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A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
A phase 1, non-randomized study of intravesical Enfortumab Vedotin for patients with BCG-unresponsive NMIBC
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Study Details
The study will comprise 2 parts. First, dose escalation will find the highest dose of EV that does not cause unacceptable side effects in participants. Second, dose expansion will use the dose found in the first part to test how well the drug works.
All participants will receive enfortumab vedotin. Treatment on the study will occur during the induction and maintenance phases, and participants will enter a follow-up period after completion of the maintenance phase.
Study Phase
1
Medical Condition
BCG-unresponsive NMIBC
Intervention Model
Sequential Assignment
Arms and Interventions
| Arm | Intervention |
|---|---|
Experimental: EV: Dose escalation cohortDuring the induction phase, participants will receive EV once a week for 6 weeks. During the maintenance phase, participants will receive EV once a month for 9 doses. |
Drug: EVGiven into the bladder (intravesically). |
Experimental: EV: Dose expansion cohortDuring the induction phase, participants will receive EV once a week for 6 weeks. During the maintenance phase, participants will receive EV once a month for 9 doses. |
Drug: EVGiven into the bladder (intravesically). |
Inclusion Criteria
- Histologically confirmed, non–muscle-invasive urothelial carcinoma with carcinoma in situ (CIS) (with or without papillary disease)
-
Must have high-risk BCG-unresponsive disease, defined as (where adequate BCG therapy is defined as one of the following:
- 5 of 6 doses of an initial induction course + at least 2 of 3 doses maintenance therapy
-
5 of 6 doses of an initial induction course + at least 2 of 6 doses of second induction course):
- Persistent or recurrent CIS alone or with recurrent Ta/T1( noninvasive papillary disease/tumor invades the subepithelial connective tissue) disease within 12 months of completion of adequate BCG therapy.
- Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy, or
- T1 high-grade disease at the first evaluation following an induction BCG course (at least 5 or 6 doses)
Exclusion Criteria
- Current or prior history of muscle-invasive urothelial carcinoma or metastatic disease
- Nodal or metastatic disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) within 3 months prior to study treatment
- Concomitant upper tract urothelial carcinoma as noted on CT or MRI program performed within 3 months prior to study treatment
- Prior or concomitant urothelial carcinoma of the prostatic urethra within 6 months prior to study treatment
- Participants with tumor-related hydronephrosis
- Participant has received other systemic anticancer therapy including chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, and/or investigational agent within 4 weeks or intravesical therapy within 6 weeks of first dose of study treatment
- Participant has had any prior radiation to the bladder for urothelial cancer
Primary Outcomes
- Incidence of Adverse Events (AEs)
- Incidence of Laboratory Abnormalities
- Incidence of Dose-Limiting Toxicities (DLTs)
Secondary Outcomes
- Pharmacokinetics (PK) of EV: Area Under the Concentration-Time Curve (AUC)
- PK of EV: Maximum Concentration (Cmax)
- PK of EV: Time to Maximum Concentration (Tmax)
- PK of EV: Apparent Terminal Half-Life (t1/2)
- PK of EV: Trough Concentration (Ctrough)
- Incidence of Antitherapeutic Antibodies (ATAs) to EV
- Complete Response (CR) Rate
- Duration of CR
- Rate of Cystectomy
- Progression-Free Survival
- Cystectomy-Free Survival
The safety and efficacy of these investigational compounds, or investigational uses of marketed products, have not been established. For an agent(s) whose safety and efficacy have not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
The EV-104 study is currently enrolling.
Refer your patientsContacts and Locations
| LOCATION | STATUS |
Reference: ClinicalTrials.gov. A study of intravesical enfortumab vedotin for treatment of patients with non-muscle invasive bladder cancer (NMIBC) (08-20-2021). https://clinicaltrials.gov/ct2/show/nct05014139. Accessed 04-18-2022.
