Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy

Официальное название

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

Обзор

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.

Вмешательства

• Препарат RYZ101
  RP3D as determined in Phase 1b
• Препарат Everolimus
  Everolimus
• Препарат Sunitinib
  Sunitinib
• Препарат Octreotide
  High-dose octreotide
• Препарат Lanreotide
  Lanreotide

Первичные конечные точки

• Phase 1b: RP3D [Срок оценки: 56 days of study treatment]
• Phase 3: PFS as determined by BICR [Срок оценки: After the target number of 143 PFS events have occurred]

Критерии участия

Inclusion:

• Histologically proven, Grade 1-2 well differentiated, inoperable, advanced GEP-NETs (Ki67 ≤20%) Eastern Cooperative Oncology Group (ECOG) status 0-2. 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

Exclusion:

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 32 центра

• Research Facility — Phoenix
• Research Facility — Duarte
• Research Facility — Irvine
• Research Facility — Los Angeles
• Research Facility — Palo Alto
• Research Facility — San Francisco
• Research Facility — New Haven
• Research Facility — Washington D.C.
• … и ещё 24 центра

Франция · 6 центров

• Research Facility — Clichy
• Research Facility — Lille
• Research Facility — Montpellier
• Research Facility — Nantes
• Research Facility — Vandœuvre-lès-Nancy
• Research Facility — Villejuif

Бельгия · 3 центра

• Research Facility — Brussels
• Research Facility — Leuven
• Research Facility — Roeselare

Бразилия · 3 центра

• Research Facility — Brasília
• Research Facility — Rio de Janeiro
• Research Facility — São Paulo

Канада · 3 центра

• Research Facility — London
• Research Facility — Toronto
• Research Facility — Montreal

Нидерланды · 3 центра

• Research Facility — Amsterdam
• Research Facility — Maastricht
• Research Facility — Utrecht

Испания · 3 центра

• Research Facility — Barcelona
• Research Facility — Madrid
• Research Facility — Zaragoza

South Korea · 1 центр

• Research Facility — Seoul

Публикации

• Taunk NK, Escorcia FE, Lewis JS, Bodei L. Radiopharmaceuticals for Cancer Diagnosis and Therapy: New Targets, New Therapies-Alpha-Emitters, Novel Targets. Cancer J. 2024 May-Jun 01;30(3):218-223. doi: 10.1097/PPO.0000000000000720. PMID 38753757

Идентификаторы

NCT: NCT05477576 · RYZ101-301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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