NCT07815665PHASE2, PHASE3Recruiting

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

Summit Therapeutics

Start Date

9/10/2026

Completion Date

12/31/2030

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)

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

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Ivonescimab Dose 1

DRUG

enfortumab vedotin (EV)

DRUG

Pembrolizumab

United States