2023-503421-19-00
Active, not recruiting
Phase 3
C5701003 - An open-label, randomized, controlled phase 3 study of enfortumab vedotin in combination with pembrolizumab versus chemotherapy alone in previously untreated locally advanced or metastatic urothelial cancer
Overview
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- Seagen Inc.
- Enrollment
- 703
- Locations
- 57
- Primary Endpoint
- 1. PFS per RECIST v1.1 by BICR.
Overview
Brief Summary
- To compare PFS between the experimental arm (enfortumab vedotin +pembrolizumab [Arm A] and the control arm (gemcitabine + cisplatin or carboplatin [Arm B]) by blinded independent central review (BICR).
- To compare overall survival (OS) between the experimental arm (Arm A) and the control arm (Arm B).
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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.
- •Subjects must be age 18 years or older.
- •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.
- •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;
Exclusion Criteria
- •Subjects who have previously received enfortumab vedotin or other MMAE-based ADCs.
- •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.
- •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
- •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).
- •History of autoimmune disease that has required systemic treatment in the past 2 years (see protocol):
- •Subjects who have previously received any prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor (see protocol).
- •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).
- •Subjects with uncontrolled diabetes (see protocol).
- •Subjects with an estimated life expectancy <12 weeks.
- •Subjects with ongoing sensory or motor neuropathy Grade 2 or higher.
Outcomes
Primary Outcomes
1. PFS per RECIST v1.1 by BICR.
1. PFS per RECIST v1.1 by BICR.
2. OS.
2. OS.
Secondary Outcomes
- 4. PFS per RECIST v1.1 by investigator assessment.
- 1. ORR per RECIST v1.1 by BICR.
- 2. TTPP.
- 3. Mean change from baseline in worst pain at Week 26.
- 5. ORR per RECIST v1.1 by investigator assessment.
- 6. DOR per RECIST v1.1 by BICR.
- 7. DOR per RECIST v1.1 by investigator assessment.
- 8. DCR per RECIST v1.1 by BICR.
- 9. DCR per RECIST v1.1 by investigator assessment.
- 10. Mean scores and change from baseline of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 (QLQ-C30), and EuroQOL 5-dimensions (EQ-5D-5L), visual analogue scale (VAS), and utility scores.
- 11. Type, incidence, relatedness, severity and seriousness of AEs.
- 12. Type, incidence and severity of laboratory abnormalities.
- 13. Treatment discontinuation rate due to AEs.
Investigators
Seagen Trial Information Support
Scientific
Seagen Inc.
Study Sites (57)
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