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

Sponsor: Summit Therapeutics

Sponsor score: 0

ClinicalTrials ID:NCT07815665

This Phase 2/3 study evaluates ivonescimab with enfortumab vedotin (EV) versus pembrolizumab with EV in untreated metastatic urothelial carcinoma. Phase 2 identifies the recommended Phase 3 dose (RP3D) of ivonescimab. Eligibility includes adults with ECOG 0-1, life expectancy ≥6 months, and adequate organ function. Interventions include ivonescimab doses, EV, and pembrolizumab.

Patient Parameters

Program Overview

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)

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

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.

Locations

FACILITYZIPCITYSTATE
Research Site85054PhoenixArizona
Research Site90067Los AngelesCalifornia
Research Site20010Washington D.C.District of Columbia
Research Site32224JacksonvilleFlorida
Research Site55905RochesterMinnesota
Research Site37203NashvilleTennessee
Research Site99208SpokaneWashington

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