Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy
                                  
                                      
                                          
                                          
                                              
                                              
                                                  Neuroendocrine Tumor
Unknown Primary
                                              
                                           
                                          
                                          
                                              
                                              
                                                  18 Years and older, Male and Female
                                              
                                           
                                          
                                       
                                      
                                          
                                          
                                              
                                              
                                                  RYZ101-301 (primary)
NCI-2022-06406
                                              
                                           
                                          
                                          
                                       
                                   
                               
                           
                          
                              
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
  -  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
 
                          
                              Treatment Sites in Georgia
                             
                           
                           
                              
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