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)
Facility
City
Region
Status
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.
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.
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