Antibody Information

General Information of This Antibody

Antibody ID	ANI0WDEHD
Antibody Name	Indusatumab
Organization	Millennium Pharmaceuticals, Inc.
Indication	Neoplasms
Synonyms	5F9; MLN2045 Click to Show/Hide
Antibody Type	Monoclonal antibody (mAb)
Antibody Subtype	Humanized IgG1-kappa
Antigen Name	Guanylyl cyclase C (GUCY2C)	Antigen Info
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence	QVQLQQWGAGLLKPSETLSLTCAVFGGSFSGYYWSWIRQPPGKGLEWIGEINHRGNTNDN PSLKSRVTISVDTSKNQFALKLSSVTAADTAVYYCARERGYTYGNFDHWGQGTLVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
Heavy Chain Varible Domain	QVQLQQWGAGLLKPSETLSLTCAVFGGSFSGYYWSWIRQPPGKGLEWIGEINHRGNTNDN PSLKSRVTISVDTSKNQFALKLSSVTAADTAVYYCARERGYTYGNFDHWGQGTLVTVSS Click to Show/Hide
Heavy Chain Constant Domain 1	ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV Click to Show/Hide
Heavy Chain Constant Domain 2	APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK Click to Show/Hide
Heavy Chain Constant Domain 3	GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS 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	INHRGNT Click to Show/Hide
Heavy Chain CDR 3	ARERGYTYGNFDH Click to Show/Hide
Light Chain Sequence	EIVMTQSPATLSVSPGERATLSCRASQSVSRNLAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTEFTLTIGSLQSEDFAVYYCQQYKTWPRTFGQGTNVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
Light Chain Varible Domain	EIVMTQSPATLSVSPGERATLSCRASQSVSRNLAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTEFTLTIGSLQSEDFAVYYCQQYKTWPRTFGQGTNVEIK Click to Show/Hide
Light Chain Constant Domain	RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
Light Chain CDR 1	QSVSRN Click to Show/Hide
Light Chain CDR 2	GAS Click to Show/Hide
Light Chain CDR 3	QQYKTWPRT Click to Show/Hide

Each Antibody-drug Conjugate Related to This Antibody

Full Information of The Activity Data of The ADC(s) Related to This Antibody

Indusatumab vedotin [Terminated in phase 2]

ADC Info

Identified from the Human Clinical Data

Click To Hide/Show 6 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[1]
Efficacy Data	Objective Response Rate (ORR)	2.56%	High GCC expression (GCC+++)
Patients Enrolled	Advanced or metastatic adenocarcinoma of the pancreas expressing GCC (H-score 10, as indicated by immunohistochemistry [IHC]), and previously treated with one or more prior chemotherapies.
Administration Dosage	1.80 mg/kg on day 1 of 3-week cycles as single 30-min intravenous (IV) infusions for up to 1 year or until disease progression (PD) or unacceptable toxicity.
*Related Clinical Trial*
NCT Number	NCT02202785	Clinical Status	Phase 2
Clinical Description	A phase 2 trial of mLN0264 in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C (GCC).
Primary Endpoint	OrR (CR+PR)=2.56% (N=1/39), one patient achieving PR, DOR=103 days. Nine (23.07%) patients achieved SD, among those nine patients, two patients (18%, low-GCC),four patients (31%, intermediate-GCC), and three patients (20%, high-GCC).
Other Endpoint	Median OS=162 days (range 36-282) and PFS=9-82 days in the low-cohort,median OS=140 days (range 43-443) and PFS=1-218 days in the intermediate-cohort,median OS=162 days (range 49-435) and PFS=16-137 days in the high-cohort,.
Experiment 2 Reporting the Activity Date of This ADC				[2]
Efficacy Data	Objective Response Rate (ORR)	2.63%	High GCC expression (GCC+++)
Patients Enrolled	GI carcinoma expressing GCC (H-score 10, as indicated by immunohistochemistry [IHC]), included gastric carcinoma, esophageal carcinoma, colorectal carcinoma, small intestine carcinoma, pancreatic carcinoma, and biliary carcinoma.
Administration Dosage	1.80 mg/kg on day 1 of 3-week cycles as single 30-min intravenous (IV) infusions for up to 1 year or until disease progression (PD) or unacceptable toxicity.
*Related Clinical Trial*
NCT Number	NCT02202785	Clinical Status	Phase 2
Clinical Description	A phase 2 trial of mLN0264 in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C (GCC).
Primary Endpoint	OrR (CR+PR)=2.63% (N=1/38), one patient identified as PR, nine patients (23.68%) had stable disease.
Experiment 3 Reporting the Activity Date of This ADC				[3]
Efficacy Data	Objective Response Rate (ORR)	5.56%	High GCC expression (GCC+++)
Patients Enrolled	Metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expressing GCC (H-score 10, as indicated by immunohistochemistry [IHC]) who progressed on at least one line of treatment.
Administration Dosage	TAK-264 1.80 mg/kg was administered as a 30 minute intravenous (IV) infusion on day 1 of a 21-day cycle for up to 1 year or until disease progression or unacceptable toxicity.
*Related Clinical Trial*
NCT Number	NCT02202759	Clinical Status	Phase 2
Clinical Description	A phase 2 trial of mLN0264 in previously treated patients with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expressing guanylyl cyclase C (GCC).
Primary Endpoint	OrR (CR+PR)=5.56% (N=2/36),2 patients achieved a PR with intermediate GCC expression.
Other Endpoint	The disease control rate (CR+PR+SD with a minimum duration of 12 weeks)=36.00%, 7 patients with high GCC expression, 4 patients with intermediate GCC expression, 4 patients with low GCC expression.
Experiment 4 Reporting the Activity Date of This ADC				[4]
Efficacy Data	Objective Response Rate (ORR)	0.00%	High GCC expression (GCC+++)
Patients Enrolled	GI carcinoma expressing GCC (H-score 10, as indicated by immunohistochemistry [IHC]), included gastric carcinoma, esophageal carcinoma, colorectal carcinoma, small intestine carcinoma, pancreatic carcinoma, and biliary carcinoma.
Administration Dosage	A conventional 3+3 dose-escalation scheme, TAK-264 doses (planned dose levels, 1.20, 1.50, 1.80, 2.10, 2.40, and 2.70 mg/kg) on day 1 of 3-week cycles as 30-minute intravenous infusions for up to 1 year or until disease progression or unacceptable toxicity.
*Related Clinical Trial*
NCT Number	NCT02391038	Clinical Status	Phase 1
Clinical Description	A phase 1/2 trial of mLN0264 in previously treated asian patients with advanced gastrointestinal (GI) carcinoma (phase 1) or metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma (phase 2) expressing guanylyl cyclase C (GCC).
Primary Endpoint	None of the patients experienced a DLT and the MTD was not determined.
Other Endpoint	There were no objective responses; three patients had stable disease.
Experiment 5 Reporting the Activity Date of This ADC				[5]
*Related Clinical Trial*
NCT Number	NCT02391038	Clinical Status	Phase 1
Clinical Description	A phase 1/2 trial of mLN0264 in previously treated asian patients with advanced gastrointestinal (GI) carcinoma (phase 1) or Metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma (phase 2) expressing guanylyl cyclase C (GCC).
Experiment 6 Reporting the Activity Date of This ADC				[6]
Patients Enrolled	GCC-expressing gastrointestinal malignancy (H-score 10, derivation described below), for whom standard treatment was no longer effective or did not offer curative or life-prolonging potential, metastatic colorectal cancer, gastric carcinoma, esophageal carcinoma, small intestine cancer, pancreatic cancer, and unknown primary malignancies.
Administration Dosage	Once every 3 weeks as a 30-minute intravenous infusion (day 1 of 21-day cycles) for up to 17 cycles or until disease progression or occurrence of unacceptable TAK-264related toxicity.
*Related Clinical Trial*
NCT Number	NCT01577758	Clinical Status	Phase 1
Clinical Description	An open-label, dose escalation, phase 1, first-in-human study of mLN0264 in Adult patients with advanced gastrointestinal malignancies expressing guanylyl cyclase C.
Primary Endpoint	21 patients (53.85%, N=39) experienced progressive disease, 3 patients (7.69%, N=39) experienced stable disease. Median PFS=44 days (95% CI,39-83). No association between GCC expression and PFS.
Other Endpoint	MTD=1.80 mg/kg.

Discovered Using Patient-derived Xenograft Model

Click To Hide/Show 10 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 34.00% (Day 17)	High GCC expression (GCC+++)
Method Description	To evaluate the efficacy of TAK-264 in mouse models of pancreatic cancer,ten pancreatic PDX models were treated with 10 mg/kg of TAK-264 for at least 17 days. Each treatment group contained 56 mice with tumor pieces (~3mm³ fragments) injected into the right and left flank to give ~10 evaluable tumors. Mice were randomized into control or TAK-264 groups when tumor volumes reached ~150-300 mm³. Click to Show/Hide
In Vivo Model	Pancreatic cancer PDX model (PDX: PANC137)
Experiment 2 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 46.00% (Day 28)	High GCC expression (GCC+++)
Method Description	To evaluate the efficacy of TAK-264 in mouse models of pancreatic cancer,ten pancreatic PDX models were treated with 10 mg/kg of TAK-264 for at least 17 days. Each treatment group contained 56 mice with tumor pieces (~3mm³ fragments) injected into the right and left flank to give ~10 evaluable tumors. Mice were randomized into control or TAK-264 groups when tumor volumes reached ~150-300 mm³. Click to Show/Hide
In Vivo Model	Pancreatic cancer PDX model (PDX: PANC129)
Experiment 3 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 48.70% (Day 28)	High GCC expression (GCC+++)
Method Description	To evaluate the efficacy of TAK-264 in mouse models of pancreatic cancer,ten pancreatic PDX models were treated with 10 mg/kg of TAK-264 for at least 17 days. Each treatment group contained 56 mice with tumor pieces (~3mm³ fragments) injected into the right and left flank to give ~10 evaluable tumors. Mice were randomized into control or TAK-264 groups when tumor volumes reached ~150-300 mm³. Click to Show/Hide
In Vivo Model	Pancreatic cancer PDX model (PDX: PANC269)
Experiment 4 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 60.90% (Day 28)	High GCC expression (GCC+++)
Method Description	To evaluate the efficacy of TAK-264 in mouse models of pancreatic cancer,ten pancreatic PDX models were treated with 10 mg/kg of TAK-264 for at least 17 days. Each treatment group contained 56 mice with tumor pieces (~3mm³ fragments) injected into the right and left flank to give ~10 evaluable tumors. Mice were randomized into control or TAK-264 groups when tumor volumes reached ~150-300 mm³. Click to Show/Hide
In Vivo Model	Pancreatic cancer PDX model (PDX: PANC277)
Experiment 5 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 61.90% (Day 50)	High GCC expression (GCC+++)
Method Description	To evaluate the efficacy of TAK-264 in mouse models of pancreatic cancer,ten pancreatic PDX models were treated with 10 mg/kg of TAK-264 for at least 17 days. Each treatment group contained 56 mice with tumor pieces (~3mm³ fragments) injected into the right and left flank to give ~10 evaluable tumors. Mice were randomized into control or TAK-264 groups when tumor volumes reached ~150-300 mm³. Click to Show/Hide
In Vivo Model	Pancreatic cancer PDX model (PDX: PANC266)
Experiment 6 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 64.20% (Day 17)	High GCC expression (GCC+++)
Method Description	To evaluate the efficacy of TAK-264 in mouse models of pancreatic cancer,ten pancreatic PDX models were treated with 10 mg/kg of TAK-264 for at least 17 days. Each treatment group contained 56 mice with tumor pieces (~3mm³ fragments) injected into the right and left flank to give ~10 evaluable tumors. Mice were randomized into control or TAK-264 groups when tumor volumes reached ~150-300 mm³. Click to Show/Hide
In Vivo Model	Pancreatic cancer PDX model (PDX: PANC193)
Experiment 7 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 67.50% (Day 29)	High GCC expression (GCC+++)
Method Description	To evaluate the efficacy of TAK-264 in mouse models of pancreatic cancer,ten pancreatic PDX models were treated with 10 mg/kg of TAK-264 for at least 17 days. Each treatment group contained 56 mice with tumor pieces (~3mm³ fragments) injected into the right and left flank to give ~10 evaluable tumors. Mice were randomized into control or TAK-264 groups when tumor volumes reached ~150-300 mm³. Click to Show/Hide
In Vivo Model	Pancreatic cancer PDX model (PDX: PANC272)
Experiment 8 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 69.60% (Day 28)	High GCC expression (GCC+++)
Method Description	To evaluate the efficacy of TAK-264 in mouse models of pancreatic cancer,ten pancreatic PDX models were treated with 10 mg/kg of TAK-264 for at least 17 days. Each treatment group contained 56 mice with tumor pieces (~3mm³ fragments) injected into the right and left flank to give ~10 evaluable tumors. Mice were randomized into control or TAK-264 groups when tumor volumes reached ~150-300 mm³. Click to Show/Hide
In Vivo Model	Pancreatic cancer PDX model (PDX: PANC150)
Experiment 9 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 69.60% (Day 24)	High GCC expression (GCC+++)
Method Description	To evaluate the efficacy of TAK-264 in mouse models of pancreatic cancer,ten pancreatic PDX models were treated with 10 mg/kg of TAK-264 for at least 17 days. Each treatment group contained 56 mice with tumor pieces (~3mm³ fragments) injected into the right and left flank to give ~10 evaluable tumors. Mice were randomized into control or TAK-264 groups when tumor volumes reached ~150-300 mm³. Click to Show/Hide
In Vivo Model	Pancreatic cancer PDX model (PDX: PANC268)
Experiment 10 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 70.10% (Day 28)	High GCC expression (GCC+++)
Method Description	To evaluate the efficacy of TAK-264 in mouse models of pancreatic cancer,ten pancreatic PDX models were treated with 10 mg/kg of TAK-264 for at least 17 days. Each treatment group contained 56 mice with tumor pieces (~3mm³ fragments) injected into the right and left flank to give ~10 evaluable tumors. Mice were randomized into control or TAK-264 groups when tumor volumes reached ~150-300 mm³. Click to Show/Hide
In Vivo Model	Pancreatic cancer PDX model (PDX: PANC122)

Revealed Based on the Cell Line Data

Click To Hide/Show 5 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	< 25.00 ug/mL
Method Description	Anti-proliferative Effects of TAK-264 Against Pancreatic Cancer Cell Lines. Eleven pancreatic cancer cell lines were treated with TAK-264 (dose range 0.4-25 ug/mL) for 72 hours and analyzed by a SRB proliferation assay. Cell lines were deemed more responsive if proliferation was less than 50% after treatment with 25g/mL of TAK-264.
In Vitro Model	Pancreatic adenosquamous carcinoma	L3.6pl cells		CVCL_0384
Experiment 2 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	< 25.00 ug/mL
Method Description	Anti-proliferative Effects of TAK-264 Against Pancreatic Cancer Cell Lines. Eleven pancreatic cancer cell lines were treated with TAK-264 (dose range 0.4-25 ug/mL) for 72 hours and analyzed by a SRB proliferation assay. Cell lines were deemed more responsive if proliferation was less than 50% after treatment with 25g/mL of TAK-264.
In Vitro Model	Pancreatic ductal adenocarcinoma	MIA PaCa-2 cells		CVCL_0428
Experiment 3 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	< 25.00 ug/mL
Method Description	Anti-proliferative Effects of TAK-264 Against Pancreatic Cancer Cell Lines. Eleven pancreatic cancer cell lines were treated with TAK-264 (dose range 0.4-25 ug/mL) for 72 hours and analyzed by a SRB proliferation assay. Cell lines were deemed more responsive if proliferation was less than 50% after treatment with 25g/mL of TAK-264.
In Vitro Model	Pancreatic adenocarcinoma	Panc 03.27 cells		CVCL_1635
Experiment 4 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	< 25.00 ug/mL	High GCC expression (GCC+++)
Method Description	Anti-proliferative Effects of TAK-264 Against Pancreatic Cancer Cell Lines. Eleven pancreatic cancer cell lines were treated with TAK-264 (dose range 0.4-25 ug/mL) for 72 hours and analyzed by a SRB proliferation assay. Cell lines were deemed more responsive if proliferation was less than 50% after treatment with 25g/mL of TAK-264.
In Vitro Model	Pancreatic ductal adenocarcinoma	Panc 05.04 cells		CVCL_1637
Experiment 5 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	< 25.00 ug/mL
Method Description	Anti-proliferative Effects of TAK-264 Against Pancreatic Cancer Cell Lines. Eleven pancreatic cancer cell lines were treated with TAK-264 (dose range 0.4-25 ug/mL) for 72 hours and analyzed by a SRB proliferation assay. Cell lines were deemed more responsive if proliferation was less than 50% after treatment with 25g/mL of TAK-264.
In Vitro Model	Pancreatic adenocarcinoma	Panc 02.03 cells		CVCL_1633

References

Ref 1	A phase II study of antibody-drug conjugate, TAK-264 (MLN0264) in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C. Invest New Drugs. 2017 Oct;35(5):634-641.
Ref 2	A phase II trial of TAK-264, a novel antibody-drug conjugate (ADC), in patients with pancreatic adenocarcinoma expressing guanylyl cyclase C (GCC).
Ref 3	Phase II study of the antibody-drug conjugate TAK-264 (MLN0264) in patients with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expressing guanylyl cyclase C. Invest New Drugs. 2017 Apr;35(2):235-241.
Ref 4	TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open-Label, Non-randomized Phase 1 Study. Cancer Res Treat. 2018 Apr;50(2):398-404.
Ref 5	A Phase 1/2 Trial of MLN0264 in Previously Treated Asian Patients With Advanced Gastrointestinal (GI) Carcinoma (Phase 1) or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma (Phase 2) Expressing Guanylyl Cyclase C (GCC), NCT02391038
Ref 6	Phase I Study of the Investigational Anti-Guanylyl Cyclase Antibody-Drug Conjugate TAK-264 (MLN0264) in Adult Patients with Advanced Gastrointestinal Malignancies. Clin Cancer Res. 2016 Oct 15;22(20):5049-5057.
Ref 7	Evaluation of TAK-264, an Antibody-Drug Conjugate in Pancreatic Cancer Cell Lines and Patient-Derived Xenograft Models. Clin Cancer Drugs. 2018;5(1):42-49.

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Correspondence

Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xiaowu DONG (dongxw@zju.edu.cn)

Prof. Luo FANG (fangluo@zjcc.org.cn)