A study of enfortumab vedotin alone or in combination with other anticancer therapies for the treatment of urothelial cancer

Phase 1

• Conditions: rothelial cancer; MedDRA version: 20.0Level: LLTClassification code: 10046714Term: Urothelial carcinoma bladder Class: 10029104; MedDRA version: 20.0Level: LLTClassification code: 10046728Term: Urothelial carcinoma urethra Class: 10029104; MedDRA version: 20.0Level: LLTClassification code: 10046723Term: Urothelial carcinoma ureter Class: 10029104; MedDRA version: 21.1Level: LLTClassification code: 10077840Term: Urothelial cancer of renal pelvis Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-503391-24-00
• Lead Sponsor: Seagen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-08-21
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 355

Inclusion Criteria

Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Histologically documented la/mUC, including squamous differentiation or mixed cell types., Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months, Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the following: Glomerular filtration rate (GFR) <60 mL/min and =30 mL/min, ECOG performance status of 2, NCI CTCAE Version 4.03 Grade =2 hearing loss, New York Heart Association (NYHA) Class III heart failure. No prior systemic treatment for locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based therapy within 12 months prior to randomization., Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Histologically confirmed MIBC with predominant >50% urothelial histology: Cohorts H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1 disease on imaging. Mixed cell types are eligible if urothelial cancer is predominant (>50%); Participants with plasmacytoid and/or neuroendocrine tumors are ineligible regardless of component percentage. Urothelial tumors not originating in the bladder (eg, upper tract tumors, urethral tumors) are ineligible., Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Must be cisplatin-ineligible, Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment, chemoradiation, or radiation therapy for MIBC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-MIBC; Cohort J: Eligible for pembrolizumab., Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: ECOG performance status of 0, 1, or 2., Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Anticipated life expectancy of =3 months., Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Tumor samples with an associated pathology report from the diagnostic transurethral resection of a bladder tumor done 90 days prior to the first dose of study treatment must be available prior to enrollment and determined to be sufficient for pathology review and biomarker analysis., Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Participants must be deemed eligible for RC+PLND., Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2: Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin =10 g/dL, GFR =50 mL/min, may not have NYHA Class III heart failure, Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K:Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K Combination Arm)., Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy and no prior treatment for la/mUC, or have disease progression following at least 1 platinum

Exclusion Criteria

la/mUC - Cohorts A, B, D, E, F, G, and K: Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2 inhibitor, except Cohort F., MIBC - Cohorts H, J, and L: Received any prior treatment with a CPI, MIBC - Cohorts H, J, and L: Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists., MIBC - Cohorts H, J, and L: For participants in Cohort H, evidence of nodal disease on imaging. For participants in Cohort L, =N2 nodal disease on imaging., MIBC - Cohorts H, J, and L: Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC., MIBC - Cohorts H, J, and L: Ongoing sensory or motor neuropathy Grade 2 or higher., MIBC - Cohorts H, J, and L: Conditions requiring high doses of steroids or other immunosuppressive medications., MIBC - Cohorts H, J, and L: Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial cancer, MIBC - Cohorts H, J, and L: Participants with a history of another invasive malignancy within 3 years before first dose of study drug., la/mUC - Cohorts A, B, D, E, F, G, and K: Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonists, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F)., la/mUC - Cohorts A, B, D, E, F, G, and K: Ongoing sensory or motor neuropathy Grade 2 or higher., la/mUC - Cohorts A, B, D, E, F, G, and K: Active central nervous system (CNS) metastases., la/mUC - Cohorts A, B, D, E, F, G, and K: Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery)., la/mUC - Cohorts A, B, D, E, F, G, and K: Conditions requiring high doses of steroids or other immunosuppressive medications., la/mUC - Cohorts A, B, D, E, F, G, and K: Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs)., la/mUC - Cohorts A, B, D, E, F, G, and K: Uncontrolled diabetes mellitus., MIBC - Cohorts H, J, and L: Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive bladder cancer.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified