Payload Information

General Information of This Payload
Payload ID
PAY0CHGPD
Name
Maytansinoid derivative of TRPH-222
Synonyms
Maytansinoid derivative of TRPH-222
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Target(s) Microtubule (MT)
 Target Info 
Structure
Formula
C32H44ClN3O9
Isosmiles
CN[C@@H](C)C(=O)O[C@H]1CC(=O)N(C)c2cc(cc(OC)c2Cl)C/C(C)=C/C=C/[C@@H](OC)[C@@]2(O)C[C@H](OC(=O)N2)[C@@H](C)C2O[C@]21C
InChI
InChI=1S/C32H44ClN3O9/c1-17-10-9-11-24(42-8)32(40)16-23(43-30(39)35-32)18(2)28-31(4,45-28)25(44-29(38)19(3)34-5)15-26(37)36(6)21-13-20(12-17)14-22(41-7)27(21)33/h9-11,13-14,18-19,23-25,28,34,40H,12,15-16H2,1-8H3,(H,35,39)/b11-9+,17-10+/t18-,19+,23+,24-,25+,28?,31+,32+/m1/s1
InChIKey
ANHBJISROJTYCJ-QENSGWBVSA-N
Pharmaceutical Properties
Molecule Weight
650.169
Polar area
148.19
Complexity
649.2766077
xlogp Value
3.2755
Heavy Count
45
Rot Bonds
5
Hbond acc
10
Hbond Donor
3
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
TRPH-222 [Phase 1 (Terminated)]
 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 [1]
Efficacy Data Objective Response Rate (ORR)
22.70% (all)
Patients Enrolled
Patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL) were enrolled. Patients had received a median of 4 prior systemic therapy.
Administration Dosage
TRPH-222 was administered IV 0.60 to 5.60 mg/kg once every 3 weeks.
Related Clinical Trial
NCT Number NCT03682796  Phase Status Phase 1
Clinical Description
Phase 1, multicenter, open-label study of the antibody-drug conjugate TRPH-222 in subjects with relapsed and/or refractory B-cell lymphoma.
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 7 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 51.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In WSU-DLCL2 xenografts once weekly intravenous (IV) dosing with 1 mg/kg TRPH-222.
In Vivo Model Non-Hodgkin's lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In Granta-519 xenografts,trph-222 was dosed at 10 mg/kg once weekly intravenous (IV).
In Vivo Model Mantle cell lymphoma CDX model
In Vitro Model Mantle cell lymphoma Granta-519 cells CVCL_1818
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 91.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In SU-DHL-2 xenografts,trph-222 was dosed at 10 mg/kg once weekly intravenous (IV).
In Vivo Model Diffuse large B cell lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma SU-DHL-2 cells CVCL_9550
Experiment 4 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In SU-DHL-4 xenografts,trph-222 was dosed at 10 mg/kg once weekly intravenous (IV).
In Vivo Model Diffuse large B cell lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma SU-DHL-4 cells CVCL_0539
Experiment 5 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In WSU-DLCL2 xenografts once every three-week intravenous (IV) dosing with 10 mg/kg TRPH-222.
In Vivo Model Non-Hodgkin's lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 6 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In WSU-DLCL2 xenografts once weekly intravenous (IV) dosing with 10 mg/kg TRPH-222.
In Vivo Model Non-Hodgkin's lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 7 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 28) Positive CD22 expression (CD22+++/++)
Method Description
In WSU-DLCL2 xenografts once weekly intravenous (IV) dosing with 3 mg/kg TRPH-222.
In Vivo Model Non-Hodgkin's lymphoma CDX model
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
References
Ref 1 First-in-Human Phase I Study of ABBV-085, an Antibody-Drug Conjugate Targeting LRRC15, in Sarcomas and Other Advanced Solid Tumors. Clin Cancer Res. 2021 Jul 1;27(13):3556-3566. doi: 10.1158/1078-0432.CCR-20-4513.
Ref 2 Trph-222, a Novel Anti-CD22 Antibody Drug Conjugate (ADC), Has Signficant Anti-Tumor Activity in NHL Xenografts and Is Well Tolerated in Non-Human Primates. Blood. 2017 Dec 8;130 (Suppl_1) : 4105.
Ref 3 TRPH-222, a novel anti-CD22 antibody drug conjugate (ADC), has significant anti-tumor activity in NHL xenografts and reduces B cells in monkeys.