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Clinical Trial Details

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Genitourinary Cancer

Enfortumab vedotin

A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
Phase 1
NCT05014139

Active enrolling

Globe
Locations

United States, Canada, France, Germany, Spain, United Kingdom

Study design

Participant Group/Arm

EXPERIMENTAL: Enfortumab vedotin: Dose escalation cohort

During the induction phase, participants will receive enfortumab vedotin once a week for 6 weeks. During the maintenance phase, participants will receive enfortumab vedotin once a month for 9 doses.

Intervention/Treatment

DRUG: Enfortumab vedotin

Given into the bladder (intravesically)

Participant Group/Arm

EXPERIMENTAL: Enfortumab vedotin: Dose expansion cohort

During the induction phase, participants will receive enfortumab vedotin once a week for 6 weeks. During the maintenance phase, participants will receive enfortumab vedotin once a month for 9 doses.

Intervention/Treatment

DRUG: Enfortumab vedotin

Given into the bladder (intravesically)

Key eligibility criteria

Inclusion criteria
  • Histologically confirmed, non-muscle invasive urothelial carcinoma with carcinoma in situ (CIS) (with or without papillary disease)
  • Predominant histologic component (\>50 percent) must be urothelial (transitional cell) carcinoma
  • Participants must have high-risk Bacillus Calmette-Guerin (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 or 5 of 6 doses of an initial induction course + at least 2 of 6 doses of a 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 dose
  • Participant must be ineligible for or refusing a radical cystectomy
  • All visible papillary Ta/T1 tumors must be completely resected within 60 days prior to enrollment.
  • Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2.
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 urogram 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

Key dates

Study start date
  • December 2021
Estimated primary completion date
  • May 2028

Key endpoints

Primary Outcome Measures
Outcome Measure

Incidence of adverse events (AEs)

Measure Description

An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Time Frame

Approximately 1 year

Outcome Measure

Incidence of laboratory abnormalities

Measure Description

To be summarized using descriptive statistics.

Time Frame

Approximately 1 year

Outcome Measure

Incidence of dose limiting toxicities (DLTs)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Approximately 7 weeks

Secondary Outcome Measures:
Outcome Measure

Pharmacokinetics (PK) of enfortumab vedotin: Area under the concentration-time curve (AUC)

Measure Description

AUC will be recorded from the PK blood samples collected.

Time Frame

Approximately 1 year

Outcome Measure

PK of enfortumab vedotin: Maximum concentration (Cmax)

Measure Description

Cmax will be recorded from the PK blood samples collected.

Time Frame

Approximately 1 year

Outcome Measure

PK of enfortumab vedotin: Time to maximum concentration concentration (tmax)

Measure Description

Tmax will be recorded from the PK blood samples collected.

Time Frame

Approximately 1 year

Outcome Measure

PK of enfortumab vedotin: Apparent terminal half-life (t1/2)

Measure Description

T1/2 will be recorded from the PK blood samples collected.

Time Frame

Approximately 1 year

Outcome Measure

PK of enfortumab vedotin: Trough concentration (Ctrough)

Measure Description

Ctrough will be recorded from the PK blood samples collected.

Time Frame

Approximately 1 year

Outcome Measure

Incidence of antitherapeutic antibodies (ATAs) to enfortumab vedotin

Measure Description

Blood samples for ATA analysis will be collected.

Time Frame

Approximately 1 year

Outcome Measure

Complete response (CR) rate

Measure Description

CR rate is defined as the proportion of subjects achieving CR.

Time Frame

Up to 24 months

Outcome Measure

Duration of CR

Measure Description

The time from first documented CR to the first evidence of recurrence, progression, or death due to any cause.

Time Frame

Up to 5 years

Outcome Measure

Rate of cystectomy

Measure Description

The proportion of subjects who subsequently undergo cystectomy.

Time Frame

Up to 5 years

Outcome Measure

Progression-free survival

Measure Description

The time from start of study treatment to the first evidence of progression or death due to any cause.

Time Frame

Up to 5 years

Outcome Measure

Cystectomy-free survival

Measure Description

The time from start of study treatment to cystectomy or death due to any cause.

Time Frame

Up to 5 years

Number of participants

58

Collaborators and investigators

Sponsor: Astellas Pharma Global Development, Inc.

Collaborator: Seagen Inc.

This information is current as of May 30th 2024.