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Purpose

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)

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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.

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 2: Arm A 		Ivonescimab Dose 1 + EV
  • Drug: Ivonescimab Dose 1
    First ivonescimab dose to be tested in Phase 2
  • Drug: enfortumab vedotin (EV)
    Standard of care therapy
Experimental
Phase 2: Arm B 		Ivonescimab Dose 2 + EV
  • Drug: enfortumab vedotin (EV)
    Standard of care therapy
  • Drug: Ivonescimab Dose 2
    Second Ivonescimab dose to be tested in Phase 2 part of the study
Experimental
Phase 3: Arm 1 		Ivonescimab RP3D (recommended Phase 3 dose) + EV
  • Drug: enfortumab vedotin (EV)
    Standard of care therapy
  • Drug: Ivonescimab RP3D
    Recommended Phase 3 dose of Ivonescimab after Phase 2 data analysis
Active Comparator
Phase 3: Arm 2 		Pembrolizumab 200 mg + EV
  • Drug: enfortumab vedotin (EV)
    Standard of care therapy
  • Drug: Pembrolizumab
    200 mg

Recruiting Locations

Research Site
Los Angeles, California 90067

Research Site
Spokane, Washington 99208

More Details

Status
Recruiting
Sponsor
Summit Therapeutics

Study Contact

Summit Clinical Trial Information
1-833-256-0522
medicalinformation@smmttx.com

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.