Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0NDXRU
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| ADC Name |
Belantamab mafodotin
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| Brand Name |
Blenrep
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| Synonyms |
belantamab mafodotin; GSK2857916; GSK'916; Blenrep; belantamab mafodotin-blmf; belantamab mafadotin; belamaf
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| Organization |
Seagen (Top20 MNC) (Originator) (No Rights);GSK (Top20 MNC)
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| Drug Status |
Approved in 2020 (withdrawn in 2022, approved again in 2025)
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| Drug-to-Antibody Ratio |
4
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| Structure |
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| Antibody Name |
Belantamab
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Antibody Info | ||||
| Antigen Name |
Tumor necrosis factor receptor superfamily member 17 (TNFRSF17)
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Antigen Info | ||||
| Payload Name |
MMAF
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Maleimido-caproyl
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Linker Info | ||||
| Conjugate Type |
Random Cysteines
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| Combination Type |
mafodotin
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| Absorption |
For Belantamab mafodotin (2.5mg/kg), mean Cmax=42 g/mL, Tmax=0.78 hours, and AUC=4666 g*h/mL.
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| Distribution |
The mean steady state volume of distribution of belantamab mafodotin was 11 L.
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| Metabolism |
Monoclonal antibodies are expected to be metabolized to smaller peptides and amino acids. MMAF is expected to be metabolized by oxidation and demethylation, however further data is not readily available. The terminal half life of belantamab mafodotin was 12 days (after the first dose) and 14 days (at steady state).
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| Toxicity |
Data regarding overdose is not readily available. However, keratopathy was seen in 71% of patients. FDA black box warning: ocular toxicity. BLENREP caused changes in the corneal epithelium resulting in changes in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes.
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| Special Approval(s) |
Accelerated approval (FDA); Orphan drug (FDA)
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The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
| Indication | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | New Drug Application | Approved | ||||||||||||||||||||||||
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| Amyloidosis |
1 Trials
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1 Trials
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| Diffuse large b-cell lymphoma |
1 Trials
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| Immune thrombocytopenic purpura |
2 Trials
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| Multiple myeloma |
10 Trials
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2 Trials
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6 Trials
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2 Trials
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ADC-specific functional property(2027 Update)
Binding Affinity
| Dissocation Constant (Kd) | Binding Target | Description | Reference |
|---|---|---|---|
| 1 nM |
BCMA
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J6M0-mcMMAF (GSK2857916) binds to human BCMA protein with a Kd of ;1nM,asmeasuredbysurface plasmon resonance (SPR) at 25°C, but does not bind to related receptors BAFF-R or transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)
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[1]
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Bystander Killing Effect
| Bystander Killing Effect | Description | Reference |
|---|---|---|
| yes |
J6M0-mcMMAF selectively induces anti-MM toxicity in the cocultures while sparing BMSCs and various effector cells
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[1]
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Maximum Observed Concentration (Cmax) | 42 | ug/mL |
Belantamab mafodotin at a dose of 2.5mg/kg reaches a Cmax of 42 ug/mL, with a Tmax of 0.78 hours
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4666 | ug*h/mL |
Belantamab mafodotin at a dose of 2.5mg/kg reaches an AUC of 4666 ug*h/mL.
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[1] |
| Maximum Observed Concentration (Cmax) | 36.4 | ug/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 3606 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tlast, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 3694.6 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tau, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 4177.9 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-inf, 2.5mg/kg (n=4)
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[3] |
| Maximum Observed Concentration (Cmax) | 41.3 | ug/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, 3.4 mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 2392.3 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tlast, 3.4 mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 3807.9 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tau, 3.4 mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 4243.2 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-inf, 3.4 mg/kg (n=4)
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[3] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 4666 | ug*h/mL |
Belantamab mafodotin at a dose of 2.5mg/kg reaches an AUC of 4666 ug*h/mL.
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[1] |
| Volume of Distribution (Vd) | 11 | L |
The mean steady state volume of distribution of belantamab mafodotin was 11 L.
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[1] |
| Volume of Distribution (Vd) | 7.5 | L |
Eight patients with RRMM were screened and administered belantamab mafodotin at either 2.5 mg/kg dose Q3W (4 in each cohort).
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[3] |
| Volume of Distribution (Vd) | 8.2 | L |
Eight patients with RRMM were screened and administered belantamab mafodotin at either 3.4 mg/kg dose Q3W (4 in each cohort).
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[3] |
| Volume of Distribution (Vd) | 4.47 | L |
PK parameter estimates for the final PopPK model for ADC, central volume of distribution
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[4] |
| Volume of Distribution (Vd) | 5.96 | L |
PK parameter estimates for the final PopPK model for ADC, peripheral volume of distribution
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[4] |
| Area Under the Concentration-Time Curve (AUC) | 3606 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tlast, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 3694.6 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tau, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 4177.9 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-inf, 2.5mg/kg (n=4)
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[3] |
| Volume of Distribution (Vd) | 7.5 | L |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 2392.3 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tlast, 3.4 mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 3807.9 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tau, 3.4 mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 4243.2 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-inf, 3.4 mg/kg (n=4)
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[3] |
| Volume of Distribution (Vd) | 8.2 | L |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, 3.4 mg/kg (n=4)
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[3] |
Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 4666 | ug*h/mL |
Belantamab mafodotin at a dose of 2.5mg/kg reaches an AUC of 4666 ug*h/mL.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 3606 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tlast, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 3694.6 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tau, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 4177.9 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-inf, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 2392.3 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tlast, 3.4 mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 3807.9 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tau, 3.4 mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 4243.2 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-inf, 3.4 mg/kg (n=4)
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[3] |
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Elimination Half-Life (t1/2) | 14 | days |
The terminal half life of belantamab mafodotin was 12 days (after the first dose) and 14 days (at steady state).
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[1] |
| Clearance (CL) | 0.7 | L/day |
The clearance of belantamab mafodotin was 0.9 L/day after the first dose and 0.7 L/day at steady state
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4666 | ug*h/mL |
Belantamab mafodotin at a dose of 2.5mg/kg reaches an AUC of 4666 ug*h/mL.
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[1] |
| Clearance (CL) | 0.936 | h |
Linear, two-compartment PopPK model with time-varying clearance. Dosing: 0.03-4.6 mg/kg every 3 weeks in heavily pretreated patients with relapsed/refractory multiple myeloma
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[2] |
| Clearance (CL) | 0.936 | h |
Linear, two-compartment PopPK model with time-varying clearance. Dosing: 0.03-4.6 mg/kg every 3 weeks in heavily pretreated patients with relapsed/refractory multiple myeloma
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[2] |
| Elimination Half-Life (t1/2) | 11.5 | days |
Linear, two-compartment PopPK model with time-varying clearance. Dosing: 0.03-4.6 mg/kg every 3 weeks in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM; DREAMM-1, n = 73; DREAMM-2, n = 218).
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[3] |
| Elimination Half-Life (t1/2) | 14.3 | days |
Linear, two-compartment PopPK model with time-varying clearance. Dosing: 0.03-4.6 mg/kg every 3 weeks in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM; DREAMM-1, n = 73; DREAMM-2, n = 218).After time-varying CL reduction.
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[3] |
| Elimination Half-Life (t1/2) | 7.5 | days |
Eight patients with RRMM were screened and administered belantamab mafodotin at either 2.5 mg/kg dose Q3W (4 in each cohort).
|
[3] |
| Elimination Half-Life (t1/2) | 7.3 | days |
Eight patients with RRMM were screened and administered belantamab mafodotin at either 3.4 mg/kg dose Q3W (4 in each cohort).
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[3] |
| Clearance (CL) | 0.94 | L/day |
PK parameter estimates for the final PopPK model for ADC
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[4] |
| Clearance (CL) | 0.78 | L/day |
PK parameter estimates for the final PopPK model for ADC, inter-compartmental clearance
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[4] |
| Area Under the Concentration-Time Curve (AUC) | 3606 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tlast, 2.5mg/kg (n=4)
|
[3] |
| Area Under the Concentration-Time Curve (AUC) | 3694.6 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tau, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 4177.9 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-inf, 2.5mg/kg (n=4)
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[3] |
| Clearance (CL) | 35 | mL/h |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, 2.5mg/kg (n=4)
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[3] |
| Elimination Half-Life (t1/2) | 7.5 | day |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, 2.5mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 2392.3 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tlast, 3.4 mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 3807.9 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-tau, 3.4 mg/kg (n=4)
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[3] |
| Area Under the Concentration-Time Curve (AUC) | 4243.2 | ug*h/mL |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, AUC0-inf, 3.4 mg/kg (n=4)
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[3] |
| Clearance (CL) | 45.3 | mL/h |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, 3.4 mg/kg (n=4)
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[3] |
| Elimination Half-Life (t1/2) | 7.3 | day |
Pharmacokinetics of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11, 3.4 mg/kg (n=4)
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[3] |
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Revealed Based on the Cell Line Data
| Standard Type | Value | Units | Cell Line | Disease Model |
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| Half Maximal Effective Concentration (EC50) |
30.6
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ug/mL
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EL4 cells (BCMA expression)
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Thymoma
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Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Objective Response Rate (ORR) | 56.30% | High BCMA expression (BCMA +++) | ||
| Patients Enrolled |
Eligible adult (18 years of age) patients for part 2 had histologically or cytologically confirmed MM, Eastern Cooperative Oncology Group performance status 0 or 1, prior therapy with alkylators, proteasome inhibitors and immunomodulators, and were refractory to the last line of treatment.
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| Administration Dosage |
GSK2857916 3.4 mg/kg was administered through 1-h intravenous infusions once every 3 weeks, for a maximum of 16 cycles.
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| Related Clinical Trial | |||||
| NCT Number | NCT02064387 | Clinical Status | Phase 1 | ||
| Clinical Description | A Phase I open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity of the antibody drug conjugate GSK2857916 in subjects with relapsed/refractory multiple myeloma and other advanced hematologic malignancies expressing BCMA. | ||||
| Primary Endpoint |
Objective response rate=60.00% (95% CI 42.10-76.10),comprising 3 (9.00%) complete responses and 14.00 (40%) partial responses.
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| Other Endpoint |
The median progression-free survival was 12.00 months and the median duration of response was 14.30 months.
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| Experiment 2 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
60%
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| Patients Enrolled |
Histologically or cytologically confirmed MM, a European Cooperative Oncology Group performance status of 0 or 1, prior therapy with alkylators, PI and IMiD, had undergone stem cell transplant (if eligible) and refractory to the last line of treatment (defined as progressive disease on or within 60 days of completion of the last therapy) that included stem cell transplant and those patients with a history of autologous stem cell transplant must have received the transplant >100 days prior to study enrolment and have no active infection.
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| Administration Dosage |
Doses ranging between 0.03 mg/kg and 4.60 mg/kg was administered as a 1-hour intravenous infusion every 3 weeks for a maximum of 16 cycles.
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| Related Clinical Trial | |||||
| NCT Number | NCT02064387 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1 open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity of the antibody drug conjugate GSK2857916 in subjects with relapsed/refractory multiple myeloma and other advanced hematologic malignancies expressing BCMA. | ||||
| Primary Endpoint |
The primary endpoints of the trial were to determine the safety, tolerability, maximum tolerated dose (MTD) and RP2D and schedule of GSK2857916. Median PFS (post hoc analysis) was 7.90 months (95% CI: 3.1-not estimable),Overall response rate at 3.40 mg/kg in Part 2 was 60.00% (21/35; 95% confidence interval: 42.10%-76.10%).
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| Other Endpoint |
PK profile (single dose area under the curve, maximum serum concentration [Cmax], time to Cmax , clearance, steady-state volume of distribution [Vss], half-life [t]; repeat dose Cmax and trough plasma concentration), the incidence of anti-drug antibodies, and clinical activity measured as overall response rate (ORR), defined as the percentage of subjects achieving confirmed partial response or better (PR) and clinical benefit rate, defined as the percentages of subjects with minimal response or better (MR).
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| Experiment 3 Reporting the Activity Date of This ADC | [7] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT03769506 | Clinical Status | Phase 3 | ||
| Clinical Description | A phase 3, randomized, double-arm, open-label, controlled trial of ASP-1929 photoimmunotherapy versus physician's choice standard of care for the treatment of locoregional, recurrent head and neck squamous cell carcinoma in patients who have failed or progressed on or after at least two lines of therapy, of which at least one line must be systemic therapy. | ||||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [8] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 30.6 ug/mL | Moderate BCMA expression (BCMA++) | ||
| Method Description |
Cells (5 x 105 cells/mL) were left untreated or exposed to the indicated treatments for the indicated time. Cells were counted on a Vi-Cell-XR Cell Viability Analyzer (Beckman Coulter).
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| In Vitro Model | Thymoma | EL4 cells (BCMA expression) | CVCL_0255 | ||
References