Clinical trial • Phase I/II • Oncology
LINVOSELTAMAB for Relapsed or refractory systemic light-chain (AL) amyloidosis | Systemic light-chain (AL) amyloidosis
Phase I/II trial of LINVOSELTAMAB for Relapsed or refractory systemic light-chain (AL) amyloidosis | Systemic light-chain (AL) amyloidosis.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Relapsed or refractory systemic light-chain (AL) amyloidosis | Systemic light-chain (AL) amyloidosis
- Trial Stage
- Phase I/II
- Drug Modality
- Other antibody
Key dates
- Initial CTIS Submission Date
- 07-03-2024
- First CTIS Authorization Date
- 03-06-2024
Trial design
open-label, low dose (linvoseltamab) vs high dose (linvoseltamab); no doses or schedules specified in the provided data-controlled, adaptive Phase I/II trial in Spain, Greece.
- Open Label
- Yes
- Comparator
- Low Dose (linvoseltamab) vs High Dose (linvoseltamab); no doses or schedules specified in the provided data
- Adaptive
- True - Phase 1 includes dose-escalation cohorts (Cohort 1: Low Dose; Cohort 2: High Dose) and Phase 2 is a dose-expansion comparing two dose levels. Specific escalation rules or stopping rules are not provided in the available data.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 113
Eligibility
Recruits 113 No vulnerable population selected (isVulnerablePopulationSelected:false); consent/assent handling not specified in the available data (ICF documents referenced but content not provided)..
- Vulnerable Population
- No vulnerable population selected (isVulnerablePopulationSelected:false); consent/assent handling not specified in the available data (ICF documents referenced but content not provided).
Inclusion criteria
- {"criterion_text":"- Confirmed diagnosis of AL amyloidosis, as described in the protocol\n- Measurable disease as defined by serum difference between involved and uninvolved free light chains (dFLC) concentration, as described in the protocol\n- Previously treated after at least 1 prior therapy and requiring further treatment as assessed by the Investigator\n- N-terminal pro b-type natriuretic peptide (NT-proBNP) ≤8500 ng/L during screening\n- Adequate hepatic, hematologic, renal, and cardiac function, as described in the protocol\n- Eastern Cooperative Oncology Group (ECOG) performance score ≤2 at screening\n- NOTE: Other protocol defined inclusion criteria apply"}
Exclusion criteria
- {"criterion_text":"- History of other non-AL amyloidosis\n- Greater than 60% plasmacytosis on a bone marrow biopsy and/or aspirate during screening\n- Presence of lytic bone lesion(s) or extramedullary plasmacytoma on imaging during screening\n- Myocardial infarction within the past 6 months prior to the first screening visit\n- Known active infection requiring hospitalization or treatment with IV anti-infectives within 28 days of first administration of study drug\n- NOTE: Other protocol defined exclusion criteria apply"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Phase 1: Incidence of dose-limiting toxicity (DLTs)","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Phase 2: Achievement of hematologic complete response (CR) as determined by the Independent Review Committee (IRC)","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
Secondary endpoints
- {"endpoint_text":"- Achievement of hematologic CR, as determined by the IRC - Phase 1","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Achievement of hematologic very good partial response (VGPR) or better response (CR + VGPR), as determined by the IRC","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Achievement of overall hematologic response (PR or better), as determined by the IRC","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Time to initial hematologic response","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Time to best hematologic response","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Duration of hematologic response (ie, best response, VGPR or better, overall response), as determined by the IRC","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Hematologic progression-free survival (PFS)","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Incidence of death","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Incidence of treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Severity of TEAEs","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Incidence of serious adverse events (SAEs)","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Severity of SAEs","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Incidence of adverse events of special interest (AESIs)","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Severity of AESIs","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Achievement of overall hematologic response (PR or better), as determined by the IRC in full dose regimen 1 vs 2 - Phase 2","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Incidence of TEAEs in full dose regimen 1 vs 2 - Phase 2","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Severity of TEAEs in full dose regimen 1 vs 2 - Phase 2","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Incidence of SAEs in full dose regimen 1 vs 2 - Phase 2","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Severity of SAEs in full dose regimen 1 vs 2 - Phase 2","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Incidence of AESIs in full dose regimen 1 vs 2 - Phase 2","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Severity of AESIs in full dose regimen 1 vs 2 - Phase 2","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Time from treatment initiation to hematologic disease progression as determined by the IRC","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Time from treatment initiation to cardiac deterioration, as determined by the IRC","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Time from treatment initiation to kidney deterioration as determined by the IRC","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Time from treatment initiation to death as determined by the IRC","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Time from initiation of treatment to date of death from any cause","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Achievement of renal response in participants with renal involvement at baseline, as determined by IRC","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Achievement of cardiac response in participants with cardiac involvement at baseline, as determined by IRC","definition_or_measurement_approach":"Determined by the Independent Review Committee (IRC)"}
- {"endpoint_text":"- Time to first renal response in participants with renal involvement at baseline","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Time to first cardiac response in participants with cardiac involvement at baseline","definition_or_measurement_approach":"Not specified in the provided data"}
- {"endpoint_text":"- Linvoseltamab concentration in serum over time","definition_or_measurement_approach":"Pharmacokinetic measurement: serum concentration over time (PK)"}
- {"endpoint_text":"- Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time","definition_or_measurement_approach":"Measurement of ADA incidence over time"}
- {"endpoint_text":"- Titers of ADAs to linvoseltamab over time","definition_or_measurement_approach":"Measurement of ADA titers over time"}
Recruitment
- Digital Remote Recruitment
- True - includes banner ads, digital banner previews, online patient educational video, PRO/eCOA and Interactive Voice Response System (IRT) support
- Planned Sample Size
- 113
- Recruitment Window Months
- 128
- Consent Approach
- Informed consent documents are available (Subject information and informed consent form documents: Main, FBR, Cardiac MRI, Pregnant Partner versions referenced). Participants are adults; the participant provides informed consent. No paediatric assent documents were identified in the provided materials; detailed consent language and languages are not available in the extracted data.
Methods
- Patient educational video (third party: Simpleshow USA Corp.)
- Posters (K2_R5458-ONC-2274_Poster Layout_FP) - recruitment materials associated with Spain (application part II id 241606)
- Banner ads / digital banners (K2 banner ads layout and preview) - associated with Spain
- Caregiver brochure (K2_Caregiver Brochure_Layout_FP) - associated with Spain
- Recruitment process descriptions (K1_Recruit-ICF process) - documents present for Greece and Spain
- Central patient toolkit (third party: Clariness GmbH) referenced as patient support material
- PRO/eCOA and IRT support (third party: Yprime LLC) referenced as recruitment/assessment support
Geography
- Total Number Of Sites
- 6
- Total Number Of Participants
- 27
Spain
- Earliest CTIS Part Ii Submission Date
- 07-05-2024
- Latest Decision Or Authorization Date
- 24-09-2025
- Processing Time Days
- 505
- Number Of Sites
- 5
- Number Of Participants
- 23
Sites
- Site Name
- University Hospital Son Espases
- Department Name
- Hematology
- Principal Investigator Name
- Antonia Sampol Mayol
- Principal Investigator Email
- antonia.sampolm@ssib.es
- Contact Person Name
- Antonia Sampol Mayol
- Contact Person Email
- antonia.sampolm@ssib.es
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Hematology
- Principal Investigator Name
- Francisco Javier de la Rubia Comos
- Principal Investigator Email
- delarubia_jav@gva.es
- Contact Person Name
- Francisco Javier de la Rubia Comos
- Contact Person Email
- delarubia_jav@gva.es
- Site Name
- Clinica Universidad De Navarra
- Department Name
- Hematology
- Principal Investigator Name
- Ramon Lecumberri Villamediana
- Principal Investigator Email
- rlecumber@unav.es
- Contact Person Name
- Ramon Lecumberri Villamediana
- Contact Person Email
- rlecumber@unav.es
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- Hematology
- Principal Investigator Name
- María Teresa Cibeira López
- Principal Investigator Email
- mcibeira@clinic.cat
- Contact Person Name
- María Teresa Cibeira López
- Contact Person Email
- mcibeira@clinic.cat
- Site Name
- Hospital Universitario De Cabuenes
- Department Name
- Hematology
- Principal Investigator Name
- Maria Esther Gonzalez Garcia
- Principal Investigator Email
- mariaesther.gonzalez@sespa.es
- Contact Person Name
- Maria Esther Gonzalez Garcia
- Contact Person Email
- mariaesther.gonzalez@sespa.es
Greece
- Earliest CTIS Part Ii Submission Date
- 03-06-2025
- Latest Decision Or Authorization Date
- 15-07-2025
- Processing Time Days
- 42
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Alexandra Hospital
- Department Name
- Department of Clinical Therapeutics of National and Kapodistrian University of Athens
- Principal Investigator Name
- Efstathios Kastritis
- Principal Investigator Email
- ekastritis@med.uoa.gr
- Contact Person Name
- Efstathios Kastritis
- Contact Person Email
- ekastritis@med.uoa.gr
Sponsor
Primary sponsor
- Full Name
- Regeneron Pharmaceuticals Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Icon Clinical Research Limited
- Responsibilities
- CRO Management
Third parties
- {"country":"United States","full_name":"Simpleshow USA Corp.","duties_or_roles":"Patient educational Video","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"PRO/eCOA and translations, Interactive voice response system (IRT)","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Central Lab","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Germany","full_name":"Clariness GmbH","duties_or_roles":"Patient Toolkit","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"CRO Management","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Imaging and Adjudication","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Linvoseltamab
- Active Substance
- LINVOSELTAMAB
- Modality
- Other antibody
- Routes Of Administration
- SOLUTION FOR INFUSION; SOLUTION FOR INJECTION
- Route
- SOLUTION FOR INFUSION; SOLUTION FOR INJECTION
- Authorisation Status
- prodAuthStatus:1
- Investigational Product Name
- REGN88
- Active Substance
- SARILUMAB
- Modality
- Other antibody
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Authorisation Status
- prodAuthStatus:1
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