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

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

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 Overview

• Status: Completed
• Conditions: Metastatic Urothelial Cancer
• Intervention / Treatment: Drug: Enfortumab vedotin

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Site JP00006
  • Niigata, Japan
    • Site JP00001
  • Okayama, Japan
    • Site JP00002
  • Ibaraki
    • Tsukuba, Ibaraki, Japan
      • Site JP00003
  • Miyagi
    • Sendai, Miyagi, Japan
      • Site JP00005
  • Osaka
    • Suita, Osaka, Japan
      • Site JP00008
  • Tokyo
    • Chuo-ku, Tokyo, Japan
      • Site JP00004
    • Koto-ku, Tokyo, Japan
      • Site JP00007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 12 months
Safety assessed by laboratory tests: Hematology	Descriptive statistics will be used to summarize results.	Up to 12 months
Safety assessed by laboratory tests: Biochemistry	Descriptive statistics will be used to summarize results.	Up to 12 months
Safety assessed by laboratory tests: Urinalysis	Descriptive statistics will be used to summarize results.	Up to 12 months
Safety assessed by laboratory tests: Coagulation studies	Descriptive statistics will be used to summarize results.	Up to 12 months
Number of participants with vital sign abnormalities and/or adverse events	Number of participants with potentially clinically significant vital sign values.	Up to 12 months
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.	Up to 12 months
Pharmacokinetics (PK) parameter for total antibody (TAb): Concentration at the end of infusion (CEOI)	CEOI will be derived from the PK blood samples collected.	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
Pharmacokinetics (PK) parameter for antibody drug conjugate (ADC): CEOI	CEOI will be derived from the PK blood samples collected.	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
Pharmacokinetics (PK) parameter for Monomethyl Auristatin E (MMAE): CEOI	CEOI will be derived from the PK blood samples collected.	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
PK parameter for TAb: Maximum observed concentration (Cmax)	Cmax will be derived from the PK blood samples collected.	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
PK parameter for ADC: Cmax	Cmax will be derived from the PK blood samples collected.	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
PK parameter for MMAE: Cmax	Cmax will be derived from the PK blood samples collected.	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
PK parameter for TAb: Trough concentration (Ctrough)	Ctrough will be derived from the PK blood samples collected.	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
PK parameter for ADC: Ctrough	Ctrough will be derived from the PK blood samples collected.	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
PK parameter for MMAE: Ctrough	Ctrough will be derived from the PK blood samples collected.	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
PK parameter for TAb: Time to maximum concentration (Tmax)	Tmax will be derived from the PK blood samples collected.	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
PK parameter for ADC: Tmax	Tmax will be derived from the PK blood samples collected.	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
PK parameter for MMAE: Tmax	Tmax will be derived from the PK blood samples collected.	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
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.	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
PK parameter for ADC: AUC0-7	AUC0-7 will be derived from the PK blood samples collected.	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
PK parameter for MMAE: AUC0-7	AUC0-7 will be derived from the PK blood samples collected.	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
PK parameter for TAb: Terminal or apparent terminal half-life (t1/2)	T1/2 will be derived from the PK blood samples collected.	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
PK parameter for ADC: t1/2	T1/2 will be derived from the PK blood samples collected.	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
PK parameter for MMAE: t1/2	T1/2 will be derived from the PK blood samples collected.	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 Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Anti-Drug Antibody (ADA)	Blood samples for anti-drug antibody (ADA) analysis will be collected.	Up to 12 months
Overall Response Rate	Defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR)	Up to 12 months
Disease Control Rate	Defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD)	Up to 12 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Collaborators: Seagen Inc.

Publications and helpful links

General Publications

• 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.

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2017
• Primary Completion (Actual): February 25, 2019
• Study Completion (Actual): February 25, 2019

Study Registration Dates

• First Submitted: March 1, 2017
• First Submitted That Met QC Criteria: March 1, 2017
• First Posted (Actual): March 6, 2017

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Urothelial Carcinoma; Enfortumab vedotin; ASG-22CE; ASG-22ME; Metastatic Urothelial Cancer; Padcev
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell
• Other Study ID Numbers: 7465-CL-0101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD 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."

Drug and device information, study documents

• 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