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
Overview
- Phase
- Phase 3
- Intervention
- RYZ101
- Conditions
- GEP-NET
- Sponsor
- RayzeBio, Inc.
- Enrollment
- 288
- Locations
- 1
- Primary Endpoint
- Phase 1b: RP3D
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically proven, Grade 1-2 well differentiated, inoperable, advanced GEP-NETs (Ki67 ≤20%) Eastern Cooperative Oncology Group (ECOG) status 0-
- •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 Criteria
- •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
Arms & Interventions
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.
Intervention: RYZ101
Phase 3 - RYZ101
Actinium 225 radiolabeled somatostatin analog (SSA) for injection
Intervention: RYZ101
Phase 3 - Standard of Care
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.
Intervention: Everolimus
Phase 3 - Standard of Care
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.
Intervention: Sunitinib
Phase 3 - Standard of Care
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.
Intervention: Octreotide
Phase 3 - Standard of Care
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.
Intervention: Lanreotide
Outcomes
Primary Outcomes
Phase 1b: RP3D
Time Frame: 56 days of study treatment
Incidence of DLTs during the first 56 days of study treatment will be assessed.
Phase 3: PFS as determined by BICR
Time Frame: After the target number of 143 PFS events have occurred
PFS will be defined as the time from the date of randomization until the date of progression (as determined by BICR from tumor assessments using RECIST v1.1) or death due to any cause, whichever occurs earlier.