Phase 1/2 Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma (LINKER-MM1)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03761108 |
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Recruitment Status :
Active, not recruiting
First Posted : December 3, 2018
Last Update Posted : April 5, 2023
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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)
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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:
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: REGN5458 | Phase 1 Phase 2 |
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 309 participants |
| Allocation: | N/A |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma |
| Actual Study Start Date : | January 23, 2019 |
| Estimated Primary Completion Date : | June 15, 2023 |
| Estimated Study Completion Date : | March 14, 2032 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: REGN5458
Phase 1: Cohorts of multiple REGN5458 dose levels Phase 2: Until disease progression or other discontinuation criterion is met
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Drug: REGN5458
Administered by intravenous (IV) infusion
Other Name: linvoseltamab |
- Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period [ Time Frame: Up to 28 days ]In the phase 1 portion and Phase 2 portion for Japanese cohort only
- Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 5 years ]In the phase 1 portion
- Incidence and severity of adverse events of special interest (AESI) [ Time Frame: Up to 5 years ]In the phase 1 portion
- Objective response rate (ORR) as measured using the International Myeloma Working Group (IMWG) criteria [ Time Frame: Up to 5 years ]In the phase 2 portion, as determined by blinded Independent Review Committee (IRC).
- Concentrations of REGN5458 in serum over time [ Time Frame: Up to 5 years ]In the phase 2 portion, for Japanese pcohort only
- Concentrations of REGN5458 in the serum over time [ Time Frame: Up to 5 years ]In the phase 1 and phase 2 portions
- Incidence over time of anti-drug antibodies (ADAs) to REGN5458 [ Time Frame: Up to 5 years ]In the phase 1 and Phase 2 portions
- Duration of response (DOR) using the IMWG criteria [ Time Frame: Up to 5 years ]In the phase 1 and Phase 2 portions
- Progression-free survival (PFS) as measured using the IMWG criteria [ Time Frame: Up to 5 years ]In the phase 1 and Phase 2 portions
- Rate of minimal residual disease (MRD) negative status using the IMWG criteria [ Time Frame: Up to 5 years ]In the phase 1 and Phase 2 portions
- Overall survival (OS) [ Time Frame: Up to 5 years ]In the phase 1 and Phase 2 portions
- ORR as measured using the IMWG criteria [ Time Frame: Up to 5 years ]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) [ Time Frame: Up to 5 years ]
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]) [ Time Frame: Up to 5 years ]
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]) [ Time Frame: Up to 5 years ]
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 [ Time Frame: Baseline up to Up to 5 years ]In the phase 2 portion
- Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 [ Time Frame: Up to 5 years ]In the phase 2 portion
- Effects of REGN5458 on general health status per EQ-5D-3L [ Time Frame: Up to 5 years ]In the phase 2 portion
- Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30 [ Time Frame: Up to 5 years ]In the phase 2 portion
- Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20 [ Time Frame: Up to 5 years ]In the phase 2 portion
- Incidence and severity of TEAEs with REGN5458 [ Time Frame: Up to 5 years ]In the phase 2 portion
- Incidence and severity of AESIs with REGN5458 [ Time Frame: Up to 5 years ]In the phase 2 portion
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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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.
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03761108
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| Study Director: | Clinical Trial Management | Regeneron Pharmaceuticals |
| Responsible Party: | Regeneron Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03761108 |
| Other Study ID Numbers: |
R5458-ONC-1826 2018-003188-78 ( EudraCT Number ) |
| First Posted: | December 3, 2018 Key Record Dates |
| Last Update Posted: | April 5, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | All IPD that underlie results in a publication. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) Analytic Code |
| 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. |
| 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. |
| URL: | https://vivli.org/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Relapsed, Refractory |
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases |
Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases |