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

Phase 2RecruitingNCT05828511

Regeneron Pharmaceuticals149 enrolled

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

LinvoseltamabDRUG

Linvoseltamab will be administered by intravenous (IV) infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 2. Confirmed diagnosis of symptomatic Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria, as described in the protocol 3. Response-evaluable myeloma, according to the 2016 IMWG response criteria, as defined in the protocol 4. 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 5. Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol 6. 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. Key Exclusion Criteria: 1. 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 2. 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 3. Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy 4. 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

Locations (32)

University of California Los Angeles (UCLA)

Los Angeles, California, United States

RECRUITING

UC Irvine Health

Orange, California, United States

RECRUITING

Colorado Blood Cancer Institute/SCRI

Denver, Colorado, United States

RECRUITING

Norton Cancer Institute

Louisville, Kentucky, United States

Outcomes

Primary Outcomes

Incidence of Dose-Limiting Toxicities (DLTs)

Phase 1

Time frame: End of the Observation period; up to day 28

Incidence of Treatment-Emergent Adverse Events (TEAEs)

Phase 1

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Severity of TEAEs

Phase 1

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Incidence of Adverse Events of Special Interest (AESIs)

Phase 1

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Severity of AESIs

Phase 1

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

Phase 2

Time frame: Up to 5 years

Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy

Phase 2 Transplant-eligible cohort

Time frame: Up to 5 years

Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy

Phase 2 Transplant-eligible cohort

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

Phase 2 Transplant-ineligible cohort

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

Phase 2 Transplant ineligible cohort

Time frame: Up to 5 years

Secondary Outcomes

Concentrations of Linvoseltamab in serum

Phases 1 and 2

Time frame: Post-Last Linvoseltamab Dose, up to 12 weeks

Concentrations of total soluble B-Cell Maturation Antigen (BCMA)

Phases 1 and 2

Time frame: Post-Last Linvoseltamab Dose, up to 12 weeks

Incidence of Anti-Drug Antibodies (ADAs) to Linvoseltamab

Phases 1 and 2

Time frame: Post-Last Linvoseltamab Dose, up to 30 days

Magnitude of ADAs to Linvoseltamab

Phases 1 and 2

Time frame: Post-Last Linvoseltamab Dose, up to 30 days

Objective Response Rate (ORR) measured using the IMWG criteria

Phase 1

Time frame: Up to 5 years

Duration Of Response (DOR) measured using the IMWG criteria

Phase 1

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Progression-Free Survival (PFS) measured using the IMWG criteria

Phase 1

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

Phase 1

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Incidence of TEAEs

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Severity of TEAEs

Central Contacts

Clinical Trials Administrator

CONTACT

844-734-6643 clinicaltrials@regeneron.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Karmanos Cancer Institute

Detroit, Michigan, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

RECRUITING

Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Mineola, New York, United States

RECRUITING

Perlmutter Cancer Center

New York, New York, United States

RECRUITING

Columbia University _ New York Presbyterian

New York, New York, United States

RECRUITING

Stony Brook University Hospital

Stony Brook, New York, United States

RECRUITING

...and 22 more locations

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Incidence of AESIs

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Severity of AESIs

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician

Phase 2

Time frame: Up to 5 years

MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Time To Response (TTR) as measured using the IMWG criteria

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

ORR by risk levels

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

MRD-negative status by risk levels

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

DOR by risk levels

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

TTR by risk levels

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

PFS by risk levels

Phase 2

Time frame: Post-Last Linvoseltamab Dose, up to 90 days

Incidence of MRD-negative status

Phase 2

Time frame: Up to 5 years

Cluster of Differentiation 34+ (CD34+) stem cell yield

Phase 2 Transplant-eligible cohort

Time frame: At cycle 4 of induction (each cycle is 28 days long)

Time to neutrophil engraftment

Phase 2 Transplant-eligible cohort

Time frame: Up to 100 days post-transplant

Time to platelet engraftment

Phase 2 Transplant-eligible cohort

Time frame: Up to 100 days post-transplant

PFS after ASCT followed by 3 cycles of linvoseltamab

Phase 2 Transplant-eligible cohort

Time frame: Up to 5 years