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
- Registration Number
- NCT05955508
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
- High-risk SMM diagnosis within 5 years of study enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Adequate hematologic and hepatic function, as described in the protocol
- Estimated glomerular filtration rate ≥30 mL/min/1.73 m^2
KEY
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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)
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Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), soft tissue plasmacytoma, or symptomatic multiple myeloma
-
Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
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Any infection requiring hospitalization or treatment with IV anti-infectives within 28 days of first dose of study drug
-
Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Safety Run-In (Part 1) Linvoseltamab Evaluation of initial safety and tolerability of the step-up regimen leading up to the start of full dose linvoseltamab. Expansion (Part 2) Linvoseltamab Linvoseltamab monotherapy according to the same dosing schedule established in the safety run-in part.
- Primary Outcome Measures
Name Time Method Frequency of adverse events of special interest (AESI) during the safety run-in observation period Up to 35 days AESI include grade 2 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)
Frequency of treatment-emergent adverse events (TEAEs) during the safety run-in observation period Up to 35 days Severity of TEAEs during the safety run-in observation period Up to 35 days MRD negativity At 24 months Complete response (CR) as determined by the investigator Up to 7 years Minimal residual disease (MRD) negativity At 12 months
- Secondary Outcome Measures
Name Time Method Frequency of TEAEs during expansion part Up to 7 years As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Frequency of laboratory abnormalities Up to 7 years Frequency of serious adverse events (SAEs) Up to 7 years Severity of SAEs Up to 7 years MRD negativity among participants that achieve very good partial response (VGPR) or better Up to 3 years after end of treatment Sustained MRD negativity Up to 3 years after end of treatment Severity of TEAEs during expansion part Up to 7 years As assessed by the NCI-CTCAE grading system version 5 (for all grades)
Severity of laboratory abnormalities Up to 7 years Time from start of treatment to date of progression to MM or death Up to 7 years Time to initiation of first-line treatment for MM Up to 7 years Time from treatment initiation to date of any myeloma-defining event Up to 7 years Overall survival (OS) Up to 7 years Concentration of linvoseltamab in serum over time Up to 2 years Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time Up to 2 years Titer of ADAs to linvoseltamab over time Up to 2 years Overall response of partial response (PR) or better Up to 7 years Duration of response (DOR) Up to 7 years Biochemical progression-free-survival (PFS) Up to 7 years
Trial Locations
- Locations (17)
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Clinica Universidad de Navarra - Madrid
🇪🇸Madrid, Spain
University Hospital Doctor Peset
🇪🇸Valencia, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Spain
La Fe University Hospital
🇪🇸Valencia, Spain
Hospital Clinico Universitario Santiago de Compostela
🇪🇸Santiago de Compostela, A Coruna, Spain
Hospital Universitario Virgen de las Nieves
🇪🇸Granada, Andalusia, Spain
University Hospital of Cabuenes
🇪🇸Gijon, Asturias, Spain
Hospital Universitari Son Llatzer
🇪🇸Palma Mallorca, Baleares, Spain
Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Universitario Quiron Salud Madrid
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Clinico Universitario Virgen De La Arrixaca
🇪🇸El Palmar, Murcia, Spain
Institut Catala d'Oncologia
🇪🇸Barcelona, Spain