Transitional cell carcinoma Urothelial cancer
Conditions
Interventions
Enfortumab vedotin 1.25 mg/kg will be administered as an IV infusion over
approximately 30 minutes on
Day 1, 8, and 15 of each 28-day cycle.
Sponsors
Seattle Genetics, Inc.
Eligibility
Age
18 Years to 99 Years
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 = Grade 2 hearing loss. Patients who received platinum in the adjuvant/neoadjuvant setting and did not progress within12 months of completion will be considered platinum-naïve., • Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy., • Tumor tissue samples must be available for submission to the sponsor prior to study treatment., • Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1). , • An Eastern Cooperative Oncology Group (ECOG) PerformanceStatus score of
Exclusion criteria
Exclusion criteria: • Ongoing sensory or motor neuropathy Grade >=2., • Active central nervous system (CNS) metastases., • Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis., • 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 |
|---|---|
| Primary Endpoint * The primary efficacy endpoint of this study is ORR (confirmed CR or PR per Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1) as determined by an independent review facility (IRF) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints * DOR (confirmed CR or PR) per IRF * DCR16 (disease control rate [CR, PR or SD] at 16 weeks) per IRF * PFS per IRF * ORR per investigator assessment * DOR per investigator assessment * DCR16 per investigator assessment * PFS per investigator assessment * OS * Type, incidence, severity, seriousness, and relatedness of AEs * Laboratory abnormalities * Selected plasma or serum PK parameters of enfortumab vedotin, MMAE and total antibody (TAb) * Incidence of ATA to enfortumab vedotin Additional Endpoints * Biomarkers of biological and clinical activity, including Nectin-4 expression * Patient reported outcomes (PRO) per the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) * PRO per EuroQol 5-dimensions (EQ-5D), including health utility values, and visual analog scale | — |
Countries
Netherlands
Outcome results
None listed