Clinical Trial · NCT06411301

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

Overview

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.

Sponsor

Jules Bordet Institute

Phase

Phase 1

ClinicalTrials.gov

NCT06411301

Drug / Compound

DOTATATE

Isotope(s):

Target(s):

SSTR2

Ligand Class: Peptides

Chelator: DOTA

DOTATATE

Isotope(s):

Target(s):

SSTR2

Ligand Class: Peptides

Chelator: DOTA

Eligibility

Inclusion

Platelets count \>100 × 10\^9/L (100 × 10\^3/mm\^3)
Vasectomized men are also required to use a condom during intercourse, including with a male partner
Biologically active (relapsing or refractory) and measurable disease as defined by at least one of the following:
Estimated life expectancy above 6 months
Male study subjects whose sexual partners are WOCBP must also agree to use a second form of highly effective contraception (CTFG 2020) while receiving study treatment and for at least 4 months following their last dose
Baseline PET/CT imaging scans defined by:
Adequate coagulation function, defined by international normalized ratio or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN, unless subject is receiving anticoagulant therapy and PT or aPTT is within therapeutic range of intended use of anticoagulants
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
Bone marrow aspiration and biopsy sample available within 30 days prior study enrolment (optional under the subject agreement)
Negative serum pregnancy test within 48 hours prior to the first dose of study treatment
Hemoglobin concentration ≥5.0 mmol/L (≥8.0 g/dL)
All 18F-FDG PET/CT-avid lesions must be SSTR-positive, as defined above
Confirmed diagnosis of multiple myeloma according to the Salmon and Durie criteria
Aspartate aminotransferase and alanine aminotransferase ≤2.5 × upper limit of normal (ULN) (or ≤5 × ULN if presence of liver metastases)
Total bilirubin ≤3 × ULN
Adequate hepatic function defined by the following laboratory results:
Serum M-protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) or, for immunoglobulin (Ig) A myeloma, by quantitative IgA
Adequate hematologic function defined by the following laboratory results:
For women of childbearing potential (WOCBP):
Agreement to use barrier contraception and a second form of highly effective contraception (Clinical Trials Facilitation Group (CTFG) 2020) while receiving study treatment and for 7 months following their last dose of study treatment
Absolute neutrophil count ≥1000 cells/µL (≥1000 cells/mm\^3)
Must have progressed on their last line of myeloma therapy
Adequate renal function as measured by renal scintigraphy scans and evidenced by creatinine clearance (CrCl) ≥60 mL/min/1.73m\^2
Total white blood cell count ≥1.5 × 103/mm\^3
Serum free light chain (FLC) ≥ 100 mg/L, provided that FLC ratio is abnormal
Have received at least 3 prior lines of myeloma therapy including an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody
Sexually active male subjects must use a condom during intercourse while receiving study treatment and for at least 120 days after the last dose of the study drug and should not father a child during this period
68Ga-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
Urinary M-protein of at least 200 mg/24 hours by urine protein electrophoresis
Eastern Cooperative Oncology Group performance status ≤ 1
Serum albumin ≥3.0 g/dL

Exclusion

Prior participation in any interventional clinical study within 30 days prior to first dose of study drug
Resistant hypertension, defined as persistent uncontrolled blood pressure \>140/90 mmHg (diastolic/systolic) while on optimal doses of at least 3 antihypertensive medications with 1 being a diuretic
Known left ventricular ejection fraction \<50%
QT interval corrected for heart rate using Fridericia's formula \>470 ms, demonstrated by the average value of 3 consecutive electrocardiograms
Use of anticancer agents within the following intervals prior to the first dose of study drug:
History of hypersensitivity or allergy to 225Ac, 68Ga, octreotate, or any of the excipients of DOTATATE imaging agents
Chemotherapy: within \<6 weeks
Biological agents: within \<7 days or \<5 half-lives
Any toxicities from prior treatments that have not recovered to CTCAE Grade ≤1 at baseline, except for alopecia
Any known or underlying medical, psychiatric disease/condition, and/or social situations that, in the opinion of the investigator, would limit compliance with study requirements
Prior external beam radiotherapy on more than 25% of bone marrow
Small molecule inhibitors: within \<4 weeks
Significant cardiovascular disease, defined as:
Massive bone marrow infiltration on the baseline 68Ga-DOTATATE PET/CT scan
Uncontrolled diabetes mellitus as defined by hemoglobin A1C \>8%
Pregnancy or lactation
Impossibility to discontinue corticoids administration at a therapeutic level (total dose of 160 mg of dexamethasone or equivalent) two weeks prior dosing of study drug
New York Heart Association (NYHA) Class ≥II heart failure
History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6 months