A Phase 2, Multicenter, Randomized, Double-Blind, Active-Control Study to Evaluate the Efficacy and Safety of Nivolumab Administered in Combination With IPI-549 Compared to Nivolumab Monotherapy in the Treatment of Patients With Immune Therapy-Naïve, Advanced Urothelial Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 29
- 主要终点
- Objective Response Rate (ORR) per RECISTv1.1
研究概览
简要总结
The purpose of this study is to measure the effect of IPI-549 in combination with nivolumab when compared to nivolumab monotherapy in advanced urothelial cancer patients.
详细描述
Study IPI-549-02 is a multi-national, prospective, randomized, active-control Phase II trial to evaluate the efficacy and safety of IPI 549 administered in combination with nivolumab compared to nivolumab monotherapy.
The study will enroll approximately 160 checkpoint-naïve, advanced urothelial cancer patients who have progressed or recurred following treatment with platinum-based chemotherapy. Patients will be randomized 2:1 to receive intravenous (IV) nivolumab 480 mg every 4 weeks (Q4W) in combination with oral (PO) IPI 549 40 mg once daily (QD) or IV nivolumab 480 mg Q4W in combination with placebo PO QD.
Eligible patients who have confirmed progression of disease during treatment with nivolumab monotherapy may crossover to the combination treatment arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
- •Measurable disease by CT or MRI as defined by RECIST v1.1
- •Disease progression or recurrence after treatment:
- •i) With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
- •ii) With disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy
- •Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
- •Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Blood sample must be provided for mMDSC levels for randomization into the study
排除标准
- •Active brain metastases or leptomeningeal metastases
- •Any serious or uncontrolled medical disorder that may interfere with study treatment/interpretation
- •Prior malignancy active within the previous 3 years except for local or organ confined early stage cancer that has been apparently cured
- •Active, known, or suspected autoimmune disease
- •A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration
- •Prior therapy with anti-tumor vaccines, any T cell co-stimulation or checkpoint pathways, or IPI-549
- •Prior surgery or gastrointestinal dysfunction that may affect drug absorption
- •Past medical history of interstitial lung disease
- •History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control
- •Positive test for hepatitis B, C or HIV
- •Dependent on continuous supplemental oxygen
研究组 & 干预措施
IPI-549 + Nivolumab
Participants receive IPI-549 orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
干预措施: IPI-549 (eganelisib) (Drug)
IPI-549 + Nivolumab
Participants receive IPI-549 orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
干预措施: Nivolumab (Drug)
Placebo + Nivolumab
Participants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
干预措施: Nivolumab (Drug)
Placebo + Nivolumab
Participants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
干预措施: Placebos (Drug)
结局指标
主要结局
Objective Response Rate (ORR) per RECISTv1.1
时间窗: First dosing date to date of confirmed disease progression, assessed up to 24 months
ORR is defined as best response of complete response (CR) or partial response (PR) as measured by RECIST v1.1. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 mm in short axis. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
次要结局
- Duration of Response (DOR)(Date of first objective response to date of confirmed disease progression, assessed up to 24 months)
- Changes from baseline in respiration rate(Screening to date of confirmed disease progression, assessed up to 24 months)
- Changes from baseline in thyroid stimulating hormone (TSH)(Pre-treatment (within 7 days of first dose) to date of confirmed disease progression, assessed up to 24 months)
- Population Pharmacokinetics (PK) of IPI-549-01(Pre-dose, 0.5, 1.5, 3 and 6 hours following administration on Day 1 of Cycles 1 and 2 (each cycle is 28 days))
- Pharmacokinetics (PK) of Nivolumab(Pre-infusion and within 2 minutes of end of infusion on Day 1 of Cycles 1 and 4; Pre-infusion on Day 1 of Cycles 2 and 3, and every 4 cycles starting at Cycle 5 (each cycle is 28 days))
- Time to Response (TTR)(First dosing date to date of first objective response, assessed up to 24 months)
- Changes from baseline in temperature(Screening to date of confirmed disease progression, assessed up to 24 months)
- Changes from baseline in pulse rate(Screening to date of confirmed disease progression, assessed up to 24 months)
- Progression-Free Survival (PFS)(First dosing to date to confirmed disease progression or death, assessed up to 48 months)
- Changes from baseline in electrocardiograms (ECGs)(Screening to date of confirmed disease progression, assessed up to 24 months)
- Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance(Screening to date of confirmed disease progression, assessed up to 24 months)
- Changes from baseline in blood pressure(Screening to date of confirmed disease progression, assessed up to 24 months)