Primary:* * To determine the antitumor activity of single-agent enfortumab vedotin as measured by confirmed objective response rate (ORR) in patients with locally advanced or metastatic urothelial cancer who have previously received systemic therapy…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint
* The primary efficacy endpoint of this study is ORR (confirmed CR or PR per
Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1) as
determined by an independent review facility (IRF)
Secondary outcome
Secondary Endpoints
* DOR (confirmed CR or PR) per IRF
* DCR16 (disease control rate [CR, PR or SD] at 16 weeks) per IRF
* PFS per IRF
* ORR per investigator assessment
* DOR per investigator assessment
* DCR16 per investigator assessment
* PFS per investigator assessment
* OS
* Type, incidence, severity, seriousness, and relatedness of AEs
* Laboratory abnormalities
* Selected plasma or serum PK parameters of enfortumab vedotin, MMAE and total
antibody (TAb)
* Incidence of ATA to enfortumab vedotin
Additional Endpoints
* Biomarkers of biological and clinical activity, including Nectin-4 expression
* Patient reported outcomes (PRO) per the European Organisation for Research
and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30)
* PRO per EuroQol 5-dimensions (EQ-5D), including health utility values, and
visual analog scale
Background summary
Enfortumab vedotin is a type of drug called an antibody drug conjugate or ADC.
ADCs usually have 2 parts:
• The antibody, which finds the cancer cells in your body. Antibodies are part
of the immune system. They can stick to and attack specific targets on cells.
The antibody part of enfortumab vedotin is designed to stick to a target called
Nectin-4. Nectin-4 is an important part of some cancer cells and some normal
cells.
• The chemotherapy, which is the cell-killing medicine. The cell-killing part
of enfortumab vedotin is a chemotherapy called MMAE. It can kill the cells that
the antibody sticks to in your body.
More than 830 people with cancer have already been given enfortumab vedotin in
other clinical studies. These clinical studies were done to test the safety of
different doses of enfortumab vedotin. They were also done to find out if
enfortumab vedotin works to treat cancer.
Study objective
Primary:
* * To determine the antitumor activity of single-agent enfortumab vedotin as
measured by confirmed objective response rate (ORR) in patients with locally
advanced or metastatic urothelial cancer who have previously received systemic
therapy with a CPI and either previously received platinum-containing
chemotherapy or are platinum-naïve and cisplatin-ineligible
Secondary:
* To assess duration of response (DOR)
* To assess disease control rate (DCR)
* To assess progression-free survival (PFS)
* To assess overall survival (OS)
* To assess the safety and tolerability of enfortumab vedotin
* To assess the pharmacokinetics (PK) of enfortumab vedotin
* To assess the incidence of antitherapeutic antibodies (ATA)
Additional:
* To explore potential correlations between biomarkers and clinical outcomes
* To evaluate the treatment effect of enfortumab vedotin on quality of life
(QoL)
Study design
This is a single-arm, open-label, multicenter trial designed to assess the
efficacy and safety of enfortumab vedotin as a single agent in locally advanced
or metastatic urothelial cancer patients who have previously received systemic
therapy with a CPI. For the purpose of this study a CPI is defined as a
programmed cell death protein 1 (PD-1) inhibitor or programmed death-ligand 1
(PD L1) inhibitor (including, but not limited to: atezolizumab, pembrolizumab,
durvalumab, avelumab, and nivolumab). Patients must either have received prior
treatment with platinum-containing chemotherapy (Cohort 1) or received no prior
treatment with platinum-containing or other chemotherapy and are ineligible for
treatment with cisplatin at time of enrollment (Cohort 2).
Enfortumab vedotin at a dose of 1.25 mg/kg will be administered as an
intravenous (IV) infusion over approximately 30 minutes on Days 1, 8, and 15 of
each 28-day cycle. Patients will continue to receive study treatment until
disease progression, unacceptable toxicity, investigator decision, consent
withdrawal, start of a subsequent anticancer therapy, pregnancy, or study
termination by the sponsor. After discontinuation of study treatment, patients
will be followed every 8 weeks (±1 week) for response assessments, ECOG
performance status, and physical exams. After 1 year of on study, the frequency
of follow-up exams including response assessments will be reduced to every 12
weeks (±1 week). Patients that have progressed or begun subsequent anticancer
therapy will be contacted every 8 weeks (±1 week) up to 1 year on study, and
every 12 weeks (±1 week) thereafter to obtain information on subsequent
anticancer therapy, and survival status until death, study closure, or
withdrawal of consent, whichever occurs first. The study will be closed 5 years
after enrollment of the last patient, or when no patients remain in long-term
follow-up, whichever occurs first. Additionally, the sponsor may terminate the
study at any time.
On a periodic basis, an independent data monitoring committee (IDMC) will
monitor the safety of patients participating in this trial. The IDMC will be
responsible for evaluating the results of safety analyses and will make
recommendations to the sponsor.
An ongoing real-time review of patient safety and serious adverse events (SAEs)
will also be conducted by the sponsor*s Drug Safety Department.
Intervention
Enfortumab vedotin 1.25 mg/kg will be administered as an IV infusion over
approximately 30 minutes on
Day 1, 8, and 15 of each 28-day cycle.
Study burden and risks
- Blood collection (See E6 and additional information)
- Study visits
- Questionnaires: EORTC and QLQ-C30
- Scans: CT or MRI scan of chest, abdomen and pelvis (every 8 weeks).
- Side effects (see question E9)
- Risks related to the study procedures:
Blood Samples: Blood draws may cause local pain, bleeding and/or bruising, and
dizziness. You may faint and/or get an infection with redness and irritation at
the place where the needle enters your vein. In very rare cases, nerve damage
may occur.
Heart monitoring: When you have your heart monitored, you may have itching or
get bruising of the skin where the machine patches are placed. ECG patch
adhesive may also be cold and sticky. Sometimes a small area needs to be shaved
to help the patch stick.
Intravenous infusion (IV dosing): Medications administered into veins
(intravenously) can sometimes cause pain, swelling and redness of the vein and
surrounding tissues, which may not go away quickly, even if the medication is
stopped.
CT/MRI scans: A CT scan or MRI scan may cause you to feel *closed in* while
lying in the scanner. However, the scanner is open at both ends and an intercom
allows you to talk with doctors and staff. If you feel ill or anxious during
scanning, doctors and/or technicians will give comfort or the scanning will be
stopped.
CT scans: CT scans expose your body to radiation. While the dose is small
(about the same as 3 years of natural background radiation that you would
normally receive going about your daily life), all radiation adds up over a
lifetime. The study doctor can provide more information.
MRI scans: There are no known risks or side effects resulting directly from
exposure to MRI scans. However, subjects who have a pacemaker or metal objects
in their body should not have the scan performed. If you have kidney disease,
there is a small risk that the contrast agent used for the MRI scan may cause
stiffening of the skin (nephrogenic systemic fibrosis). The study doctor can
provide more information.
Tumor biopsy (if needed): If you do not have a tumor tissue sample available
for this study, this sample will be obtained by a biopsy. Risks related to
tumor biopsies include bleeding from the biopsy site, pain, local reaction to
the anesthesia, infection, and scarring. Your study doctor will further discuss
the risks involved with these biopsies if you are providing a sample of your
tumor tissue.
Bone scans: Before the scan, we will inject a tiny amount of radioactive dye
into your vein. There is a small risk of allergic reaction or radiation
exposure with this material. Nearly all of the radioactivity from the dye will
be gone from your body in 2 or 3 days. Your study doctor can provide more
information.
Eye exam: An eye doctor will test the health of your eyes. Some parts of the
test involve bright lights which can be dazzling, and other tests may be
uncomfortable. In addition, the eye doctor may need to give you eye drops.
These can cause blurry vision and you should not drive for about 4 hours
afterwards.
Unknown risks
Because the number of patients who have received enfortumab vedotin to date is
small, we do not know all the risks of this study drug. It*s possible that side
effects we don*t know about yet could happen. The side effect may be a minor
inconvenience or could be severe enough to be life-threatening or cause death.
We will watch you closely for side effects. The study drug will be stopped if
unwanted or serious side effects develop.
We haven*t studied enfortumab vedotin in many patients with liver problems. We
don*t know if people with liver problems will have side effects that we don*t
know about yet.
We have only studied enfortumab vedotin in a few patients with serious kidney
problems. We don*t know if people with serious kidney problems will have side
effects that we don*t know about yet.
There may also be other unknown effects that could harm you during the time you
take part in the study or after the study is finished. These side effects could
also harm your unborn child, if you become pregnant or father a child.
30th Drive SE 21823
Bothell WA 98021
US
30th Drive SE 21823
Bothell WA 98021
US
Listed location countries
Age
Inclusion criteria
• Histologically documented urothelial (previously known as transitional cell)
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. 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. A CPI is
defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand
1 (PD-L1) inhibitor., • Must be one of the following:
a. Platinum-treated (Cohort 1): Patients who received prior treatment with
platinumcontaining chemotherapy defined as those who received platinum in the
adjuvant/neoadjuvant 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;
OR
b.Platinum-naïve and cisplatin ineligible (Cohort 2): Patients who have not
received prior treatment with platinum-containing or other chemotherapy in the
locally advanced or metastatic setting and are ineligible for treatment with
cisplatin at time of enrollment due to one of the following: ECOG performance
status score of 2; impaired renal function (defined as creatinine clearance
[CrCl] >=30 and <60 mL/min), or a >= Grade 2 hearing loss. Patients who received
platinum in the adjuvant/neoadjuvant setting and did not progress within12
months of completion will be considered platinum-naïve., • 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) PerformanceStatus score
of <=1 for Cohort 1, or <=2 for Cohort 2.
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 monomethyl auristatin E
(MMAE)-based antibody-drug conjugates (ADCs).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003479-78-NL |
| ClinicalTrials.gov | NCT03219333 |
| CCMO | NL64755.031.18 |