A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment

Official title

Phase 1/2 Study of Linvoseltamab (Anti-BCMA X Anti-CD3 Bispecific Antibody) in Previously Untreated Patients With Symptomatic Multiple Myeloma

Overview

This study is researching an experimental drug called linvoseltamab (called "study drug"). The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are eligible for high dose chemotherapy with autologous stem cell transplantation (transplant-eligible) or ineligible for autologous stem cell transplantation (transplant-ineligible). The aim of this clinical trial is to study the safety, tolerability (how the body reacts to the drug), and effectiveness (tumor shrinkage) of linvoseltamab in study participants with NDMM as a first step in determining if the study drug has a role in the treatment of NDMM. This study consists of 2 phases: * In Phase 1 Parts A and B, the study drug will be given to participants to study the side effects of the study drug and to establish the regimen (initial doses and full dose) of the study drug to be given to participants in Phase 2. * In Phase 1 Part C, the study drug will be given to participants to study the side effects when using different initial doses of the study drug. * In Phase 2, the study drug will be given to more participants to continue to assess the side effects of the study drug and to evaluate the activity of the study drug to shrink the tumor (multiple myeloma) in participants with NDMM. The study is looking at several research questions, including: * What side effects may happen from taking linvoseltamab? * What the right dosing regimen is for linvoseltamab? * How many participants treated with linvoseltamab have improvement of their disease and for how long? * The effects of linvoseltamab study treatment before and after transplant * How much linvoseltamab is in the blood at different times? * Whether the body makes antibodies against linvoseltamab (which could make the drug less effective or could lead to side effects).

Interventions

• Drug Linvoseltamab
  Linvoseltamab will be administered by intravenous (IV) infusion

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: End of the Observation period; up to day 28]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]
• Severity of TEAEs [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]
• Incidence of Adverse Events of Special Interest (AESIs) [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]
• Severity of AESIs [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]
• Proportion of participants with a Very Good Partial Response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria [Time frame: Up to 5 years]
• Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy [Time frame: Up to 5 years]
• Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy [Time frame: Up to 5 years]
• Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II [Time frame: Up to 5 years]
• Proportion of participants achieving MRD-negative status as their best response after treatment period I without continuing to treatment period II [Time frame: Up to 5 years]

Secondary outcome measures (12)

• Concentrations of Linvoseltamab in serum [Time frame: Post-Last Linvoseltamab Dose, up to 12 weeks]
• Concentrations of total soluble B-Cell Maturation Antigen (BCMA) [Time frame: Post-Last Linvoseltamab Dose, up to 12 weeks]
• Incidence of Anti-Drug Antibodies (ADAs) to Linvoseltamab [Time frame: Post-Last Linvoseltamab Dose, up to 30 days]
• Magnitude of ADAs to Linvoseltamab [Time frame: Post-Last Linvoseltamab Dose, up to 30 days]
• Objective Response Rate (ORR) measured using the IMWG criteria [Time frame: Up to 5 years]
• Duration Of Response (DOR) measured using the IMWG criteria [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]
• Progression-Free Survival (PFS) measured using the IMWG criteria [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]
• Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]
• Incidence of TEAEs [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]
• Severity of TEAEs [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]
• Incidence of AESIs [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]
• Severity of AESIs [Time frame: Post-Last Linvoseltamab Dose, up to 90 days]

Eligibility criteria

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Confirmed diagnosis of symptomatic Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria, as described in the protocol
• Response-evaluable myeloma, according to the 2016 IMWG response criteria, as defined in the protocol
• No prior therapy for MM, with the exception of prior emergent or palliative radiation and up to 1 month of single-agent corticosteroids, with washout periods as per the protocol
• Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol
• Participants must be age <70 and have adequate hepatic, renal, pulmonary and cardiac function to be considered transplant-eligible. The specific thresholds for adequate organ function are as per institutional guidance.

Exclusion criteria

• Receiving any concurrent investigational agent with known or suspected activity against MM, or agents targeting the A proliferation-inducing ligand (APRIL)/ Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)/BCMA axis
• Known Central Nervous System (CNS) involvement with MM, known or suspected Progressive Multifocal Leukoencephalopathy (PML), a history of neurocognitive conditions, or CNS movement disorder, or history of seizure within 12 months prior to study enrollment
• Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy
• Diagnosis of non-secretory MM, active plasma cell leukemia primary light-chain (AL) amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (Plasma cell dyscrasia with polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes)

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

United States · 13 centers

• University of California Los Angeles (UCLA) — Los Angeles
• UC Irvine Health — Orange
• Colorado Blood Cancer Institute/SCRI — Denver
• Norton Cancer Institute — Louisville
• Karmanos Cancer Institute — Detroit
• Rutgers Cancer Institute of New Jersey — New Brunswick
• Perlmutter Cancer Center at NYU Langone Hospital - Long Island — Mineola
• Perlmutter Cancer Center — New York
• … and 5 more centers

Spain · 11 centers

• Hospital Germans Trias i Pujol — Badalona
• Hospital Universitario Quiron Salud Madrid — Pozuelo de Alarcón
• Clinica Universidad de Navarra — Pamplona
• Hospital Universitario Central de Asturias — Oviedo
• Hospital General Universitario Doctor Balmis Alicante — Alicante
• Hospital Clinic de Barcelona — Barcelona
• Institut Catala dOncologia (ICO Hospitalet) — Barcelona
• Universitary Hospital La Princesa — Madrid
• … and 3 more centers

France · 8 centers

• Centre Hospitalier Universitaire (CHU) de Poitiers — Poitiers
• CHU De Lille — Lille
• Centre Hospitalier Universitaire (CHU) Montpellier — Montpellier
• Hopital Saint Louis — Paris
• University Hospitals Pitie Salpetriere - Charles Foix — Paris
• Hopital Prive d'Antony — Antony
• Hopital Necker — Paris
• Gustave Roussy — Villejuif

Identifiers

NCT: NCT05828511 · R5458-ONC-2158 · 2022-500800-24-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗