Relapsed/Refractory Systemic Light Chain AmyloidosisPhase 1/2LINKER-AL2NCT06292780
A Trial to Learn if Linvoseltamab is Safe and Works in Adults With Relapsed or Refractory Systemic Light Chain Amyloidosis (AL Amyloidosis)
A Phase 1/2 study testing Linvoseltamab in people with Relapsed/Refractory Systemic Light Chain Amyloidosis, run by Regeneron Pharmaceuticals at 21 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Systemic Light Chain Amyloidosis
- What is being tested?
- Linvoseltamab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 21 sitesin 6 countries
- Study dates
- 7 Aug 2024to 20 Feb 2035
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
21 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 6 countries
United States8 sites, 8 recruiting
- Recruiting
Boston Medical Center
Boston, Massachusetts, 02118
- Recruiting
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
- Recruiting
Ohio State University
Columbus, Ohio, 43210
- Recruiting
Colorado Blood Cancer Institute/SCRI
Denver, Colorado, 80218
- Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201
- Recruiting
City of Hope
Duarte, California, 91010
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
Spain5 sites, 5 recruiting
- Recruiting
Universität de Barcelona- Institut d' Investigacions Biomediques August Pi i Sunyer (IDIBAPS)
Barcelona, 08036
- Recruiting
Hospital de Cabuenes
Gijón, Principality of Asturias, 33203
- Recruiting
Hospital Universitari Son Espases
Palma, Balearic Islands, 07120
- Recruiting
Clinica Universidad de Navarra - Pamplona
Pamplona, Navarre, 31008
- Recruiting
University Hospital La Fe
Valencia, 46026
South Korea4 sites, 4 recruiting
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
Asan Medical Center
Seoul, 05505
- Recruiting
Samsung Medical Center
Seoul, 06351
- Recruiting
Seoul St. Mary's Hospital - The Catholic University of Korea
Seoul, 065791
United Kingdom2 sites, 1 recruiting
- Recruiting
University College London Hospitals
London, NW1 2PG
- Withdrawn
The Christie NHS Foundation Trust
Manchester, M20 4BQ
Greece1 site, 1 recruiting
- Recruiting
National and Kapodistrian University of Athens
Athens, 11528
Taiwan1 site, 1 recruiting
- Recruiting
Taipei Municipal Wan Fang Hospital
Taipei, 116
About this study
Official title: 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.
Read more
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)
- Being tested
- Linvoseltamab
- Keywords
- Amyloid light-chain (AL), Multiple Myeloma (MM), Pathogenic light chains
- Medical subject headings
- Recurrence, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinvoseltamabDrug
Also called REGN5458, Lynozyfic™
anti-B-cell maturation antigen x anti-Cluster of differentiation 3 bispecific antibody
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Cohort 1: Low Dose | Experimental | Dose Escalation: Non-Randomized Receives: Drug: Linvoseltamab |
| Phase 1: Cohort 2: High Dose | Experimental | Dose Escalation: Non-Randomized Receives: Drug: Linvoseltamab |
| Phase 2: Low Dose | Experimental | Dose Expansion: Participants will be randomized in a 1:1 ratio Receives: Drug: Linvoseltamab |
| Phase 2: High Dose | Experimental | Dose Expansion: Participants will be randomized in a 1:1 ratio Receives: Drug: Linvoseltamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicity (DLTs)
Phase 1
Measured: Up to 28 Days
Achievement of hematologic complete response (CR) as determined by the Independent Review Committee (IRC)
Phase 2
Measured: Up to 3 years
Secondary outcomes (33)
Achievement of hematologic CR, as determined by the IRC
Phase 1
Measured: Up to 3 years
Achievement of hematologic very good partial response (VGPR) or better response (CR + VGPR), as determined by the IRC
Measured: Up to 3 years
Achievement of overall hematologic response (PR or better), as determined by the IRC
Measured: Up to 3 years
Time to initial hematologic response
Measured: Up to 3 years
Time to best hematologic response
Measured: Up to 3 years
Duration of hematologic response (ie, best response, VGPR or better, overall response), as determined by the IRC
Measured: Up to 7 years
Hematologic progression-free survival (PFS)
Measured: Up to 7 years
Incidence of death
Measured: Up to 7 years
Incidence of treatment-emergent adverse events (TEAEs)
Measured: Up to 39 months
Severity of TEAEs
Measured: Up to 39 months
Incidence of serious adverse events (SAEs)
Measured: Up to 39 months
Severity of SAEs
Measured: Up to 39 months
Incidence of adverse events of special interest (AESIs)
Measured: Up to 39 months
Severity of AESIs
Measured: 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
Measured: Up to 39 months
Incidence of TEAEs in dose regimen 1 vs 2
Phase 2
Measured: Up to 39 months
Severity of TEAEs in dose regimen 1 vs 2
Phase 2
Measured: Up to 39 months
Incidence of SAEs in dose regimen 1 vs 2
Phase 2
Measured: Up to 39 months
Severity of SAEs in dose regimen 1 vs 2
Phase 2
Measured: Up to 39 months
Incidence of AESIs in dose regimen 1 vs 2
Phase 2
Measured: Up to 39 months
Severity of AESIs in dose regimen 1 vs 2
Phase 2
Measured: Up to 39 months
Time from treatment initiation to hematologic disease progression as determined by the IRC
Measured: Up to 7 years
Time from treatment initiation to cardiac deterioration, as determined by the IRC
Measured: Up to 7 years
Time from treatment initiation to kidney deterioration as determined by the IRC
Measured: Up to 7 years
Time from treatment initiation to death as determined by the IRC
Measured: Up to 7 years
Time from initiation of treatment to date of death from any cause
Measured: Up to 7 years
Achievement of renal response in participants with renal involvement at baseline, as determined by IRC
Measured: Up to 7 years
Achievement of cardiac response in participants with cardiac involvement at baseline, as determined by IRC
Measured: Up to 7 years
Time to first renal response in participants with renal involvement at baseline
Measured: Up to 7 years
Time to first cardiac response in participants with cardiac involvement at baseline
Measured: Up to 7 years
Linvoseltamab concentration in serum over time
Measured: Up to 39 months
Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time
Measured: Up to 39 months
Titers of ADAs to linvoseltamab over time
Measured: Up to 39 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2024
- Study start7 Aug 2024
- Primary completion20 Aug 2028 (estimated)
- Study completion20 Feb 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory Systemic Light Chain AmyloidosisStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Note: Participants enrolled in Phase 2 will be randomized 1:1
- Masking
- None (open label)
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06292780
- Sponsor's protocol ID
- R5458-ONC-2274
- Other IDs
- 2023-507809-34-00, 2023
- Acronym
- LINKER-AL2
- Status last verified
- Aug 2026
- First submitted
- 27 Feb 2024
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of Linvoseltamab in Patients With Relapsed or Refractory Systemic Light Chain Amyloidosis
- ClinicalTrials.gov ID
- NCT06292780
- Acronym / sponsor ID
- LINKER-AL2 / R5458-ONC-2274
- Keywords
- Amyloid light-chain (AL), Multiple Myeloma (MM), Pathogenic light chains
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Aug 2024 (actual)
- Primary completion
- 20 Aug 2028 (estimated)
- Study completion
- 20 Feb 2035 (estimated)
- First posted
- 5 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Note: Participants enrolled in Phase 2 will be randomized 1:1
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Cohort 1: Low Dose | Experimental | Drug: LinvoseltamabDose Escalation: Non-Randomized |
| Phase 1: Cohort 2: High Dose | Experimental | Drug: LinvoseltamabDose Escalation: Non-Randomized |
| Phase 2: Low Dose | Experimental | Drug: LinvoseltamabDose Expansion: Participants will be randomized in a 1:1 ratio |
| Phase 2: High Dose | Experimental | Drug: LinvoseltamabDose Expansion: Participants will be randomized in a 1:1 ratio |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LinvoseltamabAlso: REGN5458, Lynozyfic™anti-B-cell maturation antigen x anti-Cluster of differentiation 3 bispecific antibody | Drug | Phase 1: Cohort 1: Low Dose, Phase 1: Cohort 2: High Dose, Phase 2: High Dose, Phase 2: Low Dose |
Primary outcome
Incidence of dose-limiting toxicity (DLTs)
Time frame: Up to 28 Days
Phase 1
Achievement of hematologic complete response (CR) as determined by the Independent Review Committee (IRC)
Time frame: Up to 3 years
Phase 2
33 secondary outcomes
Achievement of hematologic CR, as determined by the IRC
Time frame: Up to 3 years
Achievement of hematologic very good partial response (VGPR) or better response (CR + VGPR), as determined by the IRC
Time frame: Up to 3 years
Achievement of overall hematologic response (PR or better), as determined by the IRC
Time frame: Up to 3 years
Time to initial hematologic response
Time frame: Up to 3 years
Time to best hematologic response
Time frame: Up to 3 years
Duration of hematologic response (ie, best response, VGPR or better, overall response), as determined by the IRC
Time frame: Up to 7 years
Hematologic progression-free survival (PFS)
Time frame: Up to 7 years
Incidence of death
Time frame: Up to 7 years
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: Up to 39 months
Severity of TEAEs
Time frame: Up to 39 months
Incidence of serious adverse events (SAEs)
Time frame: Up to 39 months
Severity of SAEs
Time frame: Up to 39 months
Incidence of adverse events of special interest (AESIs)
Time frame: Up to 39 months
Severity of AESIs
Time frame: Up to 39 months
Achievement of overall hematologic response (PR or better), as determined by the IRC in dose regimen 1 vs 2
Time frame: Up to 39 months
Incidence of TEAEs in dose regimen 1 vs 2
Time frame: Up to 39 months
Severity of TEAEs in dose regimen 1 vs 2
Time frame: Up to 39 months
Incidence of SAEs in dose regimen 1 vs 2
Time frame: Up to 39 months
Severity of SAEs in dose regimen 1 vs 2
Time frame: Up to 39 months
Incidence of AESIs in dose regimen 1 vs 2
Time frame: Up to 39 months
Severity of AESIs in dose regimen 1 vs 2
Time frame: Up to 39 months
Time from treatment initiation to hematologic disease progression as determined by the IRC
Time frame: Up to 7 years
Time from treatment initiation to cardiac deterioration, as determined by the IRC
Time frame: Up to 7 years
Time from treatment initiation to kidney deterioration as determined by the IRC
Time frame: Up to 7 years
Time from treatment initiation to death as determined by the IRC
Time frame: Up to 7 years
Time from initiation of treatment to date of death from any cause
Time frame: Up to 7 years
Achievement of renal response in participants with renal involvement at baseline, as determined by IRC
Time frame: Up to 7 years
Achievement of cardiac response in participants with cardiac involvement at baseline, as determined by IRC
Time frame: Up to 7 years
Time to first renal response in participants with renal involvement at baseline
Time frame: Up to 7 years
Time to first cardiac response in participants with cardiac involvement at baseline
Time frame: Up to 7 years
Linvoseltamab concentration in serum over time
Time frame: Up to 39 months
Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time
Time frame: Up to 39 months
Titers of ADAs to linvoseltamab over time
Time frame: Up to 39 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Clinical Trial Management study director
Regeneron Pharmaceuticals
21 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Linvoseltamab in people with Relapsed/Refractory Systemic Light Chain Amyloidosis, run by Regeneron Pharmaceuticals at 21 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Spain, South Korea, United Kingdom, Greece and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials Administrator (844-734-6643, clinicaltrials@regeneron.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicity (DLTs) (time frame: Up to 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026; AzTrials last refreshed its copy on 26 Oct 2026.