A Proof-of-Concept Trial to Study the Safety and Activity of Linvoseltamab in Participants With Smoldering Multiple Myeloma at High Risk of Developing Multiple Myeloma

Smoldering Multiple Myeloma (SMM) Clinical Trial

Official title:

Phase 2 Study of Linvoseltamab in Patients With Smoldering Multiple Myeloma at High Risk of Progression to Multiple Myeloma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05955508
• Other study ID #: R5458-ONC-2256
• Secondary ID: 2023-503524-11-0
• Status: Recruiting
• Phase: Phase 2
• Start date: January 30, 2024
• Est. completion date: December 19, 2032

Study information

• Verified date: February 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is researching an investigational drug called linvoseltamab ("study drug") in participants at high risk of developing multiple myeloma (MM), a group commonly labeled as high-risk smoldering multiple myeloma (HR-SMM). The aim of the study is to understand the safety and tolerability (how your body reacts to linvoseltamab) as well as the effectiveness (how well linvoseltamab eliminates plasma cells and prevents the development of MM) of the study drug. There are 2 parts to the study. - In Part 1, linvoseltamab will be given to a small number of participants to study the early side effects (safety) of the study drug and make sure the treatment is acceptable. - In Part 2, linvoseltamab will be given to more participants to continue to assess the side effects of the study drug and to evaluate the ability of linvoseltamab to treat HR-SMM and prevent progression to MM. The study is looking at several other research questions, including: - How many participants treated with linvoseltamab (study drug) have improvement of their HR-SMM? - What side effects may happen from taking the study drug? - How much study drug is in your blood at different times? - Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 19, 2032
• Est. primary completion date: December 19, 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

KEY Inclusion Criteria:

1. High-risk SMM diagnosis within 5 years of study enrollment

2. Eastern Cooperative Oncology Group (ECOG) performance status =1

3. Adequate hematologic and hepatic function, as described in the protocol

4. Estimated glomerular filtration rate =30 mL/min/1.73 m^2

KEY Exclusion Criteria:

1. Evidence of myeloma defining events *SLiM CRAB, as described in the protocol *SLiM (greater than or equal to Sixty percent clonal plasma cells in the bone marrow, involved/uninvolved free Light chain ratio of =100 with the involved free light chain (FLC) being =100 mg/L, MRI with >1 focal lesion) CRAB (hyperCalcemia, Renal insufficiency, Anemia, or lytic Bone lesions)

2. Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), soft tissue plasmacytoma, or symptomatic multiple myeloma

3. Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol

4. Any infection requiring hospitalization or treatment with IV anti-infectives within 28 days of first dose of study drug

5. Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection

6. History of severe allergic reaction attributed to compounds with a similar chemical or biologic composition as the study drug or excipient NOTE: Other protocol defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Smoldering Multiple Myeloma
• Smoldering Multiple Myeloma (SMM)

Intervention

Drug:
• Linvoseltamab
Administration by intravenous (IV) infusion

Locations

Country	Name	City	State
Spain	University Hospital of Cabuenes	Gijon	Asturias
Spain	Hospital Universitario Virgen de las Nieves	Granada	Andalusia
Spain	Clinica Universidad de Navarra - Madrid	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitari Son Llatzer	Palma Mallorca	Baleares
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Quiron Salud Madrid	Pozuelo de Alarcón	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	University Hospital Doctor Peset	Valencia
Spain	University Hospital La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse events of special interest (AESI) during the safety run-in observation period	AESI include grade 2 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)	Up to 35 days
Primary	Frequency of treatment-emergent adverse events (TEAEs) during the safety run-in observation period		Up to 35 days
Primary	Severity of TEAEs during the safety run-in observation period		Up to 35 days
Primary	Complete response (CR) as determined by the investigator		Up to 7 years
Primary	Minimal residual disease (MRD) negativity		At 12 months
Primary	MRD negativity		At 24 months
Secondary	Frequency of TEAEs during expansion part	As assessed by the NCI-CTCAE grading system version 5 (for all grades)	Up to 7 years
Secondary	Severity of TEAEs during expansion part	As assessed by the NCI-CTCAE grading system version 5 (for all grades)	Up to 7 years
Secondary	Frequency of serious adverse events (SAEs)		Up to 7 years
Secondary	Severity of SAEs		Up to 7 years
Secondary	Frequency of laboratory abnormalities		Up to 7 years
Secondary	Severity of laboratory abnormalities		Up to 7 years
Secondary	Overall response of partial response (PR) or better		Up to 7 years
Secondary	Duration of response (DOR)		Up to 7 years
Secondary	Biochemical progression-free-survival (PFS)		Up to 7 years
Secondary	MRD negativity among participants that achieve very good partial response (VGPR) or better		Up to 3 years after end of treatment
Secondary	Sustained MRD negativity		Up to 3 years after end of treatment
Secondary	Time from treatment initiation to date of any myeloma-defining event		Up to 7 years
Secondary	Time from start of treatment to date of progression to MM or death		Up to 7 years
Secondary	Time to initiation of first-line treatment for MM		Up to 7 years
Secondary	Overall survival (OS)		Up to 7 years
Secondary	Concentration of linvoseltamab in serum over time		Up to 2 years
Secondary	Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time		Up to 2 years
Secondary	Titer of ADAs to linvoseltamab over time		Up to 2 years