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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05730036

Registration number

NCT05730036

Ethics application status

Date submitted

6/02/2023

Date registered

15/02/2023

Date last updated

7/06/2024

Titles & IDs

Public title

A Trial to Learn How Well Linvoseltamab Works Compared to the Combination of Elotuzumab, Pomalidomide and Dexamethasone for Adult Participants With Relapsed/Refractory Multiple Myeloma

Scientific title

An Open-label, Randomized, Phase 3 Study of Linvoseltamab (REGN5458; Anti- BCMA x Anti-CD3 Bispecific Antibody) Versus the Combination of Elotuzumab, Pomalidomide, and Dexamethasone (EPd), in Patients With Relapsed/Refractory Multiple Myeloma (LINKER-MM3)

Secondary ID [1]

2022-501396-62-00

Secondary ID [2]

R5458-ONC-2245

Universal Trial Number (UTN)

Trial acronym

LINKER-MM3

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Relapsed Refractory Multiple Myeloma (RRMM)

Condition category

Condition code

Cancer

Other cancer types

Intervention/exposure

Study type

Interventional(has expanded access)

Description of intervention(s) / exposure

Treatment: Drugs - Linvoseltamab
Treatment: Drugs - Elotuzumab
Treatment: Drugs - Pomalidomide
Treatment: Drugs - Dexamethasone

Experimental: Linvoseltamab - Randomization 1:1

Active Comparator: Elotuzumab/Pomalidomide/Dexamethasone (EPd) - Randomization 1:1

Treatment: Drugs: Linvoseltamab
REGN5458 will be administered by intravenous (IV) infusion

Treatment: Drugs: Elotuzumab
Elotuzumab will be administered by IV infusion

Treatment: Drugs: Pomalidomide
Pomalidomide capsules will administered by mouth (PO)

Treatment: Drugs: Dexamethasone
Dexamethasone tablets/capsules will be administered PO and/or by IV infusion

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

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

Timepoint [1]

Up to approximatively 5 years

Secondary outcome [1]

PFS per IMWG response criteria determined by IRC in all participants

Timepoint [1]

Up to approximatively 5 years

Secondary outcome [2]

Objective Response (OR) of Partial Response (PR) or better per IMWG response criteria as determined by the IRC in CD38 antibody exposed participants

Timepoint [2]

Up to approximatively 5 years

Secondary outcome [3]

OR of PR or better per IMWG response criteria as determined by the IRC in all participants

Timepoint [3]

Up to approximatively 5 years

Secondary outcome [4]

OR of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by IRC in CD38 antibody exposed participants

Timepoint [4]

Up to approximatively 5 years

Secondary outcome [5]

OR of VGPR or better per IMWG response criteria as determined by IRC in all participants

Timepoint [5]

Up to approximatively 5 years

Secondary outcome [6]

OR of Complete Response (CR) or better per IMWG response criteria as determined by IRC in CD38 antibody exposed participants

Timepoint [6]

Up to approximatively 5 years

Secondary outcome [7]

OR of CR or better per IMWG response criteria as determined by IRC in all participants

Timepoint [7]

Up to approximatively 5 years

Secondary outcome [8]

Incidence of minimal residual disease (MRD) negative status in participants previously exposed to CD38 antibodies

Timepoint [8]

Up to approximatively 5 years

Secondary outcome [9]

Incidence of MRD negative status in all participants

Timepoint [9]

Up to approximatively 5 years

Secondary outcome [10]

Overall Survival (OS) in participants previously exposed to CD38 antibodies

Timepoint [10]

Up to approximatively 5 years

Secondary outcome [11]

OS in all participants

Timepoint [11]

Up to approximatively 5 years

Secondary outcome [12]

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

Timepoint [12]

Baseline to week 12

Secondary outcome [13]

Mean change in the worst pain score measured by BPI-SF Item 3 in all participants

Timepoint [13]

Baseline to week 12

Secondary outcome [14]

Incidence of treatment emergent adverse events (TEAEs) in participants previously exposed to CD38 antibodies

Timepoint [14]

Up to approximatively 5 years

Secondary outcome [15]

Incidence TEAEs in all participants

Timepoint [15]

Up to approximatively 5 years

Secondary outcome [16]

Severity of TEAEs in participants previously exposed to CD38 antibodies

Timepoint [16]

Up to approximatively 5 years

Secondary outcome [17]

Severity of TEAEs in all participants

Timepoint [17]

Up to approximatively 5 years

Secondary outcome [18]

Incidence of adverse events of special interest (AESI) in participants previously exposed to CD38 antibodies

Timepoint [18]

Up to approximatively 5 years

Secondary outcome [19]

Incidence of AESI in all participants

Timepoint [19]

Up to approximatively 5 years

Secondary outcome [20]

Severity of AESI in participants previously exposed to CD38 antibodies

Timepoint [20]

Up to approximatively 5 years

Secondary outcome [21]

Severity AESI in all participants

Timepoint [21]

Up to approximatively 5 years

Secondary outcome [22]

Incidence of Serious Adverse Events (SAE) in participants previously exposed to CD38 antibodies

Timepoint [22]

Up to approximatively 5 years

Secondary outcome [23]

Incidence of SAE in all participants

Timepoint [23]

Up to approximatively 5 years

Secondary outcome [24]

Severity of SAE in participants previously exposed to CD38 antibodies

Timepoint [24]

Up to approximatively 5 years

Secondary outcome [25]

Severity of SAE in all participants

Timepoint [25]

Up to approximatively 5 years

Secondary outcome [26]

PFS per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Timepoint [26]

Up to approximatively 5 years

Secondary outcome [27]

PFS per IMWG response criteria as determined by the investigator in all participants

Timepoint [27]

Up to approximatively 5 years

Secondary outcome [28]

OR of PR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Timepoint [28]

Up to approximatively 5 years

Secondary outcome [29]

OR of PR or better per IMWG response criteria as determined by the investigator in all participants

Timepoint [29]

Up to approximatively 5 years

Secondary outcome [30]

OR of VGPR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Timepoint [30]

Up to approximatively 5 years

Secondary outcome [31]

OR of VGPR or better per IMWG response criteria as determined by the investigator in all participants

Timepoint [31]

Up to approximatively 5 years

Secondary outcome [32]

OR of CR or better per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Timepoint [32]

Up to approximatively 5 years

Secondary outcome [33]

OR of CR or better per IMWG response criteria as determined by the investigator in all participants

Timepoint [33]

Up to approximatively 5 years

Secondary outcome [34]

Duration of Response (DoR) as per IMWG response criteria as determined by the investigator in participants previously exposed to CD38 antibodies

Timepoint [34]

Up to approximatively 5 years

Secondary outcome [35]

DoR as per IMWG response criteria as determined by the investigator in all participants

Timepoint [35]

Up to approximatively 5 years

Secondary outcome [36]

DoR as per IMWG response criteria as determined by the IRC in participants previously exposed to CD38 antibodies

Timepoint [36]

Up to approximatively 5 years

Secondary outcome [37]

DoR as per IMWG response criteria as determined by the IRC in all participants

Timepoint [37]

Up to approximatively 5 years

Secondary outcome [38]

Duration of MRD negative status in the bone marrow in participants previously exposed to CD38 antibodies

Timepoint [38]

Up to approximatively 5 years

Secondary outcome [39]

Duration of MRD negative status in the bone marrow in all participants

Timepoint [39]

Up to approximatively 5 years

Secondary outcome [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

Timepoint [40]

Up to approximatively 5 years

Secondary outcome [41]

Time from randomization to objective response (=PR) as per IMWG response criteria as determined by the investigator in all participants

Timepoint [41]

Up to approximatively 5 years

Secondary outcome [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

Timepoint [42]

Up to approximatively 5 years

Secondary outcome [43]

Time from randomization to objective response (=PR) as per IMWG response criteria as determined by the IRC in all participants

Timepoint [43]

Up to approximatively 5 years

Secondary outcome [44]

Concentration of linvoseltamab in the serum over time in participants previously exposed to CD38 antibodies

Timepoint [44]

Up to approximatively 5 years

Secondary outcome [45]

Concentration of linvoseltamab in the serum over time in all participants

Timepoint [45]

Up to approximatively 5 years

Secondary outcome [46]

Incidence of antidrug antibodies (ADAs) in participants previously exposed to CD38 antibodies

Timepoint [46]

Up to approximatively 5 years

Secondary outcome [47]

Incidence of ADAs in all participants

Timepoint [47]

Up to approximatively 5 years

Secondary outcome [48]

Titer of ADAs in participants previously exposed to CD38 antibodies

Timepoint [48]

Up to approximatively 5 years

Secondary outcome [49]

Titer of ADAs in all participants

Timepoint [49]

Up to approximatively 5 years

Secondary outcome [50]

Incidence of neutralizing antibodies (Nabs) to linvoseltamab over time in participants previously exposed to CD38 antibodies

Timepoint [50]

Up to approximatively 5 years

Secondary outcome [51]

Incidence of Nabs to linvoseltamab over time in all participants

Timepoint [51]

Up to approximatively 5 years

Secondary outcome [52]

Proportion of Pain Responders in participants previously exposed to CD38 antibodies

Timepoint [52]

At week 12

Secondary outcome [53]

Proportion of Pain Responders in all participants

Timepoint [53]

At week 12

Secondary outcome [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

Timepoint [54]

Baseline to week 12

Secondary outcome [55]

Change in patient-reported QoL, per EORTC QLQ-C30 in all participants

Timepoint [55]

Baseline to week 12

Secondary outcome [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

Timepoint [56]

Baseline to week 12

Secondary outcome [57]

Change in patient reported disease symptoms per EORTC QLQ-MY20 in all participants

Timepoint [57]

Baseline to week 12

Secondary outcome [58]

Patient-Reported Outcomes in Patient Global Impression of Symptom Severity (PGIS) in participants previously exposed to CD38 antibodies

Timepoint [58]

Baseline to week 12

Secondary outcome [59]

Patient-Reported Outcomes in PGIS in all participants

Timepoint [59]

Baseline to week 12

Secondary outcome [60]

Patient-Reported Outcomes in Patient Global Impression of Change (PGIC) in participants previously exposed to CD38 antibodies

Timepoint [60]

Baseline to week 12

Secondary outcome [61]

Patient-Reported Outcomes in PGIC in all participants

Timepoint [61]

Baseline to week 12

Secondary outcome [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

Timepoint [62]

Baseline to week 12

Secondary outcome [63]

Change in patient-reported general health status per EQ-5D-5L in all participants

Timepoint [63]

Baseline to week 12

Eligibility

Key inclusion criteria

Key

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. 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, as described in the protocol.

Note: Participants in Israel also must have previously received a CD38 antibody.
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

Key

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Diagnosis of plasma cell leukemia, amyloidosis, Waldenström macroglobulinemia, or
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
skin changes).

2. Prior treatment with elotuzumab and/or pomalidomide

3. Participants with known MM brain lesions or meningeal involvement

4. Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days
before first administration of study drug, whichever is shorter

5. History of allogeneic stem cell transplantation within 6 months, or autologous stem
cell transplantation within 12 weeks of the start of study treatment. Participants who
have received an allogeneic transplant must be off all immunosuppressive medications
for 6 weeks without signs of graft-versus-host disease. Steroids at doses equivalent
to suppletion doses may be acceptable.

6. Prior treatment with B-cell maturation antigen (BCMA) directed immunotherapies Note:
BCMA antibody-drug conjugates are allowed.

7. History of progressive multifocal leukoencephalopathy (PML), known or suspected PML,
or history of a neurocognitive condition or central nervous system (CNS) movement
disorder.

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.

NOTE: Other protocol defined inclusion/exclusion criteria apply

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

18/09/2023

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

26/12/2032

Actual

Sample size

Target

380

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,VIC

Recruitment hospital [1]

Royal Prince Alfred Hospital - Camperdown

Recruitment hospital [2]

Royal North Shore Hospital - St Leonards

Recruitment hospital [3]

Royal Brisbane Hospital - Herston

Recruitment hospital [4]

Integrated Clinical Oncology Network - South Brisbane

Recruitment hospital [5]

University Hospital Geelong - Geelong

Recruitment hospital [6]

Austin Hospital - Heidelberg

Recruitment hospital [7]

St Vincents Hospital Melbourne - Melbourne

Recruitment postcode(s) [1]

2050 - Camperdown

Recruitment postcode(s) [2]

2065 - St Leonards

Recruitment postcode(s) [3]

4029 - Herston

Recruitment postcode(s) [4]

4101 - South Brisbane

Recruitment postcode(s) [5]

3220 - Geelong

Recruitment postcode(s) [6]

3084 - Heidelberg

Recruitment postcode(s) [7]

3065 - Melbourne

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

Kentucky

Country [3]

United States of America

State/province [3]

New York

Country [4]

United States of America

State/province [4]

North Carolina

Country [5]

United States of America

State/province [5]

Oregon

Country [6]

United States of America

State/province [6]

Washington

Country [7]

Brazil

State/province [7]

Bahia

Country [8]

Brazil

State/province [8]

Rio Grade Do Sul

Country [9]

Brazil

State/province [9]

Rio Grande Do Sul

Country [10]

Brazil

State/province [10]

Santa Catarina

Country [11]

Brazil

State/province [11]

São Paulo

Country [12]

Canada

State/province [12]

Ontario

Country [13]

France

State/province [13]

Gironde

Country [14]

France

State/province [14]

Paris

Country [15]

France

State/province [15]

Lille

Country [16]

Israel

State/province [16]

Hamerkaz

Country [17]

Israel

State/province [17]

Haifa

Country [18]

Israel

State/province [18]

Jerusalem

Country [19]

Israel

State/province [19]

Tel Aviv

Country [20]

Italy

State/province [20]

Foggia

Country [21]

Italy

State/province [21]

Forli Cesena

Country [22]

Italy

State/province [22]

Lombardy

Country [23]

Italy

State/province [23]

Ancona

Country [24]

Italy

State/province [24]

Bologna

Country [25]

Italy

State/province [25]

Pavia

Country [26]

Italy

State/province [26]

Ravenna

Country [27]

Italy

State/province [27]

Reggio Emilia

Country [28]

Italy

State/province [28]

Torino

Country [29]

Italy

State/province [29]

Turin

Country [30]

Korea, Republic of

State/province [30]

Busan

Country [31]

Korea, Republic of

State/province [31]

Hwasun

Country [32]

Korea, Republic of

State/province [32]

Incheon

Country [33]

Korea, Republic of

State/province [33]

Jeonju

Country [34]

Korea, Republic of

State/province [34]

Seoul

Country [35]

Netherlands

State/province [35]

Gelderland

Country [36]

Netherlands

State/province [36]

Zuid-Holland

Country [37]

Poland

State/province [37]

Pomorskie

Country [38]

Poland

State/province [38]

Katowice

Country [39]

Singapore

State/province [39]

Kent Ridge

Country [40]

Singapore

State/province [40]

Singapore

Country [41]

Spain

State/province [41]

Asturias

Country [42]

Spain

State/province [42]

Baleares

Country [43]

Spain

State/province [43]

Barcelona

Country [44]

Spain

State/province [44]

Cantabria

Country [45]

Spain

State/province [45]

Islas Baleares

Country [46]

Spain

State/province [46]

Madrid

Country [47]

Spain

State/province [47]

Navarra

Country [48]

Spain

State/province [48]

Alicante

Country [49]

Spain

State/province [49]

Girona

Country [50]

Spain

State/province [50]

Santiago de Compostela

Country [51]

Spain

State/province [51]

Valencia

Country [52]

Spain

State/province [52]

Zaragoza

Country [53]

Taiwan

State/province [53]

Changhua County

Country [54]

Taiwan

State/province [54]

Hualien City

Country [55]

Taiwan

State/province [55]

Kaohsiung

Country [56]

Taiwan

State/province [56]

Taipei

Country [57]

Taiwan

State/province [57]

Taoyuan

Country [58]

United Kingdom

State/province [58]

Surrey

Country [59]

United Kingdom

State/province [59]

Cambridge

Country [60]

United Kingdom

State/province [60]

London

Funding & Sponsors

Primary sponsor type

Commercial sector/Industry

Name

Regeneron Pharmaceuticals

Address

Country

Ethics approval

Ethics application status

Summary

Brief summary

This study is researching an experimental drug called linvoseltamab, also called REGN5458.

Linvoseltamab has previously been studied by itself (without other cancer drugs) in
participants who had advanced multiple myeloma that returned and needed to be treated again
after many other therapies had failed. These participants were no longer benefiting from
standard medications and had no good treatment options. In that study, some participants who
were treated with linvoseltamab had improvement of their myeloma (shrinkage of their tumors),
including some participants who had complete responses (that is, the treatment got rid of all
evidence of myeloma in their bodies).

This study is focused on participants who have multiple myeloma that has returned or needs to
be treated again after one to four prior treatments and have standard cancer treatment
options available to them. The aim of this study is to see how safe and effective
linvoseltamab is compared to a combination of three cancer drugs: elotuzumab, pomalidomide
and dexamethasone, (called EPd) in participants who have returned after having received prior
treatment that included lenalidomide, a proteosome inhibitor, and (for participants in some
countries) a cluster of differentiation 38 (CD38) antibody. Half of the participants in this
study will get linvoseltamab, and the other half will get EPd.

This study is looking at several other research questions, including:

- How long participants benefit from receiving linvoseltamab compared with EPd

- How many participants treated with linvoseltamab or EPd have improvement of their
multiple myeloma and by how much

- What side effects happen from taking linvoseltamab compared to EPd

- How long participants live while receiving treatment or after treatment with
linvoseltamab compared to EPd

- If there is any improvement in pain after treatment with linvoseltamab compared to EPd

Trial website

https://clinicaltrials.gov/ct2/show/NCT05730036

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Clinical Trial Management

Address

Regeneron Pharmaceuticals

Country

Phone

Fax

Contact person for public queries

Name

Clinical Trials Administrator

Address

Country

Phone

844-734-6643

Fax

clinicaltrials@regeneron.com

Contact person for scientific queries

Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05730036

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05730036