A Study of Ivonescimab in Combination With Enfortumab Vedotin vs Pembrolizumab in Combination With Enfortumab Vedotin in Metastatic Urothelial Carcinoma

NCT07815665
clinicaltrials.gov
Phase
Phase 2/Phase 3
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Recruitment status
Recruiting
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Participants
800
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Lead sponsor
Summit Therapeutics
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Start date
2026-09-10
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Number of sites
7
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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)
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Acronym
HARMONi-GU1
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Short title
A Study of Ivonescimab in Combination With Enfortumab Vedotin vs Pembrolizumab in Combination With Enfortumab Vedotin in Metastatic Urothelial Carcinoma
clinicaltrials.gov
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)
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 2/Phase 3
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Study type
Interventional
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Completion date
2030-12-31
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First posted
2026-09-11
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Registry last updated
2026-09-11
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Primary completion date
2030-10-31
clinicaltrials.gov
Start date
2026-09-10
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Participants
800
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Participant count basis
Estimated
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Planned participants
800
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Protocol amendments
0
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Randomisation ratio
1:1
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Number of sites
7
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Summit Therapeutics
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07815665
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ClinicalTrials.gov ID
NCT07815665
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Phase 2 Primary Outcome Measure

    Timeframe: Through 90 days after the last study treatment

    Adverse events (AEs) as characterized by type, incidence, severity, seriousness, and relationship to study treatment

  2. Phase 2 Primary Outcome Measure

    Timeframe: From first dose until approximately 30 days after the last study treatment, assessed up to 3 years

    Number of participants with clinical laboratory abnormalities

  3. Phase 2 Primary Outcome measure

    Timeframe: 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)

  4. Phase 2 Primary Outcome Measure

    Timeframe: From first dose until end of treatment, assessed up to 3 years

    PK characteristics: ivonescimab serum concentration profiles

  5. Phase 3 Primary Outcome Measure

    Timeframe: 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)

  6. Phase 3 Primary Outcome Measure

    Timeframe: From date of randomization until the end of study, assessed up to 4 years

    Overall Survival (OS)

  1. Phase 2 Secondary Outcome Measure

    Timeframe: 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 investigator

  2. Phase 2 Secondary Outcome Measure

    Timeframe: From date of randomization until the end of study, assessed up to 4 years

    Overall Survival (OS)

  3. Phase 2 Secondary Outcome Measure

    Timeframe: 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

    Duration of Response (DOR)

  4. Phase 2 Secondary Outcome Measure

    Timeframe: From time of initiation of first dose to 30 days after end of treatment.

    Incidence of anti-drug antibodies (ADA) against ivonescimab

  5. Phase 3 Secondary Outcome Measure

    Timeframe: 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

    ORR

  6. Phase 3 Secondary Outcome Measure

    Timeframe: 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

    DOR

  7. Phase 3 Secondary Outcome Measure

    Timeframe: Through 90 days after the last study treatment

    AEs as characterized by type, incidence, severity, seriousness, and relationship to study treatment

  8. Phase 3 Secondary Outcome Measure

    Timeframe: From first dose until approximately 30 days after the last study treatment, assessed up to 3 years

    Number of participants with clinical laboratory abnormalities

  9. Phase 3 Secondary Outcome Measure

    Timeframe: From first dose until end of treatment, assessed up to 3 years

    PK characteristics: ivonescimab serum concentration profiles

  10. Phase 3 Secondary Outcome Measure

    Timeframe: From time of initiation of first dose to 30 days after end of treatment

    Incidence of ADA against ivonescimab

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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.
Sources for eligibility
clinicaltrials.gov

  • Research SitePhoenix, United StatesNot yet recruiting
  • Research SiteLos Angeles, United StatesRecruiting
  • Research SiteWashington D.C., United StatesNot yet recruiting
  • Research SiteJacksonville, United StatesNot yet recruiting
  • Research SiteRochester, United StatesNot yet recruiting
  • Research SiteNashville, United StatesNot yet recruiting
  • Research SiteSpokane, United StatesRecruiting
Sources for sites
clinicaltrials.gov

Related records

Drugs (3)

Lead sponsors (1)

Conditions (1)

Targets (17)