Description:
This is a study that will test how an experimental drug (enfortumab vedotin) affects patients
with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of
the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other
areas of the body.
This clinical trial will enroll patients who were previously treated with a kind of
anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for
the treatment of urothelial cancer.
This study will test if the cancer shrinks with treatment. This study will also look at the
side effects of the drug. A side effect is a response to a drug that is not part of the
treatment effect.
Patients who sign up for this trial must also fall into one of these categories:
- Patients have already received treatment with platinum-containing chemotherapy
- Patients have never received platinum-containing treatment and are not eligible for
treatment with cisplatin.
Title
- Brief Title: A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
- Official Title: A Single-arm, Open-label, Multicenter Study of Enfortumab Vedotin (ASG-22CE) for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy
Clinical Trial IDs
- ORG STUDY ID:
SGN22E-001
- NCT ID:
NCT03219333
Conditions
- Carcinoma, Transitional Cell
- Urinary Bladder Neoplasms
- Urologic Neoplasms
- Renal Pelvis Neoplasms
- Urothelial Cancer
- Ureteral Neoplasms
- Urethral Neoplasms
Interventions
| Drug | Synonyms | Arms |
|---|
| Enfortumab vedotin | ASG-22CE, ASG-22ME | Enfortumab vedotin |
Purpose
This is a study that will test how an experimental drug (enfortumab vedotin) affects patients
with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of
the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other
areas of the body.
This clinical trial will enroll patients who were previously treated with a kind of
anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for
the treatment of urothelial cancer.
This study will test if the cancer shrinks with treatment. This study will also look at the
side effects of the drug. A side effect is a response to a drug that is not part of the
treatment effect.
Patients who sign up for this trial must also fall into one of these categories:
- Patients have already received treatment with platinum-containing chemotherapy
- Patients have never received platinum-containing treatment and are not eligible for
treatment with cisplatin.
Detailed Description
This study will examine the safety and anticancer activity of enfortumab vedotin given
intravenously to patients with locally advanced or metastatic urothelial cancer who
previously received a CPI and either previously received platinum-containing chemotherapy
(Cohort 1) or are platinum-naïve and cisplatin-ineligible (Cohort 2). Patients who received
platinum in the adjuvant/neoadjuvant setting and did not progress within 12 months of
completion will be considered platinum-naïve. Approximately 100 patients are expected to be
enrolled in each cohort. The primary goal of the study is to determine the confirmed ORR of
enfortumab vedotin.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Enfortumab vedotin | Experimental | Enfortumab vedotin on days 1, 8 and 15 every 28 days | |
Eligibility Criteria
Inclusion Criteria:
- Histologically documented urothelial carcinoma (squamous differentiation or mixed cell
types allowed).
- Metastatic disease or locally advanced disease that is not resectable.
- Must have received prior treatment with a CPI in the locally advanced or metastatic
urothelial cancer setting. A CPI is defined as a programmed cell death protein 1
(PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI
therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease
either during therapy or within 3 months of therapy completion are eligible.
- Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or
be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment
(Cohort 2).
- Must have had progression or recurrence of urothelial cancer during or following
receipt of most recent therapy.
- Tumor tissue samples must be available for submission to the sponsor prior to study
treatment.
- Must have measurable disease according to Response Evaluation Criteria in Solid Tumors
(RECIST) (Version 1.1).
- An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort
1 or ≤2 for Cohort 2.
- Anticipated life expectancy of ≥3 months as assessed by the investigator.
Exclusion Criteria:
- Ongoing sensory or motor neuropathy Grade ≥2.
- Active central nervous system (CNS) metastases.
- Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis.
- Prior enrollment in an enfortumab vedotin study or prior treatment with other
monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
- Uncontrolled tumor-related pain or impending spinal cord compression.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Objective response rate (ORR) by an independent review facility (IRF) |
| Time Frame: | Up to 3 years |
| Safety Issue: | |
| Description: | The proportion of patients with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) |
Secondary Outcome Measures
| Measure: | Duration of response (DOR) by an IRF |
| Time Frame: | Up to 7.5 years |
| Safety Issue: | |
| Description: | The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause, whichever comes first |
| Measure: | Disease control rate at 16 weeks (DCR16) by an IRF |
| Time Frame: | 16 weeks |
| Safety Issue: | |
| Description: | Proportion of patients with CR, PR, or stable disease (SD) at Week 16 visit |
| Measure: | Progression free survival (PFS) by an IRF |
| Time Frame: | Up to 7.5 years |
| Safety Issue: | |
| Description: | The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first |
| Measure: | ORR by investigator assessment |
| Time Frame: | Up to 7.5 years |
| Safety Issue: | |
| Description: | Confirmed CR and PR per RECIST 1.1 |
| Measure: | DOR by investigator assessment |
| Time Frame: | Up to 7.5 years |
| Safety Issue: | |
| Description: | The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or to death due to any cause, whichever comes first |
| Measure: | DCR16 by investigator assessment |
| Time Frame: | 16 weeks |
| Safety Issue: | |
| Description: | Proportion of patients with CR, PR, or SD at Week 16 visit |
| Measure: | Progression free survival (PFS) by investigator assessment |
| Time Frame: | Up to 7.5 years |
| Safety Issue: | |
| Description: | The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first |
| Measure: | Overall survival (OS) |
| Time Frame: | Up to 7.5 years |
| Safety Issue: | |
| Description: | The time from start of study treatment to date of death due to any cause |
| Measure: | Incidence of adverse events (AEs) |
| Time Frame: | Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years |
| Safety Issue: | |
| Description: | Descriptive statistics will be used to summarize results |
| Measure: | Incidence of laboratory abnormalities |
| Time Frame: | Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years |
| Safety Issue: | |
| Description: | Descriptive statistics will be used to summarize results |
| Measure: | Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) |
| Time Frame: | Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years |
| Safety Issue: | |
| Description: | Cmax will be derived from the PK blood samples collected |
| Measure: | PK parameter for enfortumab vedotin: Trough concentration (Ctrough) |
| Time Frame: | Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years |
| Safety Issue: | |
| Description: | Ctrough will be derived from the PK blood samples collected |
| Measure: | PK parameter for monomethyl auristatin E (MMAE): Cmax |
| Time Frame: | Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years |
| Safety Issue: | |
| Description: | Cmax will be derived from the PK blood samples collected |
| Measure: | PK parameter for MMAE: Ctrough |
| Time Frame: | Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years |
| Safety Issue: | |
| Description: | Ctrough will be derived from the PK blood samples collected |
| Measure: | PK parameter for Total Antibody (TAb): Cmax |
| Time Frame: | Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years |
| Safety Issue: | |
| Description: | Cmax will be derived from the PK blood samples collected |
| Measure: | PK parameter for Total Antibody (TAb): Ctrough |
| Time Frame: | Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years |
| Safety Issue: | |
| Description: | Ctrough will be derived from the PK blood samples collected |
| Measure: | Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin |
| Time Frame: | Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years |
| Safety Issue: | |
| Description: | Blood samples for ATA analysis will be collected |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Astellas Pharma Global Development, Inc. |
Trial Keywords
- Enfortumab vedotin
- Metastatic Urothelial Cancer
- ASG-22CE
- Locally Advanced Urothelial Cancer
- Antibody-Drug Conjugate
- Nectin-4
- Platinum-naïve
- Cisplatin-ineligible
- Antineoplastic Agents
- Drug Therapy
- ASG-22ME
Last Updated
August 11, 2021
