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 |
GSK-2857916;GSK'916;GSK2857916;J6M0-mcMMAF;anti-BCMA-ADC;Belamaf;belantamab mafodotin-blmf
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| Organization |
GSK Plc; GlaxoSmithKline (Ireland) Ltd; Glaxosmithkline Intellectual Property Development Ltd.
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| Drug Status |
Approved (FDA): Aug 5, 2020; Approved (EMA): Aug 25, 2020; Withdrawn (FDA): Feb 6, 2023; Withdrawn (EMA); Dec 15, 2023
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| Indication |
In total 2 Indication(s)
Multiple myeloma [ICD11:2A83]
Approved
Plasmacytoid lymphoma [ICD11:XH9TT4]
Phase 2
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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 |
Monomethyl auristatin F
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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 conjugation through reduced inter-chain 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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| Elimination |
Monoclonal antibodies undergo phagocytosis and are then broken down into smaller peptides and amino acids. These components are eliminated in a manner similar to other proteins. Typically, monoclonal antibodies are not excreted through urine, with only a minor quantity being eliminated through bile.
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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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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 | [1] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
60.00%
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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 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Objective Response Rate (ORR) | 60.00% | 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 5 (14.29%) achieving complete responses and 16 (45.71%) achieving 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 3 Reporting the Activity Date of This ADC | [3] | ||||
| 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 | [4] | ||||
| Efficacy Data | Half Maximal Effective Concentration (EC50) | 30.60 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
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