General Information of This Linker
Linker ID
LIN0WUDSA
Linker Name
APN-PEG5-Val-Cit-PABC
Linker Type
Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C41H55N9O10
Isosmiles
OCC1=CC=C(C=C1)NC([C@@H](NC([C@H](C(C)C)NC(CCOCCOCCOCCOCCOCC2=CN(N=N2)C3=CC=C(C=C3)C#CC#N)=O)=O)CCCNC(N)=O)=O
InChI
InChI=1S/C41H55N9O10/c1-30(2)38(40(54)46-36(6-4-17-44-41(43)55)39(53)45-33-11-7-32(28-51)8-12-33)47-37(52)15-18-56-19-20-57-21-22-58-23-24-59-25-26-60-29-34-27-50(49-48-34)35-13-9-31(10-14-35)5-3-16-42/h7-14,27,30,36,38,51H,4,6,15,17-26,28-29H2,1-2H3,(H,45,53)(H,46,54)(H,47,52)(H3,43,44,55)/t36-,38-/m0/s1
InChIKey
MXELVYAVFGAIOV-BAEGBANDSA-N
Pharmaceutical Properties
Molecule Weight
833.944
Polar area
263.3
Complexity
1781.819553
xlogp Value
1.32058
Heavy Count
60
Rot Bonds
29
Hbond acc
14
Hbond Donor
6
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
INA03 [Phase 1]
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Patients Enrolled
Eligible patients include adults (&ge;18 years) with relapsed/refractory ALL, AML, or MPAL (WHO 2016, CD71+ &ge;20% blasts), controlled blast count (<20,000/mm <sup>3</sup>), adequate organ function, and ECOG 0-2. Exclusions cover APL, prior anti-TfR therapy, recent transplant, CNS disease, uncontrolled cardiac/liver disease, active infection, pregnancy, and major surgery within 4 weeks.

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Administration Dosage
INA03 will be administered IV on Day 1, Day 14 of 28-day cycles. The administration of INA03 will begin at 0.02 mg/kg. Study Part I is a titration study to determine the dose for the first INA03 infusion. Patients will be enrolled in sequential cohorts of 2 patients to receive ascending starting doses of INA03, starting from the lowest starting dose (0.02 mg/kg), and followed by subsequent administrations of INA03 (D14 and beyond) at a fixed dose of 0.1 mg/kg. The starting dose will be increased every cohort of 2 patients until evidence of absence of marrow residual erythroblasts by D14 myelogram. This dose is referred to as the MEID and will be selected as the D1 dose for the study Part 2. Patient accumulation in Part I of the study will continue until no evidence of non-hematological DLT within 28 days post dosing

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Related Clinical Trial
NCT Number NCT03957915  Clinical Status EARLY_PHASE1
Clinical Description
A Phase I, First in Human, Open-label Study of Escalating Doses of INA03 Administered Intravenously as Single Agent in Adult Patients With Relapse/Refractory Acute Leukemia
Primary Endpoint
The study assesses the minimal erythroblastopenia-inducing dose (MEID) of INA03 in adults with refractory/relapsed acute leukemia within 2 weeks post-dose, defined by erythroblast depletion or Grade ≥2 non-hematologic toxicity, followed by determining the maximum tolerated dose (MTD) for subsequent administrations (Day 15 onwards) over 28 days.
Other Endpoint
Safety is evaluated via NCI-CTCAE v5.0-graded adverse events. Pharmacokinetic analysis includes Cmax, AUC, and half-life (t½) from dosing to Day 42, while pharmacodynamics tracks erythroblast/blast reduction via bone marrow aspirates. Anti-INA03 antibodies are measured, and preliminary efficacy is assessed per ELN 2017 criteria for up to 182 days.

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References
Ref 1 Study of Escalating Doses of INA03 Administered Intravenously as Single Agent in Adult Patients With Relapse/Refractory Acute Leukemia