A Study to Learn How Linvoseltamab (REGN5458) Will Work Compared to the Elotuzumab, Pomalidimide and Dexamethasone (EPd) Combination, in Participants With Relapsed/Refractory Multiple Myeloma (LINKER-MM3)

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

12 Dec 2023 → ongoing

Decision date (initial)

2023-09-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-501396-62-00

ClinicalTrials.gov

NCT05730036

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare Progression-Free-Survival per Independent Review Committee (IRC) between linvoseltamab monotherapy and EPd in randomized participants previously treated with CD38 antibodies

Secondary objectives 15

1. Unless noted, analyses will be conducted separately in participants who have been previously exposed to CD38 antibodies and in all study participants. To compare PFS per IRC between linvoseltamab monotherapy and EPd in all study participants
2. To compare anti-tumor activity per IRC between linvoseltamab monotherapy and EPd, as measured by ≥CR
3. To compare the treatment effects on overall survival (OS) between linvoseltamab monotherapy and EPd
4. To compare the incidence of minimal residual disease (MRD) negative status (10^-5) in the bone marrow between linvoseltamab monotherapy and EPd
5. To evaluate the treatment effects on pain symptom between linvoseltamab monotherapy and EPd
6. To evaluate the safety and tolerability of linvoseltamab monotherapy compared to EPd
7. To compare PFS per the investigator between linvoseltamab monotherapy and EPd
8. To compare anti-tumor activity per IRC between Linvoseltamab monotherapy and EPd, as measured by: Objective response, ≥ Very good partial Response (VGPR)
9. To compare the anti-tumor activity of linvoseltamab monotherapy vs EPd as measured per investigator by Objective response, ≥VGPR, ≥CR
10. To evaluate duration of response (DOR) per investigator and IRC for participants achieving objective response on linvoseltamab monotherapy and on EPd
11. To evaluate the duration of MRD negative status (10^-5) in the bone marrow in participants receiving linvoseltamab monotherapy and EPd
12. To evaluate the time to response for participants achieving objective response on linvoseltamab monotherapy and EPd
13. To evaluate the pharmacokinetics (PK) of linvoseltamab in an earlier line of therapy than previously studied
14. To evaluate the immunogenicity of linvoseltamab
15. To evaluate the effects on patient reported quality of life (QoL), functioning and symptoms in participants receiving linvoseltamab monotherapy and EPd

Conditions and MedDRA coding

Relapsed Refractory Multiple Myeloma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003175-PIP01-21

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age 18 years or older (or legal adult age in the country) at the time of the screening visit.
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients with ECOG 2 solely due to local symptoms of myeloma (eg. pain) may be allowed after discussion with the Medical Monitor.
3. Participants with MM who have received at least 1 and no more than 4 prior lines of anti-neoplastic MM therapies including lenalidomide and a proteasome inhibitor and demonstrated disease progression on or after the last therapy as defined by the 2016 IMWG criteria. Participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory (including participants with progression on or within 60 days of the last dose of lenalidomide given as maintenance). Participants in the EU and the UK must have previously received 2 to 4 prior lines of therapy, including a CD38 antibody.
4. Patients must have measurable disease for response assessment as per the 2016 IMWG response assessment criteria, as described in the protocol
5. Adequate hematologic, hepatic, renal and cardiac function, as well as evidence of adequate bone marrow reserves
6. Life expectancy of at least 6 months
7. Other protocol defined inclusion criteria apply

Exclusion criteria 11

1. Diagnosis of plasma cell leukemia, amyloidosis, Waldenström macroglobulinemia, or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
2. Other protocol defined exclusion criteria apply
3. Prior treatment with elotuzumab and/or pomalidomide
4. Participants with known MM brain lesions or meningeal involvement
5. Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter
6. History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment, as described in the protocol.
7. Prior treatment with B-cell maturation antigen (BCMA) directed immunotherapies. Prior treatments with BCMA antibody-drug conjugates are allowed
8. Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first administration of study drug
9. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); or another uncontrolled infection, as defined in the protocol.
10. Cardiac ejection fraction <40%
11. History of progressive multifocal leukoencephalopathy (PML), known or suspected PML, or history of a neurocognitive condition or central nervous system (CNS) movement disorder (Parkinson’s disease or Parkinsonism).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) response criteria determined by Independent Review Committee (IRC) in CD38 antibody exposed participants

Secondary endpoints 63

1. PFS per IMWG response criteria, determined by IRC, in all study participants
2. Objective Response (OR) of complete Response (CR) or better per IMWG response criteria as determined by IRC in CD38 antibody exposed participants
3. OR of CR or better per IMWG response criteria as determined by IRC in all participants
4. Overall Survival (OS) in participants previously exposed to CD38 antibodies
5. OS in all participants
6. Incidence of minimal residual disease (MRD) negative status in participants previously exposed to CD38 antibodies
7. Incidence of MRD negative status in all participants
8. Mean change in the worst pain score measured by Brief Pain Inventory-Short Form (BPI-SF) Item 3 in participants previously exposed to CD38 antibodies
9. Mean change in the worst pain score measured by BPI-SF Item 3 in all participants
10. Incidence of treatment emergent adverse events (TEAEs) in participants previously exposed to CD38 antibodies
11. Incidence TEAEs in all participants
12. Severity of TEAEs in participants previously exposed to CD38 antibodies
13. Severity of TEAEs in all participants
14. Incidence of adverse events of special interest (AESI) in participants previously exposed to CD38 antibodies
15. Incidence of AESI in all participants
16. Severity of AESI in participants previously exposed to CD38 antibodies
17. Severity AESI in all participants
18. Incidence of Serious Adverse Events (SAE) in participants previously exposed to CD38 antibodies
19. Incidence of SAE in all participants
20. Severity of SAE in participants previously exposed to CD38 antibodies
21. Severity of SAE in all participants
22. PFS per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies
23. PFS per IMWG response criteria as determined by the investigator in all participants
24. OR of Partial Response (PR) or better per IMWG response criteria as determined by the IRC in CD38 antibody exposed participants
25. OR of PR or better per IMWG response criteria as determined by the IRC in all participants
26. OR of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by IRC in CD38 antibody exposed participants
27. OR of VGPR or better per IMWG response criteria as determined by IRC in all participants
28. OR of PR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies
29. OR of PR or better per IMWG response criteria as determined by the investigator in all participants
30. OR of VGPR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies
31. OR of VGPR or better per IMWG response criteria as determined by the investigator in all participants
32. OR of CR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies
33. OR of CR or better per IMWG response criteria as determined by the investigator in all participants
34. Duration of Response (DoR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies
35. DoR as per IMWG response criteria as determined by the investigator in all participants
36. DoR as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 antibodies
37. DoR as per IMWG response criteria as determined by the IRC in all participants
38. Duration of MRD negative status in the bone marrow in participants previously exposed to CD38 antibodies
39. Duration of MRD negative status in the bone marrow in all participants
40. Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies
41. Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the investigator in all participants
42. Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 antibodies
43. Time from randomization to objective response (≥PR) as per IMWG response criteria as determined by the IRC in all participants
44. Concentration of linvoseltamab in the serum over time in participants previously exposed to CD38 antibodies
45. Concentration of linvoseltamab in the serum over time in all participants
46. Incidence of antidrug antibodies (ADAs) in participants previously exposed to CD38 antibodies
47. Incidence of ADAs in all participants
48. Titer of ADAs in participants previously exposed to CD38 antibodies
49. Titer of ADAs in all participants
50. Incidence of neutralizing antibodies (Nabs) to linvoseltamab over time in participants previously exposed to CD38 antibodies
51. Incidence of Nabs to linvoseltamab over time in all participants
52. Proportion of Pain Responders in participants previously exposed to CD38 antibodies
53. Proportion of Pain Responders in all participants
54. Change in patient-reported global health status/quality of life (QoL), per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in participants previously exposed to CD38 antibodies
55. Change in patient-reported QoL, per EORTC QLQ-C30 in all participants
56. Change in patient reported disease symptoms per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20]) in participants previously exposed to CD38 antibodies
57. Change in patient reported disease symptoms per EORTC QLQ-MY20 in all participants
58. Patient-Reported Outcomes in Patient Global Impression of Symptom Severity (PGIS) in participants previously exposed to CD38 antibodies
59. Patient-Reported Outcomes in PGIS in all participants
60. Patient-Reported Outcomes in Patient Global Impression of Change (PGIC) in participants previously exposed to CD38 antibodies
61. Patient-Reported Outcomes in PGIC in all participants
62. Change in patient-reported general health status per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L]) in participants previously exposed to CD38 antibodies
63. Change in patient-reported general health status per EQ-5D-5L in all participants

Investigational products

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

Test 2

Comparator 9

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

7 EU/EEA countries · 65 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 84 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