Payload Information

General Information of This Payload

Payload ID	PAY0WCEKW
Name	Pseudomonas exotoxin PE38
Synonyms	Pseudomonas exotoxin PE38 Click to Show/Hide
Target(s)	Eukaryotic elongation factor 2 (EEF2)	Target Info

The activity data of This Payload

Standard Type	Value	Units	Cell line	Disease Model	Cell line ID	Reference
Half-maximal effective concentration (EC50)	3.311	ng/mL	CCRF-CEM cells	T acute lymphoblastic leukemia	CVCL_0207	[1]
Half-maximal effective concentration (EC50)	3.479	ng/mL	Acute lymphoblastic leukemia cells	Acute lymphoblastic leukemia	Undisclosed	[1]
Half-maximal effective concentration (EC50)	5.998	ng/mL	Jurkat cells	T acute lymphoblastic leukemia	CVCL_0065	[1]

Each Antibody-drug Conjugate Related to This Payload

Full Information of The Activity Data of The ADC(s) Related to This Payload

Moxetumomab pasudotox [Approved]

ADC Info

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				[2]
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	Phase 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				[3]
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	Phase 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%). Click to Show/Hide
Experiment 3 Reporting the Activity Date of This ADC				[4]
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	Phase 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				[5]
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	Phase 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				[6]
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	Phase 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%). Click to Show/Hide
Experiment 6 Reporting the Activity Date of This ADC				[7]
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	Phase 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				[8]
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	Phase 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).

scFv(H32)-PE38KDEL [Investigative]

ADC Info

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 0.81% (Day 3)	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm³ (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.70 pM	Positive HER2 expression (HER2 +++/++)
Method Description	N87 cells (10000) were seeded in 96-well plates for the IC50 measurements of cell viability. After incubation at 37°C for 16 h, the medium was replaced by fresh normal medium with serum and the cytotoxicity was assessed using the WST-1 reagent after 72 h of incubation at 37°C.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

scFv(GH2-61)-PE38KDEL [Investigative]

ADC Info

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 2 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 2.97% (Day 3)	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm³ (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 10.94% (Day 14)	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm³ (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	16.70 pM	Positive HER2 expression (HER2 +++/++)
Method Description	N87 cells (10000) were seeded in 96-well plates for the IC50 measurements of cell viability. After incubation at 37°C for 16 h, the medium was replaced by fresh normal medium with serum and the cytotoxicity was assessed using the WST-1 reagent after 72 h of incubation at 37°C.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

scFv(GH2-75)-PE38KDEL [Investigative]

ADC Info

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 4.32% (Day 3)	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm³ (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	7.30 pM	Positive HER2 expression (HER2 +++/++)
Method Description	N87 cells (10000) were seeded in 96-well plates for the IC50 measurements of cell viability. After incubation at 37°C for 16 h, the medium was replaced by fresh normal medium with serum and the cytotoxicity was assessed using the WST-1 reagent after 72 h of incubation at 37°C.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

scFv(trastuzumab)-PE38KDEL [Investigative]

ADC Info

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 13.00% (Day 3)	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm³ (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.00 pM	Positive HER2 expression (HER2 +++/++)
Method Description	N87 cells (10000) were seeded in 96-well plates for the IC50 measurements of cell viability. After incubation at 37°C for 16 h, the medium was replaced by fresh normal medium with serum and the cytotoxicity was assessed using the WST-1 reagent after 72 h of incubation at 37°C.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

scFv(GH2-20)-PE38KDEL [Investigative]

ADC Info

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 18.19% (Day 3)	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm³ (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Revealed Based on the Cell Line Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	33.00 pM	Positive HER2 expression (HER2 +++/++)
Method Description	N87 cells (10000) were seeded in 96-well plates for the IC50 measurements of cell viability. After incubation at 37°C for 16 h, the medium was replaced by fresh normal medium with serum and the cytotoxicity was assessed using the WST-1 reagent after 72 h of incubation at 37°C.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

scFv (Herceptin)-PE [Investigative]

ADC Info

Revealed Based on the Cell Line Data

Click To Hide/Show 2 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	19.98 ug/mL	Positive HER2 expression (HER2 +++/++)
Method Description	The cytotoxic effect of recombinant proteins was evaluated by the MTT assay using SKBR-3 and MCF-7 cells.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 100.00 ug/mL	Low HER2 expression (HER2 -)
Method Description	The cytotoxic effect of recombinant proteins was evaluated by the MTT assay using SKBR-3 and MCF-7 cells.
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031

LMB-7 [Terminated in phase 1]

ADC Info

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				[11]
Patients Enrolled	Patients with leptomeningeal metastases.
*Related Clinical Trial*
NCT Number	NCT00003020	Phase Status	Phase 1
Clinical Description	Phase 1 dose-escalation study of intravenous CMD-193 in subjects with advanced malignant solid tumors.

References

Ref 1	Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential. Int J Nanomedicine. 2017 Mar 13;12:1969-1983.
Ref 2	Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018 Aug;32(8):1768-1777.
Ref 3	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 4	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 5	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 6	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 7	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 8	Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia. Blood. 2017 Oct 5;130(14):1620-1627.
Ref 9	Antibody-drug conjugates with HER2-targeting antibodies from synthetic antibody libraries are highly potent against HER2-positive human gastric tumor in xenograft models. MAbs. 2019 Jan;11(1):153-165. doi: 10.1080/19420862.2018.1541370. Epub 2018 Nov 8.
Ref 10	Breast cancer targeted/ therapeutic with double and triple fusion Immunotoxins. J Steroid Biochem Mol Biol. 2020 Jun;200:105651. doi: 10.1016/j.jsbmb.2020.105651. Epub 2020 Mar 5.
Ref 11	Protocol for a Phase I Study of Intrathecal LMB-7 (Single-Chain Immunotoxin Constructed From Monoclonal Antibody B3-Pseudomonas Exotoxin PE 38) [IND 5863, NSC 658931] in the Treatment of Patients With Leptomeningeal Neoplasms

Payload Information

Citation

Visitor Map

Correspondence

Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xiaowu DONG (dongxw@zju.edu.cn)

Prof. Luo FANG (fangluo@zjcc.org.cn)