Antibody Information
General Information of This Antibody
Antibody ID | ANI0WKJOW |
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Antibody Name | Datopotamab |
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Organization | Daiichi Sankyo Co., Ltd. |
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Indication | Solid tumors |
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Synonyms |
DATO
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Antibody Type | Monoclonal antibody (mAb) |
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Antibody Subtype | Humanized IgG1-kappa |
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Antigen Name | Tumor-associated calcium signal transducer 2 (TACSTD2) |
Antigen Info | ||||
Click to Show/Hide the Sequence Information of This Antibody | ||||||
Heavy Chain Sequence |
QVQLVQSGAEVKKPGASVKVSCKASGYTFTTAGMQWVRQAPGQGLEWMGWINTHSGVPKY
AEDFKGRVTISADTSTSTAYLQLSSLKSEDTAVYYCARSGFGSSYWYFDVWGQGTLVTVS SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
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Heavy Chain Varible Domain |
QVQLVQSGAEVKKPGASVKVSCKASGYTFTTAGMQWVRQAPGQGLEWMGWINTHSGVPKY
AEDFKGRVTISADTSTSTAYLQLSSLKSEDTAVYYCARSGFGSSYWYFDVWGQGTLVTVS S Click to Show/Hide
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Heavy Chain Constant Domain 1 |
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRV Click to Show/Hide
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Heavy Chain Constant Domain 2 |
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK Click to Show/Hide
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Heavy Chain Constant Domain 3 |
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
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Heavy Chain Hinge Region |
EPKSCDKTHTCPPCP
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Heavy Chain CDR 1 |
GYTFTTAG
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Heavy Chain CDR 2 |
INTHSGVP
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Heavy Chain CDR 3 |
ARSGFGSSYWYFDV
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Light Chain Sequence |
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGVPS
RFSGSGSGTDFTLTISSLQPEDFAVYYCQQHYITPLTFGQGTKLEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
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Light Chain Varible Domain |
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGVPS
RFSGSGSGTDFTLTISSLQPEDFAVYYCQQHYITPLTFGQGTKLEIK Click to Show/Hide
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Light Chain Constant Domain |
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
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Light Chain CDR 1 |
QDVSTA
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Light Chain CDR 2 |
SAS
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Light Chain CDR 3 |
QQHYITPLT
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The Activity Data of This Antibody
Antibody Activity Information 1 | [1] | |||||
Antibody Function | In vivo Antitumor activity of TROP2specific ADCs in cell line-derived xenograft models. | |||||
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Antibody Antigen Binding Assay | Datopotamab is a human IgG1 mAb generated by humanization of the mouse mAb against human TROP2, which was obtained by immunization of mice with NCI-H322 human lung adenocarcinoma cells followed by screening of the mAbs that internalized into tumor cells using Adv-FZ33 and DT3C technology. |
Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
Datopotamab deruxtecan [Phase 3]
Identified from the Human Clinical Data
Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
Efficacy Data | Objective Response Rate (ORR) |
24.00% (NSCLC, 4 mg/kg)
26.00% (NSCLC, 6 mg/kg) 24.00% (NSCLC, 8 mg/kg) 39.00% (TNBC, 6 mg/kg) |
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Patients Enrolled |
Patients were unselected for TROP2 expression and had measurable disease per RECIST version 1.1; patients with stable/treated brain metastases were permitted.
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Administration Dosage |
Dato-DXd 4 mg/kg (n=50), 6 mg/kg (n=50), or 8 mg/kg (n=80) intravenously every 3 weeks.
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Related Clinical Trial | |||||
NCT Number | NCT03401385 | Clinical Status | Phase 1/2 | ||
Clinical Description |
Phase 1, two-part, multicenter, open-label, multiple dose, first-in-human study of DS-1062a in subjects with advanced solid tumors (TROPION-PanTumor01).
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Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
Efficacy Data | Objective Response Rate (ORR) |
34.00
52.00% (in a subset nave to TOPO I-based ADCs) |
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Patients Enrolled |
Unresectable a/mTNBC pts eligible for 1L treatment, regardless of PD-L1/TROP2 status.
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Administration Dosage |
Intravenous Dato-DXd 6 mg/kg + durvalumab 1120 mg every 3 weeks.
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Related Clinical Trial | |||||
NCT Number | NCT03742102 | Clinical Status | Phase 1/2 | ||
Clinical Description |
A phase 1b/2, 2-stage, open-label, multicenter study to determine the efficacy and safety of durvalumab (MEDI4736) + paclitaxel and durvalumab (MEDI4736) in combination with novel oncology therapies with or without paclitaxel for first-line metastatic triple negative breast cancer.
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Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
Efficacy Data | Objective Response Rate (ORR) |
22.00%
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High TROP2 expression (TROP2 +++) | ||
Patients Enrolled |
Two hundred ten adults with locally advanced/metastatic non-small cell lung cancer (NSCLC).
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Administration Dosage |
0.27-10 mg/kg Dato-DXd once every 3 weeks during escalation or 4 mg/kg Dato-DXd once every 3 weeks during expansion.
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Related Clinical Trial | |||||
NCT Number | NCT03401385 | Clinical Status | Phase 1 | ||
Clinical Description |
Phase 1, two-part, multicenter, open-label, multiple dose, first-in-human study of DS-1062a in subjects with advanced solid tumors (TROPION-PanTumor01).
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Experiment 4 Reporting the Activity Date of This ADC | [4] | ||||
Efficacy Data | Objective Response Rate (ORR) |
23.80%
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High TROP2 expression (TROP2 +++) | ||
Patients Enrolled |
Two hundred ten adults with locally advanced/metastatic non-small cell lung cancer (NSCLC).
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Administration Dosage |
0.27-10 mg/kg Dato-DXd once every 3 weeks during escalation or 8 mg/kg Dato-DXd once every 3 weeks during expansion.
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Related Clinical Trial | |||||
NCT Number | NCT03401385 | Clinical Status | Phase 1 | ||
Clinical Description |
Phase 1, two-part, multicenter, open-label, multiple dose, first-in-human study of DS-1062a in subjects with advanced solid tumors (TROPION-PanTumor01).
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Experiment 5 Reporting the Activity Date of This ADC | [4] | ||||
Efficacy Data | Objective Response Rate (ORR) |
26.00%
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High TROP2 expression (TROP2 +++) | ||
Patients Enrolled |
Two hundred ten adults with locally advanced/metastatic non-small cell lung cancer (NSCLC).
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Administration Dosage |
0.27-10 mg/kg Dato-DXd once every 3 weeks during escalation or 6 mg/kg Dato-DXd once every 3 weeks during expansion.
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Related Clinical Trial | |||||
NCT Number | NCT03401385 | Clinical Status | Phase 1 | ||
Clinical Description |
Phase 1, two-part, multicenter, open-label, multiple dose, first-in-human study of DS-1062a in subjects with advanced solid tumors (TROPION-PanTumor01).
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Primary Endpoint |
Patients receiving 6 mg/kg (n = 50), median duration on study, including follow-up, and median exposure were 13.30 and 3.50 months, respectively. The most frequent any-grade treatment-emergent adverse events (TEAEs) were nausea (64.00%), stomatitis (60.00%), and alopecia (42.00%).
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Experiment 6 Reporting the Activity Date of This ADC | [5] | ||||
Efficacy Data | Objective Response Rate (ORR) |
50.00% (doublet)
57.00% (triplet) |
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Patients Enrolled |
Pts in escalation may have received 2 prior lines of therapy for a non-small cell lung cancer (NSCLC). Pts in expansion were primarily treatment (tx) naive (pts receiving Dato-DXd + pembro may have 1 prior Pt-based tx).
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Administration Dosage |
Dato-DXd (4 or 6 mg/kg) + pembro 200 mg Pt-CT (cisplatin 75 mg/m2 or carboplatin AUC 5) every 21 days across 6 cohorts.
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Related Clinical Trial | |||||
NCT Number | NCT04526691 | Clinical Status | Phase 1 | ||
Clinical Description |
Phase 1b, multicenter, open-label study of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy in subjects with advanced or metastatic non-small cell lung cancer (TROPION-Lung02).
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Experiment 7 Reporting the Activity Date of This ADC | [6] | ||||
Related Clinical Trial | |||||
NCT Number | NCT05687266 | Clinical Status | Phase 3 | ||
Clinical Description |
A phase 3, randomised, open-label, multicentre, global study of datopotamab deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin versus pembrolizumab in combination with platinum-based chemotherapy for the first-line treatment of patients with locally advanced or metastatic NSCLC without actionable genomic alterations (D926NC00001; AVANZAR).
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Experiment 8 Reporting the Activity Date of This ADC | [7] | ||||
Related Clinical Trial | |||||
NCT Number | NCT05629585 | Clinical Status | Phase 3 | ||
Clinical Description |
A phase 3 open-label, randomised study of datopotamab deruxtecan (DatoDXd) with or without durvalumab versus investigator's choice of therapy in patients with stage i-2i triple-negative breast cancer who have residual invasive disease in the breast and/or axillary lymph nodes at surgical resection following neoadjuvant systemic therapy (TROPION-Breast03).
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Experiment 9 Reporting the Activity Date of This ADC | [8] | ||||
Patients Enrolled |
Patients with previously untreated, advanced or metastatic non-squamous NSCLC with less than 50% programmed death-ligand (PD-L1) expression (tumor proportion score [TPS] < 50%) and without actionable genomic alterations.
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Administration Dosage |
Arm A (datopotamab deruxtecan [6 mg/kg] plus pembrolizumab 200 mg IV plus platinum chemotherapy every three weeks), Arm B (datopotamab deruxtecan [6 mg/kg] plus pembrolizumab 200 mg IV every three weeks), and Arm C (pembrolizumab 200 mg IV plus pemetrexed [500 mg/m2] plus platinum chemotherapy every three weeks).
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Related Clinical Trial | |||||
NCT Number | NCT05555732 | Clinical Status | Phase 3 | ||
Clinical Description |
A randomized phase 3 study of datopotamab deruxtecan (Dato-DXd) and pembrolizumab with or without platinum chemotherapy in subjects with no prior therapy for advanced or metastatic PD-L1 TPS <50% non-squamous non-small cell lung cancer without actionable genomic alterations (TROPION-Lung07).
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Experiment 10 Reporting the Activity Date of This ADC | [9] | ||||
Related Clinical Trial | |||||
NCT Number | NCT05374512 | Clinical Status | Phase 3 | ||
Clinical Description |
A phase 3, open-label, randomised study of datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy in patients who are not candidates for PD-1/PD-L1 inhibitor therapy in first-line locally recurrent inoperable or metastatic triple-negative breast cancer (TROPION Breast02).
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Experiment 11 Reporting the Activity Date of This ADC | [10] | ||||
Patients Enrolled |
Advanced non-small cell lung cancer (NSCLC).
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Administration Dosage |
Dato-DXd 6 mg/kg plus pembrolizumab 200 mg every 3 weeks (arm 1) and pembrolizumab 200 mg every 3 weeks (arm 2).
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Related Clinical Trial | |||||
NCT Number | NCT05215340 | Clinical Status | Phase 3 | ||
Clinical Description |
A randomized, open-label, phase 3 trial of Dato-DXd plus pembrolizumab vs pembrolizumab alone in treatment-nave subjects with advanced or metastatic PD-L1 high (TPS 50%) non-small cell lung cancer without actionable genomic alterations (TROPION-Lung08).
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Experiment 12 Reporting the Activity Date of This ADC | [11] | ||||
Patients Enrolled |
Patients with inoperable or metastatic HR+/HER2 breast cancer.
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Administration Dosage |
Dato-DXd 6 mg/kg IV Q3W or ICC (eribulin, capecitabine, vinorelbine, or gemcitabine).
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Related Clinical Trial | |||||
NCT Number | NCT05104866 | Clinical Status | Phase 3 | ||
Clinical Description |
A phase-3, open-label, randomized study of Dato-DXd versus investigator's choice of chemotherapy (ICC) in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy (TROPION-Breast01).
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Experiment 13 Reporting the Activity Date of This ADC | [12] | ||||
Related Clinical Trial | |||||
NCT Number | NCT04656652 | Clinical Status | Phase 3 | ||
Clinical Description |
Phase 3 randomized study of DS-1062a versus docetaxel in previously treated advanced or metastatic non-small cell lung cancer (TROPION-LUNG01).
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Experiment 14 Reporting the Activity Date of This ADC | [13] | ||||
Related Clinical Trial | |||||
NCT Number | NCT05489211 | Clinical Status | Phase 2 | ||
Clinical Description |
A phase 2, multicentre, open-label, master protocol to evaluate the efficacy and safety of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with anticancer agents in patients with advanced/metastatic solid tumours (TROPION-PanTumor03).
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Experiment 15 Reporting the Activity Date of This ADC | [14] | ||||
Related Clinical Trial | |||||
NCT Number | NCT05061550 | Clinical Status | Phase 2 | ||
Clinical Description |
A phase 2, open-label, multicentre, randomised study of neoadjuvant and adjuvant treatment in patients with resectable, early-stage (2 to 2IB) non-small cell lung cancer (NeoCOAST-2).
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Experiment 16 Reporting the Activity Date of This ADC | [15] | ||||
Related Clinical Trial | |||||
NCT Number | NCT04940325 | Clinical Status | Phase 2 | ||
Clinical Description |
Phase 2, open label study of DS-1062a, an anti-TROP-2-antibody-drug conjugate (ADC), in patients with advanced and/or unresectable non-small cell lung cancer (NSCLC), with biomarker analysis to characterize response to therapy.
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Experiment 17 Reporting the Activity Date of This ADC | [16] | ||||
Related Clinical Trial | |||||
NCT Number | NCT04484142 | Clinical Status | Phase 2 | ||
Clinical Description |
Phase 2, single-arm, open-label study of DS-1062A in advanced or metastatic non-small cell lung cancer with actionable genomic alterations and progressed on or after applicable targeted therapy and platinum based chemotherapy (TROPION-Lung05).
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Experiment 18 Reporting the Activity Date of This ADC | [17] | ||||
Related Clinical Trial | |||||
NCT Number | NCT03944772 | Clinical Status | Phase 2 | ||
Clinical Description |
A biomarker-directed phase 2 platform study in patients with advanced non-small lung cancer whose disease has progressed on first-line osimertinib therapy.
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Experiment 19 Reporting the Activity Date of This ADC | [18] | ||||
Related Clinical Trial | |||||
NCT Number | NCT01042379 | Clinical Status | Phase 2 | ||
Clinical Description |
I-SPY trial (investigation of serial studies to predict your therapeutic response with imaging and molecular analysis 2).
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Experiment 20 Reporting the Activity Date of This ADC | [19] | ||||
Related Clinical Trial | |||||
NCT Number | NCT05460273 | Clinical Status | Phase 1/2 | ||
Clinical Description |
Phase 1/2, multicentre, open-label, multiple-cohort study of Dato-DXd in Chinese patients with advanced non-small-cell lung cancer, triple-negative breast cancer, gastric/gastroesophageal junction cancer, urothelial cancer, and other solid tumours (TROPION-PanTumor02).
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Experiment 21 Reporting the Activity Date of This ADC | [20] | ||||
Related Clinical Trial | |||||
NCT Number | NCT04644068 | Clinical Status | Phase 1 | ||
Clinical Description |
A modular phase 1/2a, open-label, multicentre study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of ascending doses of AZD5305 as monotherapy and in combination with anti-cancer agents in patients with advanced solid malignancies.
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Experiment 22 Reporting the Activity Date of This ADC | [21] | ||||
Related Clinical Trial | |||||
NCT Number | NCT04612751 | Clinical Status | Phase 1 | ||
Clinical Description |
A phase 1b, multicenter, 2-part, open-label study of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy with or without carboplatin in participants with advanced or metastatic non-small cell lung cancer (Tropion-Lung04).
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Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 96.00% (Day 21) | High TROP2 expression (TROP2+++) | ||
Method Description |
Dato-DXd was intravenously administered at 10 mg/kg to NCI-N87 xenograft model mice. When the tumor volume reached approximately 150-300 mm3,the tumor-bearing mice were assigned to the vehicle control group,the treatment groups and the satellite sampling groups,and Dato-DXd or other test substances were administered intravenously once on day 0.
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In Vivo Model | NCI-N87 cell line xenograft model | ||||
In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 |
References
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