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

Multiple Myeloma Clinical Trial

— LINKER-MM4  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05828511
• Other study ID #: R5458-ONC-2158
• Secondary ID: 2022-500800-24-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 19, 2023
• Est. completion date: November 2, 2035

Study information

• Verified date: March 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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, 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 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 ability 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 132
• Est. completion date: November 2, 2035
• Est. primary completion date: November 2, 2035
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

3. Measurable disease, 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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

Locations

Country	Name	City	State
France	CHU De Lille	Lille
France	Hopital Universitaire Necker Enfants Malades	Paris
United States	Atrium Health Levine Cancer	Charlotte	North Carolina
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	MD Anderson Cancer Centre	Houston	Texas
United States	University of California	Los Angeles	California
United States	Norton Healthcare, Inc.	Louisville	Kentucky
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	NYU Langone Health	New York	New York
United States	UCI Health	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities (DLTs)	Phase 1	End of the Observation period; up to day 28
Primary	Incidence of treatment-emergent adverse events (TEAEs)	Phase 1	Post-Last Linvoseltamab Dose, up to 90 days
Primary	Severity of TEAEs	Phase 1	Post-Last Linvoseltamab Dose, up to 90 days
Primary	Incidence of adverse events of special interest (AESIs)	Phase 1	Post-Last Linvoseltamab Dose, up to 90 days
Primary	Severity of AESIs	Phase 1	Post-Last Linvoseltamab Dose, up to 90 days
Primary	Proportion of participants with a very good partial response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria	Phase 2	Up to 5 years
Primary	Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy	Phase 2 Transplant-eligible cohort	Up to 5 years
Primary	Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy	Phase 2 Transplant-eligible cohort	Up to 5 years
Primary	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	Up to 5 years
Primary	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	Up to 5 years
Secondary	Concentrations of Linvoseltamab in serum	Phases 1 and 2	Post-Last Linvoseltamab Dose, up to 12 weeks
Secondary	Concentrations of total soluble B-cell maturation antigen (BCMA)	Phases 1 and 2	Post-Last Linvoseltamab Dose, up to 12 weeks
Secondary	Incidence of anti-drug antibodies (ADAs) to Linvoseltamab	Phases 1 and 2	Post-Last Linvoseltamab Dose, up to 30 days
Secondary	Titer of ADAs to Linvoseltamab	Phases 1 and 2	Post-Last Linvoseltamab Dose, up to 30 days
Secondary	Objective response rate (ORR) measured using the IMWG criteria	Phase 1	Up to 5 years
Secondary	Duration of Response (DOR) measured using the IMWG criteria	Phase 1	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	Progression-free survival (PFS) measured using the IMWG criteria	Phase 1	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria	Phase 1	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	Incidence of TEAEs	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	Severity of TEAEs	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	Incidence of AESIs	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	Severity of AESIs	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician	Phase 2	Up to 5 years
Secondary	MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	Time to response (TTR) as measured using the IMWG criteria	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	ORR by risk levels	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	MRD-negative rstatus by risk levels	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	DOR by risk levels	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	TTR by risk levels	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	PFS by risk levels	Phase 2	Post-Last Linvoseltamab Dose, up to 90 days
Secondary	Incidence of MRD-negative status	Phase 2	Up to 5 years
Secondary	Cluster of differentiation 34+ (CD34+) stem cell yield	Phase 2 Transplant-eligible cohort	At cycle 4 of induction (each cycle is 28 days long)
Secondary	Time to neutrophil engraftment	Phase 2 Transplant-eligible cohort	Up to 100 days post-transplant
Secondary	Time to platelet engraftment	Phase 2 Transplant-eligible cohort	Up to 100 days post-transplant
Secondary	PFS after ASCT followed by 3 cycles of linvoseltamab	Phase 2 Transplant-eligible cohort	Up to 5 years