A Trial to Learn if Linvoseltamab is Safe and Works in Adults With Relapsed or Refractory Systemic Light Chain Amyloidosis (AL Amyloidosis) (LINKER-AL2)

A Phase 1/2 Study of Linvoseltamab in Patients With Relapsed or Refractory Systemic Light Chain Amyloidosis

This study is researching an experimental drug called linvoseltamab ("study drug").

This study is focused on patients who have AL amyloidosis that has returned or have failed other therapies and need to be treated again.

The study consists of 2 phases (Phase 1 and Phase 2):

• In Phase 1, linvoseltamab will be given to a small number of participants to study the side effects of the study drug and to determine the recommended doses of the study drug to be given to participants in Phase 2.
• In Phase 2, linvoseltamab will be given to more participants to continue to assess the side effects of the study drug and to evaluate the ability of linvoseltamab to treat AL amyloidosis.

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

• How many participants treated with linvoseltamab have improvement in the abnormal proteins that cause organ problems and for how long
• How many participants treated with linvoseltamab have improvement in the heart or kidney and for how long
• What the right dosing regimen is for linvoseltamab
• What side effects may happen from taking linvoseltamab
• How much linvoseltamab is in your 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 Overview

• Status: Not yet recruiting
• Conditions: Relapsed/Refractory Systemic Light Chain Amyloidosis
• Intervention / Treatment: Drug: Linvoseltamab

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2; Phase 1

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. Confirmed diagnosis of AL amyloidosis, as described in the protocol
2. Measurable disease as defined by serum difference between involved and uninvolved free light chains (dFLC) concentration, as described in the protocol
3. Previously treated after at least 1 prior therapy and no more than 4 lines of therapy (including autologous stem cell transplant) and requiring further treatment as assessed by the Investigator
4. N-terminal pro b-type natriuretic peptide (NT-proBNP) ≤8500 ng/L during screening
5. Adequate hepatic, hematologic, renal, and cardiac function, as described in the protocol
6. Eastern Cooperative Oncology Group (ECOG) performance score ≤2 at screening

Key Exclusion Criteria:

1. History of other non-AL amyloidosis
2. Greater than 60% plasmacytosis on a bone marrow biopsy and/or aspirate during screening
3. Presence of lytic bone lesion(s) or extramedullary plasmacytoma on imaging during screening
4. Myocardial infarction within the past 6 months prior to the first screening visit
5. Known active infection requiring hospitalization or treatment with IV anti-infectives within 28 days of first administration of study drug

NOTE: Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Cohort 1: Low Dose; Dose Escalation: Non-Randomized	Drug: Linvoseltamab; anti-B-cell maturation antigen x anti-Cluster of differentiation 3 bispecific antibody; Other Names: REGN5458
Experimental: Phase 1: Cohort 2: High Dose; Dose Escalation: Non-Randomized	Drug: Linvoseltamab; anti-B-cell maturation antigen x anti-Cluster of differentiation 3 bispecific antibody; Other Names: REGN5458
Experimental: Phase 2: Low Dose; Dose Expansion: Participants will be randomized in a 1:1 ratio	Drug: Linvoseltamab; anti-B-cell maturation antigen x anti-Cluster of differentiation 3 bispecific antibody; Other Names: REGN5458
Experimental: Phase 2: High Dose; Dose Expansion: Participants will be randomized in a 1:1 ratio	Drug: Linvoseltamab; anti-B-cell maturation antigen x anti-Cluster of differentiation 3 bispecific antibody; Other Names: REGN5458

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicity (DLTs)	Phase 1	Up to 28 Days
Achievement of hematologic complete response (CR) as determined by the Independent Review Committee (IRC)	Phase 2	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of hematologic CR, as determined by the IRC	Phase 1	Up to 3 years
Achievement of hematologic very good partial response (VGPR) or better response (CR + VGPR), as determined by the IRC		Up to 3 years
Achievement of overall hematologic response (PR or better), as determined by the IRC		Up to 3 years
Time to initial hematologic response		Up to 3 years
Time to best hematologic response		Up to 3 years
Duration of hematologic response (ie, best response, VGPR or better, overall response), as determined by the IRC		Up to 7 years
Hematologic progression-free survival (PFS)		Up to 7 years
Incidence of death		Up to 7 years
Incidence of treatment-emergent adverse events (TEAEs)		Up to 39 months
Severity of TEAEs		Up to 39 months
Incidence of serious adverse events (SAEs)		Up to 39 months
Severity of SAEs		Up to 39 months
Incidence of adverse events of special interest (AESIs)		Up to 39 months
Severity of AESIs		Up to 39 months
Achievement of overall hematologic response (PR or better), as determined by the IRC in dose regimen 1 vs 2	Phase 2	Up to 39 months
Incidence of TEAEs in dose regimen 1 vs 2	Phase 2	Up to 39 months
Severity of TEAEs in dose regimen 1 vs 2	Phase 2	Up to 39 months
Incidence of SAEs in dose regimen 1 vs 2	Phase 2	Up to 39 months
Severity of SAEs in dose regimen 1 vs 2	Phase 2	Up to 39 months
Incidence of AESIs in dose regimen 1 vs 2	Phase 2	Up to 39 months
Severity of AESIs in dose regimen 1 vs 2	Phase 2	Up to 39 months
Time from treatment initiation to hematologic disease progression as determined by the IRC		Up to 7 years
Time from treatment initiation to cardiac deterioration, as determined by the IRC		Up to 7 years
Time from treatment initiation to kidney deterioration as determined by the IRC		Up to 7 years
Time from treatment initiation to death as determined by the IRC		Up to 7 years
Time from initiation of treatment to date of death from any cause		Up to 7 years
Achievement of renal response in participants with renal involvement at baseline, as determined by IRC		Up to 7 years
Achievement of cardiac response in participants with cardiac involvement at baseline, as determined by IRC		Up to 7 years
Time to first renal response in participants with renal involvement at baseline		Up to 7 years
Time to first cardiac response in participants with cardiac involvement at baseline		Up to 7 years
Linvoseltamab concentration in serum over time		Up to 39 months
Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time		Up to 39 months
Titers of ADAs to linvoseltamab over time		Up to 39 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): April 29, 2024
• Primary Completion (Estimated): August 26, 2028
• Study Completion (Estimated): February 26, 2035

Study Registration Dates

• First Submitted: February 27, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Estimated): March 5, 2024

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma (MM); Amyloid light-chain (AL); Pathogenic light chains
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: R5458-ONC-2274; 2023-507809-34-00 (Other Identifier: EUCT Number)

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, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has 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