A Window of Opportunity Trial To Learn If Linvoseltamab Is Safe And Well Tolerated, And How Well It Works In adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment

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

19 Sep 2024 → ongoing

Decision date (initial)

2023-09-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Regeneron Pharmaceutical Inc

External identifiers

EU CT number

2022-500800-24-00

ClinicalTrials.gov

NCT05828511

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Dose response

For Phase 1:

• (Part A, Dose Escalation): Assess the safety and tolerability of linvoseltamab in participants with NDMM who are either transplant-eligible or transplant-ineligible.
• (Part B, Dose Expansion): Determine a recommended phase 2 dose regimen (RP2DR) for linvoseltamab in phase 2 of the study in participants with NDMM who are either transplant-eligible or transplant-ineligible.
• (Part C, Alternative Step-up Cohort): Assess the safety and tolerability of linvoseltamab when employing an alternative step-up (5 mg/25 mg) followed by a 200 mg full dose in participants with NDMM who are either transplant-eligible or transplant-ineligible.



For Phase 2:

• To assess the preliminary anti-tumor activity of linvoseltamab in participants with newly diagnosed multiple myeloma (NDMM) who are eligible for high dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) (transplant-eligible)
• To assess the preliminary anti-tumor activity of linvoseltamab in participants with NDMM who are ineligible for ASCT (transplant-ineligible)

Secondary objectives 11

1. For Phase 1 and 2: To evaluate the pharmacokinetic (PK) properties of linvoseltamab
2. For Phase 1 and 2: To evaluate total soluble B-cell maturation antigen (BCMA) concentrations in serum at baseline and over time
3. For Phase 1 and 2: To assess the immunogenicity of linvoseltamab
4. For Phase 1: To assess the preliminary anti-tumor activity of linvoseltamab
5. For Phase 2: To evaluate the safety and tolerability of linvoseltamab
6. For Phase 2: To evaluate the preliminary anti-tumor activity of linvoseltamab in participants who are transplant-eligible and transplant-ineligible
7. For Phase 2 Transplant-eligible cohort only: To evaluate duration of response (DOR), progression-free survival (PFS), and rate of minimal residual disease (MRD) negative status after ASCT
8. For Phase 2 Transplant-eligible cohort only: To evaluate the impact of therapy with single-agent linvoseltamab on the ability to collect stem cells in any participants who subsequently undergo stem cell mobilization
9. For Phase 2 Transplant-eligible cohort only: To evaluate the kinetics of engraftment
10. For Phase 2 Transplant-eligible cohort only: To evaluate the overall PFS
11. For Phase 2 Transplant-ineligible cohort only: To evaluate DOR, PFS, and rate of MRD-negative status

Conditions and MedDRA coding

Multiple Myeloma

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
2. Confirmed diagnosis of symptomatic multiple myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria, as described in the protocol
3. Response evaluable myeloma, according to the 2016 IMWG response criteria, as defined in the protocol
4. No prior therapy for MM, with the exception of prior emergent or palliative radiation and up to 1 month of single-agent corticosteroids, with washout periods as per the protocol
5. Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol
6. Participants must be age <70 and have adequate hepatic, renal, pulmonary and cardiac function to be considered transplant-eligible. The specific thresholds for adequate organ function are as per institutional guidance.

Exclusion criteria 5

1. Receiving any concurrent investigational agent with known or suspected activity against MM, or agents targeting the A proliferation-inducing ligand (APRIL)/ Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)/BCMA axis
2. Known central nervous system (CNS) involvement with MM, known or suspected progressive multifocal leukoencephalopathy (PML), a history of neurocognitive conditions, or CNS movement disorder, or history of seizure within 12 months prior to study enrollment
3. Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy
4. Diagnosis of non-secretory MM, active plasma cell leukemia, primary light-chain (AL) amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
5. Note: Other protocol-defined Exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 10

1. Phase 1: Incidence of dose-limiting toxicities (DLTs)
2. Phase 1: Incidence of treatment-emergent adverse events (TEAEs)
3. Phase 1: Severity of treatment-emergent adverse events (TEAEs)
4. Phase 1: Incidence of adverse events of special interest (AESIs)
5. Phase 1: Severity of adverse events of special interest (AESIs)
6. Phase 2: Proportion of participants with a very good partial response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria
7. Phase 2 Transplant-eligible cohort: Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy
8. Phase 2 Transplant-eligible cohort: Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy
9. Phase 2 Transplant-ineligible cohort: Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II
10. Phase 2 Transplant ineligible cohort: Proportion of participants achieving MRD-negative status as their best response after treatment period I without continuing to treatment period II

Secondary endpoints 28

1. Phase 1 and 2: Concentrations of Linvoseltamab in serum
2. Phase 1 and 2: Concentrations of total soluble B-cell maturation antigen (BCMA)
3. Phase 1 and 2: Incidence of anti-drug antibodies (ADAs) to Linvoseltamab
4. Phase 1 and 2: Magnitude of ADAs to Linvoseltamab
5. Phase 1: Objective response rate (ORR) measured using the IMWG criteria
6. Phase 1: Duration of Response (DOR) measured using the IMWG criteria
7. Phase 1: Progression-free survival (PFS) measured using the IMWG criteria
8. Phase 1: Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria
9. Phase 2: Incidence of treatment-emergent adverse events (TEAEs)
10. Phase 2: Severity of TEAEs
11. Phase 2: Incidence of adverse events of special interest (AESIs)
12. Phase 2: Severity of AESIs
13. Phase 2: ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
14. Phase 2: MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician
15. Phase 2: DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician
16. Phase 2: PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician
17. Phase 2: Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician
18. Phase 2: Time to response (TTR) as measured using the IMWG criteria
19. Phase 2: ORR by risk levels
20. Phase 2: MRD-negative status by risk levels
21. Phase 2: DOR by risk levels
22. Phase 2: TTR by risk levels
23. Phase 2: PFS by risk levels
24. Phase 2: Incidence of MRD-negative status
25. Phase 2 Transplant-eligible cohort: Cluster of differentiation 34+ (CD34+) stem cell yield
26. Phase 2 Transplant-eligible cohort: Time to neutrophil engraftment
27. Phase 2 Transplant-eligible cohort: Time to platelet engraftment
28. Phase 2 Transplant-eligible cohort: PFS after ASCT followed by 3 cycles of linvoseltamab

Investigational products

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

Test 2

Auxiliary 2

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 11

Locations

2 EU/EEA countries · 20 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 19 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