A multi-center, open-label, phase 2 study of Elranatamab in patients with high-risk smoldering multiple myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Myeloma Network B.V., Emn Trial Office S.r.l. Impresa Sociale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Apr 2024 → ongoing

Decision date (initial)

2024-02-13

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

The primary objective is to determine the efficacy of Elranatamab in patients with previously untreated high-risk SMM.

Secondary objectives 3

1. The key-secondary objective is to determine the safety of Elranatamab in patients with previously untreated high-risk SMM.
2. - To further evaluate the efficacy of Elranatamab in patients with previously untreated high risk SMM - To assess Quality of Life (QoL)
3. - To evaluate the PK of Elranatamab in patients with previously untreated high-risk SMM - To determine tumor and microenvironment factors

Conditions and MedDRA coding

High risk smoldering multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. ≥ 18 years of age
2. Diagnosis of SMM for ≤5 years with measurable disease, defined as serum M protein: ≥1g/dL or urine M protein ≥200 mg/24 hours or involved serum FLC ≥100 mg/Land abnormal serum FLC ratio.
3. BMPCs ≥10% and <60%
4. Presence of at least 2 high risk factors, including a. Serum M protein ≥2 g/dL, b. BMPC >20% c. Serum involved/uninvolved FLC ratio > 20
5. ECOG performance status score of 0 or 1
6. Subjects must meet the following laboratory parameters, per laboratory reference range (performed at most 15 days before cycle 1 day 1) a. Absolute neutrophil count ≥1.0 x 10^9 /L (ie, ≥1000/μL) b. Platelet count ≥75 x 10^9 /L c. Aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN) d. Alanine aminotransferase (ALT) ≤2.5 x ULN e. Total bilirubin ≤1.5 x ULN, except in subjects with congenital bilirubinemia,such as Gilbert syndrome (in which case direct bilirubin ≤2.0 x ULN is required)
7. Subject must sign an informed consent form (ICF) or their legally acceptable representative must sign indicating that he or she understands the purpose of, and procedures required for the study and is willing to participate in the study.
8. Women of childbearing potential must have a negative serum or urine pregnancy test at screening and before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (One highly effective method and one additional effective method) used at the same time, and continuing for at least 5 months after the last dose of Elranatamab. Women must also agree to notify pregnancy during the study.

Exclusion criteria 18

1. Previous therapy with any systemic therapy for multiple myeloma.
2. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer free of disease for 5 years.
3. Female subject who is pregnant or breast-feeding.
4. Serious medical or psychiatric illness likely to interfere with participation in study.
5. Uncontrolled diabetes mellitus
6. Known HIV infection; Known active hepatitis B or C viral infection; known active COVID-19/SARS-CoV-2 infection.
7. Live attenuated vaccine administered within 4 weeks of the first dose of study intervention.
8. Ongoing treatment with corticosteroids : dose >10mg prednisone
9. Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision.
10. Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): a. Increased calcium levels: Corrected serum calcium >1 mg/dL above the ULN or >11 mg/dL b. Renal insufficiency: Determined by glomerular filtration rate (GFR) <40 mL/min/1.73 m² (Modification of Diet in Renal Disease [MDRD] Formula) or serum creatinine >2 mg/dL c. Anemia (hemoglobin 2 g/dL below lower limit of normal or <10 g/dL or both) transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted d. ≥ 1 bone lytic lesion e. BMPCs ≥60% f. Serum involved/uninvolved FLC ratio ≥100 and an involved FLC ≥100mg/L g. Whole body magnetic resonance imaging (WB-MRI) or positron emission tomography-computed tomography (PET-CT) with more than 1 bone focal lesion (≥5 mm in diameter)
11. Diagnosis of primary amyloidosis, POEMS syndrome, monoclonal gammopathy of undetermined significance, symptomatic multiple myeloma, or solitary plasmacytoma.
12. Subject has a diagnosis of Waldenström’s macroglobulinemia, or other conditions in which IgM Mprotein is present in theabsence of a clonal plasma cell infiltration with lytic bone lesions.
13. Subject has had plasmapheresis within 14 days of C1D1.
14. Myocardial infarction within 6 months prior to enrolment according to NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
15. Ongoing Grade 2 or higher peripheral sensory/motor peripheral neuropathy (PN), history of GBS or GBS variants, or history of grade 3 or higher peripheral motor polyneuropathy.
16. Subject has had major surgery within 2 weeks before eligibility confirmation or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study.
17. Clinically relevant active infection or serious co-morbid medical conditions.
18. Participants with known or suspected hypersensitivity to the study interventions or any of their excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Complete remission rate at the end of cycle 6, assessed by International Myeloma Working Group [IMWG] criteria.
2. Rate of grade >3-4 non hematologic adverse events, assessed according to CTCAE 5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Myeloma Network B.V.

Sponsor organisation

European Myeloma Network B.V.

Address

Blaak 555

City

Rotterdam

Postcode

3011 GB

Country

Netherlands

Scientific contact point

Organisation

European Myeloma Network Stichting

Contact name

Trial Manager

Public contact point

Organisation

European Myeloma Network Stichting

Contact name

Trial Manager

Third parties 6

Emn Trial Office S.r.l. Impresa Sociale

Sponsor organisation

Emn Trial Office S.r.l. Impresa Sociale

Address

Via Saluzzo 1/a, TO

City

Turin

Postcode

10125

Country

Italy

Locations

6 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 56 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications