<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03288545</url>
  </required_header>
  <id_info>
    <org_study_id>SGN22E-002</org_study_id>
    <secondary_id>MK-3475-869</secondary_id>
    <secondary_id>KEYNOTE KN-869</secondary_id>
    <nct_id>NCT03288545</nct_id>
  </id_info>
  <brief_title>A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer</brief_title>
  <acronym>EV-103</acronym>
  <official_title>A Study of Enfortumab Vedotin (ASG-22CE) as Monotherapy or in Combination With Other Anticancer Therapies for the Treatment of Urothelial Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Astellas Pharma Global Development, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Astellas Pharma Inc</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will test an experimental drug (enfortumab vedotin) alone and with different&#xD;
      combinations of anticancer therapies. Pembrolizumab is an immune checkpoint inhibitor (CPI)&#xD;
      that is used to treat patients with cancer of the urinary system (urothelial cancer). This&#xD;
      type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra. Some parts of&#xD;
      the study will look at locally advanced or metastatic urothelial cancer (la/mUC), which means&#xD;
      the cancer has spread to nearby tissues or to other areas of the body. Other parts of the&#xD;
      study will look at muscle-invasive bladder cancer (MIBC), which is cancer at an earlier stage&#xD;
      that has spread into the muscle wall of the bladder. This study will look at the side effects&#xD;
      of enfortumab vedotin alone and with other anticancer therapies. A side effect is a response&#xD;
      to a drug that is not part of the treatment effect. This study will also test if the cancer&#xD;
      shrinks with the different treatment combinations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will examine the safety and anticancer activity of enfortumab vedotin (EV) given&#xD;
      intravenously as monotherapy and in combination with other anticancer therapies as first line&#xD;
      (1L) and second line (2L) treatment for patients with urothelial cancer. The primary goal of&#xD;
      the study is to determine the safety, tolerability, and efficacy of enfortumab vedotin alone&#xD;
      and in combination with pembrolizumab and/or chemotherapy. The study will be conducted in&#xD;
      multiple parts:&#xD;
&#xD;
      Locally advanced or metastatic urothelial cancer:&#xD;
&#xD;
        -  Dose escalation&#xD;
&#xD;
        -  Expansion&#xD;
&#xD;
             -  Part 1: Cohorts A and Optional B&#xD;
&#xD;
             -  Part 2: Cohorts D, E, and Optional F&#xD;
&#xD;
             -  Part 3: Cohort G.&#xD;
&#xD;
        -  Randomized Cohort K&#xD;
&#xD;
             -  EV Monotherapy Arm&#xD;
&#xD;
             -  EV Combination Arm&#xD;
&#xD;
      Muscle invasive bladder cancer:&#xD;
&#xD;
        -  Cohort H&#xD;
&#xD;
        -  Optional Cohort J&#xD;
&#xD;
        -  Cohort L&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 11, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2026</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>multi-cohort, open-label, multicenter study, global</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Type, incidence, severity, seriousness, and relatedness of adverse events (Dose escalation and Expansion Parts 1 to 3 cohorts only)</measure>
    <time_frame>Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.</time_frame>
    <description>Descriptive statistics will be used to summarize results.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Type, incidence, and severity of laboratory abnormalities (Dose escalation and Expansion Parts 1 to 3 cohorts only)</measure>
    <time_frame>Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.</time_frame>
    <description>Descriptive statistics will be used to summarize results.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>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)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The proportion of patients with confirmed complete response (CR) or partial response (PR) according to RECIST 1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pathological complete response (pCR) rate per central pathology review (MIBC cohorts only)</measure>
    <time_frame>Up to approximately 5 months</time_frame>
    <description>The proportion of patients with absence of viable tumor tissue at the time of radical cystectomy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of dose-limiting toxicity (DLT)</measure>
    <time_frame>21 days</time_frame>
    <description>Incidence of DLTs (dose-escalation expansion Cohorts D, E, F, and the first 6 patients of Cohort G).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Confirmed ORR by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The proportion of patients with confirmed CR or PR according to RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Confirmed ORR by BICR according to RECIST 1.1 (Dose escalation and Cohort A only)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The proportion of patients with confirmed CR or PR according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The proportion of patients with confirmed CR or PR according to iRECIST.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts using pembrolizumab only)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Proportion of patients with CR, PR, or SD according to iRECIST.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival on study therapy (PFS) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free (EFS) on study therapy by BICR (Cohort L only)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free (EFS) on study therapy by investigator assessment (MIBC cohorts only)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) (all cohorts)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The time from start of study treatment to date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)</measure>
    <time_frame>Through 2 cycles of treatment, up to 42 days</time_frame>
    <description>Cmax will be derived from the PK blood samples collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for monomethyl auristatin E (MMAE): Cmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)</measure>
    <time_frame>Through 2 cycles of treatment, up to 42 days</time_frame>
    <description>Cmax will be derived from the PK blood samples collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for total antibody (Tab): Cmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)</measure>
    <time_frame>Through 2 cycles of treatment, up to 42 days</time_frame>
    <description>Cmax will be derived from the PK blood samples collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)</measure>
    <time_frame>Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.</time_frame>
    <description>Blood samples for ATA analysis will be collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for enfortumab vedotin: Time to maximum concentration (Tmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)</measure>
    <time_frame>Through 2 cycles of treatment, up to 42 days</time_frame>
    <description>Tmax will be derived from the PK blood samples collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for MMAE: Tmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)</measure>
    <time_frame>Through 2 cycles of treatment, up to 42 days</time_frame>
    <description>Tmax will be derived from the PK blood samples collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for Tab: Tmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)</measure>
    <time_frame>Through 2 cycles of treatment, up to 42 days</time_frame>
    <description>Tmax will be derived from the PK blood samples collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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)</measure>
    <time_frame>Through 2 cycles of treatment, up to 42 days</time_frame>
    <description>AUC will be derived from the PK blood samples collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for MMAE: AUC (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)</measure>
    <time_frame>Through 2 cycles of treatment, up to 42 days</time_frame>
    <description>AUC will be derived from the PK blood samples collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter for Tab: AUC (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only)</measure>
    <time_frame>Through 2 cycles of treatment, up to 42 days</time_frame>
    <description>AUC will be derived from the PK blood samples collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathologic downstaging (pDS) rate by central pathology review (MIBC cohorts only)</measure>
    <time_frame>Up to approximately 5 months</time_frame>
    <description>The pDS rate is defined as patients with tumors &lt;pT2 and N0 in examined tissue from radical cystectomy (RC) and pelvic lymph node dissection (PLND).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival (DFS) by investigator assessment (MIBC cohorts only)</measure>
    <time_frame>Up to approximately 5 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DFS by BICR (Cohort L only)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>DFS is defined as the time from RC to the time of first occurrence of a DFS event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type, incidence, severity, seriousness, and relatedness of AEs (Randomized Cohort K and MIBC cohorts only)</measure>
    <time_frame>Through 1 month following last dose, or end-of-treatment visit whichever is later, up to approximately 3 years</time_frame>
    <description>Descriptive statistics will be used to summarize results.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type, incidence, and severity of laboratory abnormalities (Randomized Cohort K and MIBC cohorts only)</measure>
    <time_frame>Through 1 month following last dose, or end-of-treatment visit whichever is later, up to approximately 3 years</time_frame>
    <description>Descriptive statistics will be used to summarize results.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of planned radical cystectomy and pelvic lymph node dissections (RC+PLND) delayed due to treatment-related AEs (MIBC cohorts only)</measure>
    <time_frame>Up to approximately 5 months</time_frame>
    <description>Delayed is defined as greater than 12 weeks after the last dose of treatment.</description>
  </secondary_outcome>
  <number_of_arms>12</number_of_arms>
  <enrollment type="Actual">348</enrollment>
  <condition>Carcinoma, Transitional Cell</condition>
  <condition>Urinary Bladder Neoplasms</condition>
  <condition>Urologic Neoplasms</condition>
  <condition>Renal Pelvis Neoplasms</condition>
  <condition>Urothelial Cancer</condition>
  <condition>Ureteral Neoplasms</condition>
  <condition>Urethral Neoplasms</condition>
  <arm_group>
    <arm_group_label>EV + Pembrolizumab in cisplatin-ineligible 1L and in 2L</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Escalation: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1L</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2L</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort D: Enfortumab Vedotin + Cisplatin in 1L</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin on days 1 and 8 plus cisplatin on day 1 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort E: Enfortumab Vedotin + Carboplatin in 1L</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2L</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin and gemcitabine on days 1 and 8 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin on days 1 and 8 plus cisplatin or carboplatin on day 1 plus pembrolizumab on day 1 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort H: Enfortumab vedotin in MIBC neoadjuvant setting</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin on days 1 and 8 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant setting</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Randomized Cohort K: Enfortumab Vedotin Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin on days 1 and 8 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Randomized Cohort K: Enfortumab Vedotin + Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort L: Enfortumab vedotin in MIBC in perioperative setting</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enfortumab vedotin on days 1 and 8 and every 21 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>enfortumab vedotin (EV)</intervention_name>
    <description>Intravenous (IV) infusion on days 1 and 8 every 21 days</description>
    <arm_group_label>Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1L</arm_group_label>
    <arm_group_label>Cohort D: Enfortumab Vedotin + Cisplatin in 1L</arm_group_label>
    <arm_group_label>Cohort E: Enfortumab Vedotin + Carboplatin in 1L</arm_group_label>
    <arm_group_label>Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L</arm_group_label>
    <arm_group_label>Cohort H: Enfortumab vedotin in MIBC neoadjuvant setting</arm_group_label>
    <arm_group_label>Cohort L: Enfortumab vedotin in MIBC in perioperative setting</arm_group_label>
    <arm_group_label>EV + Pembrolizumab in cisplatin-ineligible 1L and in 2L</arm_group_label>
    <arm_group_label>Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2L</arm_group_label>
    <arm_group_label>Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2L</arm_group_label>
    <arm_group_label>Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant setting</arm_group_label>
    <arm_group_label>Randomized Cohort K: Enfortumab Vedotin + Pembrolizumab</arm_group_label>
    <arm_group_label>Randomized Cohort K: Enfortumab Vedotin Monotherapy</arm_group_label>
    <other_name>ASG-22CE</other_name>
    <other_name>ASG-22ME</other_name>
    <other_name>PADCEV</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <description>IV infusion on day 1 every 21 days</description>
    <arm_group_label>Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1L</arm_group_label>
    <arm_group_label>Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L</arm_group_label>
    <arm_group_label>EV + Pembrolizumab in cisplatin-ineligible 1L and in 2L</arm_group_label>
    <arm_group_label>Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2L</arm_group_label>
    <arm_group_label>Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant setting</arm_group_label>
    <arm_group_label>Randomized Cohort K: Enfortumab Vedotin + Pembrolizumab</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cisplatin</intervention_name>
    <description>IV infusion on day 1 every 21 days</description>
    <arm_group_label>Cohort D: Enfortumab Vedotin + Cisplatin in 1L</arm_group_label>
    <arm_group_label>Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>carboplatin</intervention_name>
    <description>IV infusion on day 1 every 21 days</description>
    <arm_group_label>Cohort E: Enfortumab Vedotin + Carboplatin in 1L</arm_group_label>
    <arm_group_label>Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>gemcitabine</intervention_name>
    <description>IV infusion on days 1 and 8 every 21 days</description>
    <arm_group_label>Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2L</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G&#xD;
             and K.&#xD;
&#xD;
               -  Histologically documented la/mUC, including squamous differentiation or mixed&#xD;
                  cell types.&#xD;
&#xD;
               -  An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or&#xD;
                  2: Participants with ECOG performance status of 2 must meet the following&#xD;
                  additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class&#xD;
                  III heart failure.&#xD;
&#xD;
               -  Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K&#xD;
                  Combination Arm).&#xD;
&#xD;
               -  Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy&#xD;
                  and no prior treatment for la/mUC, or have disease progression following at least&#xD;
                  1 platinum-containing treatment.&#xD;
&#xD;
               -  Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for&#xD;
                  la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12&#xD;
                  months.&#xD;
&#xD;
               -  Cohort B: Must have disease progression during/following treatment with at least&#xD;
                  1 platinum-containing regimen for la/mUC or disease recurrence.&#xD;
&#xD;
               -  Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for&#xD;
                  la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12&#xD;
                  months.&#xD;
&#xD;
               -  Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin,&#xD;
                  and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based&#xD;
                  therapy in at least 12 months.&#xD;
&#xD;
               -  Cohort F: Ineligible for platinum-based chemotherapy, or disease progression&#xD;
                  during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine.&#xD;
&#xD;
               -  Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or&#xD;
                  carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant&#xD;
                  platinum-based therapy in at least 12 months.&#xD;
&#xD;
               -  Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the&#xD;
                  following: Glomerular filtration rate (GFR) &lt;60 mL/min and ≥30 mL/min, ECOG&#xD;
                  performance status of 2, NCI CTCAE Version 4.03 Grade ≥2 hearing loss, New York&#xD;
                  Heart Association (NYHA) Class III heart failure. No prior systemic treatment for&#xD;
                  locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based&#xD;
                  therapy within 12 months prior to randomization.&#xD;
&#xD;
          -  Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.&#xD;
&#xD;
               -  Histologically confirmed MIBC with predominant &gt;50% urothelial histology: Cohorts&#xD;
                  H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or&#xD;
                  cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1&#xD;
                  disease on imaging. Mixed cell types are eligible if urothelial cancer is&#xD;
                  predominant (&gt;50%); Participants with plasmacytoid and/or neuroendocrine tumors&#xD;
                  are ineligible regardless of component percentage. Urothelial tumors not&#xD;
                  originating in the bladder (eg, upper tract tumors, urethral tumors) are&#xD;
                  ineligible.&#xD;
&#xD;
               -  Must be cisplatin-ineligible.&#xD;
&#xD;
               -  Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment,&#xD;
                  chemoradiation, or radiation therapy for MIBC. May have received prior&#xD;
                  intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for&#xD;
                  non-MIBC; Cohort J: Eligible for pembrolizumab.&#xD;
&#xD;
               -  ECOG performance status of 0, 1, or 2.&#xD;
&#xD;
               -  Anticipated life expectancy of ≥3 months.&#xD;
&#xD;
               -  Tumor samples with an associated pathology report from the diagnostic&#xD;
                  transurethral resection of a bladder tumor done 90 days prior to the first dose&#xD;
                  of study treatment must be available prior to enrollment and determined to be&#xD;
                  sufficient for pathology review and biomarker analysis.&#xD;
&#xD;
               -  Participants must be deemed eligible for RC+PLND.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  la/mUC - Cohorts A, B, D, E, F, G, and K&#xD;
&#xD;
               -  Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2&#xD;
                  inhibitor, except Cohort F.&#xD;
&#xD;
               -  Received any prior treatment with stimulatory or co-inhibitory T-cell receptor&#xD;
                  agents, such as CD137 agonists, OX-40 agonists, or cytotoxic&#xD;
                  T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).&#xD;
&#xD;
               -  Ongoing sensory or motor neuropathy Grade 2 or higher.&#xD;
&#xD;
               -  Active central nervous system (CNS) metastases.&#xD;
&#xD;
               -  Ongoing clinically significant toxicity (Grade 2 or greater) associated with&#xD;
                  prior treatment (including radiotherapy or surgery).&#xD;
&#xD;
               -  Conditions requiring high doses of steroids or other immunosuppressive&#xD;
                  medications.&#xD;
&#xD;
               -  Prior treatment with enfortumab vedotin or other monomethyl auristatin E&#xD;
                  (MMAE)-based antibody-drug conjugates (ADCs).&#xD;
&#xD;
               -  Uncontrolled diabetes mellitus.&#xD;
&#xD;
          -  MIBC - Cohorts H, J, and L&#xD;
&#xD;
               -  Received prior systemic treatment, chemoradiation, and/or radiation therapy of&#xD;
                  muscle invasive bladder cancer.&#xD;
&#xD;
               -  Received any prior treatment with a CPI.&#xD;
&#xD;
               -  Received any prior treatment with stimulatory or co-inhibitory T-cell receptor&#xD;
                  agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.&#xD;
&#xD;
               -  For participants in Cohort H, evidence of nodal disease on imaging. For&#xD;
                  participants in Cohort L, ≥N2 nodal disease on imaging.&#xD;
&#xD;
               -  Participant has undergone partial cystectomy of the bladder to remove any NMIBC&#xD;
                  or MIBC.&#xD;
&#xD;
               -  Ongoing sensory or motor neuropathy Grade 2 or higher.&#xD;
&#xD;
               -  Conditions requiring high doses of steroids or other immunosuppressive&#xD;
                  medications.&#xD;
&#xD;
               -  Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial&#xD;
                  cancer.&#xD;
&#xD;
               -  Participants with a history of another invasive malignancy within 3 years before&#xD;
                  first dose of study drug.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anne-Sophie Carret, MD</last_name>
    <role>Study Director</role>
    <affiliation>Seagen Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jason Lukas, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Seagen Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alaska Urological Institute</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Banner MD Anderson Cancer Center</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Arizona</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Oncology Associates, PC - HOPE</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Highlands Oncology Group</name>
      <address>
        <city>Fayetteville</city>
        <state>Arkansas</state>
        <zip>72703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tower Hematology Oncology Medical Group</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Diego / Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Irvine - Newport</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California at San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Heritage Medical Group</name>
      <address>
        <city>Santa Rosa</city>
        <state>California</state>
        <zip>95403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Cancer Center / Blood &amp; Marrow Transplant Program</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Southern California</name>
      <address>
        <city>Woodland Hills</city>
        <state>California</state>
        <zip>91367</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers - Aurora</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital / University of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045-0510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eastern CT Hematology and Oncology Associates</name>
      <address>
        <city>Norwich</city>
        <state>Connecticut</state>
        <zip>06360</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boca Raton Regional Hospital / Lynn Cancer Institute</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Florida</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Institute / Emory University School of Medicine</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637-1470</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital - Illinois</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Medicine Cancer Center - Kishwaukee / Kishwaukee Cancer Center</name>
      <address>
        <city>DeKalb</city>
        <state>Illinois</state>
        <zip>60115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Medicine Cancer Center Delnor</name>
      <address>
        <city>Geneva</city>
        <state>Illinois</state>
        <zip>60134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardinal Bernardin Cancer Center / Loyola University Medical Center</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Medicine Cancer Center - Warrenville / Central DuPage Hospital - Cancer Care</name>
      <address>
        <city>Warrenville</city>
        <state>Illinois</state>
        <zip>60555</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tulane University Hospital and Clinic</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Clinic Foundation</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology Hematology, P.A.</name>
      <address>
        <city>Silver Spring</city>
        <state>Maryland</state>
        <zip>20904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southcoast Centers for Cancer Care - Fairhaven Site</name>
      <address>
        <city>Fairhaven</city>
        <state>Massachusetts</state>
        <zip>02719</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Greater Lansing Hospital</name>
      <address>
        <city>Lansing</city>
        <state>Michigan</state>
        <zip>48910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine - Siteman Cancer Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Hematology Oncology P.C.</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OptumCare Cancer Center</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center - Basking Ridge</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center - Monmouth</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center - Bergen</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Cancer Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Oncology Hematology, P.C.</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center - Commack</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center - Westchester</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwell Cancer Center / Monter Cancer Center</name>
      <address>
        <city>Lake Success</city>
        <state>New York</state>
        <zip>11042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Winthrop Hospital</name>
      <address>
        <city>Mineola</city>
        <state>New York</state>
        <zip>11501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University (NYU) Cancer Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10087-9049</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center - Nassau</name>
      <address>
        <city>Uniondale</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNC Lineberger Comprehensive Cancer Center / University of North Carolina</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vidant Medical Center</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gabrail Cancer Center Research, LLC</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Case Western Reserve University / University Hospitals Case Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toledo Clinic Cancer Center</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43623</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CMOH Broomall</name>
      <address>
        <city>Broomall</city>
        <state>Pennsylvania</state>
        <zip>19008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Milton S. Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina/Hollings Cancer Center</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Hospital Cancer Center</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Urologic Research Center</name>
      <address>
        <city>Myrtle Beach</city>
        <state>South Carolina</state>
        <zip>29572</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology / Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Fort Worth Cancer Center</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Health Science Center at San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Tyler</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Utah Cancer Specialists</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Oncology Associates - Norfolk</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology Associates</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin (Milwaukee)</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site CA11008</name>
      <address>
        <city>East Brampton</city>
        <state>Ontario</state>
        <zip>L6R 3J7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site CA11011</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <zip>K7L 2V7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site CA11001</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site CA11005</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site CA11013</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site CA11002</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H 5N4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site FR33008</name>
      <address>
        <city>Bordeaux</city>
        <zip>33000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site FR33005</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site FR33003</name>
      <address>
        <city>Lyon</city>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site FR33004</name>
      <address>
        <city>Marseilles</city>
        <zip>13273</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site FR33010</name>
      <address>
        <city>Moselle</city>
        <zip>54519</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site FR33002</name>
      <address>
        <city>Nice Cedex</city>
        <zip>06189</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site FR33006</name>
      <address>
        <city>Pierre-Benite</city>
        <zip>69310</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site FR33001</name>
      <address>
        <city>Strasbourg</city>
        <zip>67200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site IT39002</name>
      <address>
        <city>Terni</city>
        <zip>05100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site PR78701</name>
      <address>
        <city>Rio Piedras</city>
        <zip>00935</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site ES34006</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site ES34008</name>
      <address>
        <city>Madrid</city>
        <zip>28033</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site ES34001</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site ES34012</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site ES34007</name>
      <address>
        <city>Pamplona</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site ES34005</name>
      <address>
        <city>Sabadell</city>
        <zip>08208</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site ES34004</name>
      <address>
        <city>Santander</city>
        <zip>39008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>France</country>
    <country>Italy</country>
    <country>Puerto Rico</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ASG-22ME</keyword>
  <keyword>ASG-22CE</keyword>
  <keyword>Antibody-drug conjugate</keyword>
  <keyword>Antineoplastic agents</keyword>
  <keyword>CPI</keyword>
  <keyword>Enfortumab vedotin</keyword>
  <keyword>MIBC</keyword>
  <keyword>Locally advanced urothelial cancer</keyword>
  <keyword>Cisplatin</keyword>
  <keyword>Drug therapy</keyword>
  <keyword>Carboplatin</keyword>
  <keyword>Metastatic urothelial cancer</keyword>
  <keyword>Nectin-4</keyword>
  <keyword>Gemcitabine</keyword>
  <keyword>Muscle invasive bladder cancer</keyword>
  <keyword>Checkpoint Inhibitors</keyword>
  <keyword>Pembrolizumab</keyword>
  <keyword>PD-1 inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
    <mesh_term>Urologic Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Transitional Cell</mesh_term>
    <mesh_term>Ureteral Neoplasms</mesh_term>
    <mesh_term>Urethral Neoplasms</mesh_term>
    <mesh_term>Pelvic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03288545
org study id: SGN22E-002
secondary id: MK-3475-869
secondary id: KEYNOTE KN-869
nct id: NCT03288545
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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 or metastatic urothelial cancer (la/mUC), 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.
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
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: multi-cohort, open-label, multicenter study, global
primary purpose: Treatment
masking: None (Open Label)
measure: Type, incidence, severity, seriousness, and relatedness of adverse events (Dose escalation and Expansion Parts 1 to 3 cohorts only)
time frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.
description: Descriptive statistics will be used to summarize results.
measure: Type, incidence, and severity of laboratory abnormalities (Dose escalation and Expansion Parts 1 to 3 cohorts only)
time frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated.
description: Descriptive statistics will be used to summarize results.
measure: 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
description: The proportion of patients with confirmed complete response (CR) or partial response (PR) according to RECIST 1.1
measure: Pathological complete response (pCR) rate per central pathology review (MIBC cohorts only)
time frame: Up to approximately 5 months
description: The proportion of patients with absence of viable tumor tissue at the time of radical cystectomy.
measure: Incidence of dose-limiting toxicity (DLT)
time frame: 21 days
description: Incidence of DLTs (dose-escalation expansion Cohorts D, E, F, and the first 6 patients of Cohort G).
measure: Confirmed ORR by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
time frame: Up to 3 years
description: The proportion of patients with confirmed CR or PR according to RECIST 1.1.
measure: Confirmed ORR by BICR according to RECIST 1.1 (Dose escalation and Cohort A only)
time frame: Up to 3 years
description: The proportion of patients with confirmed CR or PR according to RECIST 1.1
measure: 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
description: The proportion of patients with confirmed CR or PR according to iRECIST.
measure: Disease control rate (DCR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
time frame: Up to 5 years
description: Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1.
measure: DCR by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)
time frame: Up to 3 years
description: Proportion of patients with CR, PR, or stable disease (SD) according to RECIST 1.1
measure: DCR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts using pembrolizumab only)
time frame: Up to 3 years
description: Proportion of patients with CR, PR, or SD according to iRECIST.
measure: Duration of response (DOR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only)
time frame: Up to 5 years
description: 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.
measure: DOR by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)
time frame: Up to 5 years
description: 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
measure: DOR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only)
time frame: Up to 5 years
description: 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.
measure: 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
description: 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.
measure: PFS by BICR according to RECIST 1.1 (Dose escalation, Cohort A, and randomized Cohort K only)
time frame: Up to 5 years
description: 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
measure: PFS by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only)
time frame: Up to 5 years
description: 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.
measure: Event-free (EFS) on study therapy by BICR (Cohort L only)
time frame: Up to 3 years
description: 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.
measure: Event-free (EFS) on study therapy by investigator assessment (MIBC cohorts only)
time frame: Up to 3 years
description: 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.
measure: Overall survival (OS) (all cohorts)
time frame: Up to 5 years
description: The time from start of study treatment to date of death due to any cause.
measure: 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
description: Cmax will be derived from the PK blood samples collected.
measure: 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
description: Cmax will be derived from the PK blood samples collected.
measure: PK parameter for total antibody (Tab): 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
description: Cmax will be derived from the PK blood samples collected.
measure: 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.
description: Blood samples for ATA analysis will be collected.
measure: 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
description: Tmax will be derived from the PK blood samples collected.
measure: 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
description: Tmax will be derived from the PK blood samples collected.
measure: PK parameter for Tab: 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
description: Tmax will be derived from the PK blood samples collected.
measure: 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
description: AUC will be derived from the PK blood samples collected.
measure: 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
description: AUC will be derived from the PK blood samples collected.
measure: PK parameter for Tab: 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
description: AUC will be derived from the PK blood samples collected.
measure: Pathologic downstaging (pDS) rate by central pathology review (MIBC cohorts only)
time frame: Up to approximately 5 months
description: 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).
measure: Disease-free survival (DFS) by investigator assessment (MIBC cohorts only)
time frame: Up to approximately 5 years
description: 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.
measure: DFS by BICR (Cohort L only)
time frame: Up to 3 years
description: DFS is defined as the time from RC to the time of first occurrence of a DFS event
measure: 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
description: Descriptive statistics will be used to summarize results.
measure: 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
description: Descriptive statistics will be used to summarize results.
measure: Percentage of planned radical cystectomy and pelvic lymph node dissections (RC+PLND) delayed due to treatment-related AEs (MIBC cohorts only)
time frame: Up to approximately 5 months
description: Delayed is defined as greater than 12 weeks after the last dose of treatment.
arm group label: EV + Pembrolizumab in cisplatin-ineligible 1L and in 2L
arm group type: Experimental
description: Dose Escalation: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
arm group label: Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1L
arm group type: Experimental
description: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
arm group label: Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2L
arm group type: Experimental
description: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
arm group label: Cohort D: Enfortumab Vedotin + Cisplatin in 1L
arm group type: Experimental
description: Enfortumab vedotin on days 1 and 8 plus cisplatin on day 1 every 21 days
arm group label: Cohort E: Enfortumab Vedotin + Carboplatin in 1L
arm group type: Experimental
description: Enfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days
arm group label: Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2L
arm group type: Experimental
description: Enfortumab vedotin and gemcitabine on days 1 and 8 every 21 days
arm group label: Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L
arm group type: Experimental
description: Enfortumab vedotin on days 1 and 8 plus cisplatin or carboplatin on day 1 plus pembrolizumab on day 1 every 21 days
arm group label: Cohort H: Enfortumab vedotin in MIBC neoadjuvant setting
arm group type: Experimental
description: Enfortumab vedotin on days 1 and 8 every 21 days
arm group label: Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant setting
arm group type: Experimental
description: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
arm group label: Randomized Cohort K: Enfortumab Vedotin Monotherapy
arm group type: Experimental
description: Enfortumab vedotin on days 1 and 8 every 21 days
arm group label: Randomized Cohort K: Enfortumab Vedotin + Pembrolizumab
arm group type: Experimental
description: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
arm group label: Cohort L: Enfortumab vedotin in MIBC in perioperative setting
arm group type: Experimental
description: Enfortumab vedotin on days 1 and 8 and every 21 days
intervention type: Drug
intervention name: enfortumab vedotin (EV)
description: Intravenous (IV) infusion on days 1 and 8 every 21 days
arm group label: Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1L
arm group label: Cohort D: Enfortumab Vedotin + Cisplatin in 1L
arm group label: Cohort E: Enfortumab Vedotin + Carboplatin in 1L
arm group label: Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L
arm group label: Cohort H: Enfortumab vedotin in MIBC neoadjuvant setting
arm group label: Cohort L: Enfortumab vedotin in MIBC in perioperative setting
arm group label: EV + Pembrolizumab in cisplatin-ineligible 1L and in 2L
arm group label: Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2L
arm group label: Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2L
arm group label: Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant setting
arm group label: Randomized Cohort K: Enfortumab Vedotin + Pembrolizumab
arm group label: Randomized Cohort K: Enfortumab Vedotin Monotherapy
other name: ASG-22CE
other name: ASG-22ME
other name: PADCEV
intervention type: Drug
intervention name: pembrolizumab
description: IV infusion on day 1 every 21 days
arm group label: Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1L
arm group label: Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L
arm group label: EV + Pembrolizumab in cisplatin-ineligible 1L and in 2L
arm group label: Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2L
arm group label: Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant setting
arm group label: Randomized Cohort K: Enfortumab Vedotin + Pembrolizumab
other name: Keytruda
intervention type: Drug
intervention name: cisplatin
description: IV infusion on day 1 every 21 days
arm group label: Cohort D: Enfortumab Vedotin + Cisplatin in 1L
arm group label: Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L
intervention type: Drug
intervention name: carboplatin
description: IV infusion on day 1 every 21 days
arm group label: Cohort E: Enfortumab Vedotin + Carboplatin in 1L
arm group label: Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L
intervention type: Drug
intervention name: gemcitabine
description: IV infusion on days 1 and 8 every 21 days
arm group label: Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2L
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anne-Sophie Carret, MD
role: Study Director
affiliation: Seagen Inc.
last name: Jason Lukas, MD, PhD
role: Study Director
affiliation: Seagen Inc.
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country: Canada
country: France
country: Italy
country: Puerto Rico
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Urinary Bladder Neoplasms
mesh term: Urologic Neoplasms
mesh term: Carcinoma, Transitional Cell
mesh term: Ureteral Neoplasms
mesh term: Urethral Neoplasms
mesh term: Pelvic Neoplasms
mesh term: Carboplatin
mesh term: Gemcitabine
mesh term: Pembrolizumab
sharing ipd: Undecided