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A Study of Enfortumab Vedotin in Japanese Subjects With Locally Advanced or Metastatic Urothelial Carcinoma

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03070990
Recruitment Status : Completed
First Posted : March 6, 2017
Last Update Posted : March 4, 2020
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc

Brief Summary:
The objective of this study is to assess the safety, tolerability and pharmacokinetics of enfortumab vedotin (ASG-22CE) when administered intravenously to Japanese subjects with locally advanced or metastatic urothelial carcinoma. This study will also assess the immunogenicity as defined by the incidence of anti-drug antibody (ADA) and anti-tumor activity of enfortumab vedotin (ASG-22CE) when administered intravenously to Japanese subjects with locally advanced or metastatic urothelial carcinoma.

Condition or disease Intervention/treatment Phase
Metastatic Urothelial Cancer Drug: Enfortumab vedotin Phase 1

Detailed Description:
All subjects will receive a single 30 minute intravenous (IV) infusion of enfortumab vedotin (ASG-22CE) once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 28 days.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Randomized, Phase 1 Safety and Pharmacokinetic Study of Enfortumab Vedotin (ASG-22CE) in Japanese Patients With Locally Advanced or Metastatic Urothelial Carcinoma
Actual Study Start Date : April 24, 2017
Actual Primary Completion Date : February 25, 2019
Actual Study Completion Date : February 25, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A: Enfortumab vedotin 1.0 mg/kg
All subjects assigned will receive a single 30 minute intravenous infusion of enfortumab vedotin (ASG-22CE) once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 28 days.
Drug: Enfortumab vedotin
All subjects assigned will receive a single 30 minute intravenous infusion of enfortumab vedotin (ASG-22CE) once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 28 days.
Other Names:
  • ASG-22CE
  • Padcev

Experimental: Arm B: Enfortumab vedotin 1.25 mg/kg
All subjects assigned will receive a single 30 minute intravenous infusion of enfortumab vedotin (ASG-22CE) once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 28 days.
Drug: Enfortumab vedotin
All subjects assigned will receive a single 30 minute intravenous infusion of enfortumab vedotin (ASG-22CE) once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 28 days.
Other Names:
  • ASG-22CE
  • Padcev




Primary Outcome Measures :
  1. Safety assessed by incidence of adverse events [ Time Frame: Up to 12 months ]
    Adverse events will be coded using MedDRA. Adverse events collection begins after signing informed consent and collected until 28 days after the last dose of study drug.

  2. Safety assessed by laboratory tests: Hematology [ Time Frame: Up to 12 months ]
    Descriptive statistics will be used to summarize results.

  3. Safety assessed by laboratory tests: Biochemistry [ Time Frame: Up to 12 months ]
    Descriptive statistics will be used to summarize results.

  4. Safety assessed by laboratory tests: Urinalysis [ Time Frame: Up to 12 months ]
    Descriptive statistics will be used to summarize results.

  5. Safety assessed by laboratory tests: Coagulation studies [ Time Frame: Up to 12 months ]
    Descriptive statistics will be used to summarize results.

  6. Number of participants with vital sign abnormalities and/or adverse events [ Time Frame: Up to 12 months ]
    Number of participants with potentially clinically significant vital sign values.

  7. Safety assessed by electrocardiogram (ECG) [ Time Frame: Up to 12 months ]
    Before measurement of ECGs, the participant should be resting in a supine position for at least 5 minutes. The investigator will assess the ECG charts as "normal", "abnormal (not clinically significant)" or "abnormal (clinically significant)". "Abnormal (not clinically significant)" and "abnormal (clinically significant)" findings will be recorded.

  8. Pharmacokinetics (PK) parameter for total antibody (TAb): Concentration at the end of infusion (CEOI) [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    CEOI will be derived from the PK blood samples collected.

  9. Pharmacokinetics (PK) parameter for antibody drug conjugate (ADC): CEOI [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    CEOI will be derived from the PK blood samples collected.

  10. Pharmacokinetics (PK) parameter for Monomethyl Auristatin E (MMAE): CEOI [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    CEOI will be derived from the PK blood samples collected.

  11. PK parameter for TAb: Maximum observed concentration (Cmax) [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    Cmax will be derived from the PK blood samples collected.

  12. PK parameter for ADC: Cmax [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    Cmax will be derived from the PK blood samples collected.

  13. PK parameter for MMAE: Cmax [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    Cmax will be derived from the PK blood samples collected.

  14. PK parameter for TAb: Trough concentration (Ctrough) [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    Ctrough will be derived from the PK blood samples collected.

  15. PK parameter for ADC: Ctrough [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    Ctrough will be derived from the PK blood samples collected.

  16. PK parameter for MMAE: Ctrough [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    Ctrough will be derived from the PK blood samples collected.

  17. PK parameter for TAb: Time to maximum concentration (Tmax) [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    Tmax will be derived from the PK blood samples collected.

  18. PK parameter for ADC: Tmax [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    Tmax will be derived from the PK blood samples collected.

  19. PK parameter for MMAE: Tmax [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    Tmax will be derived from the PK blood samples collected.

  20. PK parameter for TAb: Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7) [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    AUC0-7 will be derived from the PK blood samples collected.

  21. PK parameter for ADC: AUC0-7 [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    AUC0-7 will be derived from the PK blood samples collected.

  22. PK parameter for MMAE: AUC0-7 [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    AUC0-7 will be derived from the PK blood samples collected.

  23. PK parameter for TAb: Terminal or apparent terminal half-life (t1/2) [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    T1/2 will be derived from the PK blood samples collected.

  24. PK parameter for ADC: t1/2 [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    T1/2 will be derived from the PK blood samples collected.

  25. PK parameter for MMAE: t1/2 [ Time Frame: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months ]
    T1/2 will be derived from the PK blood samples collected.


Secondary Outcome Measures :
  1. Incidence of Anti-Drug Antibody (ADA) [ Time Frame: Up to 12 months ]
    Blood samples for anti-drug antibody (ADA) analysis will be collected.

  2. Overall Response Rate [ Time Frame: Up to 12 months ]
    Defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR)

  3. Disease Control Rate [ Time Frame: Up to 12 months ]
    Defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD)



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must have histologically confirmed, locally advanced (TNM classification T3b and any N; or T and N2-3) or metastatic Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
  • Subject must be able to submit a tumor tissue samples for Nectin-4 expression analysis at central laboratory.
  • Subject must have failed at least one prior chemotherapy regimen for advanced disease. Urothelial and bladder cancer subjects are not required to have failed prior chemotherapy regimen if considered unfit for cisplatin-based chemotherapy.
  • Subject must have measurable disease according to Response Evaluation Criteria in Solid Tumor (RECIST) (version 1.1).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

  • Preexisting sensory neuropathy Grade ≥ 2.
  • Preexisting motor neuropathy Grade ≥ 2.
  • Uncontrolled central nervous system metastasis that requires active treatment.
  • Any anticancer therapy within 14 days prior to the first dose of study drug.
  • Subjects with pre-existing immunotherapy-related adverse events requiring high doses of systemic steroids are not eligible.

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): NCT03070990


Locations
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Japan
Site JP00003
Tsukuba, Ibaraki, Japan
Site JP00005
Sendai, Miyagi, Japan
Site JP00008
Suita, Osaka, Japan
Site JP00004
Chuo-ku, Tokyo, Japan
Site JP00007
Koto-ku, Tokyo, Japan
Site JP00006
Fukuoka, Japan
Site JP00001
Niigata, Japan
Site JP00002
Okayama, Japan
Sponsors and Collaborators
Astellas Pharma Inc
Seattle Genetics, Inc.
Investigators
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Study Director: Medical Director Astellas Pharma Inc
Additional Information:
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Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT03070990    
Other Study ID Numbers: 7465-CL-0101
First Posted: March 6, 2017    Key Record Dates
Last Update Posted: March 4, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Astellas Pharma Inc:
Urothelial Carcinoma
Enfortumab vedotin
ASG-22CE
Padcev
ASG-22ME
Metastatic Urothelial Cancer
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms