NCT07815665 · Summit Therapeutics
A Study of Ivonescimab in Combination With Enfortumab Vedotin vs Pembrolizumab in Combination With Enfortumab Vedotin in Metastatic Urothelial Carcinoma
(HARMONi-GU1)
What this study is about
A randomly assigned, where both patients and doctors know the treatment given, conducted at multiple hospitals, 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)
View original scientific description
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)
Interventions
DRUG
Ivonescimab Dose 1
First ivonescimab dose to be tested in Phase 2
DRUG
enfortumab vedotin (EV)
Standard of care therapy
DRUG
Pembrolizumab
200 mg
DRUG
Ivonescimab Dose 2
Second Ivonescimab dose to be tested in Phase 2 part of the study
DRUG
Ivonescimab RP3D
Recommended Phase 3 dose of Ivonescimab after Phase 2 data analysis
Primary outcome measures
Phase 2 Primary Outcome Measure
Time frame: 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
Time frame: From first dose until approximately 30 days after the last study treatment, assessed up to 3 years
Number of participants with clinical laboratory abnormalities
Phase 2 Primary Outcome measure
Time frame: 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 2 Primary Outcome Measure
Time frame: From first dose until end of treatment, assessed up to 3 years
PK characteristics: ivonescimab serum concentration profiles
Phase 3 Primary Outcome Measure
Time frame: 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)
Phase 3 Primary Outcome Measure
Time frame: From date of randomization until the end of study, assessed up to 4 years
Overall Survival (OS)
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 18 years and older
- 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.
Where
- Phoenix, Arizona
- Los Angeles, California
- Washington D.C., District of Columbia
- Jacksonville, Florida
- Rochester, Minnesota
- Nashville, Tennessee
- Spokane, Washington
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 11, 2026 · Source of record for eligibility and locations