Clinical trial NCT03070990: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Urothelial Cancer
Keywords: Urothelial Carcinoma
Enfortumab vedotin
ASG-22CE
Padcev
ASG-22ME
Metastatic Urothelial Cancer
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Seagen Inc.
First posted: 2017-03-06
Enrollment: 19
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety assessed by incidence of adverse events
timeFrame: Up to 12 months
measure: Safety assessed by laboratory tests: Hematology
timeFrame: Up to 12 months
measure: Safety assessed by laboratory tests: Biochemistry
timeFrame: Up to 12 months
measure: Safety assessed by laboratory tests: Urinalysis
timeFrame: Up to 12 months
measure: Safety assessed by laboratory tests: Coagulation studies
timeFrame: Up to 12 months
measure: Number of participants with vital sign abnormalities and/or adverse events
timeFrame: Up to 12 months
measure: Safety assessed by electrocardiogram (ECG)
timeFrame: Up to 12 months
measure: Pharmacokinetics (PK) parameter for total antibody (TAb): Concentration at the end of infusion (CEOI)
timeFrame: 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
measure: Pharmacokinetics (PK) parameter for antibody drug conjugate (ADC): CEOI
timeFrame: 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
measure: Pharmacokinetics (PK) parameter for Monomethyl Auristatin E (MMAE): CEOI
timeFrame: 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
measure: PK parameter for TAb: Maximum observed concentration (Cmax)
timeFrame: 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
measure: PK parameter for ADC: Cmax
timeFrame: 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
measure: PK parameter for MMAE: Cmax
timeFrame: 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
measure: PK parameter for TAb: Trough concentration (Ctrough)
timeFrame: 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
measure: PK parameter for ADC: Ctrough
timeFrame: 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
measure: PK parameter for MMAE: Ctrough
timeFrame: 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
measure: PK parameter for TAb: Time to maximum concentration (Tmax)
timeFrame: 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
measure: PK parameter for ADC: Tmax
timeFrame: 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
measure: PK parameter for MMAE: Tmax
timeFrame: 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
measure: PK parameter for TAb: Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7)
timeFrame: 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
measure: PK parameter for ADC: AUC0-7
timeFrame: 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
measure: PK parameter for MMAE: AUC0-7
timeFrame: 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
measure: PK parameter for TAb: Terminal or apparent terminal half-life (t1/2)
timeFrame: 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
measure: PK parameter for ADC: t1/2
timeFrame: 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
measure: PK parameter for MMAE: t1/2
timeFrame: 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:
measure: Incidence of Anti-Drug Antibody (ADA)
timeFrame: Up to 12 months
measure: Overall Response Rate
timeFrame: Up to 12 months
measure: Disease Control Rate
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Tsukuba
country: Japan
facility: Site JP00003
state: Ibaraki
city: Sendai
country: Japan
facility: Site JP00005
state: Miyagi
city: Suita
country: Japan
facility: Site JP00008
state: Osaka
city: Chuo-ku
country: Japan
facility: Site JP00004
state: Tokyo
city: Koto-ku
country: Japan
facility: Site JP00007
state: Tokyo
city: Fukuoka
country: Japan
facility: Site JP00006
city: Niigata
country: Japan
facility: Site JP00001
city: Okayama
country: Japan
facility: Site JP00002
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
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.