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

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Smoldering Multiple Myeloma (SMM)

Treatments: Drug: Linvoseltamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05955508

R5458-ONC-2256

2023-503524-11-00 (Other Identifier)

Details and patient eligibility

About

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)

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Safety Run-In (Part 1)

Experimental group

Description:

Evaluation of initial safety and tolerability of the step-up regimen leading up to the start of full dose linvoseltamab.

Treatment:

Drug: Linvoseltamab

Expansion (Part 2)

Experimental group

Description:

Linvoseltamab monotherapy according to the same dosing schedule established in the safety run-in part.

Treatment:

Drug: Linvoseltamab