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

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

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

Conditions8

Interventions5

Locations32 sites

Find trials near these locations

Related trials

• Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0 — Gustave Roussy, Cancer Campus, Grand Paris
• Chidamide/Everolimus for PIK3CA Wild-type/Mutant HR+/HER2- Advanced Breast Cancer — Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Combination of Everolimus and 177Lu-DOTATATE in the Treatment of Grades 2 and 3 Refractory Meningioma: a Phase IIb Clinical Trial — Central Hospital, Nancy, France
• Efficacy and Safety of Radiotherapy Compared to Everolimus in Somatostatin Receptor Positive Neuroendocrine Tumors of the Lung and Thymus. — Grupo Espanol de Tumores Neuroendocrinos
• Efficacy of Organoid-Based Drug Screening to Guide Treatment for Locally Advanced Thyroid Cancer — West China Hospital
• Elacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i. — MedSIR
• European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors — Gustave Roussy, Cancer Campus, Grand Paris
• Everolimus With Investigator's Choice of Chemotherapy in Advanced Triple-Negative Breast Cancer (TNBC) With Luminal Androgen Receptor (LAR) Subtype — Fudan University

Browse More Trials