RYZ101 for the Treatment of Progressive or Recurrent Intracranial Meningioma

NCT07150806 | Suspended Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-24368NCI-2025-06045
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II tests the safety, side effects, best dose and how well giving RYZ101 works for the treatment of patients with intracranial meningioma that is growing, spreading, or getting worse (progressive) or that has come back after a period of improvement (recurrent). RYZ101 is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177-dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Giving RYZ101 may be safe, tolerable and/or effective in treating patients with progressive or recurrent intracranial meningioma.

Conditions

Recurrent Meningioma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Defined as survival without progression of disease (progressive disease, based on Response Assessment in Neuro-Oncology Criteria \[RANO\] 2.0 criteria) or death. Kaplan-Meier analyses will be used to estimate PFS.

  At 6 months

Secondary Outcomes (4)

• Objective response rate (ORR)

  At 6 months and 1 year

• Overall survival (OS)

  From the date of trial enrolment to date of death, up to 2 years

• Incidence of adverse events

  Up to 2 years

• PET standardized uptake value uptake

  Up to 2 years

Study Arms (1)

Treatment (RYZ101)

EXPERIMENTAL

Patients receive RYZ101 IV and amino acids, with L-arginine and L-lysine, IV on day 1 of each cycle. Cycles repeat every 8 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-DOTATATE IV and undergo PET scan or SSTR PET scan, CT scan, MRI and undergo blood and urine sample collection and may undergo echocardiography or MUGA scan throughout the study.

Drug: Actinium Ac 225 DOTATATE RYZ101; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Radiation: Gallium Ga 68-DOTATATE; Drug: L-lysine/L-arginine-containing Amino Acid; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Procedure: Somatostatin Receptor Positron Emission Tomography

Interventions

Actinium Ac 225 DOTATATE RYZ101 DRUG

Given IV

Also known as: 225Ac-DOTA-TATE RYZ101, 225Ac-Oxodotreotide, Actinium Ac 225-Dotatate RYZ101, ACTINIUM AC-225 DOTATATE, RYZ 101, RYZ-101, RYZ101

Treatment (RYZ101)

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (RYZ101)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (RYZ101)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Treatment (RYZ101)

Gallium Ga 68-DOTATATE RADIATION

Given IV

Also known as: (68)Ga-DOTA-TATE, 68Ga-DOTA-0-Tyr3-Octreotate, 68Ga-DOTATATE, Gallium Ga 68 Oxodotreotide, Gallium Oxodotreotide Ga-68, Gallium-68 DOTA-DPhe1, Tyr3-octreotate

Treatment (RYZ101)

L-lysine/L-arginine-containing Amino Acid DRUG

Given IV

Also known as: Amino Acid Renal Protectant Solution, Amino Acid Solution-containing L-lysine and L-arginine, Intravenous L-lysine/L-arginine-containing Amino Acid Solution, L-lysine/L-arginine AA Solution, Lysine-Arginine Amino Acid Solution, Lysine/Arginine Amino Acid Solution, Radioprotective Amino Acid Solution

Treatment (RYZ101)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (RYZ101)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (RYZ101)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (RYZ101)

Somatostatin Receptor Positron Emission Tomography PROCEDURE

Undergo SSTR PET scan

Also known as: SSTR-PET

Treatment (RYZ101)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients of age \> 18 years
• Patients with 68Ga-DOTATATE positive recurrent or progressive meningiomas, any World Health Organization (WHO) grade, who have progressed after first line treatment.
• For Grade I meningioma, patients must have either:
• Progressive disease after at least surgical resection and radiotherapy, as defined as an increase in size of the measurable primary lesion (bidirectional area) on imaging by 25% or more between scans separated by no more than 12 months; or
• Progressive residual tumor after maximal safe resection, located at or near critical organs at-risk and considered to be high-risk for radiation injury by the treating investigator. Prior external beam radiotherapy is not required for these subjects.
• For Grade II or III meningioma, subjects must have either:
• Progressive disease after at least surgical resection and radiotherapy, as defined as an increase in size of the measurable primary lesion (bi-directional area) on imaging by 25% or more between scans separated by no more than 12 months or
• Residual measurable disease after prior surgery without requirement of progression, or
• Unsuitable for, or decline other standard of care treatment.
• Positive 68Ga-DOTATATE uptake on PET/CT at baseline, defined as target lesion uptake higher than the background with SUV ratios adjusted to the liver uptake (Krenning score ≥ 2)
• Presence of measurable disease defined as at least one lesion measuring ≥ 5 mm in at least one dimension by contrast-enhanced MRI performed within 30 days prior to study registration
• Multifocal disease allowed but limited to ≤ 3 measurable intracranial lesions on the most recent post-contrast MRI
• There is no limit on the number of prior surgeries, radiation therapy, radiosurgery, systemically administered therapeutic agents or theranostic agents
• For patients treated with external beam radiation, interstitial brachytherapy or radiosurgery, an interval ≥ 24 weeks must have elapsed from completion from these therapies to registration unless there is histopathologic confirmation of recurrent tumor or there is new enhancing tumor outside the radiation field (beyond the high dose region or the 80% isodose line)
• An interval of ≥ 28 days (or 5 half-lives, whichever is shorter) from prior cytotoxic chemotherapy (6 weeks from nitrosoureas), biologic agent, investigational agent or any other systemic agent prescribed for the purpose of treating meningioma

You may not qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status \> 2
• Received radiation therapy to the brain in last 24 weeks
• History of hypersensitivity or allergy to Actinium Ac-225 (225Ac), Gallium Ga 68 (68Ga), Copper Cu 64 (64Cu), octreotate, or any of the excipients of DOTATATE imaging agents
• Prior radiopharmaceutical therapies (RPT), including radioembolization
• Prior solid organ or bone marrow transplantation
• Any toxicities from prior treatments that have not recovered to CTCAE grade ≤1, except for alopecia
• Significant cardiovascular disease, defined as:
• New York Heart Association (NYHA) Class ≥ II heart failure.
• Known left ventricular ejection fraction (LVEF) \< 50%.
• History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6 months.
• QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 470 ms, demonstrated by the average value of 3 consecutive electrocardiograms (ECGs).
• Resistant hypertension, defined as persistent uncontrolled blood pressure (BP) \> 140/90 mmHg while on optimal doses of at least 3 antihypertensive medications with 1 being a diuretic. Patients with baseline hypertension may be eligible after initiation of antihypertensive therapy
• Uncontrolled diabetes mellitus as defined by hemoglobin A1C (HgB A1c) \> 8% in patients with known diagnosis of diabetes mellitus)
• Liver cirrhosis
• Pregnancy or lactation

Sponsors & Collaborators

• Joshua Palmer: lead
• RayzeBio, Inc.: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Meningioma

Interventions

Specimen Handling; Ga(III)-DOTATOC; gallium Ga 68 dotatate; Arginine; Lysine; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Joshua D Palmer, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 27, 2025
• First Posted: September 2, 2025
• Study Start: November 12, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (1)