Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0ICRYT
ADC Name
Oportuzumab monatox
Synonyms
Anti-ECAM exotoxin A fusion protein; oportuzumab monatox-qqrs; Proxinium; Vicineum; Vysyneum; VB4-845; 4D5MOCB-ETA; B-4845; VB-4847; VB-845; Vicinium
   Click to Show/Hide
Organization
Sesen Bio; Qilu Pharmaceutical Co., Ltd.; Baxter Oncology GmbH; Viventia Bio, Inc.
Drug Status
Phase 3
Indication
In total 3 Indication(s)
Bladder cancer [ICD11:2C94]
Phase 3
Head and neck squamous carcinoma [ICD11:2C31]
Terminated in phase 3
Mouth neoplasm [ICD11:2E90]
Terminated in phase 3
Antibody Name
Oportuzumab
  Antibody Info 
Antigen Name
Epithelial cell adhesion molecule (EPCAM)
  Antigen Info 
Payload Name
Pseudomonas exotoxin ETA-252-608
  Payload Info 
Therapeutic Target
Eukaryotic elongation factor 2 (EEF2)
  Target Info 
Linker Name
Undisclosed
Conjugate Type
Amide bonds of recombinant proteins.
Special Approval(s)
Fast track(FDA)
Puchem SID
472407545 , 381125916 , 472225346 , 160698798 , 347910078
Drugbank ID
DB05319
TTD ID
D0OF1R
ChEBI ID
CHEMBL1743052
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Complete Remission (CR)  NCT00462488
Phase 2
Phase 2 study to evaluate the efficacy and tolerability of intravesical vicinium in patients with non-invasive urothelial carcinoma in situ (CIS) previously treated with bacille calmette-gurin (BCG).
Complete Remission (CR)  Undisclosed
Phase 1
An open-label, multicenter, dose-escalating trial of intravesically administered VB4-845. Eight dose levels were initially evaluated, starting at 0.10 mg once weekly for 6 consecutive weeks and escalating through 0.20, 0.33, 0.66, 1.32, 2.64, 5.28, and 10.56 mg/dose. The maximum tolerated dose (MTD) was not reached; therefore, an additional escalation through 13.73, 17.85, 23.20, and 30.16 mg was undertaken. Each dose was administered to the bladder through a catheter and held for 2 h prior to voiding.

   Click to Show/Hide
Undisclosed  Undisclosed
Phase 1
An open-label, multicenter, single-arm dose-escalating trial assessing the safety and tolerability of VB4-845 injected IT once weekly for four consecutive weeks. Twenty patients were treated in six dose cohorts, and were followed for four weeks after the last dose. The ascending modifi ed Fibonacci dose cohorts were 100, 200, 330, 500, 700, and 930 g. VB4-845 was supplied as a 1 mg/mL formulation and was diluted in phosphate buffered saline.

   Click to Show/Hide
Full List of Activity Data of This Antibody-drug Conjugate
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 Complete Remission (CR)
44.44% (all)
41.91% (in cohort 1)
39.13% (in cohort 2)
Patients Enrolled
Histologically confirmed TCC of the bladder and residual CIS, with or without concurrent Ta or T1 tumors, refractory/intolerant to 1 or more cycles of BCG in the 24 months before enrollment and whose tumor was EpCAM positive.
Administration Dosage
1 induction cycle of 6 (cohort 1) or 12 (cohort 2) weekly intravesical oportuzumab monatox (VB4-845) instillations of 30 mg, followed by up to 3 maintenance cycles of 3 weekly administrations every 3 months; lasting up to 1 year.
Related Clinical Trial
NCT Number NCT00462488  Clinical Status Phase 2
Clinical Description Phase 2 study to evaluate the efficacy and tolerability of intravesical vicinium in patients with non-invasive urothelial carcinoma in situ (CIS) previously treated with bacille calmette-gurin (BCG).
Primary Endpoint
Evaluable patients treated with OM 44.44% (20 of 45) achieved a CR.
Other Endpoint
A complete response to oportuzumab monatox was seen in 9 of 22 patients (40.91%) in cohort 1 and 9 of 23 (39.13%) in cohort 2 at the 3-month evaluation. A total of 20 patients (44.44%) achieved a complete response.
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Complete Remission (CR)
39.94% (in all patients)
29.41% (In the TIS% (in situ carcinoma) group)
43.75% (In the T1 group)
42.86% (In the Ta group)
Patients Enrolled
Immunohistochemically confirmed EpCAM-positive Grade 2 or 3 nonmuscle invasive bladder cancer (NMIBC) (Ta, T1, in situ carcinoma [TIS]), either refractory to (recurrence within 2 years following at least one complete cycle of BCG therapy) or intolerant of BCG therapy.
Administration Dosage
Eight dose levels were initially evaluated, starting at 0.10 mg once weekly for 6 consecutive weeks and escalating through 0.20, 0.33, 0.66, 1.32, 2.64, 5.28, and 10.56 mg/dose. Each dose was administered to the bladder through a catheter and held for 2 h prior to voiding.
Experiment 3 Reporting the Activity Date of This ADC [3]
Patients Enrolled
Histologically confirmed recurrent squamous cell carcinomas of the head and neck (SCCHN) following radiotherapy and/or chemotherapy.
Administration Dosage
Twenty patients were treated in six dose cohorts, and were followed for four weeks after the last dose. The ascending modified Fibonacci dose cohorts were 100, 200, 330, 500, 700, and 930 ug. Injected IT once weekly for four consecutive weeks.
References
Ref 1 A phase II study of oportuzumab monatox: an immunotoxin therapy for patients with noninvasive urothelial carcinoma in situ previously treated with bacillus Calmette-Gurin. J Urol. 2012 Nov;188(5):1712-8.
Ref 2 A Phase I study of an intravesically administered immunotoxin targeting EpCAM for the treatment of nonmuscle-invasive bladder cancer in BCGrefractory and BCG-intolerant patients. Drug Des Devel Ther. 2010 Nov 15;4:313-20.
Ref 3 A phase I clinical study of VB4-845: weekly intratumoral administration of an anti-EpCAM recombinant fusion protein in patients with squamous cell carcinoma of the head and neck. Drug Des Devel Ther. 2009 Feb 6;2:105-14.

If you find any error in data or bug in web service, please kindly report it to Dr. Shen et al.