Ireland
--:--IST
Active, not recruiting Phase 3

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

NCT05477576 · tracked via the Priya Life Science Belgium tracker
Phase
Phase 3
Started
2022-03-24
Last updated
2026-10-05

Condition(s) studied

GEP-NETGastroenteropancreatic Neuroendocrine TumorGastroenteropancreatic Neuroendocrine Tumor DiseaseNeuroendocrine TumorsCarcinoidCarcinoid TumorPancreatic NET

Investigational drug(s) / intervention(s)

RYZ101 →Everolimus →Sunitinib →Octreotide →Lanreotide →

RYZ101: RP3D as determined in Phase 1b

Everolimus: Everolimus

Sunitinib: Sunitinib

Octreotide: High-dose octreotide

Lanreotide: Lanreotide

Study summary

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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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

Primary outcome measure(s)

  • Phase 1b: RP3D — 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 — 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.

Trial sites (54)

FacilityCityRegionStatus
Research Facility Phoenix Arizona
Research Facility Duarte California
Research Facility Irvine California
Research Facility Los Angeles California
Research Facility Palo Alto California
Research Facility San Francisco California
Research Facility New Haven Connecticut
Research Facility Washington D.C. District of Columbia
Research Facility Jacksonville Florida
Research Facility Miami Florida
Research Facility Tampa Florida
Research Facility Atlanta Georgia
Research Facility Iowa City Iowa
Research Facility Lexington Kentucky
Research Facility Glen Burnie Maryland
Research Facility Boston Massachusetts
Research Facility Boston Massachusetts
Research Facility Troy Michigan
Research Facility Rochester Minnesota
Research Facility St Louis Missouri
Research Facility Omaha Nebraska
Research Facility New York New York
Research Facility New York New York
Research Facility Cleveland Ohio
Research Facility Columbus Ohio
Research Facility Portland Oregon
Research Facility Philadelphia Pennsylvania
Research Facility Pittsburgh Pennsylvania
Research Facility Nashville Tennessee
Research Facility Houston Texas
Research Facility Salt Lake City Utah
Research Facility Seattle Washington
Research Facility Brussels Belgium
Research Facility Leuven Belgium
Research Facility Roeselare Belgium
Research Facility Brasília Brazil
Research Facility Rio de Janeiro Brazil
Research Facility São Paulo Brazil
Research Facility London Ontario
Research Facility Toronto Ontario

+ 14 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05477576 on ClinicalTrials.gov ↗ ← All trials in Belgium