Payload Information
General Information of This Payload
| Payload ID | PAY0UCFUY |
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| Name | Pseudomonas exotoxin ETA-252-608 |
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| Synonyms |
Pseudomonas exotoxin ETA-252-608
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| Target | Eukaryotic elongation factor 2 kinase (EEF2K) | |||||
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
VB4-845 [Phase 3]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Patients Enrolled |
Inclusion: Adults (≥18y) with EpCAM+ CIS bladder TCC failing BCG therapy (last 24 months), residual unresectable disease post-TURBT, life expectancy ≥12 months, adequate organ function. Exclusion: Upper tract TCC/hydronephrosis, recent intravesical therapy (<2 months), active UTIs, uncontrolled comorbidities, pregnancy, or inability to tolerate intravesical procedures. Contraception required for reproductive-age patients.
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| Administration Dosage |
Induction Phase is a single intravesical dose of Vicinium at 30 mg in 40 mL PBS once per week for 6 weeks. If free of disease at 12 weeks after the first instillation, the subject enters Maintenance dosing in which 30 mg of Vicinium is administered once per week for 3 weeks followed by 9 weeks of no therapy.
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| Related Clinical Trial | |||||
| NCT Number | NCT00462488 | Phase Status | PHASE2 | ||
| Clinical Description |
Phase II Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium<sup>TM</sup> in Patients With Non-Invasive Urothelial Carcinoma in Situ (CIS) Previously Treated With Bacille Calmette-Guérin (BCG)
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| Primary Endpoint |
A complete response to oportuzumab monatox was seen in 9 of 22 patients (41%) in cohort 1 and 9 of 23 (39%) in cohort 2 at the 3-month evaluation. A total of 20 patients (44%) achieved a complete response. Two other patients without carcinoma in situ who achieved a complete response were not included in the study due to the development of noninvasive papillary (Ta) disease. Median time to recurrence in patients who achieved a complete response was 274 and 408 days in cohorts 1 and 2, respectively. Overall 7 patients (16%) remained disease-free. Post-study assessment demonstrated that these patients were still disease-free at last followup (18 to 25 months).
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| Other Endpoint |
The most common adverse events were mild to moderate reversible bladder symptoms.
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
Eligibility: BCG-refractory/relapsed non-muscle-invasive bladder cancer (CIS/Ta/T1) patients (≥18y) with adequate organ function, stratified by disease type/time since BCG. Exclusions: upper tract TCC/hydronephrosis, recent chemotherapy (<2 weeks), active UTIs, QTc>470ms, uncontrolled comorbidities, or second malignancies (except localized/low-risk cancers). Contraception required during treatment +120 days.
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| Administration Dosage |
Induction - 30 mg of Vicinium in 50 mL of saline administered twice weekly (BIW) for 6 weeks followed by once weekly for 6 weeks, for a total of 12 weeks.
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| Related Clinical Trial | |||||
| NCT Number | NCT02449239 | Phase Status | PHASE3 | ||
| Clinical Description |
Open-Label, Multicenter, Ph 3 [Phase 3] Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium<sup>TM</sup> in Subjects With Non Muscle-Invasive Carcinoma in Situ and/or High-Grade Papillary Disease of the Bladder Treated With BCG
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| Primary Endpoint |
Primary endpoints include complete response rate (CRR) at 3 months (absence of high-grade disease confirmed by cytology/cystoscopy) and duration of response (time from CR to treatment failure/death) assessed up to 24 months in CIS patients receiving Vicinium therapy.
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| Other Endpoint |
Secondary endpoints comprise event-free survival (time to disease recurrence/progression/cystectomy/death), CRR at 3-month intervals (6-24 months), time to cystectomy (up to 48 months), progression-free/overall survival (24/48 months respectively), and safety (AE incidence/treatment discontinuations monitored for 25 months).
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| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Patients Enrolled |
Eligibility: BCG-unresponsive NMIBC (CIS/Ta/T1) patients (≥18y, ECOG 0-1) with adequate organ function. Exclusions: prior PD-1/PD-L1 therapy, active infections/autoimmunity, QTc≥470ms, other malignancies (except localized cancers), hydronephrosis, or immunosuppressant use within 28 days. Contraception required during/4 months post-treatment.
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| Related Clinical Trial | |||||
| NCT Number | NCT03258593 | Phase Status | PHASE1 | ||
| Clinical Description |
A Phase I Single-Arm Study of the Combination of Durvalumab (MEDI4736) and Vicineum (Oportuzumab Monatox, VB4-845) in Subjects With High-Grade Non-Muscle-Invasive Bladder Cancer Previously Treated With Bacillus Calmette-Guerin (BCG)
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| Primary Endpoint |
Safety assessment includes incidence and severity of adverse events (Grades 1-5 per CTCAE v5.0) recorded over an average 315-day period, covering non-serious AEs to life-threatening/serious events (hospitalization, disability, death).
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| Other Endpoint |
Efficacy and biomarker analyses evaluate urinary EpCAM/PD-L1/PD-1 changes between responders/non-responders (Wilcoxon tests), pharmacokinetics (urinary Vicineum Cmax), disease-free survival (Kaplan-Meier), and immune parameter dynamics in blood/biopsies at baseline/3/6 months. Response criteria include cytology/cystoscopy-confirmed recurrence/progression.
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| Experiment 4 Reporting the Activity Date of This ADC | [4] | ||||
| Patients Enrolled |
Eligibility: BCG-refractory/relapsed non-muscle-invasive bladder cancer patients (≥18y, Karnofsky≥60) with adequate prior BCG exposure (≥2 courses). Exclusions: upper tract disease, active hydronephrosis, recent chemotherapy (<2 weeks), QTc>470ms, concurrent malignancies, or intravesical procedure intolerance. Contraception required during/120 days post-treatment.
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| Administration Dosage |
Induction - 30 mg of Vicinium in 50 mL of saline administered twice weekly (BIW) for 6 weeks followed by once weekly for 6 weeks, for a total of 12 weeks.Maintenance - 30 mg of Vicinium in 50 mL of saline administered once weekly every other week for up to 104 weeks.
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| Related Clinical Trial | |||||
| NCT Number | NCT04859751 | Phase Status | PHASE3 | ||
| Clinical Description |
An Open-Label, Single Arm, Multicenter Study to Evaluate the Efficacy and Safety of Intravesical VB4-845 Injection in Patients With Non-Muscle Invasive Bladder Cancer
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| Primary Endpoint |
Primary efficacy endpoints include complete response rate (CRR) at 3 and 6 months in CIS patients (with/without papillary disease) receiving VB4-845 therapy, assessed through cystoscopic and pathological evaluation.
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| Other Endpoint |
Secondary endpoints comprise recurrence-free rates at 3/6 months for high-grade Ta/T1 patients, along with comprehensive safety monitoring (CTCAE v5.0-graded AEs, lab abnormalities, vital signs) throughout the 104-week study duration.
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| Experiment 5 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Complete Remission (CR) |
44.44
40.91 39.13 % |
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| 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.
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| 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.
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| Related Clinical Trial | |||||
| NCT Number | NCT00462488 | Phase 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).
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| Primary Endpoint |
Evaluable patients treated with OM 44.44% (20 of 45) achieved a CR.
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| 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.
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| Experiment 6 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Complete Remission (CR) |
39.94
29.41 43.75 42.86 % |
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| 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.
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| 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.
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| Experiment 7 Reporting the Activity Date of This ADC | [7] | ||||
| Patients Enrolled |
Histologically confirmed recurrent squamous cell carcinomas of the head and neck (SCCHN) following radiotherapy and/or chemotherapy.
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| 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.
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References