Metastatic Urothelial CarcinomaPhase 2/3HARMONi-GU1NCT07815665
A Study of Ivonescimab in Combination With Enfortumab Vedotin vs Pembrolizumab in Combination With Enfortumab Vedotin in Metastatic Urothelial Carcinoma
A Phase 2/3 study testing Ivonescimab Dose 1, enfortumab vedotin (EV) and Pembrolizumab in people with Metastatic Urothelial Carcinoma and Metastatic Urothelial Carcinoma (UC), run by Summit Therapeutics at 7 sites in United States.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Urothelial Carcinoma, Metastatic Urothelial Carcinoma (UC)
- What is being tested?
- Ivonescimab Dose 1, enfortumab vedotin (EV) and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 800 participants
- Where
- 7 sitesUnited States
- Study dates
- 10 Sep 2026to 31 Dec 2030
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Not yet recruiting
Research Site
Jacksonville, Florida, 32224
- Recruiting
Research Site
Los Angeles, California, 90067
- Not yet recruiting
Research Site
Nashville, Tennessee, 37203
- Not yet recruiting
Research Site
Phoenix, Arizona, 85054
- Not yet recruiting
Research Site
Rochester, Minnesota, 55905
- Recruiting
Research Site
Spokane, Washington, 99208
- Not yet recruiting
Research Site
Washington D.C., District of Columbia, 20010
About this study
Official title: 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)
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)
Read the 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
- Being tested
- Ivonescimab Dose 1, enfortumab vedotin (EV), Pembrolizumab, Ivonescimab Dose 2, Ivonescimab RP3D
- Keywords
- LA/mUC, Ivonescimab
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivonescimab Dose 1Drug
First ivonescimab dose to be tested in Phase 2
enfortumab vedotin (EV)Drug
Standard of care therapy
PembrolizumabDrug
200 mg
Ivonescimab Dose 2Drug
Second Ivonescimab dose to be tested in Phase 2 part of the study
Ivonescimab RP3DDrug
Recommended Phase 3 dose of Ivonescimab after Phase 2 data analysis
| Study group | Role | What they receive |
|---|---|---|
| Phase 2: Arm A | Experimental | Ivonescimab Dose 1 + EV Receives: Drug: Ivonescimab Dose 1; Drug: enfortumab vedotin (EV) |
| Phase 2: Arm B | Experimental | Ivonescimab Dose 2 + EV Receives: Drug: enfortumab vedotin (EV); Drug: Ivonescimab Dose 2 |
| Phase 3: Arm 1 | Experimental | Ivonescimab RP3D (recommended Phase 3 dose) + EV Receives: Drug: enfortumab vedotin (EV); Drug: Ivonescimab RP3D |
| Phase 3: Arm 2 | Active comparator | Pembrolizumab 200 mg + EV Receives: Drug: enfortumab vedotin (EV); Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 2 Primary Outcome Measure
Adverse events (AEs) as characterized by type, incidence, severity, seriousness, and relationship to study treatment
Measured: Through 90 days after the last study treatment
Phase 2 Primary Outcome Measure
Number of participants with clinical laboratory abnormalities
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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)
Measured: From date of randomization until the end of study, assessed up to 4 years
Secondary outcomes (10)
Phase 2 Secondary Outcome Measure
PFS per RECIST v1.1 by investigator
Measured: 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)
Measured: From date of randomization until the end of study, assessed up to 4 years
Phase 2 Secondary Outcome Measure
Duration of Response (DOR)
Measured: 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
Measured: From time of initiation of first dose to 30 days after end of treatment.
Phase 3 Secondary Outcome Measure
ORR
Measured: 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
Measured: 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
Measured: Through 90 days after the last study treatment
Phase 3 Secondary Outcome Measure
Number of participants with clinical laboratory abnormalities
Measured: 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
Measured: From first dose until end of treatment, assessed up to 3 years
Phase 3 Secondary Outcome Measure
Incidence of ADA against ivonescimab
Measured: From time of initiation of first dose to 30 days after end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2026
- Study start10 Sep 2026 (estimated)
- Primary completion31 Oct 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Urothelial CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Summit Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07815665
- Sponsor's protocol ID
- SMT112-3008
- Acronym
- HARMONi-GU1
- Status last verified
- Sep 2026
- First submitted
- 31 Aug 2026
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Not provided
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT07815665
- Acronym / sponsor ID
- HARMONi-GU1 / SMT112-3008
- Keywords
- LA/mUC, Ivonescimab
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- Summit TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 10 Sep 2026 (estimated)
- Primary completion
- 31 Oct 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 11 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 2: Arm A | Experimental | Drug: Ivonescimab Dose 1, Drug: enfortumab vedotin (EV)Ivonescimab Dose 1 + EV |
| Phase 2: Arm B | Experimental | Drug: enfortumab vedotin (EV), Drug: Ivonescimab Dose 2Ivonescimab Dose 2 + EV |
| Phase 3: Arm 1 | Experimental | Drug: enfortumab vedotin (EV), Drug: Ivonescimab RP3DIvonescimab RP3D (recommended Phase 3 dose) + EV |
| Phase 3: Arm 2 | Active comparator | Drug: enfortumab vedotin (EV), Drug: PembrolizumabPembrolizumab 200 mg + EV |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ivonescimab Dose 1First ivonescimab dose to be tested in Phase 2 | Drug | Phase 2: Arm A |
| enfortumab vedotin (EV)Standard of care therapy | Drug | Phase 2: Arm A, Phase 2: Arm B, Phase 3: Arm 1, Phase 3: Arm 2 |
| Pembrolizumab200 mg | Drug | Phase 3: Arm 2 |
| Ivonescimab Dose 2Second Ivonescimab dose to be tested in Phase 2 part of the study | Drug | Phase 2: Arm B |
| Ivonescimab RP3DRecommended Phase 3 dose of Ivonescimab after Phase 2 data analysis | Drug | Phase 3: Arm 1 |
Primary outcome
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)
10 secondary outcomes
Phase 2 Secondary 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
Phase 2 Secondary Outcome Measure
Time frame: From date of randomization until the end of study, assessed up to 4 years
Phase 2 Secondary 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
Phase 2 Secondary Outcome Measure
Time frame: From time of initiation of first dose to 30 days after end of treatment.
Phase 3 Secondary 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
Phase 3 Secondary 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
Phase 3 Secondary Outcome Measure
Time frame: Through 90 days after the last study treatment
Phase 3 Secondary Outcome Measure
Time frame: From first dose until approximately 30 days after the last study treatment, assessed up to 3 years
Phase 3 Secondary Outcome Measure
Time frame: From first dose until end of treatment, assessed up to 3 years
Phase 3 Secondary Outcome Measure
Time frame: From time of initiation of first dose to 30 days after end of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2026.
- Individual participant dataSharing planned: Undecided. Not provided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ivonescimab Dose 1, enfortumab vedotin (EV) and Pembrolizumab in people with Metastatic Urothelial Carcinoma and Metastatic Urothelial Carcinoma (UC), run by Summit Therapeutics at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Summit Clinical Trial Information (1-833-256-0522, medicalinformation@smmttx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 2 Primary Outcome Measure (time frame: Through 90 days after the last study treatment). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.