Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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 : November 4, 2019
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

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 urothelial cancer, 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.

Condition or disease Intervention/treatment Phase
Carcinoma, Transitional Cell Urinary Bladder Neoplasms Urologic Neoplasms Renal Pelvis Neoplasms Urothelial Cancer Ureteral Neoplasms Urethral Neoplasms Drug: enfortumab vedotin Drug: pembrolizumab Drug: cisplatin Drug: carboplatin Drug: gemcitabine Phase 1

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Detailed Description:
This study will examine the safety and anticancer activity of enfortumab vedotin given intravenously as monotherapy and in combination with other anticancer therapies to 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: dose escalation (enfortumab vedotin + pembrolizumab) and dose expansion (cohorts of enfortumab vedotin + pembrolizumab and/or chemotherapy) for locally advanced and metastatic urothelial cancer, and enfortumab alone and combination with pembrolizumab in patients with earlier stage of the disease (muscle invasive urothelial cancer).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 257 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: multi-cohort, open-label, multicenter study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study of Enfortumab Vedotin (ASG-22CE) as Monotherapy or in Combination With Other Anticancer Therapies for the Treatment of Urothelial Cancer
Actual Study Start Date : October 11, 2017
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : March 2026

Arm Intervention/treatment
Experimental: Dose Escalation: Enfortumab Vedotin + Pembrolizumab
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Drug: enfortumab vedotin
Intravenous (IV) infusion on days 1 and 8 every 21 days
Other Names:
  • ASG-22CE
  • ASG-22ME

Drug: pembrolizumab
IV infusion on day 1 every 21 days
Other Name: Keytruda

Experimental: Cohort A: Enfortumab Vedotin + Pembrolizumab
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Drug: enfortumab vedotin
Intravenous (IV) infusion on days 1 and 8 every 21 days
Other Names:
  • ASG-22CE
  • ASG-22ME

Drug: pembrolizumab
IV infusion on day 1 every 21 days
Other Name: Keytruda

Experimental: Optional Cohort B: Enfortumab Vedotin + Pembrolizumab
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Drug: enfortumab vedotin
Intravenous (IV) infusion on days 1 and 8 every 21 days
Other Names:
  • ASG-22CE
  • ASG-22ME

Drug: pembrolizumab
IV infusion on day 1 every 21 days
Other Name: Keytruda

Experimental: Cohort D: Enfortumab Vedotin + Cisplatin
Enfortumab vedotin on days 1 and 8 plus cisplatin on day 1 every 21 days
Drug: enfortumab vedotin
Intravenous (IV) infusion on days 1 and 8 every 21 days
Other Names:
  • ASG-22CE
  • ASG-22ME

Drug: cisplatin
IV infusion on day 1 every 21 days

Experimental: Cohort E: Enfortumab Vedotin + Carboplatin
Enfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days
Drug: enfortumab vedotin
Intravenous (IV) infusion on days 1 and 8 every 21 days
Other Names:
  • ASG-22CE
  • ASG-22ME

Drug: carboplatin
IV infusion on day 1 every 21 days

Experimental: Optional Cohort F: Enfortumab Vedotin + Gemcitabine
Enfortumab vedotin and gemcitabine on days 1 and 8 every 21 days
Drug: enfortumab vedotin
Intravenous (IV) infusion on days 1 and 8 every 21 days
Other Names:
  • ASG-22CE
  • ASG-22ME

Drug: gemcitabine
IV infusion on days 1 and 8 every 21 days

Experimental: Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab
Enfortumab vedotin on days 1 and 8 plus cisplatin or carboplatin on day 1 plus pembrolizumab on day 1 every 21 days
Drug: enfortumab vedotin
Intravenous (IV) infusion on days 1 and 8 every 21 days
Other Names:
  • ASG-22CE
  • ASG-22ME

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

Experimental: Cohort H: Enfortumab vedotin
Enfortumab vedotin on days 1 and 8 every 21 days
Drug: enfortumab vedotin
Intravenous (IV) infusion on days 1 and 8 every 21 days
Other Names:
  • ASG-22CE
  • ASG-22ME

Experimental: Cohort J: Enfortumab vedotin + Pembrolizumab
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Drug: enfortumab vedotin
Intravenous (IV) infusion on days 1 and 8 every 21 days
Other Names:
  • ASG-22CE
  • ASG-22ME

Drug: pembrolizumab
IV infusion on day 1 every 21 days
Other Name: Keytruda




Primary Outcome Measures :
  1. Type, incidence, severity, seriousness, and relatedness of adverse events (locally advanced/metastatic urothelial cancer [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.

  2. Type, incidence, and severity of laboratory abnormalities (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.

  3. Pathological complete response (pCR) rate per local pathology review (muscle invasive urothelial cancer [MIUC] cohorts 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).


Secondary Outcome Measures :
  1. 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).

  2. Confirmed objective response rate (ORR) by investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) (la/mUC cohorts only) [ Time Frame: Up to 5 years ]
    The proportion of patients with confirmed complete response (CR) or partial response (PR) according to RECIST 1.1.

  3. Confirmed ORR per the modified RECIST 1.1 for immune-based therapeutics (iRECIST) (la/mUC cohorts using pembrolizumab only) [ Time Frame: Up to 5 years ]
    The proportion of patients with confirmed CR or PR according to iRECIST 1.1.

  4. 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.

  5. DCR by investigator assessment according to iRECIST 1.1 (la/mUC cohorts using pembrolizumab only) [ Time Frame: Up to 5 years ]
    Proportion of patients with CR, PR, or SD according to iRECIST 1.1.

  6. 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.

  7. DOR by investigator assessment according to iRECIST 1.1 (la/mUC cohorts using 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 progressive disease (PD per iRECIST 1.1) or to death due to any cause, whichever comes first.

  8. Progression free survival (PFS) by investigator assessment according to RECIST 1.1 (all cohorts) [ 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.

  9. PFS by investigator assessment according to iRECIST 1.1 (la/mUC cohorts using 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 1.1), or to death due to any cause, whichever comes first.

  10. 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.

  11. Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) (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.

  12. PK parameter for monomethyl auristatin E (MMAE): Cmax (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.

  13. PK parameter for enfortumab vedotin: Time to maximum concentration (Tmax) (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.

  14. PK parameter for MMAE: Tmax (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.

  15. PK parameter for enfortumab vedotin: Area under the concentration-time curve (AUC) (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.

  16. PK parameter for MMAE: AUC (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.

  17. Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin (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.

  18. pCR rate per central pathology review (MIUC cohorts only) [ Time Frame: Up to approximately 5 months ]
    Defined as the proportion of patients with pCR at the time of RC.

  19. Pathological response (PaR) rate per central pathology review (MIUC cohorts only) [ Time Frame: Up to approximately 5 months ]
    The PaR rate is defined as the proportion of patients with pathologic downstaging to ≤ pT1pN0 at the time of RC.

  20. PaR rate per local pathology review (MIUC cohorts only) [ Time Frame: Up to approximately 5 months ]
    The PaR rate is defined as the proportion of patients with pathologic downstaging to ≤ pT1pN0 at the time of RC.

  21. Disease-free survival (DFS) by investigator assessment according to RECIST 1.1 (MIUC cohorts only) [ Time Frame: Up to approximately 5 months ]
    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.

  22. Type, incidence, severity, seriousness, and relatedness of AEs (MIUC cohorts only) [ Time Frame: Up to approximately 5 months ]
    Descriptive statistics will be used to summarize results.

  23. Type, incidence, and severity of laboratory abnormalities (MIUC cohorts only) [ Time Frame: Up to approximately 5 months ]
    Descriptive statistics will be used to summarize results.

  24. Percentage of planned surgeries delayed due to treatment-related AEs (MIUC cohorts only) [ Time Frame: Up to approximately 5 months ]
    Delayed is defined as greater than 12 weeks after the last dose of treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

    • 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.
    • Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, and G).
    • 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.
  • Muscle Invasive Urothelial Cancer (MIUC) - Cohorts H and J

    • Histologically confirmed muscle invasive urothelial cancer of the bladder at clinical stage cT2-T4a.
    • Medically fit (i.e. eligible for surgery) and scheduled for radical cystectomy.
    • ECOG performance status of 0, 1, or 2.
    • Cohort H and J: Ineligible for cisplatin-based chemotherapy and no prior systemic treatment, chemoradiation, or radiation therapy for MIUC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-muscle invasive urothelial cancer.
    • Cohort J: Eligible for pembrolizumab.

Exclusion Criteria:

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

    • 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.
  • MIUC - Cohorts H and J

    • Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive urothelial 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 measurable nodal or metastatic disease.
    • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03288545


Contacts
Layout table for location contacts
Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
Show Show 27 study locations
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Seattle Genetics, Inc.
Investigators
Layout table for investigator information
Study Director: Anne-Sophie Carret, MD Seattle Genetics, Inc.

Layout table for additonal information
Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT03288545    
Other Study ID Numbers: SGN22E-002
First Posted: September 20, 2017    Key Record Dates
Last Update Posted: November 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
MIUC
ASG-22ME
ASG-22CE
Antibody-drug conjugate
Antineoplastic agents
CPI
Enfortumab vedotin
MIBC
Locally advanced urothelial cancer
Cisplatin
Drug therapy
Carboplatin
Metastatic urothelial cancer
Nectin-4
Gemcitabine
Muscle invasive urothelial cancer
Muscle invasive bladder cancer
Checkpoint Inhibitors
Pembrolizumab
Additional relevant MeSH terms:
Layout table for MeSH terms
Urinary Bladder Neoplasms
Urologic Neoplasms
Carcinoma, Transitional Cell
Ureteral Neoplasms
Urethral Neoplasms
Pelvic Neoplasms
Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Ureteral Diseases
Urethral Diseases
Gemcitabine
Cisplatin
Carboplatin
Pembrolizumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs