A Randomized Phase 2/3 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)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 15
- 主要终点
- Phase II • Adverse events (AEs) as characterized by type, incidence, severity, seriousness, and relationship to study treatment
研究概览
简要总结
Phase II: • To evaluate the safety and activity of ivonescimab in combination with EV in previously untreated locally advanced or metastatic urothelial carcinoma (LA/mUC) • To evaluate the pharmacokinetics (PK) profile and select recommended phase 3 dose (RP3D) for ivonescimab in combination with EV in previously untreated LA/mUC Phase III To compare the progression free survival (PFS) and overall survival (OS) of patients with LA/mUC treated with ivonescimab in combination with EV (experimental arm) to the PFS and OS of patients treated with pembrolizumab in combination with EV (standard of care [SoC] arm)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •ECOG performance status (PS) score of 0 or
- •Expected 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. Patients with mixed histology tumors with squamous, glandular, micropapillary, or sarcomatoid differentiation are permitted, provided that the urothelial component comprises ≥50% of the tumor as determined by pathology review.
- •No prior systemic therapy for LA/mUC with the following exceptions: a. Neoadjuvant or adjuvant therapy (eg, chemotherapy, checkpoint inhibitor with or without ADC therapy) is permitted only if recurrence occurred >12 months after the last administration of treatment.
- •At least one measurable noncerebral lesion according to RECIST v1.
- •Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions since radiotherapy. Note: The exact same image acquisition and processing parameters should be used throughout the study.
- •Patients must have one of the following to determine PD-L1 status at the time of study entry: a. An existing PD-L1 score; or b. Ability to provide formalin-fixed, paraffin-embedded (FFPE) tumor tissue for PD-L1 testing. Note: PD-L1 status availability is not required for study entry, but at least one of the above must be fulfilled prior to randomization.
排除标准
- •Locally advanced disease that is resectable or suitable for local therapy with curative intent.
- •Tumors containing any small cell or neuroendocrine differentiation, regardless of percentage, are not eligible. Patients with predominantly squamous, glandular, micro papillary, or sarcomatoid histology (>50%) are not eligible.
- •Ongoing sensory or motor neuropathy Grade 2 or higher.
- •Active keratitis or corneal ulcerations. Note: Patients with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator.
- •Radiographic findings consistent with a high risk of bleeding, including but not limited to: any tumor invasion of major blood vessels; or encasement of major blood vessels that in the opinion of investigator poses an increased risk of bleeding.
- •History of major diseases before first dose, specifically: a. Conditions that required hospitalization within 12 months prior to first dose including unstable angina, myocardial infarction, congestive heart failure (NYHA >class II) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) b. Other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia).
研究组 & 干预措施
Padcev 30 mg powder for concentrate for solution for infusion, Padcev 20 mg powder for concentrate for solution for infusion
干预措施: Padcev 30 mg powder for concentrate for solution for infusion (Drug)
Padcev 30 mg powder for concentrate for solution for infusion, Padcev 20 mg powder for concentrate for solution for infusion
干预措施: Padcev 20 mg powder for concentrate for solution for infusion (Drug)
KEYTRUDA 25 mg/mL concentrate for solution for infusion.
干预措施: KEYTRUDA 25 mg/mL concentrate for solution for infusion. (Drug)
ivonescimab
干预措施: ivonescimab (Drug)
结局指标
主要结局
Phase II • Adverse events (AEs) as characterized by type, incidence, severity, seriousness, and relationship to study treatment
Phase II • Adverse events (AEs) as characterized by type, incidence, severity, seriousness, and relationship to study treatment
Phase II • Laboratory abnormalities as characterized by type, incidence, and severity
Phase II • Laboratory abnormalities as characterized by type, incidence, and severity
Phase II • Objective response rate (ORR)a
Phase II • Objective response rate (ORR)a
Phase II • PK characteristics: ivonescimab serum concentration profiles
Phase II • PK characteristics: ivonescimab serum concentration profiles
Phase III • PFS per RECIST v1.1 by Independent Radiology Review Committee (IRRC)
Phase III • PFS per RECIST v1.1 by Independent Radiology Review Committee (IRRC)
Phase III • OS
Phase III • OS
次要结局
- ORRa
- DORa
- AEs as characterized by type, incidence, severity, seriousness, and relationship to study treatment
- Laboratory abnormalities as characterized by type, incidence, and severity
- PK characteristics: ivonescimab serum concentration profiles
- Incidence of ADA against ivonescimab
研究者
David Johnson
Scientific
Summit Therapeutics Inc.