Antibody ID	ANI0GBIAA
Antibody Name	Patritumab
Organization	Amgen, Inc.; Daiichi Sankyo Co., Ltd.; U3 Pharma GmbH
Indication	Non-small cell lung cancer; Breast cancer;
Synonyms	AMG888; U3-1287    Click to Show/Hide
Antibody Type	Monoclonal antibody (mAb)
Antibody Subtype	Humanized IgG1-kappa
Antigen Name	Receptor tyrosine-protein kinase erbB-3 (ERBB3)					Antigen Info
ChEMBI ID	CHEMBL2109406
DrugBank ID	DB12090
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYN PSLKSRVTISVETSKNQFSLKLSSVTAADTAVYYCARDKWTWYFDLWGRGTLVTVSSAST KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK     Click to Show/Hide
Heavy Chain Varible Domain	QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYN PSLKSRVTISVETSKNQFSLKLSSVTAADTAVYYCARDKWTWYFDLWGRGTLVTVSS     Click to Show/Hide
Heavy Chain Constant Domain 1	ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRV     Click to Show/Hide
Heavy Chain Constant Domain 2	APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK     Click to Show/Hide
Heavy Chain Constant Domain 3	GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK     Click to Show/Hide
Heavy Chain Hinge Region	EPKSCDKTHTCPPCP     Click to Show/Hide
Heavy Chain CDR 1	GGSFSGYY     Click to Show/Hide
Heavy Chain CDR 2	INHSGST     Click to Show/Hide
Heavy Chain CDR 3	ARDKWTWYFDL     Click to Show/Hide
Light Chain Sequence	DIEMTQSPDSLAVSLGERATINCRSSQSVLYSSSNRNYLAWYQQNPGQPPKLLIYWASTR ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPRTFGQGTKVEIKRTVAAPS VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC     Click to Show/Hide
Light Chain Varible Domain	DIEMTQSPDSLAVSLGERATINCRSSQSVLYSSSNRNYLAWYQQNPGQPPKLLIYWASTR ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPRTFGQGTKVEIK     Click to Show/Hide
Light Chain Constant Domain	RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC     Click to Show/Hide
Light Chain CDR 1	QSVLYSSSNRNY     Click to Show/Hide
Light Chain CDR 2	WAS     Click to Show/Hide
Light Chain CDR 3	QQYYSTPRT     Click to Show/Hide

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Objective Response Rate (ORR)	39.00%
Patients Enrolled	In dose escalation phase, pts with metastatic or unresectable non-small cell lung cancer (NSCLC) with EGFR activating mutation after disease progression during/after EGFR TKI therapy; In Dose Expansion phase, pts with metastatic or unresectable NSCLC with EGFR activating mutation or squamous or non-squamous NSCLC with disease progression during/after systemic treatment for locally advanced or metastatic disease.    Click to Show/Hide
Administration Dosage	Dose of 3.20, 4.80, 5.60, 6.40, iv Q3W in Dose Escalation phase; EGFR mutant pts at 5.60 mg/kg IV, Q3W, and EGFR wild-type pts at RDE IV, Q3W, in Dose Expansion phase.
Related Clinical Trial
NCT Number	NCT03260491	Clinical Status	Phase 1
Clinical Description	A multicenter, open-label phase 1 study of U3-1402 in subjects with metastatic or unresectable non-small cell lung cancer.
Primary Endpoint	The confirmed ORR by blinded independent central review (BICR) was 39.00% [95% confidence interval (CI), 26.00-52.40] in patients who received HER3-DXd at a dose of 5.60 mg/kg i.v. once every 3 weeks. There was 1 complete response (CR) and 21 partial responses (PR); 19 patients had stable disease (SD) as a best response.
Other Endpoint	At a median follow-up of 10.20 months, median PFS was 8.20 (95% CI, 4.40-8.30) months (16 of 57 patients were ongoing without events), and the median OS was not reached at the time of data cutoff (95% CI, 9.40-NE months; 35 of 57 patients were ongoing without events).

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 40.30% (Day 28)	Negative HER3 expression (HER3-; IHC H score=1)
Method Description	Single-agent efficacy of HER3DXd in EGFR inhibitorresistant models of NSCLC. The dose was ten mg/kg HER3DXd or IgG control, weekly.
In Vivo Model	Non-small cell lung cancer PDX model (PDX: DFCI-306)
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 78.30% (Day 28)	High HER3 expression (HER3+++; IHC H score=202)
Method Description	Single-agent efficacy of HER3DXd in EGFR inhibitorresistant models of NSCLC. The dose was ten mg/kg HER3DXd or IgG control, weekly.
In Vivo Model	Non-small cell lung cancer PDX model (PDX: DFCI-259)
Experiment 3 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 82.20% (Day 38)	Moderate HER3 expression (HER3++; IHC H score=181)
Method Description	Single-agent efficacy of HER3DXd in EGFR inhibitorresistant models of NSCLC. The dose was ten mg/kg HER3DXd or IgG control, weekly.
In Vivo Model	Non-small cell lung cancer PDX model (PDX: DFCI-161)
Experiment 4 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 86.20% (Day 22)	High HER3 expression (HER3+++; IHC H score=248)
Method Description	Single-agent efficacy of HER3DXd in EGFR inhibitorresistant models of NSCLC. The dose was ten mg/kg HER3DXd or IgG control, weekly.
In Vivo Model	Non-small cell lung cancer PDX model (PDX: DFCI-284)

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 78.50% (Day 7)	Positive HER3 expression (HER3 +++/++)
Method Description	U3-1402 (30 mg/kg body weight in 200 uL ABS, weekly), ABS (200 L, weekly; vehicle), anti-PD-1 antibody (10 mg/kg body weight in 200 L PBS, twice a week), or a combination of U3-1402 and anti-PD-1 were received intraperitoneal injections.
In Vivo Model	B16-F10 CDX model
In Vitro Model	Mouse melanoma	B16-F10 cells		CVCL_0159
Experiment 2 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 95.10% (Day 21)	Positive HER3 expression (HER3+++/++)
Method Description	U3-1402 (6 m ug/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of breast cancer cell line MDA-MB-453 with HER2 expression with high expression.
In Vivo Model	MDA-MB-453 CDX model
In Vitro Model	Breast adenocarcinoma	MDA-MB-453 cells		CVCL_0418

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Maximum inhibition efficiency (MIE)	64.70%	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	4.79 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Maximum inhibition efficiency (MIE)	65.10%	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	3.18 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Maximum inhibition efficiency (MIE)	66.10%	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	3.17 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Maximum inhibition efficiency (MIE)	67.90%	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	2.23 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Maximum inhibition efficiency (MIE)	68.90%	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	3.45 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Maximum inhibition efficiency (MIE)	74.10%	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	1.29 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Maximum inhibition efficiency (MIE)	75.60%	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.53 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Maximum inhibition efficiency (MIE)	77.70%	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.37 nM	Positive HER2 expression (HER2 +++/++)
Method Description	Seeding cells (HCC1569) into 96-well plate, at 2E3 cell per well (80 uL/well). Overnight incubation.
In Vitro Model	Breast ductal carcinoma	HCC1569 cells		CVCL_1255

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Maximum inhibition efficiency (MIE)	78.20%	High HER2 expression (HER2+++)
Method Description	The in vitro potency of ADC was measured in a panel of cancer cell lines usingthe CellTiter-Glo Luminescent Viability Assay.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.32 nM	High HER2 expression (HER2+++)
Method Description	The in vitro potency of ADC was measured in a panel of cancer cell lines usingthe CellTiter-Glo Luminescent Viability Assay.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Ref 1	Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in EGFR Inhibitor-Resistant, EGFR-Mutated Non-Small Cell Lung Cancer. Cancer Discov. 2022 Jan;12(1):74-89.
Ref 2	EGFR Inhibition Enhances the Cellular Uptake and Antitumor-Activity of the HER3 Antibody-Drug Conjugate HER3-DXd. Cancer Res. 2022 Jan 1;82(1):130-141.
Ref 3	Two drugs for advanced HER2-positive breast cancer (Enhertu and Tukysa). Med Lett Drugs Ther. 2020 Nov 16;62(1611):182-184.
Ref 4	A Novel HER3-Targeting Antibody-Drug Conjugate, U3-1402, Exhibits Potent Therapeutic Efficacy through the Delivery of Cytotoxic Payload by Efficient Internalization. Clin Cancer Res. 2019 Dec 1;25(23):7151-7161. doi: 10.1158/1078-0432.CCR-19-1745. Epub 2019 Aug 30.
Ref 5	Antibody drug conjugates; 2023-07-06.