Adult Outpatient Linvoseltamab With Tocilizumab Prophylaxis to Mitigate the Risk of Cytokine Release Syndrome (CRS) (POPLIN)

A Phase 4, Single-Arm, Multicenter Study of Prophylactic Tocilizumab in Participants With Relapsed/Refractory Multiple Myeloma Treated With Linvoseltamab in the Outpatient Setting

This study is researching whether the use of tocilizumab before the first dose of linvoseltamab will decrease the risk of Cytokine Release Syndrome (CRS) in participants who have Relapsed or Refractory Multiple Myeloma (RRMM) who have already been treated with at least four lines of treatment for their multiple myeloma, including medicines called a proteasome inhibitor, an immunomodulatory drug, and an anti-Cluster of Differentiation (CD) 38 antibody.

The aim of the study is to see how safe, tolerable and effective linvoseltamab is when given after tocilizumab.

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

• What side effects may happen from taking tocilizumab before the first dose of linvoseltamab
• Whether tocilizumab has an impact on CRS, including whether participants require hospital care and, if so, how many hospital visits occur and how long they last
• How frequently other medications (for example, corticosteroids or additional doses of tocilizumab) are used to support participants' care if needed

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma (RRMM)
• Intervention / Treatment: Drug: Linvoseltamab; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Disease progression on or after at least 4 prior lines of therapy including a(n) Protease Inhibitor (PI), Immunomodulatory imide Drug (IMiD), and anti-CD 38 antibody
2. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2
3. Confirmed progressive disease according to IMWG criteria during or after the most recent line of therapy

Key Exclusion Criteria:

1. Diagnosis of plasma cell leukemia, symptomatic amyloidosis (including myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome
2. Known myeloma brain lesions or meningeal involvement
3. History of neurodegenerative condition, Progressive Multifocal Leukoencephalopathy [PML], or Central Nervous System (CNS) movement disorder

NOTE: Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Linvoseltamab	Drug: Linvoseltamab; Administered per the protocol; Other Names: REGN5458; Lynozyfic™; Drug: Tocilizumab; Administered per the protocol; Other Names: ACTEMRA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of any grade CRS per American Society for Transplantation and Cellular Therapy (ASTCT) grading	Up to 28 days
Severity of any grade CRS per ASTCT grading	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		Up to 12 months
Duration Of Response (DOR)		Up to 12 months
Progression-Free Survival (PFS)		Up to 12 months
Occurrence of CRS of any grade		Up to 12 months
Occurrence of recurrent CRS of any grade		Up to 12 months
Occurrence of grade ≥2 CRS per ASTCT grading		Up to 12 months
Occurrence of recurrent grade ≥2 CRS per ASTCT grading		Up to 12 months
Occurrence of any grade infections per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0	NCI CTCAE grade 1 to 5 version 5.0	Up to 12 months
Occurrence of grade ≥3 infections per NCI-CTCAE version 5.0		Up to 12 months
Occurrence of any grade Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) per ASTCT grading		Up to 12 months
Occurrence of grade ≥3 ICANS per ASTCT grading		Up to 12 months
Occurrence of any grade neurotoxicity per NCI-CTCAE version 5.0 grading		Up to 12 months
Occurrence of any grade neurotoxicity per ASTCT grading		Up to 12 months
Occurrence of grade ≥3 neurotoxicity per NCI-CTCAE version 5.0 grading		Up to 12 months
Occurrence of grade ≥3 neurotoxicity per ASTCT grading		Up to 12 months
Occurrence of any grade neutropenia per NCI-CTCAE version 5.0 grading		Up to 12 months
Occurrence of grade ≥3 neutropenia per NCI-CTCAE version 5.0 grading		Up to 12 months
Number of treatment doses of tocilizumab following at least 1 dose of linvoseltamab for the management CRS		Up to 12 months
Number of treatment doses of corticosteroid following at least 1 dose of linvoseltamab for the management CRS		Up to 12 months
Total duration of corticosteroid treatment following at least 1 dose of linvoseltamab for the management CRS		Up to 12 months
Number of hospitalizations per participant treated with at least 1 dose of linvoseltamab		Up to 12 months
Total length of each Adverse Event (AE)-related hospital stay		Up to 12 months
Occurrence of Treatment-Emergent Adverse Events (TEAEs) in participants treated with at least 1 dose of linvoseltamab		Up to 12 months
Severity of TEAEs in participants treated with at least 1 dose of linvoseltamab		Up to 12 months
Occurrence of Adverse Events of Special Interest (AESI) in participants treated with at least 1 dose of linvoseltamab		Up to 12 months
Severity of AESI in participants treated with at least 1 dose of linvoseltamab		Up to 12 months
Occurrence of Serious Adverse Events (SAEs) in participants treated with at least 1 dose of linvoseltamab		Up to 12 months
Severity of SAEs in participants treated with at least 1 dose of linvoseltamab		Up to 12 months
Achievement of Partial Response or better (≥PR) per International Myeloma Working Group (IMWG) criteria		Up to 12 months
Time To Response (TTR)		Up to 12 months

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): July 17, 2026
• Primary Completion (Estimated): October 11, 2027
• Study Completion (Estimated): December 6, 2028

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Tocilizumab; Cytokine Release Syndrome (CRS); Bispecific antibodies; Linvoseltamab
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Systemic Inflammatory Response Syndrome; Inflammation; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Shock; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Cytokine Release Syndrome; Multiple Myeloma; tocilizumab
• Other Study ID Numbers: R5458-HM-2514

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No