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

ArmDescriptionAssigned 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.
  • Drug: RYZ101
    RP3D as determined in Phase 1b
Active Comparator
Phase 3 - RYZ101
Actinium 225 radiolabeled somatostatin analog (SSA) for injection
  • Drug: RYZ101
    RP3D as determined in Phase 1b
Active Comparator
Phase 3 - Standard of Care
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.
  • Drug: Everolimus
    Everolimus
  • Drug: Sunitinib
    Sunitinib
  • Drug: Octreotide
    High-dose octreotide
  • Drug: Lanreotide
    Lanreotide

Recruiting Locations

More Details

Status
Recruiting
Sponsor
RayzeBio, Inc.

Study Contact

RayzeBio Clinical Trials
+1 619 657 0057
clinicaltrials@rayzebio.com