A Phase 2/3 interventional study of Ivonescimab Dose 1 and enfortumab vedotin (EV) in Metastatic Urothelial Carcinoma and Metastatic Urothelial Carcinoma (UC), sponsored by Summit Therapeutics. Recruiting at 7 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-11.
Sponsored by Summit Therapeutics · Phase 2/3, Interventional, and Treatment
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)
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.
Exclusion Criteria:
Ivonescimab Dose 1 + EV
Drug: Ivonescimab Dose 1 · Drug: enfortumab vedotin (EV)
Ivonescimab Dose 2 + EV
Drug: enfortumab vedotin (EV) · Drug: Ivonescimab Dose 2
Ivonescimab RP3D (recommended Phase 3 dose) + EV
Drug: enfortumab vedotin (EV) · Drug: Ivonescimab RP3D
Pembrolizumab 200 mg + EV
Drug: enfortumab vedotin (EV) · Drug: Pembrolizumab
First ivonescimab dose to be tested in Phase 2
Standard of care therapy
200 mg
Second Ivonescimab dose to be tested in Phase 2 part of the study
Recommended Phase 3 dose of Ivonescimab after Phase 2 data analysis
Phase 2 Primary Outcome Measure
Adverse events (AEs) as characterized by type, incidence, severity, seriousness, and relationship to study treatment
Time frame: Through 90 days after the last study treatment
Phase 2 Primary Outcome Measure
Number of participants with clinical laboratory abnormalities
Time frame: 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)
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
Phase 2 Primary Outcome Measure
PK characteristics: ivonescimab serum concentration profiles
Time frame: 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)
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.
Phase 3 Primary Outcome Measure
Overall Survival (OS)
Time frame: From date of randomization until the end of study, assessed up to 4 years
Phase 2 Secondary Outcome Measure
PFS per RECIST v1.1 by investigator
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
Phase 2 Secondary Outcome Measure
Overall Survival (OS)
Time frame: From date of randomization until the end of study, assessed up to 4 years
Phase 2 Secondary Outcome Measure
Duration of Response (DOR)
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
Phase 2 Secondary Outcome Measure
Incidence of anti-drug antibodies (ADA) against ivonescimab
Time frame: From time of initiation of first dose to 30 days after end of treatment.
Phase 3 Secondary Outcome Measure
ORR
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
Phase 3 Secondary Outcome Measure
DOR
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
Phase 3 Secondary Outcome Measure
AEs as characterized by type, incidence, severity, seriousness, and relationship to study treatment
Time frame: Through 90 days after the last study treatment
Phase 3 Secondary Outcome Measure
Number of participants with clinical laboratory abnormalities
Time frame: From first dose until approximately 30 days after the last study treatment, assessed up to 3 years
Phase 3 Secondary Outcome Measure
PK characteristics: ivonescimab serum concentration profiles
Time frame: From first dose until end of treatment, assessed up to 3 years
Phase 3 Secondary Outcome Measure
Incidence of ADA against ivonescimab
Time frame: From time of initiation of first dose to 30 days after end of treatment
Plan to share: Undecided — Not provided
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Summit Therapeutics