A Study of Ivonescimab in Combination With Enfortumab Vedotin vs Pembrolizumab in Combination With Enfortumab Vedotin in Metastatic Urothelial Carcinoma
HARMONi-GU1
A Randomized Phase 2/3 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)
1 other identifier
interventional
800
1 country
7
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2026
Typical duration for phase_2
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 31, 2026
CompletedStudy Start
First participant enrolled
September 10, 2026
CompletedFirst Posted
Study publicly available on registry
September 11, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2030
September 11, 2026
September 1, 2026
4.1 years
August 31, 2026
September 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Phase 2 Primary Outcome Measure
Adverse events (AEs) as characterized by type, incidence, severity, seriousness, and relationship to study treatment
Through 90 days after the last study treatment
Phase 2 Primary Outcome Measure
Number of participants with clinical laboratory abnormalities
From first dose until approximately 30 days after the last study treatment, assessed up to 3 years
Phase 2 Primary Outcome measure
Objective response rate (ORR)
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
Phase 2 Primary Outcome Measure
PK characteristics: ivonescimab serum concentration profiles
From first dose until end of treatment, assessed up to 3 years
Phase 3 Primary Outcome Measure
PFS per RECIST v1.1 by Independent Radiology Review Committee (IRRC)
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.
Phase 3 Primary Outcome Measure
Overall Survival (OS)
From date of randomization until the end of study, assessed up to 4 years
Secondary Outcomes (10)
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
Phase 2 Secondary Outcome Measure
From date of randomization until the end of study, assessed up to 4 years
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
Phase 2 Secondary Outcome Measure
From time of initiation of first dose to 30 days after end of treatment.
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
- +5 more secondary outcomes
Study Arms (4)
Phase 2: Arm A
EXPERIMENTALIvonescimab Dose 1 + EV
Phase 2: Arm B
EXPERIMENTALIvonescimab Dose 2 + EV
Phase 3: Arm 1
EXPERIMENTALIvonescimab RP3D (recommended Phase 3 dose) + EV
Phase 3: Arm 2
ACTIVE COMPARATORPembrolizumab 200 mg + EV
Interventions
Standard of care therapy
Second Ivonescimab dose to be tested in Phase 2 part of the study
Recommended Phase 3 dose of Ivonescimab after Phase 2 data analysis
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Research Site
Phoenix, Arizona, 85054, United States
Research Site
Los Angeles, California, 90067, United States
Research Site
Washington D.C., District of Columbia, 20010, United States
Research Site
Jacksonville, Florida, 32224, United States
Research Site
Rochester, Minnesota, 55905, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Spokane, Washington, 99208, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 31, 2026
First Posted
September 11, 2026
Study Start
September 10, 2026
Primary Completion (Estimated)
October 31, 2030
Study Completion (Estimated)
December 31, 2030
Last Updated
September 11, 2026
Record last verified: 2026-09