Phase 1b/3 Global, Randomized, Controlled, Open-label Trial Comparing Treatment With RYZ101 to Standard of Care Therapy in Subjects With Inoperable, Advanced, SSTR+, Well-differentiated GEP-NETs That Have Progressed Following Prior 177Lu-SSA Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 288
- 试验地点
- 1
- 主要终点
- Phase 1b: RP3D
研究概览
简要总结
This study aims to determine the safety, pharmacokinetics (PK) and recommended Phase 3 dose (RP3D) of RYZ101 in Part 1, and the safety, efficacy, and PK of RYZ101 compared with investigator-selected standard of care (SoC) therapy in Part 2 in subjects with inoperable, advanced, well-differentiated, somatostatin receptor expressing (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have progressed following treatment with Lutetium 177-labelled somatostatin analogue (177Lu-SSA) therapy, such as 177Lu-DOTATATE or 177Lu-DOTATOC (177Lu-DOTATATE/TOC), or 177Lu-high affinity [HA]-DOTATATE.
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
- None
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 proven, Grade 1-2 well differentiated, inoperable, advanced GEP-NETs (Ki67 ≤20%) Eastern Cooperative Oncology Group (ECOG) status 0-
- •Ki67% <20% is not required for the ad hoc subcohort of the PK/ECG substudy.
- •Progressive, SSTR-PET positive (i.e., Krenning score 3 or 4) GEP-NET (GI or pancreas) following 2-4 cycles of treatment with 177Lu-labeled SSA. Must have achieved disease control for at least 6 months following Lu-177 SSA (archival tissue is not required for the ad hoc subcohort of the PK/ECG substudy). No time limit is defined between 177Lu-SSA treatment and randomization. There must be at least 1 SSTR-PET imaging-positive measurable site of disease (according to RECIST v1.1) and no RECIST v1.1 measurable metastatic lesions that are SSTR imaging-negative.
- •Adequate renal function, as evidenced by estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) (Levey et al. 2009)
- •Adequate hematologic function, defined by the following laboratory results:
- •Part 2: Hemoglobin concentration ≥5.0 mmol/L (≥8.0 g/dL); ANC ≥1000 cells/µL (≥1000 cells/mm3); platelets ≥75 x 109/L (75 x 103/mm3).
- •Total bilirubin ≤3 x upper limit normal (ULN)
- •Serum albumin ≥3.0 g/dL unless prothrombin time is within the normal range
排除标准
- •Prior radioembolization
- •Significant cardiovascular disease, such as New York Heart Association (NYHA) Class ≥II heart failure, left ventricular ejection fraction (LVEF) <40% or QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms for males and >470 ms for females.
- •Resistant hypertension, defined as uncontrolled blood pressure (BP) >140/90 mmHg while on optimal doses of at least 3 antihypertensive medications with 1 being a diuretic (Whelton et al. 2018)
- •Uncontrolled diabetes mellitus as defined by hemoglobin A1C (HgB A1C) ≥8%
- •PRRT other than Lu-177 SSA (not applicable for ad hoc subcohort of the PK/ECG substudy)
- •Any condition requiring systemic treatment with high-dose glucocorticoids within 14 days prior to first dose of study treatment and/or which cannot be stopped while on study. Inhaled or topical steroids are permitted.
- •Prior history of liver cirrhosis or liver transplantation
研究组 & 干预措施
Phase 1b - RYZ101
Part 1 is an uncontrolled dose de-escalation study to confirm the safety and determine the RP3D of RYZ101 based on Bayesian optimal interval design.
干预措施: RYZ101 (Drug)
Phase 3 - RYZ101
Actinium 225 radiolabeled somatostatin analog (SSA) for injection
干预措施: RYZ101 (Drug)
Phase 3 - Standard of Care
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.
干预措施: Everolimus (Drug)
Phase 3 - Standard of Care
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.
干预措施: Sunitinib (Drug)
Phase 3 - Standard of Care
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.
干预措施: Octreotide (Drug)
Phase 3 - Standard of Care
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.
干预措施: Lanreotide (Drug)
结局指标
主要结局
Phase 1b: RP3D
时间窗: 56 days of study treatment
Incidence of DLTs during the first 56 days of study treatment will be assessed.
Phase 3: PFS as determined by BICR
时间窗: After the target number of 143 PFS events have occurred
PFS will be defined as the time from the date of randomization until the date of progression (as determined by BICR from tumor assessments using RECIST v1.1) or death due to any cause, whichever occurs earlier.
次要结局
未报告次要终点