Antibody Information

General Information of This Antibody
Antibody ID
ANI0INDAF
Antibody Name
PF-06281192
Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG1-kappa
Antigen Name
Trophoblast glycoprotein (TPBG)
  Antigen Info 
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNFGMNWVRQAPGKGLEWVAWINTNTGEPRY
AEEFKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDWDGAYFFDYWGQGTLVTVSS
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Light Chain Sequence
DIQMTQSPSSLSASVGDRVTITCKASQSVSNDVAWYQQKPGKAPKLLIYFATNRYTGVPS
RFSGSGYGTDFTLTISSLQPEDFATYYCQQDYSSPWTFGQGTKVEIK
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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
PF-06263507 [Phase 1 (discontinued)]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data stable disease (SD)
7.60%
Patients Enrolled
Eligible participants had advanced/metastatic solid tumors refractory to standard therapy, ECOG 0-1, and adequate organ function. Exclusion criteria included uncontrolled brain metastases, recent major surgery/anticancer therapy, and active infections.
Administration Dosage
Drug: PF-06263507 Part 1 - PF-06263507 will be administered intravenously in 21-day cycles in cohorts of 2 or more patients starting at a dose of 0.05 mg/kg. Increases in dose will continue until MTD is determined. Drug: PF-06263507 Part 2 - Patients with select tumor types will be treated at the MTD or Recommended Phase 2 dose selected in Part 1.
Related Clinical Trial
NCT Number NCT01891669  Clinical Status PHASE1
Clinical Description
A PHASE 1, DOSE ESCALATION STUDY OF PF-06263507 IN PATIENTS WITH ADVANCED SOLID TUMORS
Primary Endpoint
The study assessed dose-limiting toxicities (DLTs) occurring within the first treatment cycle (21 days), including severe neutropenia, febrile neutropenia, thrombocytopenia with bleeding, non-hematologic toxicities, or cardiac troponin abnormalities. AEs were graded per CTCAE v4.0, and persistent toxicity delaying treatment by >2 weeks was considered a DLT.

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Other Endpoint
Treatment-emergent adverse events (TEAEs) and treatment-related AEs were monitored from baseline through treatment cycles and follow-up, with severity graded per NCI CTCAE v4.0. Hematologic, chemistry, and urine protein abnormalities were tracked, along with vital sign changes meeting predefined criteria. Anti-drug antibodies and pharmacokinetic parameters (Tmax for PF-06263507 and metabolites) were also evaluated.

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Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 71.70% Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was further evaluated in a tumor xenograft model derived from the H1975 human lung carcinoma cell line [5T4+; 15, 800 binding sites per cell]. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of PF-06263507 was 3 mg/kg Q4D 4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung cancer Lung cancer cells Homo sapiens
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was further evaluated in a tumor xenograft model derived from the H1975 human lung carcinoma cell line [5T4+; 15, 800 binding sites per cell]. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of PF-06263507 was 10 mg/kg Q4D 4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung cancer Lung cancer cells Homo sapiens
References
Ref 1 First-in-human trial of an anti-5T4 antibody-monomethylauristatin conjugate, PF-06263507, in patients with advanced solid tumors
Ref 2 ASN004, A 5T4-targeting scFv-Fc Antibody-Drug Conjugate with High Drug-to-Antibody Ratio, Induces Complete and Durable Tumor Regressions in Preclinical Models. Mol Cancer Ther. 2021 Aug;20(8):1327-1337.