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. * 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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
800
Research Site
Phoenix, Arizona, United States
NOT_YET_RECRUITINGResearch Site
Los Angeles, California, United States
RECRUITINGResearch Site
Washington D.C., District of Columbia, United States
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
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Second Ivonescimab dose to be tested in Phase 2 part of the study
Recommended Phase 3 dose of Ivonescimab after Phase 2 data analysis
Research Site
Jacksonville, Florida, United States
NOT_YET_RECRUITINGResearch Site
Rochester, Minnesota, United States
NOT_YET_RECRUITINGResearch Site
Nashville, Tennessee, United States
NOT_YET_RECRUITINGResearch Site
Spokane, Washington, United States
RECRUITINGPhase 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