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

NCT03070990 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 7465-CL-0101
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 8

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.

Conditions

Metastatic Urothelial Cancer

Keywords

Urothelial Carcinoma; Enfortumab vedotin; ASG-22CE; Padcev; ASG-22ME; Metastatic Urothelial Cancer

Outcome Measures

Primary Outcomes (25)

• 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 Outcomes (3)

• Incidence of Anti-Drug Antibody (ADA)

  Up to 12 months

• Overall Response Rate

  Up to 12 months

• Disease Control Rate

  Up to 12 months

Study Arms (2)

Arm A: Enfortumab vedotin 1.0 mg/kg

EXPERIMENTAL

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

Arm B: Enfortumab vedotin 1.25 mg/kg

EXPERIMENTAL

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

Interventions

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.

Also known as: ASG-22CE, Padcev

Arm A: Enfortumab vedotin 1.0 mg/kg; Arm B: Enfortumab vedotin 1.25 mg/kg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Inc: lead
• Seagen Inc.: collaborator

Study Sites (8)

Site JP00003

Tsukuba, Ibaraki, Japan

Location

Site JP00005

Sendai, Miyagi, Japan

Location

Site JP00008

Suita, Osaka, Japan

Location

Site JP00004

Chuo-ku, Tokyo, Japan

Location

Site JP00007

Koto-ku, Tokyo, Japan

Location

Site JP00006

Fukuoka, Japan

Location

Site JP00001

Niigata, Japan

Location

Site JP00002

Okayama, Japan

Location

Related Publications (1)

• 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.

  PMID: 31444589 DERIVED

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

enfortumab vedotin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Medical Director

  Astellas Pharma Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 6, 2017
• Study Start: April 24, 2017
• Primary Completion: February 25, 2019
• Study Completion: February 25, 2019
• Last Updated: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (8)