An open-label clinical trial evaluating enfortumab vedotin in combination with pembrolizumab versus chemotherapy alone in previously untreated locally advanced or metastatic 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: 10046723Term: Urothelial carcinoma ureter Class: 10029104; MedDRA version: 20.0Level: LLTClassification code: 10046728Term: Urothelial carcinoma urethra Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-503421-19-00
• Lead Sponsor: Seagen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-09-25
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1422

Inclusion Criteria

1. Subjects must have histologically documented, unresectable locally advanced or metastatic urothelial carcinoma (ie, cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with squamous or sarcomatoid differentiation or mixed cell types are eligible., 4a)ii. ECOG or WHO performance status of 2 (refer to Inclusion 7 for additional criteria for ECOG 2 subjects);, 4a)iii. NCI CTCAE Grade =2 audiometric hearing loss;, 4a)iv. NYHA Class III heart failure., 5. Subjects must be age 18 years or older., 6. Archival tumor tissue comprising muscle-invasive urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma must be provided for PD-L1 testing prior to randomization. If adequate archival tumor sample is not available, or evaluable, a new biopsy sample may be performed., 7. Subjects must have an ECOG Performance Status score of 0, 1, or 2:, 7a. Subjects with ECOG performance status of 2 must additionally meet the following criteria:, 7a)i. Hemoglobin =10 g/dL;, 7a)ii. GFR =50 mL/min;, 7a)iii. May not have NYHA Class III heart failure., 2.Subjects must have measurable disease by investigator assessment according to RECIST v1.1.:, 8. Subjects must have adequate hematologic and organ function as defined by the baseline laboratory values in Table 3 (see protocol)., 9. Female subjects of childbearing potential must meet the following conditions:, 9a. Agree not to try to become pregnant during the study and for at least 6 months after the final dose of study drug., 9b. Must have a negative urine or serum pregnancy test (minimum sensitivity of 25 mIU/mL or equivalent units of beta human chorionic gonadotropin [ß-hCG]) within 1 day prior to administration of study drug. Female subjects with false positive results and documented verification of negative pregnancy status are eligible for participation., 9c. If heterosexually active, must consistently use highly effective methods of birth control, with a failure rate of less than 1% starting at screening, throughout the study period, and for at least 6 months after the final dose of study drug., 9d. Female subjects must agree not to breastfeed or donate ova starting at screening and throughout the study period, and for at least 6 months after the final dose of study drug., 10. Male subjects who can father children, must meet the following conditions:, 10a. Must not donate sperm starting at screening and throughout the study period, and for at least 6 months after the final dose of study drug (see protocol);, 10b. Must consistently use highly effective methods of birth control, with a failure rate of less than 1% starting at screening and continue throughout study period and for at least 6 months after the final dose of study drug;, 10c. Male subjects with a pregnant or breastfeeding partner(s) must consistently use one of 2 contraception options for preventing secondary exposure to seminal fluid for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for at least 6 months after the final dose of study drug., 2a. Subjects with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy., 11. Subjects must provide written informed consent., 3. Subjects must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:, 3a. Subjects that re

Exclusion Criteria

1. Subjects who have previously received enfortumab vedotin or other MMAE-based ADCs., 18. Subjects with known severe (= Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin; any pembrolizumab excipient contained in the drug formulations of pembrolizumab; the platinum agent selected by the investigator for study treatment; the gemcitabine., 19. Subjects with active keratitis or corneal ulcerations. Subjects with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator, 2. Subjects who have received prior treatment with a PD-(L)-1 inhibitor for any malignancy, including earlier stage UC, defined as a PD-1 inhibitor or PD-L1 inhibitor (see protocol)., 20. History of autoimmune disease that has required systemic treatment in the past 2 years (see protocol):, 3. Subjects who have previously received any prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor (see protocol)., 4. Subjects who have received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks prior to first dose of study treatment (see protocol)., 5. Subjects with uncontrolled diabetes (see protocol)., 6. Subjects with an estimated life expectancy <12 weeks., 7. Subjects with ongoing sensory or motor neuropathy Grade 2 or higher., 8. Subjects with active CNS metastases. Subjects with treated CNS metastases are permitted on study if all of the following are true:, 10. Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted., 9. Subjects with ongoing clinically significant toxicity associated with prior treatment (including radiotherapy or surgery) that has not resolved to = Grade 1 or returned to baseline., 8a) CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis;, 8b) the subject is on a stable dose of =10 mg/day of prednisone or equivalent for at least 2 weeks (if requiring steroid treatment);, 8c) subject does not have leptomeningeal disease., 20a. Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed., 20b. Brief (<7 days) use of systemic corticosteroids is allowed when use is considered standard of care., 20c. Subjects with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy will not be excluded., 20d. Subjects requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded., 20e. Subjects with hypothyroidism that is stable with hormone replacement or Sjögren's syndrome will not be excluded., 21. Subjects with a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan., 11. Subjects who have known active hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] detected) infection, testing for hepatitis B and hepatitis C is required if mandated by country health authority. Subjects who hav

Study & Design

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