Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0FSHWJ
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| ADC Name |
Indusatumab vedotin
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| Synonyms |
GCC antibody drug conjugate; MLN-0264; TAK-264; TAK264; TAK 264; MLN0264; MLN 0264
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| Organization |
Millennium Pharmaceuticals, Inc.; Takeda Pharmaceutical Co., Ltd.; Seagen Inc.
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| Drug Status |
Terminated in phase 2
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| Indication |
In total 6 Indication(s)
Adenocarcinoma [ICD11:2D40]
Terminated in phase 2
Colorectal cancer [ICD11:2B91]
Terminated in phase 2
Gastroesophageal cancer [ICD11:2B71]
Terminated in phase 2
Pancreatic cancer [ICD11:2C10]
Terminated in phase 2
Esophageal cancer [ICD11:2B70]
Terminated in phase 1
Gastric cancer [ICD11:2B72]
Terminated in phase 1
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| Drug-to-Antibody Ratio |
4
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| Antibody Name |
Indusatumab
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Antibody Info | ||||
| Antigen Name |
Guanylyl cyclase C (GUCY2C)
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Antigen Info | ||||
| Payload Name |
Monomethyl auristatin E
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Mc-Val-Cit-PABC
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Linker Info | ||||
| Conjugate Type |
Random conjugation through reduced inter-chain cysteines.
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| Combination Type |
Vedotin
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| Puchem SID | ||||||
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| ChEBI ID | ||||||
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Discovered Using Patient-derived Xenograft Model
Revealed Based on the Cell Line Data
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
| 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.
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| 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.
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| 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).
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| 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,.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| Other Endpoint |
There were no objective responses; three patients had stable disease.
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| 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.
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| 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.
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| 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.
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| Other Endpoint |
MTD=1.80 mg/kg.
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Discovered Using Patient-derived Xenograft Model
| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| In Vivo Model | Pancreatic cancer PDX model (PDX: PANC122) | ||||
Revealed Based on the Cell Line Data
| 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.
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| 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.
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| 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.
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| 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.
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| 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.
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| In Vitro Model | Pancreatic adenocarcinoma | Panc 02.03 cells | CVCL_1633 | ||
References
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