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

Overview

This study is researching an investigational drug called linvoseltamab ("study drug") in participants at moderate risk of developing multiple myeloma (about 3 to 10% average annual risk), a group that consists of patients with precancerous conditions called High-Risk Monoclonal Gammopathy of Undetermined Significance (HR-MGUS) and Non-High-Risk Smoldering Multiple Myeloma (NHR-SMM). The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of 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).

Interventions

• Drug Linvoseltamab
  Administered per the protocol

Primary outcome measures

• Frequency of Adverse Events Interest (AEI) during the safety observation period [Time frame: 35 days]
• Frequency of Treatment-Emergent Adverse Event (TEAEs) during the safety observation period [Time frame: 35 days]
• Severity of TEAEs during the safety observation period [Time frame: 35 days]
• Achievement of Complete Response (CR) as determined by the investigator [Time frame: Up to 5.5 years]

Secondary outcome measures (12)

• Frequency of TEAEs [Time frame: Up to 5.5 years]
• Severity of TEAEs [Time frame: Up to 5.5 years]
• Frequency of Serious Adverse Events (SAEs) [Time frame: Up to 5.5 years]
• Severity of SAEs [Time frame: Up to 5.5 years]
• Frequency of laboratory abnormalities [Time frame: Up to 5.5 years]
• Severity of laboratory abnormalities [Time frame: Up to 5.5 years]
• Minimal Residual Disease (MRD) negativity among participants that achieve a response of CR [Time frame: Up to 5.5 years]
• Sustained MRD negativity on an annual basis [Time frame: Up to 3 years after achievement of CR]
• Overall response of Partial Response (PR) or better as determined by the investigator [Time frame: Up to 5.5 years]
• Duration Of Response (DOR) as determined by the investigator [Time frame: Up to 5.5 years]
• Biochemical Progression-Free Survival (PFS) as determined by the investigator [Time frame: Up to 5.5 years]
• Concentration of linvoseltamab in serum over time [Time frame: Up to 9 months]

Eligibility criteria

Inclusion criteria

• HR-MGUS or NHR-SMM as defined in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Adequate hematologic and hepatic function, as described in the protocol
• Estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73 m\^2 by the Modification of Diet in Renal Disease (MDRD) equation

Exclusion criteria

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

NOTE: Other protocol defined inclusion/exclusion criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 8 centers

• Hospital Universitario Virgen de las Nieves — Granada
• Hospital Universitari Mutua Terrassa — Terrassa
• Hospital Clinico Universitario Virgen De La Arrixaca — El Palmar
• Hospital de Cabuenes — Gijón
• Hospital Sant Pau — Barcelona
• Institut Catala dOncologia (ICO Hospitalet) — Barcelona
• Universitaru Hospital La Princesa — Madrid
• Hospital General Universitario Morales Meseguer — Murcia

United States · 7 centers

• Johns Hopkins Hospital — Baltimore
• Dana-Farber Cancer Institute — Boston
• University of Michigan Health — Ann Arbor
• NYU Langone Health Perlmutter Cancer Center — New York
• Stony Brook University Hospital — Stony Brook
• Thomas Jefferson University Hospital — Philadelphia
• University of Washington — Seattle

Italy · 7 centers

• Istituto Romagnolo per lo Studio Dei Tumori Dino Amadori — Meldola
• IRCCS Ospedale Policlinico San Martino — Genoa
• San Paolo Hospital — Milan
• Azienda Ospedaliero Universitaria (AOU) SS. Antonio e Biagio e Cesare Arrigo — Alessandria
• UOC Ematologia e Terapia Cellulare - PO Mazzoni AST Ascoli Piceno — Ascoli Piceno
• Universita degli Studi di Pavia - Fondazione IRCCS Policlini — Pavia
• Ospedale Santa Maria delle Croci — Ravenna

Belgium · 6 centers

• Algemeen Ziekenhuis (AZ) Klina — Brasschaat
• AZ St.-Elisabeth Herentals vzw — Herentals
• AZ Sint Maarten Algemeen Ziekenhuis Emmaus — Mechelen
• Algemeen Ziekenhuis St Jan Brugge Oostende Av — Bruges
• Algemeen Ziekenhuis AZ Delta — Roeselare
• Ziekenhuis Netwerk Antwerpen Cadix, Hematology — Antwerp

Poland · 6 centers

• Wojewodzki Szpital Zespolony - Ludwik Rydygier Provincial Hospital — Torun
• Specjalistyczny Szpital im A. Sokolowskiego w Walbrzychu — Wałbrzych
• Pratia MCM Krakow — Krakow
• University Clinical Center / Medical University of Gdansk — Gdansk
• Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Mikolaja Kopernika — Lodz
• Swietokrzyskie Centrum Onkologii — Kielce

Ireland · 3 centers

• Galway University Hospital — Galway
• Cork University Hospital — Cork
• Mater Misericordiae University Hospital — Dublin

France · 2 centers

• Centre Hospitalier Universitaire De Poitiers — Poitiers
• Institut Curie — Paris

Identifiers

NCT: NCT06140524 · R5458-ONC-2257 · 2023-505242-25-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗