A Study of Enfortumab Vedotin in Japanese Subjects With Locally Advanced or Metastatic Urothelial Carcinoma
- Conditions
- Metastatic Urothelial Cancer
- Interventions
- Drug: Enfortumab vedotin
- Registration Number
- NCT03070990
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Enfortumab vedotin 1.0 mg/kg 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. Arm B: Enfortumab vedotin 1.25 mg/kg 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.
- Primary Outcome Measures
Name Time Method PK parameter for ADC: AUC0-7 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.
PK parameter for ADC: Ctrough 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.
PK parameter for ADC: Cmax 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.
PK parameter for MMAE: Cmax 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.
Pharmacokinetics (PK) parameter for Monomethyl Auristatin E (MMAE): CEOI 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.
PK parameter for ADC: Tmax 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.
PK parameter for MMAE: Tmax 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.
Safety assessed by incidence of adverse events 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.
Safety assessed by laboratory tests: Urinalysis Up to 12 months Descriptive statistics will be used to summarize results.
Safety assessed by electrocardiogram (ECG) 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.
PK parameter for MMAE: Ctrough 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.
PK parameter for TAb: Time to maximum concentration (Tmax) 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.
Safety assessed by laboratory tests: Biochemistry Up to 12 months Descriptive statistics will be used to summarize results.
Number of participants with vital sign abnormalities and/or adverse events Up to 12 months Number of participants with potentially clinically significant vital sign values.
Pharmacokinetics (PK) parameter for total antibody (TAb): Concentration at the end of infusion (CEOI) 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.
Pharmacokinetics (PK) parameter for antibody drug conjugate (ADC): CEOI 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.
PK parameter for TAb: Maximum observed concentration (Cmax) 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.
PK parameter for MMAE: AUC0-7 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.
PK parameter for ADC: t1/2 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.
PK parameter for TAb: Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7) 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.
Safety assessed by laboratory tests: Hematology Up to 12 months Descriptive statistics will be used to summarize results.
Safety assessed by laboratory tests: Coagulation studies Up to 12 months Descriptive statistics will be used to summarize results.
PK parameter for TAb: Trough concentration (Ctrough) 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.
PK parameter for TAb: Terminal or apparent terminal half-life (t1/2) 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.
PK parameter for MMAE: t1/2 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
Name Time Method Overall Response Rate Up to 12 months Defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR)
Disease Control Rate Up to 12 months Defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD)
Incidence of Anti-Drug Antibody (ADA) Up to 12 months Blood samples for anti-drug antibody (ADA) analysis will be collected.
Trial Locations
- Locations (8)
Site JP00005
🇯🇵Sendai, Miyagi, Japan
Site JP00003
🇯🇵Tsukuba, Ibaraki, Japan
Site JP00008
🇯🇵Suita, Osaka, Japan
Site JP00007
🇯🇵Koto-ku, Tokyo, Japan
Site JP00006
🇯🇵Fukuoka, Japan
Site JP00004
🇯🇵Chuo-ku, Tokyo, Japan
Site JP00001
🇯🇵Niigata, Japan
Site JP00002
🇯🇵Okayama, Japan