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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

NCT05477576 · RayzeBio, Inc.
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Official title
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
About this study
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 criteria
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 design
Enrollment target: 338 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2022-03-24
Estimated completion: 2030-12
Last updated: 2026-03-30
Interventions
Drug: RYZ101Drug: EverolimusDrug: SunitinibDrug: OctreotideDrug: Lanreotide
Primary outcomes
  • Phase 1b: RP3D (56 days of study treatment)
  • Phase 3: PFS as determined by BICR (After the target number of 143 PFS events have occurred)
Sponsor
RayzeBio, Inc. · industry
Contacts & investigators
ContactRayzeBio Clinical Trials · contact · clinicaltrials@rayzebio.com · +1 619 657 0057
InvestigatorYe Yuan, MD · study_director, RayzeBio Sr. Medical Director
All locations (54)
Research FacilityActive Not Recruiting
Phoenix, Arizona, United States
Research FacilityCompleted
Duarte, California, United States
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Irvine, California, United States
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Los Angeles, California, United States
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Palo Alto, California, United States
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San Francisco, California, United States
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New Haven, Connecticut, United States
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Washington D.C., District of Columbia, United States
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Jacksonville, Florida, United States
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Miami, Florida, United States
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Tampa, Florida, United States
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Atlanta, Georgia, United States
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Iowa City, Iowa, United States
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Lexington, Kentucky, United States
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Glen Burnie, Maryland, United States
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Boston, Massachusetts, United States
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Boston, Massachusetts, United States
Research FacilityCompleted
Troy, Michigan, United States
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Rochester, Minnesota, United States
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St Louis, Missouri, United States
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Omaha, Nebraska, United States
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New York, New York, United States
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New York, New York, United States
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Cleveland, Ohio, United States
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Columbus, Ohio, United States
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Portland, Oregon, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Nashville, Tennessee, United States
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Houston, Texas, United States
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Salt Lake City, Utah, United States
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Seattle, Washington, United States
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Brussels, Belgium
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Leuven, Belgium
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Roeselare, Belgium
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Brasília, Brazil
Research FacilityCompleted
Rio de Janeiro, Brazil
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São Paulo, Brazil
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London, Ontario, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Clichy, France
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Lille, France
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Montpellier, France
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Nantes, France
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Vandœuvre-lès-Nancy, France
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Villejuif, France
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Amsterdam, Netherlands
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Maastricht, Netherlands
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Utrecht, Netherlands
Research FacilityActive Not Recruiting
Seoul, South Korea
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Barcelona, Spain
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Madrid, Spain
Research FacilityCompleted
Zaragoza, Spain
Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy · TrialPath