Metastatic Urothelial Cancer
Conditions
Keywords
Urothelial Carcinoma, Enfortumab vedotin, ASG-22CE, Padcev, ASG-22ME, Metastatic Urothelial Cancer
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.
Interventions
DRUGEnfortumab 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.
Sponsors
Seagen Inc.
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK parameter for MMAE: t1/2 | 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 | T1/2 will be derived from the PK blood samples collected. |
| PK parameter for MMAE: AUC0-7 | 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 | AUC0-7 will be derived from the PK blood samples collected. |
| PK parameter for TAb: Terminal or apparent terminal half-life (t1/2) | 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 | T1/2 will be derived from the PK blood samples collected. |
| PK parameter for ADC: t1/2 | 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 | T1/2 will be derived from the PK blood samples collected. |
| Safety assessed by incidence of adverse events | Up to 12 months | 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. |
| Safety assessed by laboratory tests: Hematology | Up to 12 months | Descriptive statistics will be used to summarize results. |
| Safety assessed by laboratory tests: Biochemistry | Up to 12 months | Descriptive statistics will be used to summarize results. |
| Safety assessed by laboratory tests: Urinalysis | Up to 12 months | Descriptive statistics will be used to summarize results. |
| Safety assessed by laboratory tests: Coagulation studies | Up to 12 months | Descriptive statistics will be used to summarize results. |
| Number of participants with vital sign abnormalities and/or adverse events | Up to 12 months | Number of participants with potentially clinically significant vital sign values. |
| Safety assessed by electrocardiogram (ECG) | Up to 12 months | 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. |
| Pharmacokinetics (PK) parameter for total antibody (TAb): Concentration at the end of infusion (CEOI) | 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 | CEOI will be derived from the PK blood samples collected. |
| Pharmacokinetics (PK) parameter for antibody drug conjugate (ADC): CEOI | 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 | CEOI will be derived from the PK blood samples collected. |
| Pharmacokinetics (PK) parameter for Monomethyl Auristatin E (MMAE): CEOI | 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 | CEOI will be derived from the PK blood samples collected. |
| PK parameter for TAb: Maximum observed concentration (Cmax) | 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 | Cmax will be derived from the PK blood samples collected. |
| PK parameter for ADC: Cmax | 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 | Cmax will be derived from the PK blood samples collected. |
| PK parameter for MMAE: Cmax | 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 | Cmax will be derived from the PK blood samples collected. |
| PK parameter for TAb: Trough concentration (Ctrough) | 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 | Ctrough will be derived from the PK blood samples collected. |
| PK parameter for ADC: Ctrough | 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 | Ctrough will be derived from the PK blood samples collected. |
| PK parameter for MMAE: Ctrough | 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 | Ctrough will be derived from the PK blood samples collected. |
| PK parameter for TAb: Time to maximum concentration (Tmax) | 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 | Tmax will be derived from the PK blood samples collected. |
| PK parameter for ADC: Tmax | 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 | Tmax will be derived from the PK blood samples collected. |
| PK parameter for MMAE: Tmax | 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 | Tmax will be derived from the PK blood samples collected. |
| PK parameter for TAb: Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7) | 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 | AUC0-7 will be derived from the PK blood samples collected. |
| PK parameter for ADC: AUC0-7 | 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 | AUC0-7 will be derived from the PK blood samples collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Up to 12 months | Defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) |
| Disease Control Rate | Up to 12 months | Defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD) |
| Incidence of Anti-Drug Antibody (ADA) | Up to 12 months | Blood samples for anti-drug antibody (ADA) analysis will be collected. |
Countries
Japan
Outcome results
None listed