General Information of This Antibody
Antibody ID
ANI0MSWWH
Antibody Name
Belantamab
Organization
GSK Plc
Indication
Multiple myeloma
Synonyms
2857916; GSK2857916; J6M0
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Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG1-kappa
Antigen Name
Tumor necrosis factor receptor superfamily member 17 (TNFRSF17)
 Antigen Info 
ChEMBI ID
CHEMBL4298208
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNYWMHWVRQAPGQGLEWMGATYRGHSDTYY
NQKFKGRVTITADKSTSTAYMELSSLRSEDTAVYYCARGAIYDGYDVLDNWGQGTLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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Heavy Chain Varible Domain
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNYWMHWVRQAPGQGLEWMGATYRGHSDTYY
NQKFKGRVTITADKSTSTAYMELSSLRSEDTAVYYCARGAIYDGYDVLDNWGQGTLVTVS
S
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Heavy Chain Constant Domain 1
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV
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Heavy Chain Constant Domain 2
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
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Heavy Chain Constant Domain 3
GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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Heavy Chain Hinge Region
EPKSCDKTHTCPPCP
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Heavy Chain CDR 1
GGTFSNYW
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Heavy Chain CDR 2
TYRGHSDT
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Heavy Chain CDR 3
ARGAIYDGYDVLDN
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Light Chain Sequence
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKLLIYYTSNLHSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYRKLPWTFGQGTKLEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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Light Chain Varible Domain
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKLLIYYTSNLHSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYRKLPWTFGQGTKLEIK
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Light Chain Constant Domain
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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Light Chain CDR 1
QDISNY
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Light Chain CDR 2
YTS
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Light Chain CDR 3
QQYRKLPWT
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Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
Belantamab mafodotin [Approved]
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
60.00%
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.
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%).
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.
Administration Dosage
GSK2857916 3.4 mg/kg was administered through 1-h intravenous infusions once every 3 weeks, for a maximum of 16 cycles.
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.
Other Endpoint
The median progression-free survival was 12.00 months and the median duration of response was 14.30 months.
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.

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Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
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).
In Vitro Model Thymoma EL4 cells (BCMA expression) CVCL_0255
Belantamab-Compound (Ia) [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 7 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
87.00 pM
Positive BCMA expression (BCMA+++/++)
Method Description
Cells were plated at about 500 cells per well in a 96-well plate in 100 uL of media. In vitro activity and targeted delivery of ADCs, the isotype-matched negative controls ADCs, and naked antibodies control were assessed in cells.
In Vitro Model Plasma cell myeloma KMS-12-BM cells CVCL_1334
Experiment 2 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.12 nM
Positive BCMA expression (BCMA+++/++)
Method Description
Cells were plated at about 500 cells per well in a 96-well plate in 100 uL of media. In vitro activity and targeted delivery of ADCs, the isotype-matched negative controls ADCs, and naked antibodies control were assessed in cells.
In Vitro Model Plasma cell myeloma OPM-2 cells CVCL_1625
Experiment 3 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.20 nM
Positive BCMA expression (BCMA+++/++)
Method Description
Cells were plated at about 500 cells per well in a 96-well plate in 100 uL of media. In vitro activity and targeted delivery of ADCs, the isotype-matched negative controls ADCs, and naked antibodies control were assessed in cells.
In Vitro Model Plasma cell myeloma MOLP-2 cells CVCL_2123
Experiment 4 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.21 nM
Positive BCMA expression (BCMA+++/++)
Method Description
Cells were plated at about 500 cells per well in a 96-well plate in 100 uL of media. In vitro activity and targeted delivery of ADCs, the isotype-matched negative controls ADCs, and naked antibodies control were assessed in cells.
In Vitro Model Plasma cell myeloma MM1.S cells CVCL_8792
Experiment 5 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
3.17 nM
Positive BCMA expression (BCMA+++/++)
Method Description
Cells were plated at about 500 cells per well in a 96-well plate in 100 uL of media. In vitro activity and targeted delivery of ADCs, the isotype-matched negative controls ADCs, and naked antibodies control were assessed in cells.
In Vitro Model Plasma cell myeloma LP-1 cells CVCL_0012
Experiment 6 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
11.90 nM
Positive BCMA expression (BCMA+++/++)
Method Description
Cells were plated at about 500 cells per well in a 96-well plate in 100 uL of media. In vitro activity and targeted delivery of ADCs, the isotype-matched negative controls ADCs, and naked antibodies control were assessed in cells.
In Vitro Model Plasma cell myeloma NCI-H929 cells CVCL_1600
Experiment 7 Reporting the Activity Date of This ADC [5]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
68.40 nM
Positive BCMA expression (BCMA+++/++)
Method Description
Cells were plated at about 500 cells per well in a 96-well plate in 100 uL of media. In vitro activity and targeted delivery of ADCs, the isotype-matched negative controls ADCs, and naked antibodies control were assessed in cells.
In Vitro Model Plasma cell myeloma MM1.R cells CVCL_8794
References
Ref 1 Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018 Dec;19(12):1641-1653.
Ref 2 Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study. Blood Cancer J. 2019 Mar 20;9(4):37. doi: 10.1038/s41408-019-0196-6.
Ref 3 Near-infrared photoimmunotherapy of cancer: a new approach that kills cancer cells and enhances anti-cancer host immunity. Int Immunol. 2021 Jan 1;33(1):7-15.
Ref 4 Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo. Mol Cancer Ther. 2021 Oct;20(10):1941-1955. doi: 10.1158/1535-7163.MCT-21-0035.
Ref 5 Neodegrader conjugates; 2021-10-07.

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