General Information of This Antibody
Antibody ID
ANI0EIMTT
Antibody Name
Vobramitamab
Organization
MacroGenics, Inc.
Indication
Prostate cancer; Melanoma; Non-small cell lung cancer
Synonyms
MGA017
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Antibody Type
Monoclonal antibody (mAb)
Antibody Subtype
Humanized IgG1-kappa
Antigen Name
CD276 antigen (CD276)
 Antigen Info 
ChEMBI ID
CHEMBL5095157
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence
EVQLVESGGGLVKPGGSLRLSCAASGFTESSYGMSWVRQAPGKGLEWVATINSGGSNTYY
PDSLKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARHDGGAMDYWGQGTTVTVSSAST
KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTEPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVESCSVMHEALHNHYTQKSLSLSPGK
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Light Chain Sequence
DIQMTQSPSSLSASVGDRVTITCRASESIYSYLAWYQQKPGKAPKLLVYNTKTLPEGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQHHYGTPPWTFGQGTRLEIKRTVAAPSVFIFP
PSDEQLKSGTASVVCLLNNEYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL
TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
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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
Vobramitamab duocarmazine [Phase 2/3]
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]
Related Clinical Trial
NCT Number NCT05551117  Clinical Status Phase 2
Clinical Description
A phase 2, randomized, open-label, study of two dose levels of obramitamab duocarmazine in participants with metastatic castration-resistant prostate cancer.
Experiment 2 Reporting the Activity Date of This ADC [2]
Patients Enrolled
Patients of multiple tumor types, which included 3 melanoma patients refractory to 2 prior lines of checkpoint therapy.
Administration Dosage
6 dose cohorts (0.50-4.00 mg/kg) every 3 weeks.
Related Clinical Trial
NCT Number NCT03729596  Clinical Status Phase 1/2
Clinical Description
A phase 1/2, first-in-human, open-label, dose-escalation study of MGC018 (anti-B7-H3 antibody drug conjugate) alone and in combination with MGA012 (anti-PD-1 antibody) in patients with advanced solid tumors.
Experiment 3 Reporting the Activity Date of This ADC [3]
Related Clinical Trial
NCT Number NCT05293496  Clinical Status Phase 1
Clinical Description
A phase 1/1b dose escalation and cohort expansion study of MGC018 in combination with checkpoint inhibitor in participants with advanced solid tumors.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 96.10% (Day 21) High MET expression (MET+++; IHC H-score=265)
Method Description
Female Athymic Nude-Foxn1nu from Envigo (head and neck,triple-negative breast cancer models),68 weeks of age,were used for the PDX studies. Low passage tumor fragments were implanted into stock animals. When tumors reached 1.01.5 cm3,they were reimplanted into prestudy animals unilaterally on the left flank. When tumors reached an average tumor volume of 150-300 mm3,animals were matched by tumor volume into treatment or vehicle control groups. Three animals were assigned to each group and dosed intravenously by tail vein injection (10 mL/kg). Tumor volumes were measured twice weekly by calipers. Prostate cancer subcutaneous PDX model treated with MGC018 or control ADC at 3 mg/kg (QW3).

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In Vivo Model Pancreatic cancer PDX model (PDX: PDX-PAX-13565)
Experiment 2 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.60% (Day 42) Moderate MET expression (MET++; IHC H-score=130)
Method Description
Male NOG mice from Taconic (prostate cancer model),68 weeks of age,were used for the PDX studies. Low passage tumor fragments were implanted into stock animals. When tumors reached 1.01.5 cm3,they were reimplanted into prestudy animals unilaterally on the left flank. When tumors reached an average tumor volume of 150-300 mm3,animals were matched by tumor volume into treatment or vehicle control groups. Three animals were assigned to each group and dosed intravenously by tail vein injection (10 mL/kg). Tumor volumes were measured twice weekly by calipers. Head and neck cancer subcutaneous PDX model treated with MGC018 or control ADC at 3 mg/kg (Q2W 2).

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In Vivo Model Head and neck cancer PDX model
Experiment 3 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.20% (Day 10) High MET expression (MET+++; IHC H-score=240)
Method Description
Female Athymic Nude-Foxn1nu from Envigo (head and neck,triple-negative breast cancer models),68 weeks of age,were used for the PDX studies. Low passage tumor fragments were implanted into stock animals. When tumors reached 1.01.5 cm3,they were reimplanted into prestudy animals unilaterally on the left flank. When tumors reached an average tumor volume of 150-300 mm3,animals were matched by tumor volume into treatment or vehicle control groups. Three animals were assigned to each group and dosed intravenously by tail vein injection (10 mL/kg). Tumor volumes were measured twice weekly by calipers. Triple-negative breast cancer subcutaneous PDX model treated with MGC018 or control ADC at 3 mg/kg (QW2).

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In Vivo Model Triple-negative breast cancer PDX model
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 25 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 22.40% (Day 50) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QWx4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 2 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 30.10% (Day 80) Moderate MET expression (MET++; IHC H-score=150)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg as a single dose,QW1.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 3 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 42.90% (Day 60) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 4 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 43.90% (Day 100) NegativeCD276 expression (CD276-)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 3 mg/kg.

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In Vivo Model Triple-negative breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 Luc cells CVCL_0419
Experiment 5 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 59.30% (Day 70) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 6 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 62.70% (Day 100) Moderate MET expression (MET++; IHC H-score=150)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3).MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QW4.

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In Vivo Model Triple-negative breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 Luc cells CVCL_0419
Experiment 7 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 62.80% (Day 70) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QW4.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 8 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 66.50% (Day 50) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 9 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 71.90% (Day 50) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg QWx4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 10 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.30% (Day 50) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 6 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 11 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.60% (Day 60) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 0.3 mg/kg QW4.

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In Vivo Model Melanoma CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 12 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 82.80% (Day 50) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg QWx4.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 13 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 83.90% (Day 60) High MET expression (MET+++; IHC H-score=265)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg.

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In Vivo Model Melanoma CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 14 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.50% (Day 50) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 10 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 15 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 88.80% (Day 60) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 6 mg/kg.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 16 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 90.50% (Day 60) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 10 mg/kg.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 17 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 91.40% (Day 80) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg as a single dose,QW4.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 18 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 94.60% (Day 70) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg QW4.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 19 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 96.70% (Day 70) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 6 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 20 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.00% (Day 100) Moderate MET expression (MET++; IHC H-score=150)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3).MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 1 mg/kg QW4.

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In Vivo Model Triple-negative breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 Luc cells CVCL_0419
Experiment 21 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.60% (Day 80) High MET expression (MET+++; IHC H-score=287)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). PA-1 ovarian cancer subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg as a single dose,Q2W4.

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In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 22 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.90% (Day 100) Moderate MET expression (MET++; IHC H-score=150)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). MDA-MB-468 triple-negative breast cancer orthotopic xenografts were treated with MGC018 or control ADC at 6 mg/kg.

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In Vivo Model Triple-negative breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 Luc cells CVCL_0419
Experiment 23 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.10% (Day 60) High MET expression (MET+++; IHC H-score=265)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 3 mg/kg.

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In Vivo Model Melanoma CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 24 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.60% (Day 70) High MET expression (MET+++; IHC H-score=255)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). Calu-6 lung cancer subcutaneous xenografts were treated with MGC018 or control ADC at 10 mg/kg.

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In Vivo Model Lung cancer CDX model
In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 25 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 99.70% (Day 60) High MET expression (MET+++; IHC H-score=265)
Method Description
Human tumor cells (5x106) were resuspended in 1:1 medium (DMEM/F-12) and Matrigel basement membrane matrix (Corning) and implanted subcutaneously into the flank (A375.S2,Calu-6,PA-1) or mammary fat pad (MDA-MB-468) of mice. Mice were randomized into groups of 5-7 individuals per group. ADCs or vehicle control (PBS) were administered intravenously by tail vein injection (10 mL/kg) following growth of established tumors (100-150 mm3). A375.S2 melanoma subcutaneous xenografts were treated with MGC018 or control ADC at 1 mg/kg QW4.

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In Vivo Model Melanoma CDX model
In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Revealed Based on the Cell Line Data
Click To Hide/Show 9 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
181.00 pM
High CD276 expression (CD276+++; 138,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Amelanotic melanoma A375.S2 cells CVCL_0136
Experiment 2 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
260.00 pM
High CD276 expression (CD276+++; 139,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Lung adenocarcinoma Calu-6 cells CVCL_0236
Experiment 3 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
275.00 pM
High CD276 expression (CD276+++; 310,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Ovarian mixed germ cell tumor PA-1 cells CVCL_0479
Experiment 4 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
319.00 pM
High CD276 expression (CD276+++; 122,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Neoplasm Hs 700T cells CVCL_0858
Experiment 5 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
585.00 pM
Moderate MET expression (MET++; IHC H-score=180)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Lung squamous cell carcinoma NCI-H1703 cells CVCL_1490
Experiment 6 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
767.00 pM
Moderate CD276 expression (CD276++; 57,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 7 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
910.00 pM
Moderate CD276 expression (CD276++; 73,700 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Glioblastoma LN-229 cells CVCL_0393
Experiment 8 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1447.00 pM
High CD276 expression (CD276+++; 153,000 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model Colon adenocarcinoma SW48 cells CVCL_1724
Experiment 9 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 nM Moderate CD276 expression (CD276++; 59,800 CD276 molecules/cell)
Method Description
MGC018-mediated in vitro cytotoxicity was evaluated across a set of tumor cell lines representing multiple cancer types expressing varying levels of B7-H3. MDA-MB-468,A375.S2,PA-1,Calu-6,Hs700T,SW48,and LN-229 tumor cell lines were obtained from ATCC and cultured in DMEM/F-12 media containing 10% FBS. NCI-H1703 and Raji tumor cell lines were obtained from ATCC and cultured in RPMI1640 media containing 10% FBS.

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In Vitro Model EBV-related Burkitt lymphoma Raji cells CVCL_0511
References
Ref 1 A Phase 2, Randomized, Open-label, Study of Two Dose Levels of Obramitamab Duocarmazine in Participants With Metastatic Castration-resistant Prostate Cancer, NCT05551117
Ref 2 Zilovertamab vedotin (MK 2140) in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Early results from the phase 2 waveLINE-004 study. J Clin Oncol. 2023 41:16_suppl, 7531-7531.
Ref 3 A Phase 1/1b Dose Escalation and Cohort Expansion Study of MGC018 in Combination With Checkpoint Inhibitor in Participants With Advanced Solid Tumors, NCT05293496
Ref 4 Preclinical Development of MGC018, a Duocarmycin-based Antibody-drug Conjugate Targeting B7-H3 for Solid Cancer. Mol Cancer Ther. 2020 Nov;19(11):2235-2244.

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