Clinical trial NCT05477576: Study of RYZ101 Compared with SOC in Pts W Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: GEP-NET
Gastroenteropancreatic Neuroendocrine Tumor
Gastroenteropancreatic Neuroendocrine Tumor Disease
Neuroendocrine Tumors
Carcinoid
Carcinoid Tumor
Pancreatic NET
Keywords: Neuroendocrine Tumors
SSTR+
GEP-NET
targeted radiotherapy
Gastroenteropancreatic Neuroendocrine Tumor
RayzeBio
Actinium
Ac 225
Dotatate
Everolimus
sunitinib
octreotide
lanreotide
PRRT
alpha emitter
Lead sponsor: RayzeBio, Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-28
Enrollment: 288
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.


Eligibility 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

Primary outcomes:
measure: Phase 1b: RP3D
timeFrame: 56 days of study treatment
measure: Phase 3: PFS as determined by BICR
timeFrame: After the target number of 143 PFS events have occurred
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Facility
state: Arizona
city: Duarte
country: United States
facility: Research Facility
state: California
city: Irvine
country: United States
facility: Research Facility
state: California
city: Los Angeles
country: United States
facility: Research Facility
state: California
city: Palo Alto
country: United States
facility: Research Facility
state: California
city: San Francisco
country: United States
facility: Research Facility
state: California
city: New Haven
country: United States
facility: Research Facility
state: Connecticut
city: Washington
country: United States
facility: Research Facility
state: District of Columbia
city: Jacksonville
country: United States
facility: Research Facility
state: Florida
city: Miami
country: United States
facility: Research Facility
state: Florida
city: Tampa
country: United States
facility: Research Facility
state: Florida
city: Atlanta
country: United States
facility: Research Facility
state: Georgia
city: Iowa City
country: United States
facility: Research Facility
state: Iowa
city: Lexington
country: United States
facility: Research Facility
state: Kentucky
city: Glen Burnie
country: United States
facility: Research Facility
state: Maryland
city: Boston
country: United States
facility: Research Facility
state: Massachusetts
city: Boston
country: United States
facility: Research Facility
state: Massachusetts
city: Troy
country: United States
facility: Research Facility
state: Michigan
city: Rochester
country: United States
facility: Research Facility
state: Minnesota
city: St. Louis
country: United States
facility: Research Facility
state: Missouri
city: Omaha
country: United States
facility: Research Facility
state: Nebraska
city: New York
country: United States
facility: Research Facility
state: New York
city: New York
country: United States
facility: Research Facility
state: New York
city: Cleveland
country: United States
facility: Research Facility
state: Ohio
city: Portland
country: United States
facility: Research Facility
state: Oregon
city: Philadelphia
country: United States
facility: Research Facility
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Facility
state: Pennsylvania
city: Nashville
country: United States
facility: Research Facility
state: Tennessee
city: Houston
country: United States
facility: Research Facility
state: Texas
city: Salt Lake City
country: United States
facility: Research Facility
state: Utah
city: Seattle
country: United States
facility: Research Facility
state: Washington
city: Brussels
country: Belgium
facility: Research Facility
city: Brussel
country: Belgium
facility: Research Facility
city: Leuven
country: Belgium
facility: Research Facility
city: Roeselare
country: Belgium
facility: Research Facility
city: Brasília
country: Brazil
facility: Research Facility
city: Rio De Janeiro
country: Brazil
facility: Research Facility
city: São Paulo
country: Brazil
facility: Research Facility
city: London
country: Canada
facility: Research Facility
state: Ontario
city: Toronto
country: Canada
facility: Research Facility
state: Ontario
city: Montréal
country: Canada
facility: Research Facility
state: Quebec
city: Clichy
country: France
facility: Research Facility
city: Lille
country: France
facility: Research Facility
city: Nantes
country: France
facility: Research Facility
city: Vandoeuvre-Lès-Nancy
country: France
facility: Research Facility
city: Villejuif
country: France
facility: Research Facility
city: Seoul
country: Korea, Republic of
facility: Research Facility
city: Utrecht
country: Netherlands
facility: Research Facility
city: Barcelona
country: Spain
facility: Research Facility
city: Madrid
country: Spain
facility: Research Facility
city: Zaragoza
country: Spain
facility: Research Facility
Study officials:
affiliation: RayzeBio Sr. Medical Director
name: Denis Ferreira, MD
role: STUDY_DIRECTOR
References: