A Trial to Learn if Linvoseltamab is Safe and Works in Adults With Relapsed or Refractory Systemic Light Chain Amyloidosis (AL Amyloidosis)
- Conditions
- Relapsed/Refractory Systemic Light Chain Amyloidosis
- Interventions
- Registration Number
- NCT06292780
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 220
- Confirmed diagnosis of AL amyloidosis, as described in the protocol
- Measurable disease as defined by serum difference between involved and uninvolved free light chains (dFLC) concentration, as described in the protocol
- Previously treated after at least 1 prior therapy and requiring further treatment as assessed by the Investigator
- N-terminal pro b-type natriuretic peptide (NT-proBNP) ≤8500 ng/L during screening
- Adequate hepatic, hematologic, renal, and cardiac function, as described in the protocol
- Eastern Cooperative Oncology Group (ECOG) performance score ≤2 at screening
Key
- History of other non-AL amyloidosis
- Greater than 60% plasmacytosis on a bone marrow biopsy and/or aspirate during screening
- Presence of lytic bone lesion(s) or extramedullary plasmacytoma on imaging during screening
- Myocardial infarction within the past 6 months prior to the first screening visit
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1: Cohort 2: High Dose Linvoseltamab Dose Escalation: Non-Randomized Phase 2: Low Dose Linvoseltamab Dose Expansion: Participants will be randomized in a 1:1 ratio Phase 1: Cohort 1: Low Dose Linvoseltamab Dose Escalation: Non-Randomized Phase 2: High Dose Linvoseltamab Dose Expansion: Participants will be randomized in a 1:1 ratio
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Time to first renal response in participants with renal involvement at baseline Up to 7 years Severity of TEAEs Up to 39 months Time from treatment initiation to kidney deterioration as determined by the IRC Up to 7 years Time to initial hematologic response Up to 3 years Hematologic progression-free survival (PFS) Up to 7 years Incidence of serious adverse events (SAEs) Up to 39 months Severity of AESIs 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 death as determined by the 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 best hematologic response Up to 3 years Incidence of treatment-emergent adverse events (TEAEs) 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
Achievement of renal response in participants with renal involvement at baseline, as determined by IRC 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 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 Duration of hematologic response (ie, best response, VGPR or better, overall response), as determined by the IRC Up to 7 years Severity of SAEs Up to 39 months 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
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
Titers of ADAs to linvoseltamab over time Up to 39 months Achievement of hematologic CR, as determined by the IRC Up to 3 years Phase 1
Incidence of death Up to 7 years Incidence of adverse events of special interest (AESIs) Up to 39 months Incidence of SAEs 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 cardiac deterioration, 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 Time to first cardiac response in participants with cardiac involvement at baseline Up to 7 years
Trial Locations
- Locations (16)
Colorado Blood Cancer Institute/SCRI
🇺🇸Denver, Colorado, United States
City of Hope
🇺🇸Duarte, California, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul St. Mary's Hospital - The Catholic University of Korea
🇰🇷Seoul, Korea, Republic of
Hospital de Cabuenes
🇪🇸Gijon, Asturias, Spain
Hospital Universitari Son Espases
🇪🇸Palma, Balearic Islands, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Universität de Barcelona- Institut d' Investigacions Biomediques August Pi i Sunyer (IDIBAPS)
🇪🇸Barcelona, Spain
University Hospital La Fe
🇪🇸Valencia, Spain
University College London Hospitals
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom