Metastatic Urothelial CancerPhase 2NCT04995419
A Study to Evaluate Enfortumab Vedotin (ASG-22CE) in Chinese Participants With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Platinum-containing Chemotherapy and Programmed Cell Death Protein-1 ( PD 1) / (Programmed Death Ligand-1 (PD-L1) Inhibitor Therapy
A Phase 2 study testing Enfortumab vedotin in people with Metastatic Urothelial Cancer, run by Astellas Pharma China, Inc. at 7 sites in China.
Trial summary
The purpose of this study was to determine the antitumor activity of enfortumab vedotin (EV) confirmed by the objective response rate (ORR). This study also evaluated the effect of antibody-drug conjugate (ADC), total antibody (TAb) and monomethyl auristatin E (MMAE) in Chinese participants with locally advanced or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Urothelial Cancer
- What is being tested?
- Enfortumab vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 7 sitesChina
- Study dates
- 22 Jul 2021to 27 Aug 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participant must have histologically or cytologically documented urothelial/transitional cell carcinoma of the bladder, renal pelvis, ureter or urethra. Other histologies including adenocarcinoma, squamous differentiation or mixed are eligible.
- Participant has locally advanced or metastatic disease that is not amenable to curative intent treatment. Participants must have measurable disease at baseline according to Response Evaluation Criteria in Solid Tumors (RECIST) ( Version 1.1). Lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable.
- Participant must have received prior treatment with PD-1/PD-L1 inhibitor therapy in the locally advanced or metastatic urothelial cancer setting. Participants who received PD-1/PD-L1 therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
- Participant who received prior treatment with platinum-containing chemotherapy defined as those who received platinum in the neoadjuvant/adjuvant setting and had recurrent or progressive disease within 12 months of completion or received treatment with platinum in the locally advanced (defined as unresectable with curative intent) or metastatic setting.
- Platinum based chemotherapy may include combination use with a PD-1 or PD-L1 inhibitor.
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- Participant has the following baseline laboratory data. If a participant has received a recent blood transfusion or growth factor, the hematology tests must be obtained ≥7 days after any growth factor and ≥ 28 days after any blood transfusion.
- absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
- platelet count ≥ 100 × 10^9/L
- hemoglobin ≥ 9 g/dL
- serum total bilirubin (TBL) ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for participants with Gilbert's disease
- creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards or as measured by 24-hour urine collection (glomerular filtration rate [GFR] can also be used instead of CrCl).
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
- Female participant is not pregnant and at least one of the following conditions apply:
- Not a woman of childbearing potential (WOCBP)
- WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after the last dose of study treatment administration.
- Female participant must agree not to breastfeed starting at screening and throughout the study period and for at least 6 months after the last dose of study treatment administration.
- Female participant must not donate ova starting at first dose of study treatment and throughout the study period and for 6 months after the last dose of study treatment administration.
- Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 6 months after the last dose of study treatment administration.
- Male participant must not donate sperm during the treatment period and for 6 months after the last dose of study treatment administration.
- Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 6 months after the last dose of study treatment administration.
- Participant agrees not to participate in another interventional study while receiving study treatment in the present study.
- Participant must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
- Participant must have an anticipated life expectancy of ≥ 3 months.
Who cannot join
- Participant has preexisting sensory or motor neuropathy Grade ≥ 2.
- Participant has active central nervous system (CNS) metastases. Participants with treated CNS metastases are permitted on study if all the following are true:
- CNS metastases have been clinically stable for ≥ 6 weeks prior to screening.
- If requiring steroid treatment for CNS metastases, the participant is on a stable dose ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks.
- Baseline imaging scans show no evidence of new or enlarged brain metastasis.
- Participant does not have leptomeningeal disease.
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- Participant has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).
- Participant with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or panhypopituitarism is excluded. Participant with ongoing immunotherapy-related colitis, uveitis, myocarditis or pneumonitis, or participants with other immunotherapy-related AEs requiring high doses of steroids (> 20 mg/day of prednisone or equivalent), is excluded. Participant with ≤ Grade 2 immunotherapy-related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of hormone replacement therapy (if indicated).
- Participant has a history of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8 percent or HbA1c between 7 percent and < 8 percent with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
- Participant has prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADCs).
- Participant has a second malignancy diagnosed within 3 years before first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Participants with non-melanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
- Participant is currently receiving systemic antimicrobial treatment for viral, bacterial or fungal infection at the time of first dose of study treatment. Routine antimicrobial prophylaxis is permitted.
- Participants with a positive hepatitis B surface antigen and/or anti-hepatitis B core antibody and a negative polymerase chain reaction (PCR) assay at baseline should receive appropriate antiviral prophylaxis or regular surveillance monitoring as per local or institutional guidelines.
- Active hepatitis C infection or known human immunodeficiency virus (HIV) infection. Participant who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of ≥ 12 weeks.
- Participant has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of study drug.
- Participant had major surgery within 2 weeks or radiotherapy, chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that is not completed 2 weeks prior to first dose of study drug. Toxicities from these therapies must have resolved or adequately stabilized before starting study treatment.
- Participant has known hypersensitivity to enfortumab vedotin or to any excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate and polysorbate 20) or participant has known hypersensitivity to biopharmaceuticals produced in CHO cells.
- Participant has known active keratitis or corneal ulcerations. Participant with superficial punctate keratitis is allowed if the disorder is being adequately treated.
- Participant has any condition which makes the participant unsuitable for study participation.
- Uncontrolled tumor-related bone pain or impending spinal cord compression. Participant requiring pain medication must be on a stable regimen for at least 2 weeks at the time of first dose.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
China7 sites
Site CN86001
Beijing
Site CN86009
Changsha
Site CN86002
Guangzhou
Site CN86006
Hangzhou
Site CN86007
Nanjing
Site CN86004
Shanghai
Site CN86003
Wuhan
About this study
Official title: A Single-arm, Open-label, Multi-center Phase 2 Study of Enfortumab Vedotin (ASG-22CE) in Chinese Subjects With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Platinum-containing Chemotherapy and PD 1/PD-L1 Inhibitor Therapy (EV-203)
The purpose of this study was to determine the antitumor activity of enfortumab vedotin (EV) confirmed by the objective response rate (ORR).
This study also evaluated the effect of antibody-drug conjugate (ADC), total antibody (TAb) and monomethyl auristatin E (MMAE) in Chinese participants with locally advanced or metastatic urothelial cancer.
Read more
In addition, the study also evaluated the duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immunogenicity determined by the incidence of antitherapeutic antibodies (ATA).
Safety and tolerability of EV in participants with locally advanced or metastatic urothelial cancer was also evaluated.
Read the detailed description
This study comprised of a single group of participants who received one dose of enfortumab vedotin (EV) on Days 1, 8 and 15 of every 4-week (28 days) cycle. Participants continued on study treatment until discontinuation.
After treatment discontinuation, participant had an end of treatment (EOT) visit for a 30-day Safety Follow-up.
Participants to discontinue to treatment for reasons other than disease progression were followed for response assessments.
A Pharmacokinetic (PK) cohort was available at some study centers. Participants enrolled at the PK cohort site(s) had intense PK samples collected after single and repeated doses.
- Conditions
- Metastatic Urothelial Cancer
- Being tested
- Enfortumab vedotin
- Keywords
- Enfortumab Vedotin, PADCEV, ASG-22CE, Pharmacokinetics, Urothelial cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enfortumab vedotinDrug
Also called PADCEV, ASG-22CE
Intravenous Infusion
| Study group | Role | What they receive |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Experimental | Participants received 1.25 milligrams per kilogram (mg/kg) of body weight enfortumab vedotin by intravenous (IV) infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first. Participants who had intense PK Sampling were enrolled in PK Cohort. Receives: Drug: Enfortumab vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors V1.1 (RECIST V1.1)
ORR was defined as the percentage of participants with best overall response (BOR) as complete response (CR) or partial response (PR) based on the RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.
Measured: From first dose up to progressive disease or death (maximum duration: 9.33 months)
Pharmacokinetics (PK) of Antibody-Drug Conjugate (ADC), Total Antibody (TAb), in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1
Cmax was derived from the PK blood samples collected.
Measured: Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of Monomethyl Auristatin E (MMAE) in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1
Cmax was derived from the PK blood samples collected.
Measured: Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15
Cmax was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of MMAE in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15
Cmax was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC , TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1
As per planned analysis, if more than 50% of PK concentrations were below the limit of quantification (i.e 0) at a given time point, standard deviation was not reported.
Measured: Cycle 1 Day 1: pre-dose
PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1
As per planned analysis, if more than 50% of PK concentrations were below the limit of quantification (i.e 0) at a given time point, standard deviation was not reported.
Measured: Cycle 1 Day 1: pre-dose
PK of ADC, TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15
Ctrough was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose
PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15
Ctrough was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose
PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 1
Tmax was derived from the PK blood samples collected.
Measured: Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 15
Tmax was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb, MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 28 (AUC0-28d) at Cycle 1 Day 1
AUC0-28d was derived from the PK blood samples collected.
Measured: Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb, MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 28 (AUC0-28d) at Cycle 1 Day 15
AUC0-28d was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1
AUC0-7d was derived from the PK blood samples collected.
Measured: Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1
AUC0-7d was derived from the PK blood samples collected.
Measured: Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15
AUC0-7d was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15
AUC0-7d was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb, MMAE in Plasma: Accumulation Ratio of Cmax (RacCmax)
Accumulation ratio is the ratio of Cmax after the dosing interval (Cycle 1 Day 15) divided by Cmax after the first dosing interval (Cycle 1 Day 1).
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb, MMAE in Serum: Accumulation Ratio of AUC0-7d ( RacAUC0-7d)
RacAUC0-7d was calculated using AUC0-7d and derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb, MMAE in Serum: Terminal Elimination Half-life (t1/2)
t1/2 was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb, MMAE in Serum: Systemic Clearance (CL)
CL was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb, MMAE in Serum: Volume of Distribution at Steady State (Vss)
Vss was derived from the PK blood samples collected.
Measured: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Secondary outcomes (11)
Objective Response Rate (ORR) as Per Investigator Assessment
ORR was defined as the percentage of participants with BOR as CR or PR based on the RECIST v1.1 as per investigator's assesment. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.
Measured: From first dose up to progressive disease or death at the time of primary analysis cut-off (maximum duration: 9.33 months)
Duration of Response (DOR) as Per RECIST V1.1 Per IRC
DOR: time from the date of the first CR/PR (whichever is first recorded) that was subsequently confirmed as assessed by IRC to the date of documented progressive disease. or death due to any cause whichever occurred first. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. Progressive Disease:>= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of >= 5 mm. Appearance of 1 or more new lesions is also considered progression.
Measured: From date of the first CR/PR up to progressive disease or death (maximum duration: 48.69 months)
Duration of Response (DOR) as Per RECIST V1.1 Per Investigator's Assessment
DOR: time from the date of the first CR/PR (whichever is first recorded) that was subsequently confirmed as assessed by Investigator's Assesment to the date of documented progressive disease or death due to any cause whichever occurred first. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. Progressive disease:>= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of >= 5 mm. Appearance of 1 or more new lesions is also considered progression.
Measured: From date of the first CR/PR up to progressive disease or death (maximum duration: 48.69 months)
Disease Control Rate (DCR) as Per RECIST V1.1 Per IRC
DCR: percentage of participants with a CR, PR or SD based on RECIST v1.1 as assessed by IRC. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug. Progressive disease:>= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of >= 5 mm. Appearance of 1 or more new lesions is also considered progression.
Measured: From first dose up to progressive disease or death at the time of primary analysis cut-off (maximum duration: 9.33 months)
Disease Control Rate (DCR) as Per RECIST V1.1 Per Investigator's Assesment
DCR: percentage of participants with a CR, PR or SD based on RECIST v1.1 as assessed by investigator's assessment. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug. Progressive disease:>= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of >= 5 mm. Appearance of 1 or more new lesions is also considered progression.
Measured: From first dose up to progressive disease or death at the time of primary analysis cut-off (maximum duration: 9.33 months)
Progression Free-Survival Per RECIST V1.1 Per IRC
PFS: time from first dose of the study drug until date of documented radiological disease progression per IRC based on RECIST V1.1, or until death due to any cause, whichever occurred first. Progressive disease: >= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of >= 5 mm. Appearance of 1 or more new lesions is also considered progression. A participant who neither progressed nor died was censored at date of last radiological assessment (RA)/ date of randomization if no post-baseline RA was available. Participants who received any further anticancer therapy (ACT) for disease before radiological progression was censored at date of last RA before ACT started and participants who had PD/death after >=2 missed RAs were censored at last RA prior to 2 or more missed RAs. Kaplan-Meier estimates was used.
Measured: From first dose up to progressive disease or death (maximum duration: 48.69 months)
Progression Free-Survival Per RECIST V1.1 Per Investigator's Assessment
PFS: time from first dose of the study drug until date of documented radiological disease progression per investigator based on RECIST V1.1, or until death due to any cause, whichever occurred first. Progressive disease: >= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of >= 5 mm. Appearance of 1 or more new lesions is also considered progression. A participant who neither progressed nor died was censored at date of last RA/ date of randomization if no post-baseline RA was available. Participants who received any further ACT for disease before radiological progression was censored at date of last RA before ACT started and participants who had progressive disease/death after >=2 missed RAs were censored at last RA prior to 2 or more missed RAs. Kaplan-Meier estimates was used.
Measured: From first dose up to progressive disease or death (maximum duration: 48.69 months)
Overall Survival (OS)
OS was defined as the time from first dose of the study drug until the documented date of death from any cause. OS was analyzed using Kaplan-Meier estimates. Participants who were still alive at the time of data cutoff date were to be censored at the last known alive date or at the data cutoff date, whichever was earlier.
Measured: From first dose up to death (maximum duration: 48.69 months)
Number of Participants With Antitherapeutic Antibodies (ATA)
Number of participants with ATA were reported.
Measured: From first dose until 9.33 months
Number of Participants With Treatment Emergent Adverse Events
An AE is any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. TEAE is defined as an adverse event observed after starting administration of the study drug and within 30 days after taking the last dose of study drug. Any post-baseline abnormal laboratory tests, vital sign measurements, or 12-lead electrocardiogram (ECG) measurements were reported as TEAEs.
Measured: Up to 47 months
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
ECOG performance status was measured on an 6 point scale. 0-Fully active, able to carry on all pre-disease performance without restriction.
- Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.
- Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
- Dead. Number of participants with ECOG PS was reported.
Measured: End of Treatment 30 day Follow-up (47 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2021
- Study start22 Jul 2021
- Primary completion13 May 2022
- Study completion27 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Urothelial CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma China, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Seagen Inc.
- Responsible party
- Sponsor
- Investigators
- Senior Medical Science Manager, Study director, Astellas Pharma China, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04995419
- Sponsor's protocol ID
- 7465-CL-1104
- Other IDs
- CTR20210922
- Status last verified
- Sep 2026
- First submitted
- 2 Aug 2021
- Last updated
- 2 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Publications
Li S, Shi Y, Dong H, Guo H, Xie Y, Sun Z, Zhang X, Kim E, Zhang J, Li Y, Xu C, Kadeerbai H, Lee S, Gorla S, Guo J, Sheng X. Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China. Cancer Med. 2024 Nov;13(21):e70368. doi: 10.1002/cam4.70368.
PubMed 39530574
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Open-label, Multi-center Phase 2 Study of Enfortumab Vedotin (ASG-22CE) in Chinese Subjects With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Platinum-containing Chemotherapy and PD 1/PD-L1 Inhibitor Therapy (EV-203)
- ClinicalTrials.gov ID
- NCT04995419
- Acronym / sponsor ID
- 7465-CL-1104
- Conditions
- Metastatic Urothelial Cancer
- Keywords
- Enfortumab Vedotin, PADCEV, ASG-22CE, Pharmacokinetics, Urothelial cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Astellas Pharma China, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Seagen Inc.
- Study start
- 22 Jul 2021 (actual)
- Primary completion
- 13 May 2022 (actual)
- Study completion
- 27 Aug 2025 (actual)
- First posted
- 9 Aug 2021 (actual)
- Results
- Posted 13 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to determine the antitumor activity of enfortumab vedotin (EV) confirmed by the objective response rate (ORR).
This study also evaluated the effect of antibody-drug conjugate (ADC), total antibody (TAb) and monomethyl auristatin E (MMAE) in Chinese participants with locally advanced or metastatic urothelial cancer.
In addition, the study also evaluated the duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immunogenicity determined by the incidence of antitherapeutic antibodies (ATA).
Safety and tolerability of EV in participants with locally advanced or metastatic urothelial cancer was also evaluated.
Detailed description
This study comprised of a single group of participants who received one dose of enfortumab vedotin (EV) on Days 1, 8 and 15 of every 4-week (28 days) cycle. Participants continued on study treatment until discontinuation.
After treatment discontinuation, participant had an end of treatment (EOT) visit for a 30-day Safety Follow-up.
Participants to discontinue to treatment for reasons other than disease progression were followed for response assessments.
A Pharmacokinetic (PK) cohort was available at some study centers. Participants enrolled at the PK cohort site(s) had intense PK samples collected after single and repeated doses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Experimental | Drug: Enfortumab vedotinParticipants received 1.25 milligrams per kilogram (mg/kg) of body weight enfortumab vedotin by intravenous (IV) infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first. Participants who had intense PK Sampling were enrolled in PK Cohort. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participant must have histologically or cytologically documented urothelial/transitional cell carcinoma of the bladder, renal pelvis, ureter or urethra. Other histologies including adenocarcinoma, squamous differentiation or mixed are eligible.
- Participant has locally advanced or metastatic disease that is not amenable to curative intent treatment. Participants must have measurable disease at baseline according to Response Evaluation Criteria in Solid Tumors (RECIST) ( Version 1.1). Lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable.
- Participant must have received prior treatment with PD-1/PD-L1 inhibitor therapy in the locally advanced or metastatic urothelial cancer setting. Participants who received PD-1/PD-L1 therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
- Participant who received prior treatment with platinum-containing chemotherapy defined as those who received platinum in the neoadjuvant/adjuvant setting and had recurrent or progressive disease within 12 months of completion or received treatment with platinum in the locally advanced (defined as unresectable with curative intent) or metastatic setting.
Key exclusion criteria (20 listed)
- Participant has preexisting sensory or motor neuropathy Grade ≥ 2.
- Participant has active central nervous system (CNS) metastases. Participants with treated CNS metastases are permitted on study if all the following are true:
- Participant has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).
- Participant with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or panhypopituitarism is excluded. Participant with ongoing immunotherapy-related colitis, uveitis, myocarditis or pneumonitis, or participants with other immunotherapy-related AEs requiring high doses of steroids (> 20 mg/day of prednisone or equivalent), is excluded. Participant with ≤ Grade 2 immunotherapy-related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of hormone replacement therapy (if indicated).
- Participant has a history of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8 percent or HbA1c between 7 percent and < 8 percent with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enfortumab vedotinAlso: PADCEV, ASG-22CEIntravenous Infusion | Drug | Enfortumab Vedotin 1.25 mg/kg |
Primary outcome
Objective Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors V1.1 (RECIST V1.1)
Time frame: From first dose up to progressive disease or death (maximum duration: 9.33 months)
ORR was defined as the percentage of participants with best overall response (BOR) as complete response (CR) or partial response (PR) based on the RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.
Pharmacokinetics (PK) of Antibody-Drug Conjugate (ADC), Total Antibody (TAb), in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1
Time frame: Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)
Cmax was derived from the PK blood samples collected.
PK of Monomethyl Auristatin E (MMAE) in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1
Time frame: Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)
Cmax was derived from the PK blood samples collected.
PK of ADC, TAb in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Cmax was derived from the PK blood samples collected.
PK of MMAE in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Cmax was derived from the PK blood samples collected.
PK of ADC , TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1
Time frame: Cycle 1 Day 1: pre-dose
As per planned analysis, if more than 50% of PK concentrations were below the limit of quantification (i.e 0) at a given time point, standard deviation was not reported.
PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1
Time frame: Cycle 1 Day 1: pre-dose
As per planned analysis, if more than 50% of PK concentrations were below the limit of quantification (i.e 0) at a given time point, standard deviation was not reported.
PK of ADC, TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15
Time frame: Cycle 1 Day 15: pre-dose
Ctrough was derived from the PK blood samples collected.
PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15
Time frame: Cycle 1 Day 15: pre-dose
Ctrough was derived from the PK blood samples collected.
PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 1
Time frame: Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Tmax was derived from the PK blood samples collected.
PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 15
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Tmax was derived from the PK blood samples collected.
PK of ADC, TAb, MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 28 (AUC0-28d) at Cycle 1 Day 1
Time frame: Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
AUC0-28d was derived from the PK blood samples collected.
PK of ADC, TAb, MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 28 (AUC0-28d) at Cycle 1 Day 15
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
AUC0-28d was derived from the PK blood samples collected.
PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1
Time frame: Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
AUC0-7d was derived from the PK blood samples collected.
PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1
Time frame: Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
AUC0-7d was derived from the PK blood samples collected.
PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
AUC0-7d was derived from the PK blood samples collected.
PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
AUC0-7d was derived from the PK blood samples collected.
PK of ADC, TAb, MMAE in Plasma: Accumulation Ratio of Cmax (RacCmax)
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Accumulation ratio is the ratio of Cmax after the dosing interval (Cycle 1 Day 15) divided by Cmax after the first dosing interval (Cycle 1 Day 1).
PK of ADC, TAb, MMAE in Serum: Accumulation Ratio of AUC0-7d ( RacAUC0-7d)
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
RacAUC0-7d was calculated using AUC0-7d and derived from the PK blood samples collected.
PK of ADC, TAb, MMAE in Serum: Terminal Elimination Half-life (t1/2)
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
t1/2 was derived from the PK blood samples collected.
PK of ADC, TAb, MMAE in Serum: Systemic Clearance (CL)
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
CL was derived from the PK blood samples collected.
PK of ADC, TAb, MMAE in Serum: Volume of Distribution at Steady State (Vss)
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Vss was derived from the PK blood samples collected.
11 secondary outcomes
Objective Response Rate (ORR) as Per Investigator Assessment
Time frame: From first dose up to progressive disease or death at the time of primary analysis cut-off (maximum duration: 9.33 months)
Duration of Response (DOR) as Per RECIST V1.1 Per IRC
Time frame: From date of the first CR/PR up to progressive disease or death (maximum duration: 48.69 months)
Duration of Response (DOR) as Per RECIST V1.1 Per Investigator's Assessment
Time frame: From date of the first CR/PR up to progressive disease or death (maximum duration: 48.69 months)
Disease Control Rate (DCR) as Per RECIST V1.1 Per IRC
Time frame: From first dose up to progressive disease or death at the time of primary analysis cut-off (maximum duration: 9.33 months)
Disease Control Rate (DCR) as Per RECIST V1.1 Per Investigator's Assesment
Time frame: From first dose up to progressive disease or death at the time of primary analysis cut-off (maximum duration: 9.33 months)
Progression Free-Survival Per RECIST V1.1 Per IRC
Time frame: From first dose up to progressive disease or death (maximum duration: 48.69 months)
Progression Free-Survival Per RECIST V1.1 Per Investigator's Assessment
Time frame: From first dose up to progressive disease or death (maximum duration: 48.69 months)
Overall Survival (OS)
Time frame: From first dose up to death (maximum duration: 48.69 months)
Number of Participants With Antitherapeutic Antibodies (ATA)
Time frame: From first dose until 9.33 months
Number of Participants With Treatment Emergent Adverse Events
Time frame: Up to 47 months
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Time frame: End of Treatment 30 day Follow-up (47 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39530574Li S, Shi Y, Dong H, Guo H, Xie Y, Sun Z, Zhang X, Kim E, Zhang J, Li Y, Xu C, Kadeerbai H, Lee S, Gorla S, Guo J, Sheng X. Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China. Cancer Med. 2024 Nov;13(21):e70368. doi: 10.1002/cam4.70368.
- Link to results and other applicable study documents on the Astellas Clinical Trials website.Link provided by the sponsor.
- Link to plain language summary of the study on the Trial Results Summaries website.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Senior Medical Science Manager study director
Astellas Pharma China, Inc.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Enfortumab vedotin in people with Metastatic Urothelial Cancer, run by Astellas Pharma China, Inc. at 7 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors V1.1 (RECIST V1.1) (time frame: From first dose up to progressive disease or death (maximum duration: 9.33 months)). The study lists 22 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04995419, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.