Payload Information
General Information of This Payload
| Payload ID | PAY0BSEDX |
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| Name | Auristatin W |
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| Synonyms |
Auristatin W
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| Target | Microtubule (MT) | |||||
| Structure |
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| Formula | C42H69N7O7 |
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| Isosmiles | C[C@@H](C(N[C@H](C(N)=O)CC1=CNC2=CC=CC=C12)=O)C(OC)[C@@H]3CCCN3C(C[C@H]([C@@H](N(C([C@H](C(C)C)NC([C@@H](N(C)C)C(C)C)=O)=O)C)[C@H](CC)C)[O]C)=O |
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| InChI |
InChI=1S/C42H69N7O7/c1-13-26(6)37(48(10)42(54)35(24(2)3)46-41(53)36(25(4)5)47(8)9)33(55-11)22-34(50)49-20-16-19-32(49)38(56-12)27(7)40(52)45-31(39(43)51)21-28-23-44-30-18-15-14-17-29(28)30/h14-15,17-18,23-27,31-33,35-38,44H,13,16,19-22H2,1-12H3,(H2,43,51)(H,45,52)(H,46,53)/t26-,27+,31-,32-,33+,35-,36-,37-,38?/m0/s1
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| InChIKey |
NSWKFKWBLMKNHC-OSKPRJHCSA-N
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| Pharmaceutical Properties | Molecule Weight |
784.056 |
Polar area |
179.4 |
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Complexity |
1559.634956 |
xlogp Value |
3.3278 |
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Heavy Count |
56 |
Rot Bonds |
21 |
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Hbond acc |
8 |
Hbond Donor |
4 |
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Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
Aprutumab ixadotin [Phase 1 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Patients Enrolled |
Advanced solid tumors from cancer indications known to be FGFR2-positive, which were refractory to any standard therapy or had no standard therapy available, patients were required to have measurable disease, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, an expected lifespan of at least 12 weeks.
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| Administration Dosage |
The starting dose was 0.1 mg/kg body weight, with doses increased in two-fold increments up to 0.80 mg/kg, after which the dose was escalated in 0.50 mg/kg increments, intravenously on day 1 of every 21-day cycle.
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| Related Clinical Trial | |||||
| NCT Number | NCT02368951 | Phase Status | Phase 1 | ||
| Clinical Description |
An open-label,phase 1, dose-escalation trial to evaluate the safety, tolerability, maximum tolerated dose, pharmacokinetic, and pharmacodynamics of the anti-FGFR2 antibody drug conjugate BAY1187982 in subjects with advanced solid tumors known to express FGFR2.
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| Primary Endpoint |
Primary endpoints included safety, tolerability, and The MTD was determined to be 0.20 mg/kg.
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| Other Endpoint |
Secondary endpoints were pharmacokinetic evaluation and tumor response to aprutumab ixadotin.
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
Eligibility requires age ≥18, ECOG 0-1, advanced FGFR2+ solid tumors refractory to standard therapy (MTD expansion limited to triple-negative breast cancer ≤4 prior lines). Exclusion covers hypersensitivity to monoclonal antibodies, recent (<4 weeks) anticancer therapy, unresolved treatment-related toxicity, active brain metastases, significant cardiac disease, coagulation disorders, and pregnancy/breastfeeding.
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| Administration Dosage |
A dose of 0.1 mg BAY 1187982 per kilogram (kg) body weight (BW) was chosen as the starting dose based on toxicology data. The investigational drug will be administered as a 1-hour IV infusion once every 21 days at the trial site (Day 1 of each 21-day Cycle). The maximum possible dose escalation will be 2-fold and not more than 0.5 mg/kg BW until maximum tolerated dose is selected
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| Related Clinical Trial | |||||
| NCT Number | NCT02368951 | Phase Status | PHASE1 | ||
| Clinical Description |
An Open-label,Phase I, Dose-escalation Trial to Evaluate the Safety, Tolerability, Maximum Tolerated Dose, Pharmacokinetic, and Pharmacodynamics of the Anti-FGFR2 Antibody Drug Conjugate BAY1187982 in Subjects With Advanced Solid Tumors Known to Express FGFR2.
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| Primary Endpoint |
The trial focuses on identifying the maximum tolerated dose (MTD) of the investigational drug, defined as the highest dose with <20% dose-limiting toxicities (DLTs) during Cycle 1. Safety and tolerability endpoints include adverse events (AEs) and serious adverse events (SAEs) monitored for up to 2 years.
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| Other Endpoint |
Pharmacokinetic (PK) assessments include single- and multiple-dose Cmax, AUC (0-tlast), AUC (0-504), and AUC (0-inf) over specified cycles (1, 3, 5, etc.). Biological markers FGFR2, CK18, and nucleosome levels in tumor/plasma are evaluated at screening and treatment milestones. Anti-drug antibodies (ADAs) and tumor response per RECIST are measured to assess immunogenicity and efficacy.
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References