A proof-of-concept study to learn whether linvoseltamab can eliminate abnormal plasma cells that may lead to multiple myeloma in adult patients with High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma

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

5 Nov 2024 → ongoing

Decision date (initial)

2025-02-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-505242-25-00

ClinicalTrials.gov

NCT06140524

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Dose response, Safety, Others, Efficacy

Safety Run-In (Part 1): To evaluate the safety and tolerability of linvoseltamab in ascending dose-level cohorts and select the highest dose level for investigation in the expansion part.
Expansion (Part 2): To evaluate the ability of linvoseltamab to induce complete responses (CR) by dosing regimen.

Secondary objectives 8

1. To characterize the safety of linvoseltamab
2. To evaluate the proportion of participants that achieve minimal residual disease (MRD) negativity
3. To evaluate the proportion of participants with sustained MRD negativity
4. To evaluate the overall response rate (ORR)
5. To evaluate the duration of response (DOR)
6. To evaluate biochemical progression-free survival (PFS)
7. To characterize the pharmacokinetic (PK) properties of linvoseltamab
8. To assess the immunogenicity of linvoseltamab

Conditions and MedDRA coding

High-Risk Monoclonal Gammopathy of Undetermined Significance; Non-High-Risk Smoldering Multiple Myeloma

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. HR-MGUS or NHR-SMM as defined in the protocol
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
3. Adequate hematologic and hepatic function, as described in the protocol
4. Estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 by the modification of diet in renal disease (MDRD) equation.
5. NOTE: Other protocol defined inclusion criteria apply

Exclusion criteria 7

1. High-risk SMM according to risk stratification models as defined in the protocol.
2. Evidence of any of myeloma-defining events, as described in the protocol
3. Diagnosis of systemic light-chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), solitary plasmacytoma, or symptomatic MM
4. Clinically significant cardiac or vascular disease within 3 months of study enrollment, as described in the protocol
5. Any infection requiring hospitalization or treatment with IV anti-infectives within 28 days of the first dose of linvoseltamab
6. Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or other uncontrolled infection or unexplained signs of infection.
7. NOTE: Other protocol defined exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1: Frequency of adverse events of special interest (AESI) during the safety observation period
2. Part 1: Frequency of treatment-emergent adverse events (TEAEs) during the safety observation period
3. Part 1: Severity of TEAEs during the safety observation period
4. Part 2: Achievement of complete response (CR) as determined by the investigator

Secondary endpoints 14

1. Frequency of TEAEs
2. Severity of TEAEs
3. Frequency of serious adverse events (SAEs)
4. Severity of SAEs
5. Frequency of laboratory abnormalities
6. Severity of laboratory abnormalities
7. Minimal residual disease (MRD) negativity among participants that achieve a response of CR
8. Sustained MRD negativity on an annual basis
9. Overall response of partial response (PR) or better as determined by the investigator
10. Duration of response (DOR) as determined by the investigator
11. Biochemical progression-free survival (PFS) as determined by the investigator
12. Concentration of linvoseltamab in serum over time
13. Incidence of anti-drug antibodies (ADAs) to linvoseltamab over the study duration
14. Magnitude of ADAs to linvoseltamab over the study duration

Investigational products

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

Test 1

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 10

Locations

6 EU/EEA countries · 34 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 100 files

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

Application history

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