A Phase I Study to Assess the Tolerability of 225Ac-DOTATATE in Patients With Refractory and Relapsing Multiple Myeloma Expressing Somatostatin Receptors

NCT06411301 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: IJB-MN-AcTRESS
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine the safety and the recommended phase II dose of RYZ101 (actinium-225 labelled DOTA-octreotate (225Ac-DOTATATE)) in participants with refractory and relapsing multiple myeloma (MM) that have received at least 3 prior lines of myeloma therapy. Participants will be selected based on somatostatin receptor (SSTR) positivity assessed by gallium-68 labelled DOTA-octreotate (68Ga-DOTATATE) PET/CT. The response to 225Ac-DOTATATE therapy will also be assessed in the target study population.

Conditions

Multiple Myeloma, Refractory; Multiple Myeloma in Relapse; Multiple Myeloma Progression

Keywords

Multiple Myeloma; Somatostatin receptor; Radionuclide therapy; Actinium-225; Targeted alpha therapy

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of 225Ac-DOTATATE

  Incidence and severity of adverse events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

  First 84 days following first 225Ac-DOTATATE injection

• Recommended phase II dose of 225Ac-DOTATATE

  Rate incidence of dose-limiting toxicities (DLT)

  First 84 days following first 225Ac-DOTATATE injection

Secondary Outcomes (1)

• Clinical activity of treatment with 225Ac-DOTATATE

  First 84 days following first 225Ac-DOTATATE injection

Study Arms (1)

225Ac-DOTATATE

EXPERIMENTAL

Dose escalation study to assess the safety and determine the recommended phase II dose, based on time-to-event Bayesian optimal interval design, with a target toxicity rate of 30%. Three dose levels are planned to be evaluated: 5 MBq (starting dose), 7.5 MBq and 10 MBq (maximum dose allowed). The cohort size will be 3, with a maximum of 10 participants within a same dose level, and a maximum of 18 evaluable participants in total. Participants are planned to receive two cycles of intravenous infusion of 225Ac-DOTATATE every 6 weeks (Q6W). Each dose escalation and potential de-escalation step will be decided based on the dose-limiting toxicities (DLT) rate observed during the study treatment period (84 days following the first infusion), in the current dose cohort.

Drug: 225Ac-DOTATATE

Interventions

225Ac-DOTATATE DRUG

Two intravenous infusions every 6 weeks (Q6W)

Also known as: RYZ101

225Ac-DOTATATE

Eligibility Criteria

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

You may qualify if:

• Written informed consent in accordance with institutional guidelines and obtained prior to any study procedure
• Age of at least 18 years at the time of signing the informed consent
• Confirmed diagnosis of multiple myeloma according to the Salmon and Durie criteria
• Have received at least 3 prior lines of myeloma therapy including an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody
• Must have progressed on their last line of myeloma therapy
• Biologically active (relapsing or refractory) and measurable disease as defined by at least one of the following:
• Serum M-protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) or, for immunoglobulin (Ig) A myeloma, by quantitative IgA
• Urinary M-protein of at least 200 mg/24 hours by urine protein electrophoresis
• Serum free light chain (FLC) ≥ 100 mg/L, provided that FLC ratio is abnormal
• If SPEP is felt to be unreliable for routine M-protein measurement (example, for IgA or IgD MM), then quantitative Ig levels by nephelometry or turbidimetry are acceptable
• Estimated life expectancy above 6 months
• Eastern Cooperative Oncology Group performance status ≤ 1
• Bone marrow aspiration and biopsy sample available within 30 days prior study enrolment (optional under the subject agreement)
• Baseline PET/CT imaging scans defined by:
• Ga-DOTATATE PET/CT-positive imaging with target lesions, defined as unequivocal tumoral uptake higher than the maximum standardized uptake value of the femoral bone marrow background

You may not qualify if:

• Massive bone marrow infiltration on the baseline 68Ga-DOTATATE PET/CT scan
• History of hypersensitivity or allergy to 225Ac, 68Ga, octreotate, or any of the excipients of DOTATATE imaging agents
• Use of anticancer agents within the following intervals prior to the first dose of study drug:
• Chemotherapy: within \<6 weeks
• Small molecule inhibitors: within \<4 weeks
• Biological agents: within \<7 days or \<5 half-lives
• Prior external beam radiotherapy on more than 25% of bone marrow
• Prior participation in any interventional clinical study within 30 days prior to first dose of study drug
• Have a history of primary malignancy within the past 3 years other than (1) MM; (2) adequately treated carcinoma in situ or non-melanoma carcinoma of the skin; (3) any other curatively treated malignancy that is not expected to require treatment for recurrence during participation in the study, or (4) an untreated cancer on active surveillance that may not affect the subject's survival status for ≥3 years based on clinician assessment/statement
• Any toxicities from prior treatments that have not recovered to CTCAE Grade ≤1 at baseline, except for alopecia
• Significant cardiovascular disease, defined as:
• New York Heart Association (NYHA) Class ≥II heart failure
• Known left ventricular ejection fraction \<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 \>470 ms, demonstrated by the average value of 3 consecutive electrocardiograms

Sponsors & Collaborators

• Jules Bordet Institute: lead
• RayzeBio, Inc.: collaborator

Study Sites (1)

Jules Bordet Institute

Brussels, 1070, Belgium

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Design

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

Study Record Dates

• First Submitted: May 8, 2024
• First Posted: May 13, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)