Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer (EV-103)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03288545
Recruitment Status : Recruiting
First Posted : September 20, 2017
Last Update Posted : April 8, 2021
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Seagen Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE September 18, 2017
First Posted Date  ICMJE September 20, 2017
Last Update Posted Date April 8, 2021
Actual Study Start Date  ICMJE October 11, 2017
Estimated Primary Completion Date July 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2020)
  • Type, incidence, severity, seriousness, and relatedness of adverse events (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated. ]
    Descriptive statistics will be used to summarize results.
  • Type, incidence, and severity of laboratory abnormalities (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated. ]
    Descriptive statistics will be used to summarize results.
  • Pathological complete response (pCR) rate per central pathology review (MIBC coohorts only) [ Time Frame: Up to approximately 5 months ]
    pCR rate is defined as the proportion of patients with pCR at the time of radical cystectomy (RC).
  • 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) [ Time Frame: Up to 3 years ]
    The proportion of patients with confirmed complete response (CR) or partial response (PR) according to RECIST 1.1
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2017)
  • Incidence of dose-limiting toxicity (DLT) [ Time Frame: 21 days ]
    Incidence of DLTs that are considered related to enfortumab vedotin and/or enfortumab vedotin + CPI, and are not attributed to CPI alone
  • Type, incidence, severity, seriousness, and relatedness of adverse events [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 22 months ]
    Descriptive statistics will be used to summarize results
  • Type, incidence, and severity of laboratory abnormalities [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 22 months ]
    Descriptive statistics will be used to summarize results
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2020)
  • Incidence of dose-limiting toxicity (DLT) [ Time Frame: 21 days ]
    Incidence of DLTs (dose-escalation expansion Cohorts D, E, F, and the first 6 patients of Cohort G).
  • Confirmed ORR by investigator assessment according to RECIST 1.1 (la/mUC cohorts only) [ Time Frame: Up to 3 years ]
    The proportion of patients with confirmed CR or PR according to RECIST 1.1.
  • Confirmed ORR by BICR according to RECIST 1.1 (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [ Time Frame: Up to 3 years ]
    The proportion of patients with confirmed CR or PR according to RECIST 1.1
  • 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) [ Time Frame: Up to 3 years ]
    The proportion of patients with confirmed CR or PR according to iRECIST.
  • Disease control rate (DCR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only) [ Time Frame: Up to 5 years ]
    Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1.
  • DCR by BICR according to RECIST 1.1 (la/mUC cohorts only) [ Time Frame: Up to 3 years ]
    Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1
  • DCR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts using pembrolizumab only) [ Time Frame: Up to 3 years ]
    Proportion of patients with CR, PR, or SD according to iRECIST.
  • Duration of response (DOR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only) [ Time Frame: Up to 5 years ]
    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.
  • DOR by BICR according to RECIST 1.1 (la/mUC cohorts only) [ Time Frame: Up to 5 years ]
    The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD per RECISTS 1.1 or to death due to any cause, whichever comes first
  • DOR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only) [ Time Frame: Up to 5 years ]
    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.
  • Progression free survival on study therapy (PFS) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only) [ Time Frame: Up to 5 years ]
    The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first.
  • Progression free survival on study therapy (PFS) by BICR according to RECIST 1.1 (la/mUC cohorts only) [ Time Frame: Up to 5 years ]
    The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first
  • PFS by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only) [ Time Frame: Up to 5 years ]
    The time from start of study treatment to first documentation of objective tumor progression (PD per iRECIST), or to death due to any cause, whichever comes first.
  • Event-free (EFS) on study therapy by BICR (Cohort L only) [ Time Frame: Up to 3 years ]
    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.
  • Event-free (EFS) on study therapy by investigator assessment (MIBC cohorts only) [ Time Frame: Up to 3 years ]
    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.
  • Overall survival (OS) (all cohorts) [ Time Frame: Up to 5 years ]
    The time from start of study treatment to date of death due to any cause.
  • Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized (la/mUC cohorts only) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Cmax will be derived from the PK blood samples collected.
  • PK parameter for monomethyl auristatin E (MMAE): Cmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Cmax will be derived from the PK blood samples collected.
  • Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated. ]
    Blood samples for ATA analysis will be collected.
  • PK parameter for enfortumab vedotin: Time to maximum concentration (Tmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Tmax will be derived from the PK blood samples collected.
  • PK parameter for MMAE: Tmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Tmax will be derived from the PK blood samples collected.
  • 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) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    AUC will be derived from the PK blood samples collected.
  • PK parameter for MMAE: AUC (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    AUC will be derived from the PK blood samples collected.
  • pCR rate by local pathology review (MIBC cohorts only) [ Time Frame: Up to approximately 5 months ]
    Defined as the proportion of patients with pCR at the time of RC.
  • Pathologic downstaging (pDS) rate by central pathology review (MIBC cohorts only) [ Time Frame: Up to approximately 5 months ]
    The pDS rate is defined as patients with tumors <pT2 and N0 in examined tissue from radical cystectomy (RC) and pelvic lymph node dissection (PLND).
  • pDS rate by local pathology review (MIBC cohorts only) [ Time Frame: Up to approximately 5 months ]
    The pDS rate is defined as patients with tumors <pT2 and N0 in examined tissue from RC+PLND
  • Disease-free survival (DFS) by investigator assessment (MIBC cohorts only) [ Time Frame: Up to approximately 5 years ]
    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.
  • DFS by BICR (Cohort L only) [ Time Frame: Up to 3 years ]
    DFS is defined as the time from RC to the time of first occurrence of a DFS event
  • Type, incidence, severity, seriousness, and relatedness of AEs (Randomized Cohort K and MIBC cohorts only) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to approximately 3 years ]
    Descriptive statistics will be used to summarize results.
  • Type, incidence, and severity of laboratory abnormalities (Randomized Cohort K and MIBC cohorts only) [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to approximately 3 years ]
    Descriptive statistics will be used to summarize results.
  • Percentage of planned surgeries delayed due to treatment-related AEs (MIBC cohorts only) [ Time Frame: Up to approximately 5 months ]
    Delayed is defined as greater than 12 weeks after the last dose of treatment.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2017)
  • Objective response rate (ORR) by investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Up to 34 months ]
    The proportion of patients with confirmed complete response (CR) or partial response (PR) according to RECIST 1.1
  • Disease control rate (DCR) by investigator assessment according to RECIST 1.1 [ Time Frame: Up to 34 months ]
    Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1
  • Duration of response (DOR) by investigator assessment according to RECIST 1.1 [ Time Frame: Up to 34 months ]
    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
  • Progression free survival (PFS) by investigator assessment according to RECIST 1.1 [ Time Frame: Up to 34 months ]
    The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first
  • Overall survival (OS) [ Time Frame: Up to 34 months ]
    The time from start of study treatment to date of death due to any cause
  • Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Cmax will be derived from the PK blood samples collected
  • PK parameter for monomethyl auristatin E (MMAE): Cmax [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Cmax will be derived from the PK blood samples collected
  • PK parameter for enfortumab vedotin: Time to maximum concentration (Tmax) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Tmax will be derived from the PK blood samples collected
  • PK parameter for MMAE: Tmax [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    Tmax will be derived from the PK blood samples collected
  • PK parameter for enfortumab vedotin: Area under the concentration-time curve (AUC) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    AUC will be derived from the PK blood samples collected
  • PK parameter for MMAE: AUC [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    AUC will be derived from the PK blood samples collected
  • PK parameter for enfortumab vedotin: Half-life (t1/2) [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    t1/2 will be derived from the PK blood samples collected
  • PK parameter for MMAE: t1/2 [ Time Frame: Through 2 cycles of treatment, up to 42 days ]
    t1/2 will be derived from the PK blood samples collected
  • Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin [ Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 22 months ]
    Blood samples for ATA analysis will be collected
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer
Official Title  ICMJE A Study of Enfortumab Vedotin (ASG-22CE) as Monotherapy or in Combination With Other Anticancer Therapies for the Treatment of Urothelial Cancer
Brief Summary This study will test an experimental drug (enfortumab vedotin) alone and with different combinations of anticancer therapies. Pembrolizumab is an immune checkpoint inhibitor (CPI) that is used to treat patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra. Some parts of the study will look at locally-advanced and metastatic urothelial cancer, which means the cancer has spread to nearby tissues or to other areas of the body. Other parts of the study will look at muscle-invasive bladder cancer (MIBC), which is cancer at an earlier stage that has spread into the muscle wall of the bladder. This study will look at the side effects of enfortumab vedotin alone and with other anticancer therapies. A side effect is a response to a drug that is not part of the treatment effect. This study will also test if the cancer shrinks with the different treatment combinations.
Detailed Description

This study will examine the safety and anticancer activity of enfortumab vedotin (EV) given intravenously as monotherapy and in combination with other anticancer therapies as first line (1L) and second line (2L) treatment for patients with urothelial cancer. The primary goal of the study is to determine the safety, tolerability, and efficacy of enfortumab vedotin alone and in combination with pembrolizumab and/or chemotherapy. The study will be conducted in multiple parts:

Locally advanced or metastatic urothelial cancer:

  • Dose escalation
  • Expansion

    • Part 1: Cohorts A and Optional B
    • Part 2: Cohorts D, E, and Optional F
    • Part 3: Cohort G.
  • Randomized Cohort K

    • EV Monotherapy Arm
    • EV Combination Arm

Muscle invasive bladder cancer:

  • Cohort H
  • Optional Cohort J
  • Cohort L
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
multi-cohort, open-label, multicenter study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma, Transitional Cell
  • Urinary Bladder Neoplasms
  • Urologic Neoplasms
  • Renal Pelvis Neoplasms
  • Urothelial Cancer
  • Ureteral Neoplasms
  • Urethral Neoplasms
Intervention  ICMJE
  • Drug: enfortumab vedotin (EV)
    Intravenous (IV) infusion on days 1 and 8 every 21 days
    Other Names:
    • ASG-22CE
    • ASG-22ME
    • PADCEV
  • Drug: pembrolizumab
    IV infusion on day 1 every 21 days
    Other Name: Keytruda
  • Drug: cisplatin
    IV infusion on day 1 every 21 days
  • Drug: carboplatin
    IV infusion on day 1 every 21 days
  • Drug: gemcitabine
    IV infusion on days 1 and 8 every 21 days
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: enfortumab vedotin (EV)
    • Drug: pembrolizumab
  • Experimental: Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1L
    Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
    Interventions:
    • Drug: enfortumab vedotin (EV)
    • Drug: pembrolizumab
  • Experimental: Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2L
    Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
    Interventions:
    • Drug: enfortumab vedotin (EV)
    • Drug: pembrolizumab
  • Experimental: Cohort D: Enfortumab Vedotin + Cisplatin in 1L
    Enfortumab vedotin on days 1 and 8 plus cisplatin on day 1 every 21 days
    Interventions:
    • Drug: enfortumab vedotin (EV)
    • Drug: cisplatin
  • Experimental: Cohort E: Enfortumab Vedotin + Carboplatin in 1L
    Enfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days
    Interventions:
    • Drug: enfortumab vedotin (EV)
    • Drug: carboplatin
  • Experimental: Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2L
    Enfortumab vedotin and gemcitabine on days 1 and 8 every 21 days
    Interventions:
    • Drug: enfortumab vedotin (EV)
    • Drug: gemcitabine
  • 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
    Interventions:
    • Drug: enfortumab vedotin (EV)
    • Drug: pembrolizumab
    • Drug: cisplatin
    • Drug: carboplatin
  • Experimental: Cohort H: Enfortumab vedotin in MIBC neoadjuvant setting
    Enfortumab vedotin on days 1 and 8 every 21 days
    Intervention: Drug: enfortumab vedotin (EV)
  • 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
    Interventions:
    • Drug: enfortumab vedotin (EV)
    • Drug: pembrolizumab
  • Experimental: Randomized Cohort K: Enfortumab Vedotin Monotherapy
    Enfortumab vedotin on days 1 and 8 every 21 days
    Intervention: Drug: enfortumab vedotin (EV)
  • Experimental: Randomized Cohort K: Enfortumab Vedotin + Pembrolizumab
    Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
    Interventions:
    • Drug: enfortumab vedotin (EV)
    • Drug: pembrolizumab
  • Experimental: Cohort L: Enfortumab Vedotin
    Enfortumab vedotin on days 1 and 8 and every 21 days
    Intervention: Drug: enfortumab vedotin (EV)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 16, 2020)
457
Original Estimated Enrollment  ICMJE
 (submitted: September 18, 2017)
85
Estimated Study Completion Date  ICMJE December 31, 2026
Estimated Primary Completion Date July 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K.

    • Histologically documented la/mUC, including squamous differentiation or mixed cell types.
    • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2: Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class III heart failure.
    • Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K Combination Arm).
    • Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy and no prior treatment for la/mUC, or have disease progression following at least 1 platinum-containing treatment.
    • Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
    • Cohort B: Must have disease progression during/following treatment with at least 1 platinum-containing regimen for la/mUC or disease recurrence.
    • Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
    • Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin, and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
    • Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine.
    • Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
    • Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the following: Glomerular filtration rate (GFR) <60 mL/min and ≥30 mL/min, ECOG performance status of 2, NCI CTCAE Version 4.03 Grade ≥2 hearing loss, New York Heart Association (NYHA) Class III heart failure. No prior systemic treatment for locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based therapy within 12 months prior to randomization.
  • Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.

    • Histologically confirmed MIBC with predominant >50% urothelial histology:Cohorts H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1 disease on imaging. Mixed cell types are eligible if urothelial cancer is predominant (>50%); Participants with plasmacytoid and/or neuroendocrine tumors are ineligible regardless of component percentage.
    • Must be cisplatin-ineligible.
    • Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment, chemoradiation, or radiation therapy for MIBC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-MIBC; Cohort J: Eligible for pembrolizumab.
    • ECOG performance status of 0, 1, or 2.
    • Anticipated life expectancy of ≥3 months.
    • Tumor samples with an associated pathology report from the diagnostic transurethral resection of a bladder tumor done 90 days prior to the first dose of study treatment must be available prior to enrollment and determined to be sufficient for pathology review and biomarker analysis.
    • Participants must be deemed eligible for radical cystectomy and pelvic lymph node dissection.

Exclusion Criteria:

  • la/mUC - Cohorts A, B, D, E, F, G, and K

    • Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2 inhibitor, except Cohort F.
    • Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonists, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).
    • Ongoing sensory or motor neuropathy Grade 2 or higher.
    • Active central nervous system (CNS) metastases.
    • Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).
    • Conditions requiring high doses of steroids or other immunosuppressive medications.
    • Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
    • Uncontrolled diabetes mellitus.
  • MIBC - Cohorts H, J, and L

    • Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive bladder cancer.
    • Received any prior treatment with a CPI.
    • Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.
    • Evidence of nodal or metastatic disease on imaging per local assessment. Participants in Cohort L with pT1 disease may not have ≥N2 nodal disease on imaging.
    • Ongoing sensory or motor neuropathy Grade 2 or higher.
    • Conditions requiring high doses of steroids or other immunosuppressive medications.
    • Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial cancer.
    • History of another malignancy within 3 years before first dose of study drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Seagen, Inc. Trial Information Support 866-333-7436 clinicaltrials@seagen.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03288545
Other Study ID Numbers  ICMJE SGN22E-002
MK-3475-869 ( Other Identifier: Merck )
KEYNOTE KN-869 ( Other Identifier: Merck )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Study Sponsor  ICMJE Astellas Pharma Global Development, Inc.
Collaborators  ICMJE
  • Merck Sharp & Dohme Corp.
  • Seagen Inc.
Investigators  ICMJE
Study Director: Anne-Sophie Carret, MD Seagen Inc.
Study Director: Sujata Narayanan, MD Seagen Inc.
PRS Account Astellas Pharma Inc
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP