Study of RYZ101 Compared with SOC in Pts W Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy (ACTION-1)

RayzeBio

Status and phase: Enrolling; Phase 3

Conditions: Gastroenteropancreatic Neuroendocrine Tumor; Pancreatic NET; Carcinoid Tumor; Neuroendocrine Tumors; Carcinoid; GEP-NET; Gastroenteropancreatic Neuroendocrine Tumor Disease

Treatments: Drug: Lanreotide; Drug: Sunitinib; Drug: Everolimus; Drug: RYZ101; Drug: Octreotide

Study type: Interventional

Funder types: Industry

Identifiers

NCT05477576

RYZ101-301

Details and patient eligibility

About

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.

Enrollment: 288 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

288 participants in 3 patient groups

Phase 1b - RYZ101

Experimental group

Description:

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.

Treatment:

Drug: RYZ101

Phase 3 - RYZ101

Active Comparator group

Description:

Actinium 225 radiolabeled somatostatin analog (SSA) for injection

Treatment:

Drug: RYZ101

Phase 3 - Standard of Care

Active Comparator group

Description:

Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.

Treatment:

Drug: Octreotide

Drug: Everolimus

Drug: Lanreotide

Drug: Sunitinib