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Clinical Trials List

Protocol Number7465-CL-0301
NCT Number(ClinicalTrials.gov Identfier)NCT03474107

2018-06-15 - 2021-06-30

Phase III

Recruiting5

Study ended1

ICD-10C67

Malignant neoplasm of bladder

An Open-Label, Randomized Phase 3 Study to Evaluate Enfortumab Vedotin vs. Chemotherapy in Subjects with Previously Treated Locally Advanced or Metastatic Urothelial Cancer(EV-301)

  • Trial Applicant

    PAREXEL INTERNATIONAL CO., LTD.

  • Sponsor

    Astellas Pharma Global Development, Inc.

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2025/08/20

Investigators and Locations

Principal Investigator Jian-Ri Li Division of Urology
Taichung Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator 鄭元佐 Division of Urology
Kaoshiung Chang Gung Memorial Hospital of the C.G.M.F.

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Wen-Pin Su Division of General Internal Medicine
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Audit

None

Principal Investigator Yu-Chieh Tsai Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Audit

None

Principal Investigator Yung-Chang Lin Division of Hematology & Oncology
Linkou Chang Gung Medical Foundation

Taiwan National PI

林永昌

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

3 Recruiting

Audit

None

Principal Investigator Wen-Jeng Wu Division of Urology
Kaohsiung Medical Univeristy Chung-Ho Memorial Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Study ended

Condition/Disease

Locally Advanced or Metastatic Urothelial Cancer

Objectives

main  For subjects suffering from locally advanced or metastatic urinary epithelial cancer, compare the overall survival (OS) of enfortumab vedotin (EV) treatment with the OS of chemotherapy treatment secondary Comparing the exacerbation-free survival (PFS1) of the subjects during the trial treatment period when receiving EV treatment and receiving chemotherapy (based on the definition of the solid tumor response assessment standard version 1.1 [RECIST V1.1]) Compare the overall response rate (ORR) of EV and chemotherapy (according to the definition of RECIST V1.1)  Assess the duration of response (DOR) of EV and chemotherapy (according to the definition of RECIST V1.1)  Compare the disease control rate (DCR) of EV and chemotherapy (according to the definition of RECIST V1.1) Assess the safety and tolerability of EV Assess quality of life (QOL) and patient self-reported results (PRO) parameters Exploratory In the tumor tissue and surrounding blood, exploratory genes and/or other biomarkers that may be related to the treatment outcome, including the performance of Nectin-4 Assess the pharmacokinetics of EVs (total antibody [TAb], antibody-drug complex [ADC] and monomethyl auristatin E Assess the incidence of anti-therapeutic antibodies (ATA) Assess the PFS (PFS2) in the next-line therapy when receiving EV treatment and chemotherapy Utilization of medical resources (HRU)

Test Drug

enfortumab vedotin

Active Ingredient

enfortumab vedotin

Dosage Form

Lyophilised Powder per Vial

Dosage

30

Endpoints

main
 OS
secondary
 PFS1 defined by RECIST V1.1
 ORR defined by RECIST V1.1 (complete response [CR] + PR)
 DCR defined by RECIST V1.1 (CR + PR + stable disease [SD])
 DOR defined by RECIST V1.1
 Safety variables (such as AE, laboratory testing, vital signs measurement, 12-lead electrocardiogram [ECG] and ECOG PS)
 QOL and PRO parameters (QLQ-C30 and EQ-5D-5L)
Exploratory
 In the tumor tissue and surrounding blood, exploratory genes and/or other biomarkers that may be related to the treatment outcome, including the performance of Nectin-4
 Plasma or serum pharmacokinetic parameters of some EVs and MMAEs
 Incidence of EV ATA
 PFS2 defined by RECIST V1.1
 HRU

Inclution Criteria

1. Before conducting any test-related procedures (including discontinuation of banned drugs, if applicable), the human testing board (IRB)/independent ethics committee (IEC) must be obtained from the subject in accordance with national regulations (for example: the health of the American test unit Written informed consent and privacy statement approved by the Insurance Portability and Attribution Act [HIPAA] authorization).
2. According to local regulations, the subject was already a legal adult when signing the informed consent.
3. The subject has urinary epithelial cancer (ie, cancer of the bladder, renal pelvis, ureter or urethra) confirmed by histological or cytological examination. Subjects suffering from urinary epithelial carcinoma (transitional epithelial cell carcinoma) with squamous cell differentiation or mixed cell types are still eligible for the test.
4. Subjects must have received CPI (anti-programmed cell death protein-1 [PD-1] or anti-programmed cell death ligand-1 [PD-L1]) during or after for locally advanced or metastatic disease , Imaging deterioration or recurrence occurred. Subjects who discontinued CPI treatment due to toxicity are eligible for testing if there is evidence that their disease worsens after discontinuation. CPI does not need to be the most recent therapy. Subjects whose most recent therapy is a course of treatment without CPI are eligible for the test if they have deteriorated/relapsed during or after receiving the most recent therapy. Locally advanced disease is not suitable for curative resection based on the judgment of the treating physician.
5. Subjects must have received platinum-containing treatment (cisplatin or carboplatin) in the context of metastatic/locally advanced, neoadjuvant or adjuvant therapy. If platinum-containing drugs have been used in the context of adjuvant/neoadjuvant therapy, the subject must get worse within 12 months after the completion of the treatment.
6. In the baseline period, the subject has metastatic or locally advanced disease confirmed by imaging studies.
7. There should be a stock of tumor tissue specimens, which can be sent to the central laboratory before the trial treatment is performed. If there are no stock tumor tissue specimens available, fresh tissue specimens should be provided. If it is not possible to provide fresh tissue samples for safety reasons, you must discuss with the medical supervisor whether to be included in the trial.
8. Subject's ECOG PS is 0 or 1
9. The subject has the following laboratory test data during the reference period:
*Absolute neutrophil count (ANC) ≥ 1500/mm3
*Platelet count ≥ 100 x 109/L
*Heme ≥ 9 g/dL
*serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN) *; or if it is a subject suffering from Gilbert’s disease, it is ≤ 3 times the ULN
*Estimated according to institutional standards, or measured by collecting 24-hour urine (the glomerular filtration rate [GFR] can also be substituted for CrCl) Creatinine clearance rate (CrCl) ≥ 30 mL/min
*Alanine transamidation (ALT) and aspartic acid transamidation (AST)≤ 2.5 times ULN (or in patients with liver metastasis,≤ 3 times ULN)*
*If total bilirubin> ULN; or if AST and/or ALT> 1.5 times ULN and alkaline phosphate > 2.5 times ULN, docetaxel should not be selected as the subject's control drug.
10. Female subjects must:
*Incapable of fertility:
* Menopause before screening (defined as at least 1 year without any menstruation, and no other obvious pathological or physiological causes); or
*Have a record of surgical sterilization (for example: hysterectomy, bilateral salpingectomy, bilateral oophorectomy).
Note: Patients who have no menstruation due to other medical reasons are not considered to have menopause and must meet the conditions applicable to subjects with fertility.
*Or, if it is a fertile female:
 *Agree not to try to get pregnant during the trial and for at least 6 months after the last trial drug administration,
 *And obtain a negative urine or serum pregnancy test result within 7 days before the first day (Women who get a false positive result and have evidence that they are not pregnant are still eligible to participate in the test);
 *Moreover, if there is heterosexual sex, it must be agreed to continue to use condoms and one type is highly effective according to local licensing standards from the beginning of the screening, throughout the trial period, and at least 6 months after the last trial drug administration. Of contraceptive methods*.
11. During the screening period and throughout the trial period, and at least 6 months after the last trial drug administration, female subjects must agree not to breastfeed or donate eggs.
12. Male subjects who have sex and whose female partner is fertile must meet the following conditions to qualify:
*Agree to use male condoms from the beginning of the screening and continue throughout the trial treatment period, and at least 6 months after the last trial drug administration. If the male subject has not undergone a vasectomy, or has not been sterilized according to the following definition, the female partner must start from the screening and continue throughout the trial treatment period, and at least after the male subject receives the last trial drug administration For 6 months, use a highly effective method of contraception according to local acceptable standards*.
*Highly effective contraceptive methods include:
#Continuous and correct use of approved hormonal contraceptives that inhibit ovulation,
#Approved intrauterine device (IUD) or intrauterine administration system (IUS).
#Bilateral tubal ligation
# Vasectomy (If azoospermia is confirmed, vasectomy is a highly effective contraceptive method. If not, another highly effective contraceptive method should be used)
#Men were sterilized due to bilateral testicular resection or radical cystoprostatectomy/resection of seminal vesicles
#Abstinence can be regarded as a highly effective method if it is defined as not having sex with the opposite sex during the entire period of risk associated with the trial drug. The reliability of abstinence must be evaluated based on the trial period and the subjects' preferences and usual lifestyles.
Please note: In Switzerland, abstinence is not sufficient as a contraceptive method.
13. From the beginning of the screening period and throughout the trial period, and for at least 6 months after the last trial drug administration, male subjects are not allowed to donate sperm.
14. If the male subject’s partner is pregnant or breastfeeding, he must agree to abstain from sex or use condoms during the pregnancy or breastfeeding during the entire trial treatment period and at least 6 months after the last trial drug administration.
15. The subject agrees not to participate in other interventional trials during the treatment period in this trial.

Exclusion Criteria

1. The subject suffers from pre-existing sensory or motor neuropathy of grade ≥ 2.
2. The subject has an active central nervous system (CNS) metastasis. Subjects with treated CNS metastases are allowed to participate in the trial if they meet all of the following conditions:
*CNS metastasis has been clinically stable for at least 6 weeks before screening
*If steroids are needed to treat CNS metastases, the subject should have received at least 2 weeks of treatment at a stable dose of ≤ 20 mg/day prednisone or equivalent drugs
*The baseline scan did not show evidence of new or enlarged brain metastases
*The subject does not suffer from leptomeningeal disease
3. Subjects have ongoing, clinically significant toxicity related to past treatments (including systemic therapy, radiotherapy or surgery) (level 2 or higher, with the exception of hair loss). When the dose of hormone replacement therapy received remains stable/controlled properly, subjects with hypothyroidism or hypopituitary gland function associated with ≥ level 2 immunotherapy can be included (if applicable). Subjects currently suffering from ≥ Level 3 immunotherapy-related hypothyroidism or hypopituitary gland hypofunction will be excluded. Subjects currently suffering from immunotherapy-related colitis, uveitis, myocarditis, or pneumonia, or other immunotherapy-related adverse events that require treatment with high-dose steroids (> 20 mg/day of prednisone or equivalent drugs) ( AE) subjects will be excluded.
4. The subject has been treated with EV or other ADC containing monomethyl auristatin E (MMAE).
5. Subjects have received all available experimental therapies in the control group (that is, in areas where vinflunine is not an approved therapy, they have received paclitaxel and docetaxel; in areas where vinflunine is an approved therapy, they have received paclitaxel, docetaxel, and vinflunine ), as a chemotherapy drug to treat urinary epithelial cancer.
Note: After reaching the upper limit of vinflunine, subjects who have used both docetaxel and paclitaxel will be excluded.
6. The subject has treated locally advanced or metastatic urinary epithelial cancer with more than one course of chemotherapy, including adjuvant chemotherapy or neoadjuvant disease (if recurrence within 12 months after the completion of the treatment). If no new chemotherapy drugs are added to the course of treatment, replacing cisplatin with carboplatin will not constitute a new course of treatment.
7. The subject had suffered from another malignant tumor within 3 years prior to the administration of the first dose of the test drug, or there is any evidence that the previously diagnosed malignant tumor has residual disease. If the subject suffers from non-melanoma skin cancer, has received curative treatment and has no evidence of deterioration of local prostate cancer, low-risk or very low-risk (determined according to standard guidelines) and is undergoing surveillance/observational treatment without intention Waiting for local prostate cancer, or any type of carcinoma in situ (if completely resected), are allowed to enter the trial.
8. At the time of the first dose of EV, the subject is being treated with systemic antimicrobial therapy for viral, bacterial or fungal infections. Allow routine antimicrobial preventive treatment.
9. The subject is known to have active hepatitis B (such as HBsAg responsiveness) or active hepatitis C (such as detection of HCV RNA [qualitative]).
10. The subject has a known history of human immunodeficiency virus (HIV) (HIV 1 or 2) infection.
11. There are records showing that the subject has had a cerebrovascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or contact with the New York Heart Association within 6 months before the administration of the first dose of the test drug. Cardiac symptoms (including congestive heart failure) that correspond to categories III-IV.
12. The subject had received radiotherapy or major surgery within 4 weeks before the first dose of the test drug was administered.
13. The subject has received anti-tumor treatment of chemotherapy, biologics, investigational drugs, and/or immunotherapy that have not been completed 2 weeks before the first dose of the test drug was administered.
14. The subject is known to be oversensitive to any excipients (including histidine, trehalose dihydrate, and polysorbate 20) contained in the EV or EV drug dosage form; or the subject is known to be sensitive to Chinese hamster ovary ( CHO) cell biopharmaceutical products are excessively sensitive.
15. The subject is known to be overly sensitive to the following items:
• Docetaxel or any other excipients listed on the product label (including polysorbate 80);
• Paclitaxel or any other excipients listed on the product label (including macrogolglycerol ricinoleate 35 [Ph.Eur.]); and
• Vinflunine or any other excipients listed on the product label (including other vinca alkaloids [vinblastine, vincristine, vindesine, vinorelbine]).
16. (Remove this condition).
17. The subject is known to have active keratitis or corneal ulcer. If the test host determines that the superficial punctate keratitis is receiving appropriate treatment, subjects suffering from this disease can be allowed.
18. The subject has other potential medical conditions, which will be determined by the trial host to impair the subject's ability to receive or tolerate the scheduled treatment and follow-up.
19. Have a history of uncontrolled diabetes within 3 months before the first dose of the test drug. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) ≥ 8%, or HbA1c between 7 and <8% and complicated by diabetes symptoms (polyuria or polythirsty) that cannot be explained by other reasons.

The Estimated Number of Participants

  • Taiwan

    60 participants

  • Global

    665 participants

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