Antibody Information

General Information of This Antibody
Antibody ID
ANI0KNFWI
Antibody Name
Aprutumab
Organization
Bayer AG
Indication
Solid tumors
Synonyms
BAY 1179470
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Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG1-lambda2
Antigen Name
Fibroblast growth factor receptor 2 (FGFR2)
  Antigen Info 
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGTSTYY
ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVRYNWNHGDWFDPWGQGTLVTV
SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL
GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ
YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
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Heavy Chain Varible Domain
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGTSTYY
ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVRYNWNHGDWFDPWGQGTLVTV
SS
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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
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
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Heavy Chain Hinge Region
EPKSCDKTHTCPPCP
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Heavy Chain CDR 1
GFTFSSYA
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Heavy Chain CDR 2
ISGSGTST
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Heavy Chain CDR 3
ARVRYNWNHGDWFDP
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Light Chain Sequence
QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYENYNRPAGVP
DRFSGSKSGTSASLAISGLRSEDEADYYCSSWDDSLNYWVFGGGTKLTVLGQPKAAPSVT
LFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS
YLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
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Light Chain Varible Domain
QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYENYNRPAGVP
DRFSGSKSGTSASLAISGLRSEDEADYYCSSWDDSLNYWVFGGGTKLTVL
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Light Chain Constant Domain
GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSK
QSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
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Light Chain CDR 1
SSNIGNNY
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Light Chain CDR 2
ENY
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Light Chain CDR 3
SSWDDSLNYWV
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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
Aprutumab ixadotin [Phase 1 (discontinued)]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Patients Enrolled
Eligibility requires age &ge;18, ECOG 0-1, advanced FGFR2+ solid tumors refractory to standard therapy (MTD expansion limited to triple-negative breast cancer &le;4 prior lines). Exclusion covers hypersensitivity to monoclonal antibodies, recent (<4 weeks) anticancer therapy, unresolved treatment-related toxicity, active brain metastases, significant cardiac disease, coagulation disorders, and pregnancy/breastfeeding.

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Administration Dosage
A dose of 0.1 mg BAY 1187982 per kilogram (kg) body weight (BW) was chosen as the starting dose based on toxicology data. The investigational drug will be administered as a 1-hour IV infusion once every 21 days at the trial site (Day 1 of each 21-day Cycle). The maximum possible dose escalation will be 2-fold and not more than 0.5 mg/kg BW until maximum tolerated dose is selected

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Related Clinical Trial
NCT Number NCT02368951  Clinical Status PHASE1
Clinical Description
An Open-label,Phase I, Dose-escalation Trial to Evaluate the Safety, Tolerability, Maximum Tolerated Dose, Pharmacokinetic, and Pharmacodynamics of the Anti-FGFR2 Antibody Drug Conjugate BAY1187982 in Subjects With Advanced Solid Tumors Known to Express FGFR2.
Primary Endpoint
The trial focuses on identifying the maximum tolerated dose (MTD) of the investigational drug, defined as the highest dose with <20% dose-limiting toxicities (DLTs) during Cycle 1. Safety and tolerability endpoints include adverse events (AEs) and serious adverse events (SAEs) monitored for up to 2 years.
Other Endpoint
Pharmacokinetic (PK) assessments include single- and multiple-dose Cmax, AUC (0-tlast), AUC (0-504), and AUC (0-inf) over specified cycles (1, 3, 5, etc.). Biological markers FGFR2, CK18, and nucleosome levels in tumor/plasma are evaluated at screening and treatment milestones. Anti-drug antibodies (ADAs) and tumor response per RECIST are measured to assess immunogenicity and efficacy.

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Experiment 2 Reporting the Activity Date of This ADC [2]
Patients Enrolled
Advanced solid tumors from cancer indications known to be FGFR2-positive, which were refractory to any standard therapy or had no standard therapy available, patients were required to have measurable disease, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, an expected lifespan of at least 12 weeks.
Administration Dosage
The starting dose was 0.1 mg/kg body weight, with doses increased in two-fold increments up to 0.80 mg/kg, after which the dose was escalated in 0.50 mg/kg increments, intravenously on day 1 of every 21-day cycle.
Related Clinical Trial
NCT Number NCT02368951  Clinical Status Phase 1
Clinical Description
An open-label,phase 1, dose-escalation trial to evaluate the safety, tolerability, maximum tolerated dose, pharmacokinetic, and pharmacodynamics of the anti-FGFR2 antibody drug conjugate BAY1187982 in subjects with advanced solid tumors known to express FGFR2.
Primary Endpoint
Primary endpoints included safety, tolerability, and The MTD was determined to be 0.20 mg/kg.
Other Endpoint
Secondary endpoints were pharmacokinetic evaluation and tumor response to aprutumab ixadotin.
References
Ref 1 Phase I, Dose-escalation Trial of BAY1187982 in Subjects With Advanced Solid Tumors Known to Express Fibroblast Growth Factor Receptor 2 (FGFR2)
Ref 2 First-in-Human Phase I Study of Aprutumab Ixadotin, a Fibroblast Growth Factor Receptor 2 Antibody-Drug Conjugate (BAY 1187982) in Patients with Advanced Cancer. Target Oncol. 2019 Oct;14(5):591-601.