TriangleNCT03219333 · CITED IN SOURCE DOCUMENTS
A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2024-08-27
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
Duration of Objective Response (DOR) Per BICR
Progression-Free Survival (PFS) Per BICR
ORR Per Investigator Assessment
DOR Per Investigator Assessment
PFS Per Investigator Assessment
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)
Incidence of Antitherapeutic Antibody (ATA)
Disease Control Rate at 16 Weeks (DCR16) Per BICR
DCR16 Per Investigator Assessment
Overall Survival (OS): Primary Analysis
Number of Participants With Adverse Events (AEs): Primary Analysis
Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)
PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)
PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)
PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)
PK Parameter for Free MMAE: Tmax (Plasma)
PK Parameter for Free MMAE: AUC (Plasma)
PK Parameter for Total Antibody (TAb): Cmax (Serum)
PK Parameter for TAb: Tmax (Serum)
PK Parameter for TAb: AUC (Serum)
Number of Participants With Adverse Events (AEs): Final Analysis
Overall Survival (OS): Final Analysis
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Enfortumab vedotin on days 1, 8 and 15 every 28 days
- intervention Names
- Drug: Enfortumab vedotin
- label
- Enfortumab vedotin
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Enfortumab vedotin
- description
- Intravenous (IV) infusion on days 1, 8 and 15 every 28 days
- name
- Enfortumab vedotin
- other Names
- ASG-22CE
- ASG-22ME
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- intervention Model Description
- single-arm, open-label, multi-cohort, multicenter study
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 219
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as a \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
- measure
- Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
- time Frame
- Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
- secondary Outcomes
- 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. CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as a \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions is also considered progression. DOR was analyzed using Kaplan-Meier methodology.
- measure
- Duration of Objective Response (DOR) Per BICR
- time Frame
- Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
- 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. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions is also considered progression.
- measure
- Progression-Free Survival (PFS) Per BICR
- time Frame
- Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
- description
- ORR was defined as the percentage of participants with confirmed CR or PR according to RECIST 1.1. CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as a \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
- measure
- ORR Per Investigator Assessment
- time Frame
- Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
- description
- CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as a \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions is also considered progression.
- measure
- DOR Per Investigator Assessment
- time Frame
- Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
- 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. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions is also considered progression.
- measure
- PFS Per Investigator Assessment
- time Frame
- Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
- description
- A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose. Abnormalities were graded based on National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
- measure
- Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)
- time Frame
- The median duration of treatment was 4.60 months for Cohort 1 [range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [range: 0.3, 24.6 months]
- description
- A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose. Abnormalities were graded based NCI CTCAE version 4.03 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
- measure
- Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)
- time Frame
- The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months]
- description
- Participants who were tested positive for ATA at any time post-baseline were considered to be transiently positive or persistently positive if \>=2 consecutive samples were confirmed as positive.
- measure
- Incidence of Antitherapeutic Antibody (ATA)
- time Frame
- The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months]
- description
- Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as a \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
- measure
- Disease Control Rate at 16 Weeks (DCR16) Per BICR
- time Frame
- Up to Week 16
- description
- Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as a \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions is also considered progression. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
- measure
- DCR16 Per Investigator Assessment
- time Frame
- Up to Week 16
- description
- OS is defined as the time from first dose of enfortumab vedotin to death from any cause.
- measure
- Overall Survival (OS): Primary Analysis
- time Frame
- Cohort 1 median follow-up time: 28.4 months [range 0.49, 32.62]; Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]
- description
- AE=untoward medical occurrence associated with use of study intervention, whether or not considered related. Treatment emergent adverse event (TEAE)=newly occurring/worsening AE after first dose of study treatment, within 30 days after last dose. According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G)3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE. Participants who discontinued treatment due to treatment related TEAEs captured under TEAEs leading to treatment discontinuation. SAE=event at any dose led to death;life-threatening;required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Treatment relatedness was judged by investigator.
- measure
- Number of Participants With Adverse Events (AEs): Primary Analysis
- time Frame
- The median duration of treatment was 4.60 months for Cohort 1 [range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [range: 0.3, 24.6 months]
Full study description
- brief Summary
- 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
- Japan Pharmaceuticals and Medical Devices Agency (PMDA) has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan. 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.
Source references
- references
- citation
- McGregor B, O'Donnell PH, Balar A, Petrylak D, Rosenberg J, Yu EY, Quinn DI, Heath EI, Campbell M, Hepp Z, McKay C, Steinberg J, Regnault A, Mazerolle F, Galsky MD. Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial. Eur Urol. 2022 May;81(5):515-522. doi: 10.1016/j.eururo.2022.01.032. Epub 2022 Feb 12.
- pmid
- 35168844
- type
- DERIVED
- citation
- Yu EY, Petrylak DP, O'Donnell PH, Lee JL, van der Heijden MS, Loriot Y, Stein MN, Necchi A, Kojima T, Harrison MR, Hoon Park S, Quinn DI, Heath EI, Rosenberg JE, Steinberg J, Liang SY, Trowbridge J, Campbell M, McGregor B, Balar AV. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):872-882. doi: 10.1016/S1470-2045(21)00094-2. Epub 2021 May 12.
- pmid
- 33991512
- type
- DERIVED
- citation
- Rosenberg JE, O'Donnell PH, Balar AV, McGregor BA, Heath EI, Yu EY, Galsky MD, Hahn NM, Gartner EM, Pinelli JM, Liang SY, Melhem-Bertrandt A, Petrylak DP. Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2019 Oct 10;37(29):2592-2600. doi: 10.1200/JCO.19.01140. Epub 2019 Jul 29.
- pmid
- 31356140
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice