Antibody Information

General Information of This Antibody
Antibody ID
ANI0PYFAC
Antibody Name
CR-011
Organization
Celldex Therapeutics, Inc.
Indication
Melanoma; Breast cancer
Synonyms
Glembatumumab
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Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG2-kappa
Antigen Name
Transmembrane glycoprotein NMB (GPNMB)
  Antigen Info 
ChEMBI ID
CHEMBL2108707
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSFNYYWSWIRHHPGKGLEWIGYIYYSGSTY
SNPSLKSRVTISVDTSKNQFSLTLSSVTAADTAVYYCARGYNWNYFDYWGQGTLVTVSSA
STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRV
VSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNV
FSCSVMHEALHNHYTQKSLSLSPGK
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Heavy Chain Varible Domain
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSFNYYWSWIRHHPGKGLEWIGYIYYSGSTY
SNPSLKSRVTISVDTSKNQFSLTLSSVTAADTAVYYCARGYNWNYFDYWGQGTLVTVSS
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Heavy Chain Constant Domain 1
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV
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Heavy Chain Constant Domain 2
APPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTK
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Heavy Chain Constant Domain 3
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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Heavy Chain Hinge Region
ERKCCVECPPCP
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Heavy Chain CDR 1
GGSISSFNYY
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Heavy Chain CDR 2
IYYSGST
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Heavy Chain CDR 3
ARGYNWNYFDY
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Light Chain Sequence
EIVMTQSPATLSVSPGERATLSCRASQSVDNNLVWYQQKPGQAPRLLIYGASTRATGIPA
RFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPPWTFGQGTKVEIKRTVAAPSVFIFP
PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL
TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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Light Chain Varible Domain
EIVMTQSPATLSVSPGERATLSCRASQSVDNNLVWYQQKPGQAPRLLIYGASTRATGIPA
RFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPPWTFGQGTKVEIK
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Light Chain Constant Domain
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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Light Chain CDR 1
QSVDNN
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Light Chain CDR 2
GAS
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Light Chain CDR 3
QQYNNWPPWT
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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
Glembatumumab vedotin [Phase 2]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Partial Response (PR)
7.69%
Patients Enrolled
Stage IIIB or IV squamous (or mixed adenosquamous) lung cancer measurable by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Administration Dosage
A dose of 1.90 mg/kg as a 90-minute intravenous infusion for the escalation phase, on the basis of previous clinical trial results using glembatumumab vedotin at 1.3 mg/kg one-dose level; every 3 weeks.
Related Clinical Trial
NCT Number NCT02713828  Clinical Status Phase 1
Clinical Description
A phase 1/2 study of glembatumumab vedotin in patients with gpNMB-expressing, advanced or metastatic squamous cell carcinoma of the lung.
Primary Endpoint
To further characterize the safety of this drug, the protocol was modified and additional three patients were added to cohort 1 for a total of nine patients at 1.90 mg/kg dose. A second DLT was observed in cohort 1. The patient experienced grade 3 treatment-related pruritus requiring hospital admission. The dose was de-escalated to dose level 1. No DLT was observed at dose level 1 of 1.30 mg/kg.

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Other Endpoint
The best objective response per RECIST 1.1 was of one patient who achieved a partial response (1 of 13 [7.69%], 90% CI: 0.40%-31.60%).The median OS in this heavily pretreated population was 5.70 months (90% CI: 2.50-16.80). All patients had disease progression or died. The median PFS was 2.50 months (90% CI: 1.60-5.30).
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
11.00% (all)
21.00% (patients who developed rash during the first cycle)
7.00% (those who did not)
Patients Enrolled
Stage III or IV, histologically confirmed melanoma. Patients must had previously received no more than one prior chemotherapy-containing treatment regimen for advanced disease, at least one checkpoint inhibitor (ie, antiCTLA-4, PD-1, PD-L1targeted immunotherapy), and at least one BRAF-targeted and/or MEK-targeted therapy if melanoma harbored a BRAFV600 mutation, unless it was not clinically indicated or was refused by the patient.

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Administration Dosage
As a 90-minute intravenous infusion every 3 weeks at a starting dose of 1.90 mg/kg. Dose reductions to 1.30 and 1.00 mg/kg were allowed for toxicity.
Related Clinical Trial
NCT Number NCT02302339  Clinical Status Phase 2
Clinical Description
A phase 2 study of glembatumumab vedotin, an anti-gpNMB antibody-drug conjugate, as monotherapy or in combination with immunotherapies in patients with advanced melanoma.
Primary Endpoint
The ORR was 11.00% and the median response duration was 6.00 months (95% confidence interval [CI],4.10 months to not reached). The median PFS was 4.40 months (95% CI,2.60-5.50 months),and the median OS was 9.00 months (95% CI,6.10-11.70 months).
Other Endpoint
For patients who developed rash during the first cycle versus those who did not,the ORR was 21.00% versus 7.00%, respectively, and there was an overall improvement in PFS (hazard ratio,0.43; P = 0.013) and OS (hazard ratio,0.43; P = 0.017).
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Objective Response Rate (ORR)
12.00% (for all evaluable patients treated at the phase II dose)
18.00% (evaluable patients with gpNMB-positive tumors)
Patients Enrolled
Locally advanced or metastatic carcinoma of the breast, progressive within 6 months of last therapy; received at least two prior chemotherapeutic regimens for breast cancer, with at least one given in the locally advanced or metastatic setting.
Administration Dosage
Glembatumumab vedotin was administered as a 90 minute intravenous infusion, once every 3 weeks (day 1 of repeated 21 day cycles). Delays of up to 3 weeks and up to two dose reductions (to dose levels of 1.34, 1.00, and 0.75 mg/kg, as applicable) were permitted for toxicity. Dosing continued until unmanageable treatment-related toxicities, disease progression, or death.

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Experiment 4 Reporting the Activity Date of This ADC [4]
Related Clinical Trial
NCT Number NCT01156753  Clinical Status Phase 2
Clinical Description
A phase 2, randomized, multicenter study of CDX-011 (CR011-vcMMAE) in patients with advanced GPNMB-expressing breast cancer.
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 93.33% (Day 35) High GPNMB expression (GPNMB+++)
Method Description
Tumor xenografts were generated by injecting UOK124 cells subcutaneously into flanks of athymic nude mice. Mice were randomized into treatment groups (n = 10 mice/group) based on tumor volume and treated with the following agents, singly or in combination CDX-011.
In Vivo Model UOK124 CDX model
In Vitro Model Papillary renal cell carcinoma UOK124 cells CVCL_B105
References
Ref 1 Efficacy and Safety of Glembatumumab Vedotin in Patients With Advanced or Metastatic Squamous Cell Carcinoma of the Lung (PrECOG 0504). JTO Clin Res Rep. 2021 Mar 24;2(5):100166.
Ref 2 A phase 2 study of glembatumumab vedotin, an antibody-drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma. Cancer. 2019 Apr 1;125(7):1113-1123.
Ref 3 Phase I/II study of the antibody-drug conjugate glembatumumab vedotin in patients with locally advanced or metastatic breast cancer. J Clin Oncol. 2014 Nov 10;32(32):3619-25.
Ref 4 EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB-Expressing Breast Cancer. J Clin Oncol. 2015 May 10;33(14):1609-19.
Ref 5 High-throughput and targeted drug screens identify pharmacological candidates against MiT-translocation renal cell carcinoma. J Exp Clin Cancer Res. 2023 Apr 25;42(1):99. doi: 10.1186/s13046-023-02667-4.

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