Back to resultsPhase 1/2 Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma (LINKER-MM1)
Primary Purpose
Multiple Myeloma
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
REGN5458
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Relapsed, Refractory
Eligibility Criteria
Key Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
- Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria as defined in the protocol.
Phase 1 Dose Escalation: Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease or intolerance of the therapy and including either:
- Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a proteasome inhibitor, an Immunomodulatory agent (IMiD), and an anti-CD38 antibody, OR
Progression on or after an anti-CD38 antibody and have disease that is "double refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor. Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
Phase 2:
- Patients must be triple-refractory, defined as being refractory to prior treatment with at least 1 anti-CD38 antibody, a proteasome inhibitor, and an IMiD. In addition, patients must be penta-exposed (ie, having prior exposure to 2 PIs, 2 IMiDs [lenalidomide and pomalidomide], and 1 anti-CD38 monoclonal antibody).
Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or less than 25% response to therapy.
Key Exclusion Criteria:
- Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Patients with known MM brain lesions or meningeal involvement
- Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs, and BCMA CAR T cells. Note: BCMA antibody-drug conjugates are not excluded
- History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment
Note: Other protocol defined inclusion / exclusion criteria apply
Sites / Locations
- University of Miami Hospital/Sylvester Comprehensive
- Moffitt Cancer Center
- Winship Cancer Institute of Emory University
- Indiana University Melvin and Bren Simon Comprehensive Cancer Center
- Norton Cancer Institute
- University of Michigan Health System
- Barbara Ann Karmanos Cancer Institute
- Rutgers Cancer Institute of New Jersey
- The Icahn School of Medicine at Mount Sinai
- Columbia University Medical Center, Herbert Irving Pavilion
- The Ohio State University, James Cancer Hospital
- Oregon Health Science University OHSU
- University of Texas MD Anderson Clinic
- Swedish Cancer Institute
- Ziekenhuis Netwerk Antwerpen (ZNA)- Stuivenberg
- Cliniques Universitaires Saint-Luc
- Universitaetsklinikum Essen
- University Medicine Mainz
- Universitatsklinikum Wurzburg
- National Cancer Center
- Soul National University Hospital Jongno-gu
- Severance Hospital, Yonsei University Health System Seodaemun-gu
- Seoul St.Mary's Hospital, The Catholic University of Korea Seocho-gu
- Clinica universidad de Navarra unidad centrak de ensayos clinicos 7a 2a fase
- Hospital Universitario Sant Pau, Carrer de Sant Antoni Maria Claret, 167
- Universitary Hospital La Princesa Calle de Diego de Leon 62
- Hospital Universitario Ramon y Cajal M-607, km 9.100
- Hospital 12 de Octubre Avda de Cordoba, s/n
- Hospital Universitario de Salamanca Paseo de San Vicente 58-182
- The Royal Marsden Hospital Downs Road Surrey
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
REGN5458
Arm Description
Phase 1: Cohorts of multiple REGN5458 dose levels Phase 2: Until disease progression or other discontinuation criterion is met
Outcomes
Primary Outcome Measures
Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
In the phase 1 portion and Phase 2 portion for Japanese cohort only
Incidence and severity of treatment-emergent adverse events (TEAEs)
In the phase 1 portion
Incidence and severity of adverse events of special interest (AESI)
In the phase 1 portion
Objective response rate (ORR) as measured using the International Myeloma Working Group (IMWG) criteria
In the phase 2 portion, as determined by blinded Independent Review Committee (IRC).
Concentrations of REGN5458 in serum over time
In the phase 2 portion, for Japanese pcohort only
Secondary Outcome Measures
Concentrations of REGN5458 in the serum over time
In the phase 1 and phase 2 portions
Incidence over time of anti-drug antibodies (ADAs) to REGN5458
In the phase 1 and Phase 2 portions
Duration of response (DOR) using the IMWG criteria
In the phase 1 and Phase 2 portions
Progression-free survival (PFS) as measured using the IMWG criteria
In the phase 1 and Phase 2 portions
Rate of minimal residual disease (MRD) negative status using the IMWG criteria
In the phase 1 and Phase 2 portions
Overall survival (OS)
In the phase 1 and Phase 2 portions
ORR as measured using the IMWG criteria
In the phase 1 and Phase 2 portions, as determined by the Investigator
Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
In the phase 2 portion
The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])
In the phase 2 portion
The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems.
Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])
In the phase 2 portion
The EQ-5D-3L is a self-administered generic standardized health status measure, consisting of an EQ-5D descriptive system and an EQ visual analog scale. The EQ-5D-3L descriptive system assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 3-level scale: no problems, some problems, and extreme problems. The EQ visual analog scale component is a vertical visual analog scale used by patients to rate their health.
Change in patient-reported global health status/QoL per EORTC QLQ-C30
In the phase 2 portion
Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
In the phase 2 portion
Effects of REGN5458 on general health status per EQ-5D-3L
In the phase 2 portion
Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30
In the phase 2 portion
Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20
In the phase 2 portion
Incidence and severity of TEAEs with REGN5458
In the phase 2 portion
Incidence and severity of AESIs with REGN5458
In the phase 2 portion
Full Information
NCT ID
NCT03761108
First Posted
November 29, 2018
Last Updated
April 3, 2023
Sponsor
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03761108
Brief Title
Phase 1/2 Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma
Acronym
LINKER-MM1
Official Title
Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 23, 2019 (Actual)
Primary Completion Date
June 15, 2023 (Anticipated)
Study Completion Date
March 14, 2032 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objectives of the study are:
In the phase 1 portion of the study: To assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine one or more recommended phase 2 dose regimens (RP2DRs) of REGN5458 as monotherapy in patients with relapsed or refractory multiple myeloma (MM)
In the phase 2 portion of the study for each cohort: To assess the anti-tumor activity of REGN5458, as measured by objective response rate (ORR) and as determined by an Independent Review Committee (IRC), in patients who have progressed on or after 3 prior lines of therapy or who are triple-refractory (defined as refractory to a(n) proteasome inhibitor (PI), immunomodulatory imide drug (IMiD), and anti-CD38 monoclonal antibody)
Applicable to the phase 2 Japan cohort only: In addition to the objectives in phase 2, the Japan cohort will also assess the safety, tolerability, DLTs, and pharmacokinetics (PK) of different regimens of REGN5458 as a monotherapy in Japanese patients.
The secondary objectives of the study are:
In the phase 1 dose escalation portion:
To assess the preliminary anti-tumor activity of REGN5458 as determined by the investigator and measured by ORR, duration of response (DOR), progression-free survival (PFS), rate of minimal residual disease (MRD) negative status, and overall survival (OS)
To evaluate the PK properties of REGN5458
To characterize the immunogenicity of REGN5458
In the phase 2 portion for each cohort:
To assess the anti-tumor activity of REGN5458 as measured by:
ORR, as determined by the investigator
DOR and PFS, as determined by an IRC and the investigator
Rate of MRD negative status
OS
To evaluate the effects of REGN5458 on health-related quality of life (HRQoL) and patient-reported functions and symptoms
To evaluate the safety and tolerability of REGN5458
To evaluate the PK properties of REGN5458
To characterize the immunogenicity of REGN5458
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Relapsed, Refractory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
309 (Actual)
8. Arms, Groups, and Interventions
Arm Title
REGN5458
Arm Type
Experimental
Arm Description
Phase 1: Cohorts of multiple REGN5458 dose levels Phase 2: Until disease progression or other discontinuation criterion is met
Intervention Type
Drug
Intervention Name(s)
REGN5458
Other Intervention Name(s)
linvoseltamab
Intervention Description
Administered by intravenous (IV) infusion
Primary Outcome Measure Information:
Title
Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
Description
In the phase 1 portion and Phase 2 portion for Japanese cohort only
Time Frame
Up to 28 days
Title
Incidence and severity of treatment-emergent adverse events (TEAEs)
Description
In the phase 1 portion
Time Frame
Up to 5 years
Title
Incidence and severity of adverse events of special interest (AESI)
Description
In the phase 1 portion
Time Frame
Up to 5 years
Title
Objective response rate (ORR) as measured using the International Myeloma Working Group (IMWG) criteria
Description
In the phase 2 portion, as determined by blinded Independent Review Committee (IRC).
Time Frame
Up to 5 years
Title
Concentrations of REGN5458 in serum over time
Description
In the phase 2 portion, for Japanese pcohort only
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Concentrations of REGN5458 in the serum over time
Description
In the phase 1 and phase 2 portions
Time Frame
Up to 5 years
Title
Incidence over time of anti-drug antibodies (ADAs) to REGN5458
Description
In the phase 1 and Phase 2 portions
Time Frame
Up to 5 years
Title
Duration of response (DOR) using the IMWG criteria
Description
In the phase 1 and Phase 2 portions
Time Frame
Up to 5 years
Title
Progression-free survival (PFS) as measured using the IMWG criteria
Description
In the phase 1 and Phase 2 portions
Time Frame
Up to 5 years
Title
Rate of minimal residual disease (MRD) negative status using the IMWG criteria
Description
In the phase 1 and Phase 2 portions
Time Frame
Up to 5 years
Title
Overall survival (OS)
Description
In the phase 1 and Phase 2 portions
Time Frame
Up to 5 years
Title
ORR as measured using the IMWG criteria
Description
In the phase 1 and Phase 2 portions, as determined by the Investigator
Time Frame
Up to 5 years
Title
Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Description
In the phase 2 portion
The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
Time Frame
Up to 5 years
Title
Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])
Description
In the phase 2 portion
The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems.
Time Frame
Up to 5 years
Title
Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])
Description
In the phase 2 portion
The EQ-5D-3L is a self-administered generic standardized health status measure, consisting of an EQ-5D descriptive system and an EQ visual analog scale. The EQ-5D-3L descriptive system assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 3-level scale: no problems, some problems, and extreme problems. The EQ visual analog scale component is a vertical visual analog scale used by patients to rate their health.
Time Frame
Up to 5 years
Title
Change in patient-reported global health status/QoL per EORTC QLQ-C30
Description
In the phase 2 portion
Time Frame
Baseline up to Up to 5 years
Title
Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
Description
In the phase 2 portion
Time Frame
Up to 5 years
Title
Effects of REGN5458 on general health status per EQ-5D-3L
Description
In the phase 2 portion
Time Frame
Up to 5 years
Title
Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30
Description
In the phase 2 portion
Time Frame
Up to 5 years
Title
Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20
Description
In the phase 2 portion
Time Frame
Up to 5 years
Title
Incidence and severity of TEAEs with REGN5458
Description
In the phase 2 portion
Time Frame
Up to 5 years
Title
Incidence and severity of AESIs with REGN5458
Description
In the phase 2 portion
Time Frame
Up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria as defined in the protocol.
Phase 1 Dose Escalation: Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease or intolerance of the therapy and including either:
Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a proteasome inhibitor, an Immunomodulatory agent (IMiD), and an anti-CD38 antibody, OR
Progression on or after an anti-CD38 antibody and have disease that is "double refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor (PI). Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
Phase 2:
Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
Patients must be triple-refractory, defined as being refractory to prior treatment with at least 1 anti-CD38 antibody, a proteasome inhibitor, and an IMiD.
Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or less than 25% response to therapy.
Key Exclusion Criteria:
Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
Patients with known MM brain lesions or meningeal involvement
Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA)
Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs, and BCMA CAR T cells. Note: BCMA antibody-drug conjugates are not excluded
History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment
Note: Other protocol defined inclusion / exclusion criteria apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Miami Hospital/Sylvester Comprehensive
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Winship Cancer Institute of Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Norton Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
The Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Medical Center, Herbert Irving Pavilion
City
New York
State/Province
New York
ZIP/Postal Code
10032-3729
Country
United States
Facility Name
The Ohio State University, James Cancer Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Oregon Health Science University OHSU
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Texas MD Anderson Clinic
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Ziekenhuis Netwerk Antwerpen (ZNA)- Stuivenberg
City
Antwerp
ZIP/Postal Code
2060
Country
Belgium
Facility Name
Cliniques Universitaires Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Universitaetsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
University Medicine Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Universitatsklinikum Wurzburg
City
Würzburg
ZIP/Postal Code
6 97080
Country
Germany
Facility Name
National Cancer Center
City
Goyang-si
State/Province
Gyeonggi-do
ZIP/Postal Code
10408
Country
Korea, Republic of
Facility Name
Soul National University Hospital Jongno-gu
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System Seodaemun-gu
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Seoul St.Mary's Hospital, The Catholic University of Korea Seocho-gu
City
Seoul
ZIP/Postal Code
137-701
Country
Korea, Republic of
Facility Name
Clinica universidad de Navarra unidad centrak de ensayos clinicos 7a 2a fase
City
Pamplona
State/Province
Navarre
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital Universitario Sant Pau, Carrer de Sant Antoni Maria Claret, 167
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Universitary Hospital La Princesa Calle de Diego de Leon 62
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital Universitario Ramon y Cajal M-607, km 9.100
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital 12 de Octubre Avda de Cordoba, s/n
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario de Salamanca Paseo de San Vicente 58-182
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
The Royal Marsden Hospital Downs Road Surrey
City
London
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All IPD that underlie results in a publication.
IPD Sharing Time Frame
Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.
IPD Sharing Access Criteria
Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in a manuscript. Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.
IPD Sharing URL
https://vivli.org/
Learn more about this trial
Phase 1/2 Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma
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