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

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

  • Metastatic Urothelial Carcinoma
  • Metastatic Urothelial Carcinoma (UC)

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