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.
633 studies on the registry are indexed under Carcinoma, Transitional Cell; 181 are open to participants now.
This study's planned enrollment of 800 is above the median of 50 across 500 interventional studies indexed under Carcinoma, Transitional Cell.
Browse Carcinoma, Transitional Cell studies →Summit Therapeutics is the lead sponsor of 13 studies on the registry; 4 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Start is estimated for Sep 2026; primary completion for Oct 2030, 49 months later.
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