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

Launched by RAYZEBIO, INC. · Jul 25, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment called RYZ101 for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that cannot be surgically removed and have worsened after previous treatment using a specific type of therapy known as 177Lu-labeled somatostatin analogs. The study is divided into two parts: the first part will look at the safety and how the body processes RYZ101, while the second part will compare how well RYZ101 works against the current standard treatments chosen by doctors.

To participate in this trial, individuals must be between the ages of 65 and 74, have a confirmed diagnosis of specific types of GEP-NETs that have progressed after receiving 2 to 4 cycles of 177Lu therapy, and meet certain health criteria, including good kidney and blood health. Participants will undergo regular check-ups and tests to monitor their health and the effects of the treatment. It’s important to know that some people may not be eligible if they have certain heart conditions or uncontrolled health issues, such as high blood pressure or diabetes. Overall, this trial aims to find a more effective treatment option for those with challenging GEP-NETs.

Gender

ALL

Eligibility 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