Patients with locally advanced or metastatic urothelial cancer. MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10046723 Term: Urothelial carcinoma ureter System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10046728 Term: Urothelial carcinoma urethra System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification
Conditions
Sponsors
Seattle Genetics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically documented urothelial (previously known as transitional cell) carcinoma (squamous differentiation or mixed cell types allowed). • Metastatic disease or locally advanced disease that is not resectable. • Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. • Must be one of the following: a. Platinum-treated (Cohort 1): Patients who received prior treatment with platinumcontaining chemotherapy defined as those who received platinum in the adjuvant/neoadjuvant setting and had recurrent or progressive disease within 12 months of completion OR received treatment with platinum in the locally advanced (defined as unresectable with curative intent) or metastatic setting; OR b.Platinum-naïve and cisplatin ineligible (Cohort 2): Patients who have not received prior treatment with platinum-containing or other chemotherapy in the locally advanced or metastatic setting and are ineligible for treatment with cisplatin at time of enrollment due to one of the following: ECOG performance status score of 2; impaired renal function (defined as creatinine clearance [CrCl] =30 and =65 years) yes F.1.3.1 Number of subjects for this age range 180
Exclusion criteria
Exclusion criteria: • Ongoing sensory or motor neuropathy Grade =2. • Active central nervous system (CNS) metastases. • Ongoing clinically significant toxicity (Grade 2 or higher) associated with prior treatment (including systemic therapy, radiotherapy or surgery). Patients with = Grade 2 hypothyroidism or panhypopituitarism related to treatment with PD-1 and PD-L1 inhibitors may be enrolled. Patients on hormone replacement therapy may be enrolled if on a stable dose. Patients with = Grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Patients with immunotherapy related myocarditis, colitis, uveitis, or pneumonitis are excluded. Patients with other immunotherapy related adverse events requiring high doses of steroids (>20 mg/day of prednisone or equivalent) are excluded. • Prior enrollment in an enfortumab vedotin study or prior treatment with monomethyl auristatin E (MMAE) based antibody-drug conjugates (ADCs).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the antitumor activity of single-agent enfortumab vedotin as measured by confirmed ORR in patients with locally advanced or metastatic urothelial cancer who have previously received systemic therapy with a CPI and either previously received platinum-containing chemotherapy or are platinum-naïve and cisplatin-ineligible;Secondary Objective: ? To assess DOR ? To assess disease control rate (DCR) ? To assess PFS ? To assess OS ? To assess the safety and tolerability of enfortumab vedotin ? To assess the pharmacokinetics (PK) of enfortumab vedotin ? To assess the incidence of antitherapeutic antibodies (ATA);Primary end point(s): The primary endpoint of this study is the confirmed Objective Response Rate (ORR) per IRF. The ORR is defined as the proportion of patients with confirmed CR or PR according to RECIST Version 1.1 . Patients who do not have at least 2 (initial response and confirmation scan) post-baseline response assessments as described in Section 7.2 of the protocol will be counted as non-responders.;Timepoint(s) of evaluation of this end point: According to protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoints are: - Duration of Response (DOR); - Disease Control Rate at Week 16 (DCR16); - Progression-free Survival (PFS); - Overall Survival (OS); -ORR per investigator.;Timepoint(s) of evaluation of this end point: According to protocol. | — |
Countries
France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Spain, United States
Contacts
Public ContactSeattle Genetics Trial Information
Seattle Genetics Trial Information Support
Outcome results
None listed