Back to resultsA Study of Enfortumab Vedotin in Japanese Subjects With Locally Advanced or Metastatic Urothelial Carcinoma
Primary Purpose
Metastatic Urothelial Cancer
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Enfortumab vedotin
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Urothelial Cancer focused on measuring Urothelial Carcinoma, Enfortumab vedotin, ASG-22CE, Padcev, ASG-22ME, Metastatic Urothelial Cancer
Eligibility 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.
Sites / Locations
- Site JP00003
- Site JP00005
- Site JP00008
- Site JP00004
- Site JP00007
- Site JP00006
- Site JP00001
- Site JP00002
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A: Enfortumab vedotin 1.0 mg/kg
Arm B: Enfortumab vedotin 1.25 mg/kg
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Safety assessed by incidence of adverse events
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: Hematology
Descriptive statistics will be used to summarize results.
Safety assessed by laboratory tests: Biochemistry
Descriptive statistics will be used to summarize results.
Safety assessed by laboratory tests: Urinalysis
Descriptive statistics will be used to summarize results.
Safety assessed by laboratory tests: Coagulation studies
Descriptive statistics will be used to summarize results.
Number of participants with vital sign abnormalities and/or adverse events
Number of participants with potentially clinically significant vital sign values.
Safety assessed by electrocardiogram (ECG)
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.
Pharmacokinetics (PK) parameter for total antibody (TAb): Concentration at the end of infusion (CEOI)
CEOI will be derived from the PK blood samples collected.
Pharmacokinetics (PK) parameter for antibody drug conjugate (ADC): CEOI
CEOI will be derived from the PK blood samples collected.
Pharmacokinetics (PK) parameter for Monomethyl Auristatin E (MMAE): CEOI
CEOI will be derived from the PK blood samples collected.
PK parameter for TAb: Maximum observed concentration (Cmax)
Cmax will be derived from the PK blood samples collected.
PK parameter for ADC: Cmax
Cmax will be derived from the PK blood samples collected.
PK parameter for MMAE: Cmax
Cmax will be derived from the PK blood samples collected.
PK parameter for TAb: Trough concentration (Ctrough)
Ctrough will be derived from the PK blood samples collected.
PK parameter for ADC: Ctrough
Ctrough will be derived from the PK blood samples collected.
PK parameter for MMAE: Ctrough
Ctrough will be derived from the PK blood samples collected.
PK parameter for TAb: Time to maximum concentration (Tmax)
Tmax will be derived from the PK blood samples collected.
PK parameter for ADC: Tmax
Tmax will be derived from the PK blood samples collected.
PK parameter for MMAE: Tmax
Tmax 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)
AUC0-7 will be derived from the PK blood samples collected.
PK parameter for ADC: AUC0-7
AUC0-7 will be derived from the PK blood samples collected.
PK parameter for MMAE: AUC0-7
AUC0-7 will be derived from the PK blood samples collected.
PK parameter for TAb: Terminal or apparent terminal half-life (t1/2)
T1/2 will be derived from the PK blood samples collected.
PK parameter for ADC: t1/2
T1/2 will be derived from the PK blood samples collected.
PK parameter for MMAE: t1/2
T1/2 will be derived from the PK blood samples collected.
Secondary Outcome Measures
Incidence of Anti-Drug Antibody (ADA)
Blood samples for anti-drug antibody (ADA) analysis will be collected.
Overall Response Rate
Defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR)
Disease Control Rate
Defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD)
Full Information
NCT ID
NCT03070990
First Posted
March 1, 2017
Last Updated
March 2, 2020
Sponsor
Astellas Pharma Inc
Collaborators
Seagen Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03070990
Brief Title
A Study of Enfortumab Vedotin in Japanese Subjects With Locally Advanced or Metastatic Urothelial Carcinoma
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
April 24, 2017 (Actual)
Primary Completion Date
February 25, 2019 (Actual)
Study Completion Date
February 25, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Inc
Collaborators
Seagen Inc.
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Urothelial Cancer
Keywords
Urothelial Carcinoma, Enfortumab vedotin, ASG-22CE, Padcev, ASG-22ME, Metastatic Urothelial Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: Enfortumab vedotin 1.0 mg/kg
Arm Type
Experimental
Arm Description
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 Title
Arm B: Enfortumab vedotin 1.25 mg/kg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Enfortumab vedotin
Other Intervention Name(s)
ASG-22CE, Padcev
Intervention Description
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 Measure Information:
Title
Safety assessed by incidence of adverse events
Description
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.
Time Frame
Up to 12 months
Title
Safety assessed by laboratory tests: Hematology
Description
Descriptive statistics will be used to summarize results.
Time Frame
Up to 12 months
Title
Safety assessed by laboratory tests: Biochemistry
Description
Descriptive statistics will be used to summarize results.
Time Frame
Up to 12 months
Title
Safety assessed by laboratory tests: Urinalysis
Description
Descriptive statistics will be used to summarize results.
Time Frame
Up to 12 months
Title
Safety assessed by laboratory tests: Coagulation studies
Description
Descriptive statistics will be used to summarize results.
Time Frame
Up to 12 months
Title
Number of participants with vital sign abnormalities and/or adverse events
Description
Number of participants with potentially clinically significant vital sign values.
Time Frame
Up to 12 months
Title
Safety assessed by electrocardiogram (ECG)
Description
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.
Time Frame
Up to 12 months
Title
Pharmacokinetics (PK) parameter for total antibody (TAb): Concentration at the end of infusion (CEOI)
Description
CEOI will be derived from the PK blood samples collected.
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
Title
Pharmacokinetics (PK) parameter for antibody drug conjugate (ADC): CEOI
Description
CEOI will be derived from the PK blood samples collected.
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
Title
Pharmacokinetics (PK) parameter for Monomethyl Auristatin E (MMAE): CEOI
Description
CEOI will be derived from the PK blood samples collected.
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
Title
PK parameter for TAb: Maximum observed concentration (Cmax)
Description
Cmax will be derived from the PK blood samples collected.
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
Title
PK parameter for ADC: Cmax
Description
Cmax will be derived from the PK blood samples collected.
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
Title
PK parameter for MMAE: Cmax
Description
Cmax will be derived from the PK blood samples collected.
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
Title
PK parameter for TAb: Trough concentration (Ctrough)
Description
Ctrough will be derived from the PK blood samples collected.
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
Title
PK parameter for ADC: Ctrough
Description
Ctrough will be derived from the PK blood samples collected.
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
Title
PK parameter for MMAE: Ctrough
Description
Ctrough will be derived from the PK blood samples collected.
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
Title
PK parameter for TAb: Time to maximum concentration (Tmax)
Description
Tmax will be derived from the PK blood samples collected.
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
Title
PK parameter for ADC: Tmax
Description
Tmax will be derived from the PK blood samples collected.
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
Title
PK parameter for MMAE: Tmax
Description
Tmax will be derived from the PK blood samples collected.
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
Title
PK parameter for TAb: Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7)
Description
AUC0-7 will be derived from the PK blood samples collected.
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
Title
PK parameter for ADC: AUC0-7
Description
AUC0-7 will be derived from the PK blood samples collected.
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
Title
PK parameter for MMAE: AUC0-7
Description
AUC0-7 will be derived from the PK blood samples collected.
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
Title
PK parameter for TAb: Terminal or apparent terminal half-life (t1/2)
Description
T1/2 will be derived from the PK blood samples collected.
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
Title
PK parameter for ADC: t1/2
Description
T1/2 will be derived from the PK blood samples collected.
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
Title
PK parameter for MMAE: t1/2
Description
T1/2 will be derived from the PK blood samples collected.
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
Secondary Outcome Measure Information:
Title
Incidence of Anti-Drug Antibody (ADA)
Description
Blood samples for anti-drug antibody (ADA) analysis will be collected.
Time Frame
Up to 12 months
Title
Overall Response Rate
Description
Defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR)
Time Frame
Up to 12 months
Title
Disease Control Rate
Description
Defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD)
Time Frame
Up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Astellas Pharma Inc
Official's Role
Study Director
Facility Information:
Facility Name
Site JP00003
City
Tsukuba
State/Province
Ibaraki
Country
Japan
Facility Name
Site JP00005
City
Sendai
State/Province
Miyagi
Country
Japan
Facility Name
Site JP00008
City
Suita
State/Province
Osaka
Country
Japan
Facility Name
Site JP00004
City
Chuo-ku
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00007
City
Koto-ku
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00006
City
Fukuoka
Country
Japan
Facility Name
Site JP00001
City
Niigata
Country
Japan
Facility Name
Site JP00002
City
Okayama
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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."
Citations:
PubMed Identifier
31444589
Citation
Takahashi S, Uemura M, Kimura T, Kawasaki Y, Takamoto A, Yamaguchi A, Melhem-Bertrandt A, Gartner EM, Inoue T, Akazawa R, Kadokura T, Tanikawa T. A phase I study of enfortumab vedotin in Japanese patients with locally advanced or metastatic urothelial carcinoma. Invest New Drugs. 2020 Aug;38(4):1056-1066. doi: 10.1007/s10637-019-00844-x. Epub 2019 Aug 14.
Results Reference
derived
Links:
URL
https://astellasclinicalstudyresults.com/hcp/study.aspx?ID=365
Description
Link to results on the Astellas Clinical Study Results website
Learn more about this trial
A Study of Enfortumab Vedotin in Japanese Subjects With Locally Advanced or Metastatic Urothelial Carcinoma
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