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Completed

NCT Number: NCT03070990

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

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.

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Key information

Conditions

Metastatic Urothelial Cancer Carcinoma Carcinoma, Transitional Cell Neoplasms Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Site JP00003, Tsukuba, Ibaraki, Japan

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Enfortumab vedotin

Drug

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 outcomes

  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 outcomes

  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)

Sponsors and collaborators

Lead sponsor

Astellas Pharma Inc

Industry

Collaborators

  • Seagen Inc.

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Mar 6, 2017
Registry last updated
Oct 18, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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