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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03070990
Other study ID # 7465-CL-0101
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date April 24, 2017
Est. completion date February 25, 2019

Study information

Verified date March 2020
Source Astellas Pharma Inc
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 information / eligibility

Status Completed
Enrollment 19
Est. completion date February 25, 2019
Est. primary completion date February 25, 2019
Accepts healthy volunteers No
Gender All
Age group 20 Years and older
Eligibility 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 Design


Intervention

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.

Locations

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

Sponsors (2)

Lead Sponsor Collaborator
Astellas Pharma Inc Seattle Genetics, Inc.

Country where clinical trial is conducted

Japan, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary Safety assessed by laboratory tests: Hematology Descriptive statistics will be used to summarize results. Up to 12 months
Primary Safety assessed by laboratory tests: Biochemistry Descriptive statistics will be used to summarize results. Up to 12 months
Primary Safety assessed by laboratory tests: Urinalysis Descriptive statistics will be used to summarize results. Up to 12 months
Primary Safety assessed by laboratory tests: Coagulation studies Descriptive statistics will be used to summarize results. Up to 12 months
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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 Incidence of Anti-Drug Antibody (ADA) Blood samples for anti-drug antibody (ADA) analysis will be collected. Up to 12 months
Secondary 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
Secondary 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
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