Clinical trial NCT06140524: A Proof-of-Concept Study to Learn Whether Linvoseltamab Can Eliminate Abnormal Plasma Cells That May Lead to Multiple Myeloma in Adult Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma
Official title: Phase 2 Dose-Ranging and Interception Study of Linvoseltamab in Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Monoclonal Gammopathy of Undetermined Significance (MGUS)
Smoldering Multiple Myeloma (SMM)
Keywords: linvoseltamab
monoclonal immunoglobulin (M-protein)
cancer interception
immunotherapy
plasma cell disorders
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-11-20
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of high-risk monoclonal gammopathy of undetermined significance (HR-MGUS) and non high-risk smoldering multiple myeloma (NHR-SMM). This requires understanding the safety and tolerability of the study drug (how the body reacts to linvoseltamab) as well as the effectiveness of the study drug (how well linvoseltamab eliminates plasma cells). All participants will start treatment with gradually increasing doses of linvoseltamab (step-up doses) before they start receiving the assigned full dose.

The study is split into 2 parts:

* In Part 1, separate groups of 3-6 patients will receive different full doses of linvoseltamab to evaluate the short-term side effects (safety) and tolerability of the study drug within the first 5 weeks after starting treatment. The data collected will help to make a decision about the dosing regimens chosen for Part 2.
* In Part 2, a larger number of participants will be randomized to different dosing regimens to further assess the side effects of linvoseltamab, and to evaluate the ability of linvoseltamab to eliminate abnormal plasma cells in HR-MGUS and NHR-SMM.

The study is looking at several other research questions, including:

* How many participants treated with linvoseltamab have improvement of their HR-MGUS or NHR-SMM?
* What side effects may happen from taking the study drug?
* How much study drug is in the 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).


Eligibility criteria: Key Inclusion Criteria:

1. HR-MGUS or NHR-SMM as defined in the protocol
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 (GFR) ≥30 mL/min/1.73 m2 by the modification of diet in renal disease (MDRD) equation

Key Exclusion Criteria:

1. High-risk SMM, as defined in the protocol
2. Evidence of any of myeloma-defining events, as described in the protocol
3. Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), solitary plasmacytoma, or symptomatic MM
4. Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
5. Any infection requiring hospitalization or treatment with IV anti-infectives within 28 days of the first dose of linvoseltamab
6. Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection

NOTE: Other protocol defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Frequency of adverse events of special interest (AESI) during the safety observation period
timeFrame: 35 days
measure: Frequency of treatment-emergent adverse event (TEAEs) during the safety observation period
timeFrame: 35 days
measure: Severity of TEAEs during the safety observation period
timeFrame: 35 days
measure: Achievement of complete response (CR) as determined by the investigator
timeFrame: Up to 5.5 years
Secondary outcomes:
measure: Frequency of TEAEs
timeFrame: Up to 5.5 years
measure: Severity of TEAEs
timeFrame: Up to 5.5 years
measure: Frequency of serious adverse events (SAEs)
timeFrame: Up to 5.5 years
measure: Severity of SAEs
timeFrame: Up to 5.5 years
measure: Frequency of laboratory abnormalities
timeFrame: Up to 5.5 years
measure: Severity of laboratory abnormalities
timeFrame: Up to 5.5 years
measure: Minimal residual disease (MRD) negativity among participants that achieve a response of CR
timeFrame: Up to 5.5 years
measure: Sustained MRD negativity on an annual basis
timeFrame: Up to 3 years after achievement of CR
measure: Overall response of partial response (PR) or better as determined by the investigator
timeFrame: Up to 5.5 years
measure: Duration of response (DOR) as determined by the investigator
timeFrame: Up to 5.5 years
measure: Biochemical progression-free survival (PFS) as determined by the investigator
timeFrame: Up to 5.5 years
measure: Concentration of linvoseltamab in serum over time
timeFrame: Up to 9 months
measure: Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time
timeFrame: Up to 9 months
measure: Titer of ADAs to linvoseltamab over time
timeFrame: Up to 9 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
state: Andalusia
city: Gijon
country: Spain
facility: Hospital de Cabuenes
state: Asturias
city: Terrassa
country: Spain
facility: Hospital Universitari Mutua Terrassa
state: Barcelona
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen De La Arrixaca
state: Murcia
city: Barcelona
country: Spain
facility: Hospital Sant Pau
city: Madrid
country: Spain
facility: Universitaru Hospital La Princesa
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: