The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
Active Not-enrolling
United States, Canada, France, Italy, Puerto Rico, Spain
for more information at clinicaltrials.gov
EXPERIMENTAL: EV + Pembrolizumab in cisplatin-ineligible 1L and in 2L
Dose Escalation: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
DRUG: pembrolizumab
IV infusion on day 1 every 21 days
EXPERIMENTAL: Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1L
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
DRUG: pembrolizumab
IV infusion on day 1 every 21 days
EXPERIMENTAL: Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2L
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
DRUG: pembrolizumab
IV infusion on day 1 every 21 days
EXPERIMENTAL: Cohort D: Enfortumab Vedotin + Cisplatin in 1L
Enfortumab vedotin on days 1 and 8 plus cisplatin on day 1 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
DRUG: cisplatin
IV infusion on day 1 every 21 days
EXPERIMENTAL: Cohort E: Enfortumab Vedotin + Carboplatin in 1L
Enfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
DRUG: carboplatin
IV infusion on day 1 every 21 days
EXPERIMENTAL: Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2L
Enfortumab vedotin and gemcitabine on days 1 and 8 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
DRUG: gemcitabine
IV infusion on days 1 and 8 every 21 days
EXPERIMENTAL: Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L
Enfortumab vedotin on days 1 and 8 plus cisplatin or carboplatin on day 1 plus pembrolizumab on day 1 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
DRUG: pembrolizumab
IV infusion on day 1 every 21 days
DRUG: cisplatin
IV infusion on day 1 every 21 days
DRUG: carboplatin
IV infusion on day 1 every 21 days
EXPERIMENTAL: Cohort H: Enfortumab vedotin in MIBC neoadjuvant setting
Enfortumab vedotin on days 1 and 8 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
EXPERIMENTAL: Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant setting
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
DRUG: pembrolizumab
IV infusion on day 1 every 21 days
EXPERIMENTAL: Randomized Cohort K: Enfortumab Vedotin Monotherapy
Enfortumab vedotin on days 1 and 8 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
EXPERIMENTAL: Randomized Cohort K: Enfortumab Vedotin + Pembrolizumab
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
DRUG: pembrolizumab
IV infusion on day 1 every 21 days
EXPERIMENTAL: Cohort L: Enfortumab vedotin in MIBC in perioperative setting
Enfortumab vedotin on days 1 and 8 and every 21 days
DRUG: enfortumab vedotin (EV)
Intravenous (IV) infusion on days 1 and 8 every 21 days
Type, incidence, severity, seriousness, and relatedness of adverse events (Dose escalation and Expansion Parts 1 to 3 cohorts only)
Descriptive statistics will be used to summarize results.
Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.
Type, incidence, and severity of laboratory abnormalities (Dose escalation and Expansion Parts 1 to 3 cohorts only)
Descriptive statistics will be used to summarize results.
Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.
Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) (Cohort K only)
The proportion of patients with confirmed complete response (CR) or partial response (PR) according to RECIST 1.1
Up to 3 years
Pathological complete response (pCR) rate per central pathology review (MIBC cohorts only)
The proportion of patients with absence of viable tumor tissue at the time of radical cystectomy.
Up to approximately 5 months
Incidence of dose-limiting toxicity (DLT)
Incidence of DLTs (dose-escalation expansion Cohorts D, E, F, and the first 6 patients of Cohort G).
21 days
Confirmed ORR by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
The proportion of patients with confirmed CR or PR according to RECIST 1.1.
Up to 3 years
Confirmed ORR by BICR according to RECIST 1.1 (Dose escalation and Cohort A only)
The proportion of patients with confirmed CR or PR according to RECIST 1.1
Up to 3 years
Confirmed ORR by investigator assessment per the modified RECIST 1.1 for immune-based therapeutics (iRECIST) (Dose escalation and Part 1-3 cohorts with pembrolizumab only)
The proportion of patients with confirmed CR or PR according to iRECIST.
Up to 3 years
Disease control rate (DCR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1.
Up to 5 years
DCR by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)
Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1
Up to 3 years
DCR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts using pembrolizumab only)
Proportion of patients with CR, PR, or SD according to iRECIST.
Up to 3 years
Duration of response (DOR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD per RECIST 1.1) or to death due to any cause, whichever comes first.
Up to 5 years
DOR by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD per RECIST 1.1 or to death due to any cause, whichever comes first
Up to 5 years
DOR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only)
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD per iRECIST or to death due to any cause, whichever comes first.
Up to 5 years
Progression free survival on study therapy (PFS) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1) on or following study therapy, or to death due to any cause, whichever comes first.
Up to 5 years
PFS by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)
The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1) on or following study therapy, or to death due to any cause, whichever comes first
Up to 5 years
PFS by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only)
The time from start of study treatment to first documentation of objective tumor progression (PD per iRECIST) on or following study therapy, or to death due to any cause, whichever comes first.
Up to 5 years
Event-free (EFS) on study therapy by BICR (Cohort L only)
The time from the start of study treatment to the first occurrence of any of the following events: (1) Radiographic disease progression precluding a curative intent surgery as assessed by BICR prior to RC+PLND. (2) Failure to undergo RC+PLND for participants with residual muscle-invasive disease and/or any radiographic disease present. (3) Gross residual disease left behind at time of RC+PLND. (4) Local or distant recurrence post-RC as assessed by CT or MRI and/or biopsy. (5) Death from any cause.
Up to 3 years
Event-free (EFS) on study therapy by investigator assessment (MIBC cohorts only)
The time from the start of study treatment to the first occurrence of any of the following events: (1) Radiographic disease progression precluding a curative intent surgery as assessed by BICR prior to RC+PLND. (2) Failure to undergo RC+PLND for participants with residual muscle-invasive disease and/or any radiographic disease present. (3) Gross residual disease left behind at time of RC+PLND. (4) Local or distant recurrence post-RC as assessed by CT or MRI and/or biopsy. (5) Death from any cause.
Up to 3 years
Overall survival (OS) (all cohorts)
The time from start of study treatment to date of death due to any cause.
Up to 5 years
Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
Cmax will be derived from the PK blood samples collected.
Through 2 cycles of treatment, up to 42 days
PK parameter for monomethyl auristatin E (MMAE): Cmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
Cmax will be derived from the PK blood samples collected.
Through 2 cycles of treatment, up to 42 days
PK parameter for total antibody (Tab): Cmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
Cmax will be derived from the PK blood samples collected.
Through 2 cycles of treatment, up to 42 days
Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
Blood samples for ATA analysis will be collected.
Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.
PK parameter for enfortumab vedotin: Time to maximum concentration (Tmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
Tmax will be derived from the PK blood samples collected.
Through 2 cycles of treatment, up to 42 days
PK parameter for MMAE: Tmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
Tmax will be derived from the PK blood samples collected.
Through 2 cycles of treatment, up to 42 days
PK parameter for Tab: Tmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
Tmax will be derived from the PK blood samples collected.
Through 2 cycles of treatment, up to 42 days
PK parameter for enfortumab vedotin: Area under the concentration-time curve (AUC) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
AUC will be derived from the PK blood samples collected.
Through 2 cycles of treatment, up to 42 days
PK parameter for MMAE: AUC (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
AUC will be derived from the PK blood samples collected.
Through 2 cycles of treatment, up to 42 days
PK parameter for Tab: AUC (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)
AUC will be derived from the PK blood samples collected.
Through 2 cycles of treatment, up to 42 days
Pathologic downstaging (pDS) rate by central pathology review (MIBC cohorts only)
The pDS rate is defined as patients with tumors \
Up to approximately 5 months
Disease-free survival (DFS) by investigator assessment (MIBC cohorts only)
DFS is defined as the time from RC to the time of first occurrence of a DFS event, including local recurrence of urothelial cancer (UC), urinary tract recurrence of UC, distant metastasis of UC, or death from any cause.
Up to approximately 5 years
DFS by BICR (Cohort L only)
DFS is defined as the time from RC to the time of first occurrence of a DFS event
Up to 3 years
Type, incidence, severity, seriousness, and relatedness of AEs (Randomized Cohort K and MIBC cohorts only)
Descriptive statistics will be used to summarize results.
Through 1 month following last dose, or end-of-treatment visit whichever is later, up to approximately 3 years
Type, incidence, and severity of laboratory abnormalities (Randomized Cohort K and MIBC cohorts only)
Descriptive statistics will be used to summarize results.
Through 1 month following last dose, or end-of-treatment visit whichever is later, up to approximately 3 years
Percentage of planned radical cystectomy and pelvic lymph node dissections (RC+PLND) delayed due to treatment-related AEs (MIBC cohorts only)
Delayed is defined as greater than 12 weeks after the last dose of treatment.
Up to approximately 5 months
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Sponsor: Astellas Pharma Global Development, Inc.
Collaborator: Merck Sharp & Dohme LLC, Seagen Inc.
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number:
NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier.
NCT03288545
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