Linker Information

General Information of This Linker
Linker ID
LIN0TCZUM
Linker Name
HIPS-4AP
Linker Type
Uncleavable linker
Antibody-Linker Relation
Uncleavable
Structure
Formula
C30H45N5O8
Isosmiles
O=C(O)CCC(N(C1CCN(CC1)C(CCN2C(CN(NC)C)=CC3=CC=CC=C23)=O)CCOCCOCCC(O)=O)=O
InChI
InChI=1S/C30H45N5O8/c1-31-32(2)22-25-21-23-5-3-4-6-26(23)34(25)15-11-27(36)33-13-9-24(10-14-33)35(28(37)7-8-29(38)39)16-18-43-20-19-42-17-12-30(40)41/h3-6,21,24,31H,7-20,22H2,1-2H3,(H,38,39)(H,40,41)
InChIKey
HCTLBFZUSUCBMW-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
603.717
Polar area
153.88
Complexity
1159.859848
xlogp Value
1.7899
Heavy Count
43
Rot Bonds
19
Hbond acc
9
Hbond Donor
3
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
TRPH-222 [Phase 1 (discontinued)]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
46%
Patients Enrolled
Eligible participants must be ≥18 with histologically confirmed relapsed/refractory B-cell NHL (DLBCL, FL, MZL, or MCL), ECOG 0-2. Key exclusions include leukemic lymphoma, double-/triple-hit DLBCL, prior organ transplants, significant neuropathy, cardiovascular disease, or other high-risk comorbidities per investigator assessment.
Administration Dosage
TRPH-222-100 is an open-label, multicenter study comprised of dose-escalation and dose-expansion stages. TRPH-222 was administered IV once every 3 weeks. 22 patients were enrolled in dose-escalating cohorts of TRPH-222 (0.6 mg/kg to 10 mg/kg) from DLBCL, FL, TFL, MCL and MZL histologies, and 10 patients in a dose-expansion cohort (7.5 mg/kg) focusing on DLBCL and FL histologies.

   Click to Show/Hide
Related Clinical Trial
NCT Number NCT03682796  Clinical Status PHASE1
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
Primary Endpoint
The study aims to determine the maximum tolerated dose (MTD) of TRPH-222 over a 21-day timeframe while evaluating safety through adverse events (AEs), serious AEs (SAEs), and treatment-related AEs leading to discontinuation or death.
Other Endpoint
Tumor activity will be assessed via objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and duration of response (DOR) using Lugano criteria in NHL subtypes. Pharmacokinetic analysis (Cmax, AUC, CL, Vd, t½) will be conducted over multiple cycles, alongside anti-drug antibody (ADA) incidence monitoring.
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Complete Response Rate (CRR)
31%
Patients Enrolled
Eligible participants must be ≥18 with histologically confirmed relapsed/refractory B-cell NHL (DLBCL, FL, MZL, or MCL), ECOG 0-2. Key exclusions include leukemic lymphoma, double-/triple-hit DLBCL, prior organ transplants, significant neuropathy, cardiovascular disease, or other high-risk comorbidities per investigator assessment.
Administration Dosage
TRPH-222-100 is an open-label, multicenter study comprised of dose-escalation and dose-expansion stages. TRPH-222 was administered IV once every 3 weeks. 22 patients were enrolled in dose-escalating cohorts of TRPH-222 (0.6 mg/kg to 10 mg/kg) from DLBCL, FL, TFL, MCL and MZL histologies, and 10 patients in a dose-expansion cohort (7.5 mg/kg) focusing on DLBCL and FL histologies.

   Click to Show/Hide
Related Clinical Trial
NCT Number NCT03682796  Clinical Status PHASE1
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
Primary Endpoint
The study aims to determine the maximum tolerated dose (MTD) of TRPH-222 over a 21-day timeframe while evaluating safety through adverse events (AEs), serious AEs (SAEs), and treatment-related AEs leading to discontinuation or death.
Other Endpoint
Tumor activity will be assessed via objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and duration of response (DOR) using Lugano criteria in NHL subtypes. Pharmacokinetic analysis (Cmax, AUC, CL, Vd, t½) will be conducted over multiple cycles, alongside anti-drug antibody (ADA) incidence monitoring.
Experiment 3 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
22.70%
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  Clinical 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 [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 51% 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 [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87% 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 [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 91% 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 [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% 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 [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% 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 [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% 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 [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% 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 Study of TRPH-222 in Patients With Relapsed and/or Refractory B-Cell Lymphoma
Ref 2 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 3 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 4 TRPH-222, a novel anti-CD22 antibody drug conjugate (ADC), has significant anti-tumor activity in NHL xenografts and reduces B cells in monkeys.