Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0VJOET
ADC Name
Moxetumomab pasudotox
Brand Name
Lumoxiti
Synonyms
HA22; CAT- 8015; GCR-8015; R490A
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Organization
AstraZeneca PLC
Drug Status
Approved (FDA): Sep 13, 2018
Indication
In total 6 Indication(s)
Hairy cell leukemia [ICD11:2A82]
Approved
Acute lymphoblastic leukemia [ICD11:2B33]
Terminated in phase 2
B-cell lymphoma [ICD11:2A86]
Terminated in phase 1
B-cell prolymphocytic leukaemia [ICD11:2A82]
Terminated in phase 1
Lymphoma [ICD11:2A85-2A90]
Terminated in phase 1
Non Hodgkin lymphoma [ICD11:2B33]
Terminated in phase 1
Antibody Name
Moxetumomab
  Antibody Info 
Antigen Name
B-cell receptor CD22 (CD22)
  Antigen Info 
Payload Name
Pseudomonas exotoxin PE38
  Payload Info 
Therapeutic Target
Eukaryotic elongation factor 2 (EEF2)
  Target Info 
Linker Name
Mc-Val-Cit-PABC
  Linker Info 
Conjugate Type
Amide bonds of recombinant proteins.
Combination Type
Pasudotox
Absorption
For moxetumomab pasudotox, serum concentration increases in a dose-proportional manner and reaches a mean steady state of 379 (ng/mL) with a Cmax of 626 (ng x h/mL).
Distribution
The mean volume of distribution is 6.5 L.
Metabolism
The metabolism of Moxetumomab pasudotox has not been well established but due to the nature of the drug, it is thought to be degraded into small peptides and individual amino acids. The half-life is reported to be of only 1.4 hours.
Elimination
The main route of elimination is thought to be through the urine as it presents a very large clearance rate. The mean systemic clearance is very fast and it is reported to be of 25 L/h. This clearance rate is decreased after subsequent dosing to 4 L/h.
Toxicity
Capillary Leak Syndrome (CLS), including life-threatening cases, occurred in patients receiving LUMOXITI. Hemolytic Uremic Syndrome (HUS), including life-threatening cases, occurred in patients receiving LUMOXITI.
Special Approval(s)
Fast track(FDA); Orphan drug(FDA); Orphan drug(EMA)
Puchem SID
472387867 , 135350821 , 160704159 , 347911362 , 135626666 , 223366010 , 378174534 , 378174535 , 378174536 , 378174537 , 472226499 , 474488701 , 378174539 , 474489036 , 481101756 , 378174538
Drugbank ID
DB12688
DrugMap ID
DMN63DZ
TTD ID
D00HPD
ChEBI ID
CHEMBL1743043
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 7 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Objective Response Rate (ORR)  NCT01829711
Phase 3
A pivotal multicenter trial of moxetumomab pasudotox in relapsed/ refractory hairy cell leukemia.
Objective Response Rate (ORR)  NCT01829711
Phase 3
A pivotal multicenter trial of moxetumomab pasudotox in relapsed/ refractory hairy cell leukemia.
Objective Response Rate (ORR)  NCT01891981
Phase 1
Phase 1/2 study of moxetumomab pasudotox in patients with relapsed and/or refractory acute lymphoblastic leukemia (ALL).
Objective Response Rate (ORR)  NCT00586924
Phase 1
A phase 1, multicenter, dose escalation study of CAT-8015 in patients with relapsed or refractory hairy cell leukemia (HCL).
Objective Response Rate (ORR)  NCT00462189
Phase 1
A phase 1, multicenter, dose escalation study of CAT-8015 in patient with relapsed or refractory hairy cell leukemia (HCL).
Complete Remission (CR)  NCT02227108
Phase 2
A phase 2, multicenter, single-arm study of moxetumomab pasudotox in pediatric subjects with relapsed or refractory pediatric acute lymphoblastic leukemia (pALL) or lymphoblastic lymphoma of B-cell origin.

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Undisclosed  NCT00659425
Phase 1
A phase 1, multicenter, dose escalation study of CAT-8015 in children, adolescents and young adults with refractory CD22+ acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL).
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 7 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
75.00%
Patients Enrolled
Hairy cell leukemia (HCL) patients have received at least two prior systemic therapies, including two courses of a purine nucleoside analog or one course of rituximab or a BRAF inhibitor following a single prior purine nucleoside analog course.
Administration Dosage
40 ug/kg intravenously on days 1, 3, and 5 every 28 days for 6 cycles.
Related Clinical Trial
NCT Number NCT01829711  Clinical Status Phase 3
Clinical Description A pivotal multicenter trial of moxetumomab pasudotox in relapsed/ refractory hairy cell leukemia.
Primary Endpoint
The durable complete response rate was 30.00% (24/80 patients; 95% CI, 20.30 to 41.30).
Other Endpoint
Objective response rate was 75.00% (60/80 patients, 95% CI, 64.10 to 84.00).The complete response rate was 41.25% (33/80 patients; 95% CI, 30.40 to 52.80).
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
78.75%
Patients Enrolled
Patients with relapsed/refractory (R/R) hairy cell leukemia (HCL) had received prior systemic therapies, including purine nucleoside analogs (PNAs), or1 PNA followed by rituximab or a BRAF inhibitor.
Administration Dosage
40 ug/kg intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles.
Related Clinical Trial
NCT Number NCT01829711  Clinical Status Phase 3
Clinical Description A pivotal multicenter trial of moxetumomab pasudotox in relapsed/ refractory hairy cell leukemia.
Primary Endpoint
The durable CR rate was 49% (39 patients; 95% CI, 37-60%).
Other Endpoint
The CR rate with HR 360 days was 45.00% (36 patients; 95% CI 34.00-57.00%). The Objective response rate was 78.75% (63 patients; 95% CI 68.00-87.00%). Both the median CR duration and median HR duration from the onset of CR were 62.80 months( 95% CI, 35.70-62.80%). The median OR duration was 66.70 months, and the median HR duration from the onset of HR was 45.80 months (95% CI, 26.50-NR%). Median PFS was 41.50 months( 95% CI, 29.50-NR%).

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Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Objective Response Rate (ORR)
13.00%
Patients Enrolled
Previously treated relapsed or refractory B-cell acute lymphocytic leukemia (ALL).
Administration Dosage
30 ug/kg (n = 6), 40 ug/kg (n = 4), and 50 ug/kg (n = 6) given intravenously over 30 min every other day 6 doses, with cycle length of 21 days.
Related Clinical Trial
NCT Number NCT01891981  Clinical Status Phase 1
Clinical Description Phase 1/2 study of moxetumomab pasudotox in patients with relapsed and/or refractory acute lymphoblastic leukemia (ALL).
Primary Endpoint
Dose limiting toxicities (DLTs) and maximum tolerated dose (MTD). Only one DLT was observed. No treatment-related deaths were observed, and the MTD was not reached.
Experiment 4 Reporting the Activity Date of This ADC [4]
Efficacy Data Objective Response Rate (ORR)
88.00%
Patients Enrolled
Relapsed/refractory hairy cell leukemia.
Administration Dosage
50 ug/kg every other day for 3 doses in 4-week cycles.
Related Clinical Trial
NCT Number NCT00586924  Clinical Status Phase 1
Clinical Description A phase 1, multicenter, dose escalation study of CAT-8015 in patients with relapsed or refractory hairy cell leukemia (HCL).
Experiment 5 Reporting the Activity Date of This ADC [5]
Efficacy Data Objective Response Rate (ORR)
100.00% (Dose Level in 5 ug/kg)
100.00% (Dose Level in 10 ug/kg)
67.00% (Dose Level in 20 ug/kg)
67.00% (Dose Level in 30 ug/kg)
75.00% (Dose Level in 40 ug/kg)
92.00% (Dose Level in 50 ug/kg)
Patients Enrolled
Relapsed/refractory hairy cell leukemia (HCL) after two prior therapies and required treatment because of abnormal blood counts.
Administration Dosage
5, 10, 20, and 30 ug/kg, four patients at 40 ug/kg, and 12 patients at 50 ug/kg QOD 3 for one to 16 cycles each (median, four cycles).
Related Clinical Trial
NCT Number NCT00462189  Clinical Status Phase 1
Clinical Description A phase 1, multicenter, dose escalation study of CAT-8015 in patient with relapsed or refractory hairy cell leukemia (HCL).
Primary Endpoint
Dose Level in 5 ug/kg QODx3 (N=3, PR=100.00%, ORR=100.00%); Dose Level in 10 ug/kg QODx3(N=3, CR=67.00%,PR=33.00%, ORR=100.00%); Dose Level in 20 ug/kg QODx3 (N=3, CR=67.00%, ORR=67.00%);Dose Level in 30 ug/kg QODx3 (N=3, CR=33.00%, PR=33.00%, ORR=67.00%); Dose Level in 40 ug/kg QODx3 (N=3, CR=50.00%, PR=25.00%, ORR=75.00%); Dose Level in 50 ug/kg QODx3 (N=3, CR=50.00%, PR=42.00%, ORR=92.00%).

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Experiment 6 Reporting the Activity Date of This ADC [6]
Efficacy Data Complete Remission (CR)
10.71%
Patients Enrolled
Relapsed or chemotherapy-refractory precursor B-ALL or B-cell lymphoblastic lymphoma who had received at least one first-line and one salvage regimen of chemotherapy or a prior allogeneic hematopoietic stem cell transplant (HSCT).
Administration Dosage
40 ug/kg administered over 30 minutes every other day with six total doses per 21-day cycle.
Related Clinical Trial
NCT Number NCT02227108  Clinical Status Phase 2
Clinical Description A phase 2, multicenter, single-arm study of moxetumomab pasudotox in pediatric subjects with relapsed or refractory pediatric acute lymphoblastic leukemia (pALL) or lymphoblastic lymphoma of B-cell origin.
Primary Endpoint
This phase 2 study was terminated at interim analysis for a CR rate that did not reach the stage 1 target. 3 of 28 evaluable patients (10.71%) attained CR none of whom were MRD negative.
Other Endpoint
Ten patients (33.33%) experienced at least 1 treatment-related serious adverse event, including capillary leak syndrome (CLS; n=6), hemolytic uremic syndrome (HUS; n=4).
Experiment 7 Reporting the Activity Date of This ADC [7]
Patients Enrolled
Multiply relapsed or chemotherapy-refractory ALL who had received 1 standard and 1 salvage regimen or allogeneic stem-cell transplant were eligible. Bone marrow involvement with 5% blasts was required, with blasts being CD22+ (ie, 30% of blasts expressing CD22 by flow cytometry).
Administration Dosage
5 to 50 ug/kg was administered via IV infusion over 30 minutes every other day in a 21-day cycle.
Related Clinical Trial
NCT Number NCT00659425  Clinical Status Phase 1
Clinical Description A phase 1, multicenter, dose escalation study of CAT-8015 in children, adolescents and young adults with refractory CD22+ acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL).
References
Ref 1 Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018 Aug;32(8):1768-1777.
Ref 2 Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial. J Hematol Oncol. 2021 Feb 24;14(1):35.
Ref 3 A phase I study of moxetumomab pasudotox in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Br J Haematol. 2018 Aug;182(3):442-444.
Ref 4 Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up. Blood. 2018 May 24;131(21):2331-2334.
Ref 5 Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol. 2012 May 20;30(15):1822-8.
Ref 6 Results from an international phase 2 study of the anti-CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B-lineage acute lymphoblastic leukemia. Pediatr Blood Cancer. 2020 May;67(5):e28112.
Ref 7 Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia. Blood. 2017 Oct 5;130(14):1620-1627.

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