Enfortumab Vedotin vs. chemotherapy in advanced or metatstatic urothel
Research type
Research Study
Full title
An Open-Label, Randomised Phase 3 Study to Evaluate Enfortumab Vedotin vs. Chemotherapy in Subjects with Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)
IRAS ID
246006
Contact name
Ariane Moseleit
Contact email
Sponsor organisation
Astellas Pharma Global Development, Inc.
Eudract number
2017-003344-21
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 5 months, 7 days
Research summary
The main purpose of this study is to determine if a medicine called enfortumab vedotin (EV) is more effective than, safe and comparable to the following standard chemotherapies: (docetaxel, paclitaxel, or vinflunine) in patients with urothelial cancer who have received previous standard therapies. Standard chemotherapy in this setting is unclear. Three drugs- docetaxel, vinflunine and paclitaxel are used interchangeably and it will be up to the study doctor to decide which of these is the best treatment option for the patient.
Urothelial cancer is a cancer of the urinary system. The urothelium ist the lining of the bladder, renal pelvis, ureter or urethra. The study is directed at patients who were previously treated with chemotherapy containing a platinum (cisplatin or carboplatin) as well as a kind of anticancer drug called an immune checkpoint inhibitor (CPI) and whose cancer has spread to nearby tissues or to other areas of the body.
Enfortumab vedotin is an experimental drug that is being studied to treat urothelial cancer. It has not been submitted to the Medicines and Healthcare Products Regulatory Agency (MHRA) and/or any other regulatory authorities for approval for the treatment of any disease or type of cancer.
Participants will be randomly assigned in a 1:1 ratio to one of the following treatment groups:
A) Enfortumab vedotin
B) either docetaxel, paclitaxel or vinflunine (as decided by the study doctor)Approximately 550 participants will participate in this study at approximately 150 research centres globally. The Sponsor of the study is Astellas Pharma Global Development, Inc.
Summary of results
Astellas is grateful to everyone who took part in this clinical study. It is important that people and the public know the results of clinical studies. Astellas reviewed the study information and prepared a report of the results. This is a summary of that report.
Overall summary
People with locally advanced or metastatic urothelial cancer took part in this study. Some received enfortumab vedotin and some received chemotherapy. For people who received enfortumab vedotin, the time at which half had died was 12.88 months. For people who received chemotherapy, the corresponding time was 8.97 months. No new safety concerns were identified for enfortumab vedotin.
Background and purpose of the study
Urothelial cancer is cancer in the lining of the bladder. Chemotherapy is usually the first treatment offered, but the cancer often returns soon afterwards, so there is an unmet medical need.
Enfortumab vedotin is a treatment for people with locally advanced or metastatic urothelial cancer. Locally advanced means that the cancer has spread to nearby tissue. Metastatic means that the cancer has spread to other parts of the body.
In this study, people with locally advanced or metastatic urothelial cancer either received enfortumab vedotin or chemotherapy. The two main questions asked were: how long people lived during the study, and whether people had medical problems from enfortumab vedotin or chemotherapy during the study.
Study treatments
In this summary, “study treatment” means the treatment given during the study. The study treatments were enfortumab vedotin and one of three chemotherapies: docetaxel, paclitaxel or vinflunine.
Enfortumab vedotin was the treatment the researchers wanted to learn more about.
Enfortumab vedotin and the chemotherapies were given slowly as an injection into a vein. This is called intravenous infusion.
The enfortumab vedotin dose depended on how much each person weighed and was measured in milligrams (mg) of enfortumab vedotin per kilogram (kg) of body weight, also called mg/kg.
People received 1.25 mg/kg. For people who weighed more than 100 kg, the maximum permitted dose was 125 mg. Chemotherapy was given according to the relevant package insert.
Who took part
People with locally advanced or metastatic urothelial cancer took part. Their cancer had come back after previous treatment with chemotherapy or immunotherapy. A total of 608 people took part: 301 were allocated to enfortumab vedotin and 307 to chemotherapy. Of these, 587 received study treatment: 296 received enfortumab vedotin and 291 received chemotherapy.
In the enfortumab vedotin group, 301 people were allocated to treatment: 238 men and 63 women, aged 34 to 85 years. In the chemotherapy group, 307 people were allocated to treatment: 232 men and 75 women, aged 30 to 88 years.
When and where the study took place
The study started in June 2018 and was completed in November 2025. It took place at 158 medical centres worldwide.
The centres were distributed as follows: Argentina, 1; Australia, 4; Austria, 3; Belgium, 9; Canada, 11; Denmark, 3; France, 14; Germany, 5; Italy, 7; Japan, 25; the Netherlands, 4; Portugal, 3; the Republic of Korea, 11; the Russian Federation, 4; Spain, 15; Switzerland, 2; Taiwan, 6; the United Kingdom, 6; and the United States, 25.
Study conduct overview
People were assigned to receive either enfortumab vedotin or chemotherapy.
Of the 608 people allocated to study treatment, 301 were allocated to enfortumab vedotin and 307 were allocated to chemotherapy.
In the enfortumab vedotin group, 296 people received enfortumab vedotin on the 1st, 8th and 15th days of each 28-day cycle. In the chemotherapy group, 291 people received chemotherapy on the 1st day of each 21-day cycle.
Scans were done every 56 days to check whether the cancer had become worse. Study treatment continued until the cancer became worse or the person could not tolerate the study treatment. After the end-of-study-treatment visit, scans continued every 56 days until the cancer became worse.
If a person stopped study treatment because their cancer had become worse, the scans were stopped and the person went directly to survival follow-up. Survival follow-up took place every 3 months.
Main efficacy result
The researchers measured the length of time when half of the people in each treatment group were still alive. They did this for people who received enfortumab vedotin and compared with people who received chemotherapy. This way of comparing results is often used in long-term cancer studies.
People who received enfortumab vedotin lived longer than those who received chemotherapy. The median overall survival was 12.88 months with enfortumab vedotin and 8.97 months with chemotherapy Medical problems during the study Much research is needed to know whether a treatment causes a medical problem. When new treatments are being studied, researchers keep track of all medical problems that people have while they are in the study. Researchers recorded all medical problems that people experienced during the study, whether or not they were considered related to treatment. These problems are called adverse events.
An adverse event that the study doctor thought might have been caused by a study treatment is called an adverse reaction.
A serious adverse reaction is one that is fatal or life-threatening, causes lasting problems, or requires hospital care.
The information below relates only to adverse reactions recorded during this study; other studies may report different adverse reactions.
Overall adverse reactions
Among the 296 people who received enfortumab vedotin, 278 people (93.9%) had adverse reactions, 47 (15.9%) stopped treatment because of adverse reactions, and 70 (23.6%) had serious adverse reactions. Among the 291 people who received chemotherapy, 267 people (91.8%) had adverse reactions, 36 (12.4%) stopped treatment because of adverse reactions, and 68 (23.4%) had serious adverse reactions.
Adverse reactions reported in at least 20 in 100 people (20%) in either treatment group during the study
• Hair loss (alopecia): enfortumab vedotin 135/296 (45.6%); chemotherapy 108/291 (37.1%).
• Loss of feeling in the hands and feet (peripheral sensory neuropathy): enfortumab vedotin 103 (34.8%); chemotherapy 63 (21.6%).
• Itching (pruritus): enfortumab vedotin 96 (32.4%); chemotherapy 14 (4.8%).
• Fatigue: enfortumab vedotin 93 (31.4%); chemotherapy 66 (22.7%).
• Decreased appetite: enfortumab vedotin 92 (31.1%); chemotherapy 69 (23.7%).
• Diarrhoea: enfortumab vedotin 74 (25.0%); chemotherapy 49 (16.8%).
• Taste changes (dysgeusia): enfortumab vedotin 73 (24.7%); chemotherapy 22 (7.6%).
• Nausea: enfortumab vedotin 71 (24.0%); chemotherapy 64 (22.0%).
Serious adverse reactions (An adverse reaction is considered serious when it is life-threatening, causes lasting problems or needs hospital care) that happened in at least 2 in 100 people (2%) of either treatment group
• Fever caused by very low neutrophil levels (febrile neutropenia): enfortumab vedotin 2/296 (0.7%); chemotherapy 16/291 (5.5%).
• Low neutrophil levels (neutropenia): enfortumab vedotin 4 (1.4%); chemotherapy 8 (2.7%).
• Diarrhoea: enfortumab vedotin 7 (2.4%); chemotherapy 4 (1.4%).
• Acute kidney injury: enfortumab vedotin 6 (2.0%); chemotherapy 1 (0.3%).
During the study, 233 people who received enfortumab vedotin died; 7 deaths were thought to be caused by enfortumab vedotin. In the chemotherapy group, 249 people died; 3 deaths were thought to be caused by chemotherapy.
Conclusion
This study helped researchers learn more about enfortumab vedotin in people with locally advanced or metastatic urothelial cancer.
The results showed that people who received enfortumab Vedotin lived for longer compared to people who received chemotherapy This summary presents the main results from this study only. Other studies of enfortumab vedotin may provide new or different results. Researchers review results from many studies before deciding on a new treatment. When this summary was completed, other studies of enfortumab vedotin were still in progress and could produce different results.REC name
London - Riverside Research Ethics Committee
REC reference
18/LO/1120
Date of REC Opinion
9 Jul 2018
REC opinion
Favourable Opinion