Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy
Purpose
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.
Conditions
- GEP-NET
- Gastroenteropancreatic Neuroendocrine Tumor
- Gastroenteropancreatic Neuroendocrine Tumor Disease
- Neuroendocrine Tumors
- Carcinoid
- Carcinoid Tumor
- Pancreatic NET
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Criteria
Subjects must meet all the following criteria for enrollment in the study:
- 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 creatinine clearance (CrCl) ≥60 mL/min
(calculated using the Cockcroft-Gault formula) (Cockcroft and Gault, 1976)
- 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
Subjects who meet any of the following criteria will be excluded from the study:
- 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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- 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.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase 1b - RYZ101 |
Part 1 is an uncontrolled dose de-escalation study to confirm the safety and determine the RP3D of RYZ101 based on Bayesian optimal interval design. |
|
|
Active Comparator Phase 3 - RYZ101 |
Actinium 225 radiolabeled somatostatin analog (SSA) for injection |
|
|
Active Comparator Phase 3 - Standard of Care |
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide. |
|
Recruiting Locations
More Details
- Status
- Recruiting
- Sponsor
- RayzeBio, Inc.