Relapsed/Refractory Systemic Light Chain Amyloidosis
Conditions
Keywords
Amyloid light-chain (AL), Multiple Myeloma (MM), Pathogenic light chains
Brief summary
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)
Interventions
DRUGLinvoseltamab
anti-B-cell maturation antigen x anti-Cluster of differentiation 3 bispecific antibody
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Note: Participants enrolled in Phase 2 will be randomized 1:1
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity (DLTs) | Up to 28 Days | Phase 1 |
| Achievement of hematologic complete response (CR) as determined by the Independent Review Committee (IRC) | Up to 3 years | Phase 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of hematologic CR, as determined by the IRC | Up to 3 years | Phase 1 |
| 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 | Up to 39 months | Phase 2 |
| Incidence of TEAEs in dose regimen 1 vs 2 | Up to 39 months | Phase 2 |
| Severity of TEAEs in dose regimen 1 vs 2 | Up to 39 months | Phase 2 |
| Incidence of SAEs in dose regimen 1 vs 2 | Up to 39 months | Phase 2 |
| Severity of SAEs in dose regimen 1 vs 2 | Up to 39 months | Phase 2 |
| Incidence of AESIs in dose regimen 1 vs 2 | Up to 39 months | Phase 2 |
| Severity of AESIs in dose regimen 1 vs 2 | Up to 39 months | Phase 2 |
| 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 | — |
Countries
Greece, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed