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Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy
Trial Status: active
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.
Inclusion Criteria
Inclusion:
- Histologically proven, Grade 1-2 well differentiated, inoperable, advanced GEP-NETs
(Ki67 ≤20%) Eastern Cooperative Oncology Group (ECOG) status 0-2
- 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. 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
- 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
Additional locations may be listed on ClinicalTrials.gov for NCT05477576.
