Metastatic Urothelial Carcinoma, Metastatic Urothelial Carcinoma (UC)
Conditions
Keywords
LA/mUC, Ivonescimab
Brief summary
A Randomized, Open-Label, Multicenter, Phase 2/3 Clinical Study of Ivonescimab in Combination with Enfortumab Vedotin vs Pembrolizumab in Combination with Enfortumab Vedotin in Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma (HARMONi-GU1)
Detailed description
This Phase 2/3 study will be conducted in 2 parts. The first part is a Phase 2 randomized, open-label, 2 dose levels, parallel-arm study with the primary objective to evaluate safety and identify the recommended Phase 3 dose (RP3D) of ivonescimab in combination with EV. The second part is a randomized, open-label Phase 3 study with the primary objective to evaluate the efficacy and safety of ivonescimab (RP3D) plus EV versus pembrolizumab plus EV in patients with previously untreated LA/mUC. For Phase 2 portion, patients will be randomized 1:1 to two arms consisting of 2 different dosages of ivonescimab. * Arm A: Ivonescimab Dose 1 + EV * Arm B: Ivonescimab Dose 2 + EV For Phase 3 portion, patients will be randomized 1:1 to the experimental arm (ivonescimab + EV) and the control arm (pembrolizumab + EV). * Arm 1 (experimental): Ivonescimab RP3D + EV * Arm 2 (SoC): Pembrolizumab 200 mg + EV
Interventions
DRUGIvonescimab Dose 1
First ivonescimab dose to be tested in Phase 2
Standard of care therapy
DRUGPembrolizumab
200 mg
DRUGIvonescimab Dose 2
Second Ivonescimab dose to be tested in Phase 2 part of the study
DRUGIvonescimab RP3D
Recommended Phase 3 dose of Ivonescimab after Phase 2 data analysis
Sponsors
Summit Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years and older * ECOG 0-1 * Life expectancy ≥ 6 months * Histologically documented unresectable LA/mUC (transitional cell carcinoma) of the bladder, renal pelvis, ureter, or urethra with ≥50% urothelial carcinoma component * No prior systemic therapy for LA/mUC * At least one measurable non-cerebral lesion according to RECIST v1.1 * Adequate organ function
Exclusion criteria
* Locally advanced disease that is resectable or suitable for local therapy with curative intent. * Tumors containing any small cell or neuroendocrine differentiation * Ongoing sensory or motor neuropathy Grade 2 or higher. * Radiographic findings consistent with a high risk of bleeding * History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction, extensive bowel resection within 6 months prior to first dose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 Primary Outcome Measure | Through 90 days after the last study treatment | Adverse events (AEs) as characterized by type, incidence, severity, seriousness, and relationship to study treatment |
| Phase 2 Primary Outcome measure | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years | Objective response rate (ORR) |
| Phase 3 Primary Outcome Measure | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years. | PFS per RECIST v1.1 by Independent Radiology Review Committee (IRRC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 Secondary Outcome Measure | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years | PFS per RECIST v1.1 by investigator |
| Phase 3 Secondary Outcome Measure | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years | ORR |
Countries
United States
Contacts
CONTACTSummit Clinical Trial Information
Outcome results
None listed