DRUG
RYZ101
RP3D as determined in Phase 1b
Status
Recruiting
Phase
Phase 3
Enrollment
338
Locations
54
Results
Not posted
Publications
1
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.
Interventions
DRUG
RP3D as determined in Phase 1b
DRUG
Everolimus
DRUG
Sunitinib
DRUG
High-dose octreotide
DRUG
Lanreotide
Timeline
First posted
Jul 28, 2022
Study start
Mar 24, 2022
Primary completion
Dec 2026
Study completion
Dec 2030
Results posted
Not reported
Registry updated
Mar 30, 2026
Outcomes
Phase 1b: RP3D
Time frame · 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
Time frame · 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.
Not reported in the indexed record.
Eligibility
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
Study locations
Belgium · Brazil · Canada · France · Netherlands · South Korea · Spain · United States. Showing up to 24 locations stored in the fast local snapshot.
Research Facility
Phoenix, Arizona, United States
Research Facility
Duarte, California, United States
Research Facility
Irvine, California, United States
Research Facility
Los Angeles, California, United States
Research Facility
Palo Alto, California, United States
Research Facility
San Francisco, California, United States
Research Facility
New Haven, Connecticut, United States
Research Facility
Washington D.C., District of Columbia, United States
Research Facility
Jacksonville, Florida, United States
Research Facility
Miami, Florida, United States
Research Facility
Tampa, Florida, United States
Research Facility
Atlanta, Georgia, United States
Research Facility
Iowa City, Iowa, United States
Research Facility
Lexington, Kentucky, United States
Research Facility
Glen Burnie, Maryland, United States
Research Facility
Boston, Massachusetts, United States
Research Facility
Boston, Massachusetts, United States
Research Facility
Troy, Michigan, United States
Research Facility
Rochester, Minnesota, United States
Research Facility
St Louis, Missouri, United States
Research Facility
Omaha, Nebraska, United States
Research Facility
New York, New York, United States
Research Facility
New York, New York, United States
Research Facility
Cleveland, Ohio, United States
Publications
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