secondary
Number of Participants With Incidences of Anti-AMG 404 Antibodies
Only samples testing positive for anti-AMG 404 binding antibodies were to be tested for NAbs as pre-specified in the protocol.
Time frame: Up to approximately 274 days
Population: Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404. Includes only participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Number of Participants With Incidences of Anti-AMG 404 Antibodies | Binding Antibody Positive at Anytime | 0 Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Number of Participants With Incidences of Anti-AMG 404 Antibodies | Binding Antibody Positive at Anytime | 0 Participants |
Secondary
Number of Participants With Incidences of Anti-Blinatumomab Antibodies
Only samples testing positive for anti-blinatumomab binding antibodies were to be tested for neutralizing antibodies (NAbs) as pre-specified in the protocol.
Time frame: Up to approximately 274 days
Population: Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404. Includes only participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Number of Participants With Incidences of Anti-Blinatumomab Antibodies | Binding Antibody Positive at Anytime | 0 Participants |
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Number of Participants With Incidences of Anti-Blinatumomab Antibodies | NAb Positive at Anytime | 0 Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Number of Participants With Incidences of Anti-Blinatumomab Antibodies | Binding Antibody Positive at Anytime | 0 Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Number of Participants With Incidences of Anti-Blinatumomab Antibodies | NAb Positive at Anytime | 0 Participants |
Secondary
Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh)
Hematological remissions were defined by the following criteria: CR: * Less than 5% blasts in the bone marrow (BM) * No evidence of disease * Full recovery of peripheral blood (PB) counts: * Platelets \> 100 000/μl * Absolute neutrophil count (ANC) \> 1000/μl CR with only CRh: * Less than 5% blasts in the BM * No evidence of disease * Partial recovery of PB counts: * Platelets \> 50 000/μl and * ANC \> 500/μl Percentage of participants with CR/CRh were summarized along with corresponding 95% exact confidence interval (CI) using the Clopper-Pearson method.
Time frame: Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
Population: Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh) | Within the First 2 Cycles | 37.5 Percentage of Participants |
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh) | Across All Cycles | 37.5 Percentage of Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh) | Within the First 2 Cycles | 62.5 Percentage of Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh) | Across All Cycles | 62.5 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved CR
Hematological remissions were defined by the following criteria: CR: * Less than 5% blasts in the BM * No evidence of disease * Full recovery of PB counts: * Platelets \> 100 000/μl * ANC \> 1000/μl Percentage of participants with CR were summarized along with corresponding 95% exact CI using the Clopper-Pearson method.
Time frame: Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
Population: Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Percentage of Participants Who Achieved CR | Within the First 2 Cycles | 25.0 Percentage of Participants |
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Percentage of Participants Who Achieved CR | Across All Cycles | 25.0 Percentage of Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Percentage of Participants Who Achieved CR | Within the First 2 Cycles | 50.0 Percentage of Participants |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Percentage of Participants Who Achieved CR | Across All Cycles | 50.0 Percentage of Participants |
Secondary
Steady-state Concentrations (Css) of Blinatumomab
Pharmacokinetic (PK) parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Time frame: Cohort 1: C1D1 and D8 (predose, 2 to 24 h postdose), and D11, D18 and D29; C2D1 (predose, 2 to 24 h postdose) and D29. Cohort 2a: C1D3 and D10 (predose, 2 to 48 h postdose), and D29, D30 and D31; C2D1 (predose, 2 to 24 h postdose), D13 and D29
Population: PK Analysis Set: Defined as all participants in the Safety Analysis Set who have at least 1 PK sample collected. Includes only participants with available data at each timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Steady-state Concentrations (Css) of Blinatumomab | 152 pg/mL | Standard Deviation 70.2 |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Steady-state Concentrations (Css) of Blinatumomab | 676 pg/mL | Standard Deviation 478 |
| Cohort 1; Cycle 2: Blinatumomab 28 μg/Day | Steady-state Concentrations (Css) of Blinatumomab | 779 pg/mL | Standard Deviation 210 |
| Cohort 2a; Cycle 1: Blinatumomab 9 μg/Day | Steady-state Concentrations (Css) of Blinatumomab | 210 pg/mL | Standard Deviation 177 |
| Cohort 2a; Cycle 1: Blinatumomab 28 μg/Day | Steady-state Concentrations (Css) of Blinatumomab | 638 pg/mL | Standard Deviation 274 |
| Cohort 2a; Cycle 2: Blinatumomab 28 μg/Day | Steady-state Concentrations (Css) of Blinatumomab | 626 pg/mL | Standard Deviation 228 |
Secondary
Time to Cmax (Tmax) of AMG 404
PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Time frame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Population: PK Analysis Set: Defined as all participants in the Safety Analysis Set who have at least 1 PK sample collected. Includes only participants with available data at each timepoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Blinatumomab + AMG 404 (240 mg) | Time to Cmax (Tmax) of AMG 404 | 2.5 Hours |
| Cohort 2a: Blinatumomab + AMG 404 (480 mg) | Time to Cmax (Tmax) of AMG 404 | 1.5 Hours |