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

Metastatic Urothelial Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03070990
• Other study ID #: 7465-CL-0101
• Status: Completed
• Phase: Phase 1
• 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
• 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Metastatic Urothelial Cancer

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

External Links

•   Link to results on the Astellas Clinical Study Results website