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

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Relapsed/Refractory Systemic Light Chain Amyloidosis

Treatments: Drug: Linvoseltamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06292780

R5458-ONC-2274

2023-507809-34-00 (Other Identifier)

Details and patient eligibility

About

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 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)

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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220 participants in 4 patient groups

Phase 1: Cohort 1: Low Dose

Experimental group

Description:

Dose Escalation: Non-Randomized

Treatment:

Drug: Linvoseltamab

Phase 1: Cohort 2: High Dose

Experimental group

Description:

Dose Escalation: Non-Randomized

Treatment:

Drug: Linvoseltamab

Phase 2: Low Dose

Experimental group

Description:

Dose Expansion: Participants will be randomized in a 1:1 ratio

Treatment:

Drug: Linvoseltamab

Phase 2: High Dose

Experimental group

Description:

Dose Expansion: Participants will be randomized in a 1:1 ratio

Treatment:

Drug: Linvoseltamab