A Trial to Learn if Linvoseltamab is Safe and Works in Adults with Relapsed or Refractory Systemic Light Chain Amyloidosis (AL Amyloidosis)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Aug 2024 → ongoing

Decision date (initial)

2025-07-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-507809-34-00

ClinicalTrials.gov

NCT06292780

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety

-Phase 1: To assess the safety, tolerability and to determine the recommended phase 2 dose regimens (RP2DRs) of linvoseltamab in participants with relapsed or refractory AL amyloidosis.
-Phase 2: To evaluate the effect of linvoseltamab on hematologic complete response in participants with relapsed or refractory AL amyloidosis

Secondary objectives 17

1. To evaluate the effect of linvoseltamab on hematologic very good partial response or better response
2. To evaluate the effect of linvoseltamab on overall hematologic response
3. To evaluate the effect of linvoseltamab on the timing of hematologic response
4. To evaluate the effect of linvoseltamab on the duration of hematologic response
5. To evaluate the effect of linvoseltamab on hematologic progression-free survival
6. To evaluate the safety of linvoseltamab
7. Phase 2 only: To compare the efficacy between the 2 dose levels of linvoseltamab
8. Phase 2 only: To compare the safety between the 2 dose levels of linvoseltamab
9. To evaluate the impact of linvoseltamab on major organ deterioration and/or death
10. To evaluate the impact of linvoseltamab on overall survival (OS)
11. To evaluate the effect of linvoseltamab on induction of a clinically meaningful renal response in participants with baseline renal involvement
12. To evaluate the effect of linvoseltamab on induction of a clinically meaningful cardiac response in participants with baseline cardiac involvement
13. To evaluate the timing of renal response to linvoseltamab in participants with baseline renal involvement
14. To evaluate the timing of cardiac response to linvoseltamab in participants with baseline cardiac involvement
15. To evaluate the pharmacokinetic of linvoseltamab
16. To assess the immunogenicity of linvoseltamab.
17. Phase 1 only: To evaluate the effect of linvoseltamab on hematologic CR in participants with relapsed or refractory AL amyloidosis

Conditions and MedDRA coding

Relapsed or Refractory Systemic Light Chain Amyloidosis

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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
7. NOTE: Other protocol defined inclusion criteria apply

Exclusion criteria 6

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
6. NOTE: Other protocol defined exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 1: Incidence of dose-limiting toxicity (DLTs)
2. Phase 2: Achievement of hematologic complete response (CR) as determined by the Independent Review Committee (IRC)

Secondary endpoints 33

1. Achievement of hematologic CR, as determined by the IRC - Phase 1
2. Achievement of hematologic very good partial response (VGPR) or better response (CR + VGPR), as determined by the IRC
3. Achievement of overall hematologic response (PR or better), as determined by the IRC
4. Time to initial hematologic response
5. Time to best hematologic response
6. Duration of hematologic response (ie, best response, VGPR or better, overall response), as determined by the IRC
7. Hematologic progression-free survival (PFS)
8. Incidence of death
9. Incidence of treatment-emergent adverse events (TEAEs)
10. Severity of TEAEs
11. Incidence of serious adverse events (SAEs)
12. Severity of SAEs
13. Incidence of adverse events of special interest (AESIs)
14. Severity of AESIs
15. Achievement of overall hematologic response (PR or better), as determined by the IRC in full dose regimen 1 vs 2 - Phase 2
16. Incidence of TEAEs in full dose regimen 1 vs 2 - Phase 2
17. Severity of TEAEs in full dose regimen 1 vs 2 - Phase 2
18. Incidence of SAEs in full dose regimen 1 vs 2 - Phase 2
19. Severity of SAEs in full dose regimen 1 vs 2 - Phase 2
20. Incidence of AESIs in full dose regimen 1 vs 2 - Phase 2
21. Severity of AESIs in full dose regimen 1 vs 2 - Phase 2
22. Time from treatment initiation to hematologic disease progression as determined by the IRC
23. Time from treatment initiation to cardiac deterioration, as determined by the IRC
24. Time from treatment initiation to kidney deterioration as determined by the IRC
25. Time from treatment initiation to death as determined by the IRC
26. Time from initiation of treatment to date of death from any cause
27. Achievement of renal response in participants with renal involvement at baseline, as determined by IRC
28. Achievement of cardiac response in participants with cardiac involvement at baseline, as determined by IRC
29. Time to first renal response in participants with renal involvement at baseline
30. Time to first cardiac response in participants with cardiac involvement at baseline
31. Linvoseltamab concentration in serum over time
32. Incidence of anti-drug antibodies (ADAs) to linvoseltamab over time
33. Titers of ADAs to linvoseltamab over time

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 6

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications