Clinical trial NCT06292780: A Trial to Learn if Linvoseltamab is Safe and Works in Adults With Relapsed or Refractory Systemic Light Chain Amyloidosis (AL Amyloidosis)
Official title: A Phase 1/2 Study of Linvoseltamab in Patients With Relapsed or Refractory Systemic Light Chain Amyloidosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Systemic Light Chain Amyloidosis
Keywords: Amyloid light-chain (AL)
Multiple Myeloma (MM)
Pathogenic light chains
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-03-05
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Note: Participants enrolled in Phase 2 will be randomized 1:1
Primary purpose: TREATMENT

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)


Eligibility 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

Primary outcomes:
measure: Incidence of dose-limiting toxicity (DLTs)
timeFrame: Up to 28 Days
measure: Achievement of hematologic complete response (CR) as determined by the Independent Review Committee (IRC)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Achievement of hematologic CR, as determined by the IRC
timeFrame: Up to 3 years
measure: Achievement of hematologic very good partial response (VGPR) or better response (CR + VGPR), as determined by the IRC
timeFrame: Up to 3 years
measure: Achievement of overall hematologic response (PR or better), as determined by the IRC
timeFrame: Up to 3 years
measure: Time to initial hematologic response
timeFrame: Up to 3 years
measure: Time to best hematologic response
timeFrame: Up to 3 years
measure: Duration of hematologic response (ie, best response, VGPR or better, overall response), as determined by the IRC
timeFrame: Up to 7 years
measure: Hematologic progression-free survival (PFS)
timeFrame: Up to 7 years
measure: Incidence of death
timeFrame: Up to 7 years
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 39 months
measure: Severity of TEAEs
timeFrame: Up to 39 months
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 39 months
measure: Severity of SAEs
timeFrame: Up to 39 months
measure: Incidence of adverse events of special interest (AESIs)
timeFrame: Up to 39 months
measure: Severity of AESIs
timeFrame: Up to 39 months
measure: Achievement of overall hematologic response (PR or better), as determined by the IRC in dose regimen 1 vs 2
timeFrame: Up to 39 months
measure: Incidence of TEAEs in dose regimen 1 vs 2
timeFrame: Up to 39 months
measure: Severity of TEAEs in dose regimen 1 vs 2
timeFrame: Up to 39 months
measure: Incidence of SAEs in dose regimen 1 vs 2
timeFrame: Up to 39 months
measure: Severity of SAEs in dose regimen 1 vs 2
timeFrame: Up to 39 months
measure: Incidence of AESIs in dose regimen 1 vs 2
timeFrame: Up to 39 months
measure: Severity of AESIs in dose regimen 1 vs 2
timeFrame: Up to 39 months
measure: Time from treatment initiation to hematologic disease progression as determined by the IRC
timeFrame: Up to 7 years
measure: Time from treatment initiation to cardiac deterioration, as determined by the IRC
timeFrame: Up to 7 years
measure: Time from treatment initiation to kidney deterioration as determined by the IRC
timeFrame: Up to 7 years
measure: Time from treatment initiation to death as determined by the IRC
timeFrame: Up to 7 years
measure: Time from initiation of treatment to date of death from any cause
timeFrame: Up to 7 years
measure: Achievement of renal response in participants with renal involvement at baseline, as determined by IRC
timeFrame: Up to 7 years
measure: Achievement of cardiac response in participants with cardiac involvement at baseline, as determined by IRC
timeFrame: Up to 7 years
measure: Time to first renal response in participants with renal involvement at baseline
timeFrame: Up to 7 years
measure: Time to first cardiac response in participants with cardiac involvement at baseline
timeFrame: Up to 7 years
measure: Linvoseltamab concentration in serum over time
timeFrame: Up to 39 months
measure: Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time
timeFrame: Up to 39 months
measure: Titers of ADAs to linvoseltamab over time
timeFrame: Up to 39 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute/SCRI
state: Colorado
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital - The Catholic University of Korea
city: Gijon
country: Spain
facility: Hospital de Cabuenes
state: Asturias
city: Palma
country: Spain
facility: Hospital Universitari Son Espases
state: Balearic Islands
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Universität de Barcelona- Institut d' Investigacions Biomediques August Pi i Sunyer (IDIBAPS)
city: Valencia
country: Spain
facility: University Hospital La Fe
city: London
country: United Kingdom
facility: University College London Hospitals
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: