Description:
This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab)
work together to treat patients with urothelial cancer. The study will compare these drugs to
other drugs that are usually used to treat this cancer (standard of care). The patients in
this study will have cancer that has spread from their urinary system to other parts of their
body.
Title
- Brief Title: Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer
- Official Title: An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer
Clinical Trial IDs
- ORG STUDY ID:
SGN22E-003
- SECONDARY ID:
2019-004542-15
- SECONDARY ID:
MK-3475-A39
- SECONDARY ID:
KEYNOTE KN-A39
- SECONDARY ID:
jRCT2031200284
- NCT ID:
NCT04223856
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Enfortumab vedotin | ASG-22CE, ASG-22ME, PADCEV | Arm A |
Pembrolizumab | Keytruda | Arm A |
Cisplatin | | Arm B |
Carboplatin | | Arm B |
Gemcitabine | | Arm B |
Purpose
This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab)
work together to treat patients with urothelial cancer. The study will compare these drugs to
other drugs that are usually used to treat this cancer (standard of care). The patients in
this study will have cancer that has spread from their urinary system to other parts of their
body.
Detailed Description
This study is being conducted to evaluate the combination of enfortumab vedotin +
pembrolizumab versus standard of care gemcitabine + platinum-containing chemotherapy, in
subjects with previously untreated locally advanced or metastatic urothelial cancer.
Enfortumab vedotin may be administered for an unlimited number of cycles until a protocol
defined reason for study discontinuation occurs. Pembrolizumab may be administered for a
maximum of 35 cycles or a protocol-defined reason for study discontinuation occurs, whichever
is first. Cisplatin or carboplatin plus gemcitabine may be administered for a maximum of 6
cycles or a protocol-defined reason for study discontinuation occurs, whichever is first.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A | Experimental | Enfortumab vedotin + pembrolizumab | - Enfortumab vedotin
- Pembrolizumab
|
Arm B | Active Comparator | Gemcitabine + cisplatin or carboplatin | - Cisplatin
- Carboplatin
- Gemcitabine
|
Arm C (Not Recruiting) | Experimental | Enfortumab vedotin + pembrolizumab + Cisplatin or carboplatin | - Enfortumab vedotin
- Pembrolizumab
- Cisplatin
- Carboplatin
|
Eligibility Criteria
Inclusion Criteria:
- Histologically documented, unresectable locally advanced or metastatic urothelial
carcinoma
- Measurable disease by investigator assessment according to RECIST v1.1
- Participants with prior definitive radiation therapy must have measurable disease
per RECIST v1.1 that is outside the radiation field or has demonstrated
unequivocal progression since completion of radiation therapy
- Participants must not have received prior systemic therapy for locally advanced or
metastatic urothelial carcinoma with the following exceptions:
- Participants that received neoadjuvant chemotherapy with recurrence >12 months
from completion of therapy are permitted
- Participants that received adjuvant chemotherapy following cystectomy with
recurrence >12 months from completion of therapy are permitted
- Must be considered eligible to receive cisplatin- or carboplatin-containing
chemotherapy, in the investigator's judgment
- Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of
metastatic urothelial carcinoma must be provided for PD-L1 testing prior to
randomization
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
- Adequate hematologic and organ function
Exclusion Criteria
- Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based
antibody-drug conjugate (ADCs)
- Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor
for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1
inhibitor or PD-L1 inhibitor
- Received prior treatment with an agent directed to another stimulatory or co
inhibitory T-cell receptor
- Received anti-cancer treatment with chemotherapy, biologics, or investigational agents
not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks
prior to first dose of study treatment
- Uncontrolled diabetes
- Estimated life expectancy of less than 12 weeks
- Active central nervous system (CNS) metastases
- Ongoing clinically significant toxicity associated with prior treatment that has not
resolved to ≤ Grade 1 or returned to baseline
- Currently receiving systemic antimicrobial treatment for active infection (viral,
bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis
is permitted.
- Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV)
infection.
- History of another invasive malignancy within 3 years before the first dose of study
drug, or any evidence of residual disease from a previously diagnosed malignancy
- Documented history of a cerebral vascular event (stroke or transient ischemic attack),
unstable angina, myocardial infarction, or cardiac symptoms consistent with New York
Heart Association (NYHA) Class IV within 6 months prior to randomization
- Receipt of radiotherapy within 2 weeks prior to randomization
- Received major surgery (defined as requiring general anesthesia and >24 hour inpatient
hospitalization) within 4 weeks prior to randomization
- Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient
contained in the drug formulation of enfortumab vedotin
- Active keratitis or corneal ulcerations
- History of autoimmune disease that has required systemic treatment in the past 2 years
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography (CT) scan
- Prior allogeneic stem cell or solid organ transplant
- Received a live attenuated vaccine within 30 days prior to randomization
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Duration of progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR) (Arms A and B only) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Defined as the time from randomization to first documentation of disease progression per RECIST v1.1 by BICR, or to death due to any cause, whichever comes first. |
Secondary Outcome Measures
Measure: | Duration of PFS per RECIST v1.1 by investigator assessment (Arms A and B only) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Defined as the time from randomization to first documentation of disease progression per RECIST v1.1, or to death due to any cause, whichever comes first |
Measure: | Overall response rate (ORR) per RECIST v1.1 by BICR (Arms A and B only) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Defined as the proportion of subjects with confirmed CR or PR according to RECIST v1.1 |
Measure: | ORR per RECIST v1.1 by investigator assessment (Arms A and B only) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Defined as the proportion of subjects with confirmed CR or PR according to RECIST v1.1 |
Measure: | Duration of response (DOR) per RECIST v1.1 by BICR (Arms A and B only) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Defined as the time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause, whichever comes first |
Measure: | DOR per RECIST v1.1 by investigator assessment (Arms A and B only) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Defined as the time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause, whichever comes first |
Measure: | Disease control rate (DCR) per RECIST v1.1 by BICR (Arms A and B only) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Defined as the proportion of subjects with confirmed CR, PR, or SD according to RECIST v1.1 |
Measure: | DCR per RECIST v1.1 by investigator assessment (Arms A and B only) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Defined as the proportion of subjects with confirmed CR, PR, or SD according to RECIST v1.1 |
Measure: | Change from baseline in patient reported outcome assessment measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. |
Measure: | Change from baseline in patient reported outcome assessment measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | EORTC-QLQ-C30 is a cancer-specific 30-item questionnaire. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change. |
Measure: | Change from baseline in patient reported outcome assessment measured by Brief Pain Inventory - Short Form (BPI-SF) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | The Short Form is a single assessment of overall pain where 0 equals no pain and 10 equals extreme pain. Low pain scores are considered a better outcome than a high pain score. |
Measure: | Incidence of adverse events (AEs) |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Descriptive statistics will be used to summarize results |
Measure: | Incidence of laboratory abnormalities |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Descriptive statistics will be used to summarize results |
Measure: | Treatment discontinuation rate due to AEs |
Time Frame: | Up to approximately 5 years |
Safety Issue: | |
Description: | Descriptive statistics will be used to summarize results |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Astellas Pharma Global Development, Inc. |
Trial Keywords
- Urothelial Cancer
- Enfortumab vedotin
- metastatic urothelial cancer
- pembrolizumab
- locally advanced urothelial cancer
Last Updated
August 30, 2021