Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0WCTHL
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| ADC Name |
Pivekimab sunirine
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| Synonyms |
pivekimab sunirine; IMGN632; PVEK
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| Organization |
ImmunoGen (Top20 MNC) (Originator)
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| Drug Status |
Apprpved in 2026
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| Drug-to-Antibody Ratio |
1.7~1.9
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| Structure |
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| Antibody Name |
Pivekimab
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Antibody Info | ||||
| Antigen Name |
Interleukin-3 receptor subunit alpha (IL3RA)
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Antigen Info | ||||
| Payload Name |
DGN549
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Payload Info | ||||
| Therapeutic Target |
Human deoxyribonucleic acid (hDNA)
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Target Info | ||||
| Linker Name |
Mal-adipamide-Ala-Ala
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Linker Info | ||||
| Conjugate Type |
Reactive Cysteines
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| Combination Type |
sunirine
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| Special Approval(s) |
Accelerated approval (FDA); Orphan drug (FDA); Orphan drug (EMA)
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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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| Acute lymphoblastic leukemia |
2 Trials
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| Acute myeloid leukaemia |
1 Trials
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3 Trials
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| Blastic plasmacytoid dendritic cell neoplasm |
1 Trials
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| Mixed phenotype acute leukaemia |
1 Trials
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
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| Maximum Observed Concentration (Cmax) | 2830 | ng/mL |
Participants in schedule A were dosed on day 1 of a 3-week cycle,0.09mg/kg
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| Area Under the Concentration-Time Curve (AUC) | 13200 | ng*h/mL |
Participants in schedule A were dosed on day 1 of a 3-week cycle,0.09mg/kg
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Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 13200 | ng*h/mL |
Participants in schedule A were dosed on day 1 of a 3-week cycle,0.09mg/kg
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Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 13200 | ng*h/mL |
Participants in schedule A were dosed on day 1 of a 3-week cycle,0.09mg/kg
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Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Elimination Half-Life (t1/2) | 7.94 | h |
Participants in schedule A were dosed on day 1 of a 3-week cycle,0.09mg/kg
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| Area Under the Concentration-Time Curve (AUC) | 13200 | ng*h/mL |
Participants in schedule A were dosed on day 1 of a 3-week cycle,0.09mg/kg
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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 | [2] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
33%
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| Patients Enrolled |
Eligibility requires CD123+ hematologic malignancies (6 cohorts: relapsed/refractory BPDCN/AML/ALL/MDS/MPN or frontline BPDCN). Key exclusions: available standard therapies (Cohorts 1-5), active CNS disease (frontline), prior VOD, grade 4 capillary leak syndrome, or anticancer therapy within 14 days (28 days for checkpoint inhibitors).
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| Administration Dosage |
IMGN632 was administered by IV on 2 different schedules for participants with relapsed/refractory AML, ALL, or BPDCN.
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| Related Clinical Trial | |||||
| NCT Number | NCT03386513 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase 1/2, Multi-center, Open-label Study of IMGN632 Monotherapy Administered Intravenously in Patients With CD123-positive Acute Myeloid Leukemia and Other CD123-positive Hematologic Malignancies | ||||
| Primary Endpoint |
Primary endpoint evaluates composite complete response rate (CR+CRc) in BPDCN patients per 21-day treatment cycles.
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| Other Endpoint |
Secondary endpoints include 24-month assessments of CR duration, treatment-emergent AEs (CTCAE v4.03), expanded response rates (CR+CRc+CRh), ORR (CR+CRc+CRh+CRi+PR), OS, transplant bridging rates, PK/immunogenicity of IMGN632, and transfusion independence conversion.
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
59%
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| Patients Enrolled |
Eligibility requires adults (≥18) with CD123+ AML (excluding APL) confirmed by local flow/IHC, adequate organ function (LVEF≥45%, eGFR>30mL/min), and specific disease status per regimen: untreated (Regimen C expansion), relapsed/refractory (≤2 prior lines), or MRD+ post-CR (Regimen D). Key exclusions: active CNS disease, SOS/VOD history, IMGN632 hypersensitivity, uncontrolled infections, or recent anticancer therapy (14-day washout, 28-day for checkpoint inhibitors). Special provisions address transplant recipients (≥120-day interval, no ≥G2 GVHD) and unfit patients (age≥75 or comorbidities precluding intensive therapy).
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| Administration Dosage |
IMGN632, administered intravenously on Day 7 of a 28 day cycle at 0.015 mg/kg, 0.045 mg/kg, or 0.09 mg/kg, in combination with azacitidine, administered subcutaneously or intravenously daily at 75 mg/m2 on Days 1 to 7 of a 28 day cycle. Cycle 1 azacitidine dose in subsequent cohorts may be reduced.
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| Related Clinical Trial | |||||
| NCT Number | NCT04086264 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase 1b/2 Study of IMGN632 as Monotherapy or Combination With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia | ||||
| Primary Endpoint |
Primary objectives include evaluating safety/tolerability and determining RP2D of IMGN632 combinations (with azacitidine/venetoclax) in relapsed/refractory CD123+ AML over ~3 years through TEAE monitoring, while assessing preliminary antileukemic activity (CR/CRh/CRp/CRi/MLFS/PR) and MRD levels via central flow cytometry over ~18-20 months.
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| Other Endpoint |
Secondary endpoints comprise TEAE incidence (12-month), pharmacokinetic profiles (IMGN632/ADA concentrations), and MRD dynamics during dose escalation/expansion phases, with all parameters monitored for approximately 7-12 months using standardized analytical methods.
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| Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
| Patients Enrolled |
Eligibility requires adults (≥18) with untreated CD123+ AML (excluding APL/FLT3-mutated cases) and ELN adverse-risk features, adequate organ function (LVEF≥45%, CrCl≥60mL/min), and TRM score ≤13.1. Exclusions include CML blast phase, uncontrolled infections, pregnancy, or prior grade ≥3 antibody hypersensitivity.
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| Administration Dosage |
.
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| Related Clinical Trial | |||||
| NCT Number | NCT06034470 | Clinical Status | PHASE1 | ||
| Clinical Description | Phase 1 Study of FLAG-Ida With Pivekimab Sunirine (PVEK [IMGN632]) for Adults With Newly Diagnosed Adverse-Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms | ||||
| Primary Endpoint |
Primary endpoint assesses dose-limiting toxicities (DLTs) during cycle 1 (42-day observation), defined as grade ≥4 organ toxicity or prolonged severe myelosuppression (ANC<500/uL & platelets<25,000/uL for >42 days post-FLAG-Ida initiation) per ELN criteria.
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| Other Endpoint |
Secondary outcomes include 5-year AE incidence (NCI CTCAE v5.0), MRD rates (flow cytometry), relapse-free/overall survival, complete remission rates, cytopenia duration, and transplant proportions, all analyzed via standard statistical methods (Wilcoxon, Fisher's exact, Kaplan-Meier).
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| Experiment 4 Reporting the Activity Date of This ADC | [5] | ||||
| Patients Enrolled |
Eligibility requires CD123+ hematologic malignancies (AML/ALL/MPAL) in patients aged 1-22 years (weight ≥10kg), stratified by cohort: relapsed/refractory disease (Cohort 1), first-relapse AML (Cohorts 2-3). Key requirements include adequate organ function (EF≥55%, CrCl≥70mL/min), CNS1-3 status without neurological symptoms, and specified washout periods from prior therapies (14 days for chemotherapy, 21 days for antibodies). Exclusions cover APL/JMML, Down syndrome, active infections, copper metabolism disorders, pregnancy/breastfeeding, and prior grade ≥3 VOD/SOS.
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| Administration Dosage |
Patients receive IMGN632 IV on days 1 and 22. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
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| Related Clinical Trial | |||||
| NCT Number | NCT05320380 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A PedAL/EuPAL Phase 1/2 Trial of IMGN632 in Pediatric Patients With Relapsed or Refractory Leukemia | ||||
| Primary Endpoint |
Primary objectives include determining RP2D for IMGN632 monotherapy (Cohort 1) and combination therapy with daunorubicin/cytarabine liposome (Cohort 2) using rolling 6 design during 42-day cycle 1 DLT evaluation, while assessing flow-based ORR (CR/CRi/CRp) in Cohort 1 and MRD-negative response rates (<0.01% blasts) after two treatment cycles in pediatric AML patients (Cohort 3) through Fisher's Exact test comparisons.
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| Other Endpoint |
Pharmacokinetic parameters (AUC, Cmax, Vss, t1/2, CL, Tmax) will be analyzed via non-compartmental methods during cycles 1-2 across all cohorts, with serial plasma sampling to characterize IMGN632 exposure profiles and establish dose-exposure relationships in pediatric/adolescent populations.
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References