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


Condition: Metastatic Urothelial Cancer

Intervention:

  • Drug: Enfortumab vedotin

Purpose: 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03070990

Sponsor: Astellas Pharma Inc

Primary Outcome Measures:

  • Measure: Safety assessed by incidence of adverse events
  • Time Frame: Up to 12 months
  • Safety Issue:
  • Measure: Safety assessed by laboratory tests: Hematology
  • Time Frame: Up to 12 months
  • Safety Issue:
  • Measure: Safety assessed by laboratory tests: Biochemistry
  • Time Frame: Up to 12 months
  • Safety Issue:
  • Measure: Safety assessed by laboratory tests: Urinalysis
  • Time Frame: Up to 12 months
  • Safety Issue:
  • Measure: Safety assessed by laboratory tests: Coagulation studies
  • Time Frame: Up to 12 months
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:
  • Measure: 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
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Incidence of Anti-Drug Antibody (ADA)
  • Time Frame: Up to 12 months
  • Safety Issue:
  • Measure: Overall Response Rate
  • Time Frame: Up to 12 months
  • Safety Issue:
  • Measure: Disease Control Rate
  • Time Frame: Up to 12 months
  • Safety Issue:

Estimated Enrollment: 17

Study Start Date: April 24, 2017

Phase: Phase 1

Eligibility:

  • Age: minimum 20 Years maximum N/A
  • Gender: All

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.

Locations:

  • 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

View trial on ClinicalTrials.gov