Durvalumab and Vicineum in Subjects With High-Grade Non-Muscle-Invasive Bladder Cancer Previously Treated With Bacillus Calmette-Guerin (BCG)
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)
2 other identifiers
interventional
15
1 country
1
Brief Summary
Background: Non-muscle-invasive bladder cancer is in the early stages. But it usually comes back after treatment. The drugs Vicineum and Durvalumab may help the immune system find and destroy cancer cells. Objective: To test if the drugs Durvalumab and Vicineum together are safe and effective to treat people with bladder cancer that has not spread to the muscle in the bladder. Eligibility: People ages 18 and older who have bladder cancer that has not spread to the muscle in the bladder and was treated unsuccessfully with Bacillus Calmette-Guerin Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Tumor sample from previous surgery. If one is not available, they will have a biopsy: A small piece of tumor is removed. Cystoscopy to examine the inside of the bladder. This may include a biopsy or removing tumors. Computed tomography (CT) or magnetic resonance imaging (MRI): They lie in a machine that takes pictures of the body. Electrocardiogram to test heart function Participants will receive Durvalumab and Vicineum in 2 phases: First phase: Durvalumab every 4 weeks and Vicineum once a week for 3 months Second phase: Durvalumab every 4 weeks and Vicineum once every other week Participants will have tumor samples taken every 3 months. They will have blood and urine tests throughout the study. Participants will continue treatment for up to 2 years. Participants will have a visit about 30 days after their last treatment. This includes blood and urine tests. It may include a cytoscopy or additional biopsies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jun 2018
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 22, 2017
CompletedFirst Posted
Study publicly available on registry
August 23, 2017
CompletedStudy Start
First participant enrolled
June 7, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
October 17, 2022
CompletedResults Posted
Study results publicly available
October 26, 2023
CompletedMarch 17, 2026
February 1, 2026
4.2 years
August 22, 2017
August 29, 2023
February 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Grades 1-5 Adverse Events
Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.
Through study completion, an average of 315 days
Secondary Outcomes (10)
Urinary Epithelial Cell Adhesion Molecule (EpCAM) Compared Between Participants Who Have a Clinical Response to Therapy vs. Those Who do Not Respond
Baseline, week 1, weeks 2-5, week 6, week 10 and week 12
Response Rate
From enrollment until event occurrence (recurrence, progression); twelve weeks.
Pharmacokinetic Parameters in Urine Maximum Concentration (Cmax) of Vicineum
Baseline, week 1, week 6, week 12
Change in Programmed Death-ligand 1 (PD-L1) Levels Between Responders and Non-Responders
Baseline and after treatment with both agents, from enrollment up to 5 weeks
Change in Programmed Cell Death Protein 1 (PD-1) Levels Between Responders and Non-Responders
baseline and after treatment with both agents
- +5 more secondary outcomes
Other Outcomes (4)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Through study completion, an average of 315 days.
Maximum Tolerated Dose (MTD) of Durvalumab
6 weeks
Maximum Tolerated Dose (MTD) of Vicineum
6 weeks
- +1 more other outcomes
Study Arms (4)
Run-In Cohort - Durvalumab 1500mg Intravenous (IV) Every 4 Weeks (Q4WK) + Vicineum 30 mg
EXPERIMENTALDurvalumab + Vicineum, escalating doses. Up to 2 dose levels will be evaluated in the first 6 - 12 participants.
Expansion Cohort - Durvalumab 1500mg Intravenous (IV) Every 4 Weeks (Q4WK) + Vicineum 30 mg
EXPERIMENTALDurvalumab + Vicineum, at the maximum tolerated dose (MTD). Up to 24 participants.
Level 1, Durvalumab 1500mg intravenous (IV) Every 4 Weeks (Q4WK) + Vicineum 20 mg
EXPERIMENTALLevel 1, Durvalumab 1500mg intravenous (IV) Every 4 Weeks (Q4WK) + Vicineum 20 mg
Arm 2, Durvalumab + Vicineum at the Maximum Tolerated Dose (MTD)
EXPERIMENTALArm 2, Durvalumab + Vicineum at the Maximum Tolerated Dose (MTD)
Interventions
Antihistamine (e.g., diphenhydramine) or equivalent medications per institutional standard may be administered at the discretion of the investigator.
Bladder biopsy at screening and every 3 months before each cystoscopy per schema.
Urine cytology at screening and every 3 months before each cystoscopy per schema.
Urine cytology at baseline and every 3 months before each cystoscopy per schema.
Electrocardiogram (ECG) at screening, pre-durvalumb infusion and as clinically indicated during the trial.
Computed tomography (CT) at screening and every 12 months while on study.
Magnetic resonance imaging (MRI) at screening and every 12 months while on study.
Durvalumab 1500 mg is administered intravenously (IV) once every 4 weeks for 12 months with an option to continue therapy for an additional 12 months (total of 24 months) provided that, participant is tolerating therapy and remains free of recurrent high grade NMIBC (see Treatment Period below). The dose of durvalumab is 1500 mg. If optional maintenance therapy continued in the second year, durvalumab 1500 mg will be administered intravenously once every 3 months to provide an immune boost.
Vicineum is administered in a 12-week Induction Phase followed by a Maintenance Phase for at least one year with an option for a total of up to 2 years of treatment. During the Induction Phase, Vicineum is administered once weekly for 12 weeks. During the Maintenance Phase, Vicineum is administered every other week. The dose of Vicineum is 30 mg in 50 mL of saline.
Acetaminophen or equivalent medications per institutional standard may be administered at the discretion of the investigator.
Transurethral resection of a bladder tumor (TURBT) at screening and every 3 months before each cystoscopy per schema.
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed by National Cancer Institute (NCI) Laboratory of Pathology as high-grade non-muscle invasive urothelial (transitional cell carcinoma) of the bladder as follows:
- Carcinoma-in-situ (CIS) with or without papillary tumors
- High-grade Ta or T1 disease based on a biopsy/transurethral resection of bladder tumor (TURBT) performed within 12 weeks of the initial dose of study treatment. If multiple bladder biopsies/TURBTs are required to confirm eligibility, the timing of the last bladder biopsy to the initial dose of study treatment must be within 12 weeks.
- Patients with persistent T1 high grade disease on TURBT following a single induction course of BCG (Bacillus Calmette-Guerin) (at least 5 of 6 doses) may also be eligible for this trial provided that the patient is surgically unfit for cystectomy as deemed by the investigator or the patient declines cystectomy.
- Subjects with BCG unresponsive disease as defined by the Society of Urologic Oncology and the Food and Drug Administration (FDA): Subjects must have received at least two courses of intravesical BCG (at least 5 of 6 induction doses of BCG and at least 2 of 3 maintenance doses of BCG under a maintenance regimen or at least 2 doses of a repeat induction course). Please note exception above for persistent T1 disease. There is no upper limit on the amount of prior BCG a subject may have received.
- Patients who have met eligibility criterion above must have received last BCG dose within a year of enrollment.
- The investigator must document that he/she believes the subject would not benefit from additional BCG treatment at the time of study entry.
- Age \>= 18 years at time of signing the informed consent form (ICF). Because no dosing or adverse event data are currently available on the use of Vicineum in combination with durvalumab in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. Furthermore, non-muscle invasive bladder cancer (NMIBC) does not occur in children.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate organ and marrow function as defined below:
- Hemoglobin \>= 9.0 g/dL
- Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (\> 1500 per mm\^3)
- Platelet count \>= 75 x 10\^9/L (\>75,000 per mm\^3)
- Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN).
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate-pyruvate transaminase (SGPT) less than or equal to 2.5 x institutional ULN
- +10 more criteria
You may not qualify if:
- Patients who are receiving any other investigational agents.
- QT interval corrected for heart rate using Fridericia's formula the corrected QT interval by Fridericia (QTcF) \>=470 ms. (Any clinically significant abnormalities detected require triplicate ECG results and a mean QT interval corrected for heart rate using Fridericia's formula (QTcF) \>=470 ms calculated from 3 ECGs.)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Vicineum or durvalumab or other agents used in the study.
- Pregnant women are excluded from this study because it is unknown whether Vicineum and/or durvalumab have any teratogenic effects. In nursing mothers, breastfeeding should be discontinued as these medications may have the potential risk for adverse events in nursing infants secondary to treatment of the mother.
- Any previous treatment with a programmed cell death 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, including durvalumab
- Evidence of non-bladder urothelial (transitional cell) carcinoma by biopsy, cytology, or radiological imaging within the past 2 years of treatment (e.g., upper tract transitional cell carcinoma, urethral urothelial carcinoma).
- Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS (carcinoma in situ), Ta, or T1 by more than 2 years) and diagnostic evaluation at screening shows no evidence of tumor causing the hydronephrosis.
- Any other anticancer therapy (e.g., chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, radiation therapy, intravesical therapy, investigational agent) within 28 days of the first dose of study therapy (and within 6 weeks for nitrosourea or mitomycin C) other than a single dose of intravesical chemotherapy which is permitted between 28 days and 14 days prior to the first dose of study treatment.
- The subject has a diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancer, localized prostate cancer on active surveillance, or localized solid tumors deemed cured by surgery and not treated with systemic anticancer therapy and not expected to require anticancer therapy in the next 2 years i.e., while the subject may be taking study treatment.
- Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
- Subjects with vitiligo or alopecia
- Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormonal replacement
- Any chronic skin condition that does not require systemic therapy
- Subjects without active disease in the last 5 years may be included but only after consultation with the Principal Investigator
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Raju Chelluri
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Raju Chelluri, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
August 22, 2017
First Posted
August 23, 2017
Study Start
June 7, 2018
Primary Completion
August 1, 2022
Study Completion
October 17, 2022
Last Updated
March 17, 2026
Results First Posted
October 26, 2023
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol genomic data sharing (GDS) plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).