Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0WJKRI
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| ADC Name |
DS-6157
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| Synonyms |
DS-6157; DS-6157a
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| Organization |
Daiichi Sankyo (Originator)
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| Drug Status |
Phase 1 (discontinued)
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| Drug-to-Antibody Ratio |
8
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| Structure |
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| Antibody Name |
Anti-GPR20 antibody
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Antibody Info | ||||
| Antigen Name |
G-protein coupled receptor 20 (GPR20)
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Antigen Info | ||||
| Payload Name |
DXd
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Payload Info | ||||
| Therapeutic Target |
DNA topoisomerase 1 (TOP1)
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Target Info | ||||
| Linker Name |
Mc-Gly-Gly-Phe-Gly
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Linker Info | ||||
| Conjugate Type |
Random Cysteines
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| Combination Type |
deruxtecan
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The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
| Indication | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | New Drug Application | Approved | ||
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| Gastrointestinal stromal cancer |
1 Trials
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General Information of The Activity Data Related to This ADC
Identified from the Human Clinical 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] | ||||
| Patients Enrolled |
Eligible patients were aged ≥18 (≥20 in Japan) with ECOG 0-1 and advanced/metastatic GIST resistant/intolerant to imatinib ± post-IM therapy (cohort-dependent). Key requirements included measurable disease (RECIST v1.1), adequate organ function, LVEF ≥50%, and tumor biopsy consent. Exclusions encompassed unresolved toxicities (NCI CTCAE >Gr 1), active CNS metastases, QTcF >470 ms, ILD, uncontrolled infections, and pregnancy/lactation, among others.
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| Administration Dosage |
Participants with advanced gastrointestinal stromal tumor (GIST) who will receive an intravenous infusion of DS-6157a (escalating doses starting at 1.6 mg/kg).
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| Related Clinical Trial | |||||
| NCT Number | NCT04276415 | Clinical Status | PHASE1 | ||
| Clinical Description | Phase 1, Multicenter, Open-Label, First-in-Human Study of DS-6157a in Subjects With Advanced Gastrointestinal Stromal Tumor | ||||
| Primary Endpoint |
The study assessed dose-limiting toxicities (DLTs) during Cycle 1 (21 days), including hematologic (e.g., Gr 4 neutropenia >7 days, Gr ≥3 febrile neutropenia) and non-hematologic (Gr ≥3 TEAEs, excluding certain exceptions). Additionally, TEAEs were evaluated using NCI CTCAE v5.0, and efficacy outcomes (ORR, DCR, DOR, PFS) were monitored for up to 5 years post-treatment per RECIST v1.1.
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| Other Endpoint |
Pharmacokinetic analysis evaluated AUClast, AUCtau, Cmax, Tmax, Ctrough, and t1/2 for DS-6157a, total anti-GPR20 antibody, and MAAA-1181a using noncompartmental methods, with blood sampling across multiple 21-day cycles. Immunogenicity (anti-drug antibodies) and efficacy (BOR, PFS) were also assessed, with responses classified based on RECIST v1.1 criteria (CR, PR, SD, PD).
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Objective Response Rate (ORR) | 2.90% | High GPR20 expression (GPR20+++) | ||
| Patients Enrolled |
Histopathologically documented unresectable and/or metastatic gastrointestinal stromal tumor (GIST) following treatment with standard of care, including imatinib.
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| Administration Dosage |
1.6 mg/kg, 3.2 mg/kg, 4.8 mg/kg, 6.4 mg/kg, and 9.6 mg/kg intravenously on Day 1 of each 21-day cycle.
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| Related Clinical Trial | |||||
| NCT Number | NCT04276415 | Clinical Status | Phase 1 | ||
| Clinical Description | Phase 1, multicenter, open-label, first-in-human study of DS-6157a in subjects with advanced gastrointestinal stromal tumor. | ||||
| Primary Endpoint |
MTD=6.40 mg/kg.
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| Other Endpoint |
Median PFS=4.20 months (95% CI, 1.60-6.90), Objective response rate=2.86%, comprising 0 complete responses and 1 (2.86%) partial responses.
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References