Phase 1/2 Study of REGN5458 in Adult 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03761108 |
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Recruitment Status :
Recruiting
First Posted : December 3, 2018
Last Update Posted : April 9, 2024
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The main purpose of this study is to learn about the safety of REGN5458 and to find out what is the best dose of REGN5458 to give to patients with multiple myeloma. An additional purpose is to look for any signs that REGN5458 can treat cancer.
The study is looking at several other research questions, including:
- Side effects that may be experienced by people receiving REGN5458
- How REGN5458 works in the body
- How much REGN5458 is present in the blood
- How REGN5458 may work to treat cancer
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: Linvoseltamab | 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) |
| Estimated Enrollment : | 387 participants |
| Allocation: | Non-Randomized |
| 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 : | May 4, 2032 |
| Estimated Study Completion Date : | June 24, 2032 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Linvoseltamab - Phase 1
Phase 1 has two parts. Part 1, consists of REGN5458/linvoseltamab intravenous (IV) dose escalation and Part 2, consists of subcutaneous (SC) administration. Note: subcutaneous (SC) administration is not applicable for US. |
Drug: Linvoseltamab
Administered by IV infusion and/or SC
Other Name: REGN5458 |
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Experimental: Linvoseltamab - Phase 2 - Cohort 1
Low Dose of REGN5458/linvoseltamab IV monotherapy.
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Drug: Linvoseltamab
Administered by IV infusion and/or SC
Other Name: REGN5458 |
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Experimental: Linvoseltamab - Phase 2 - Cohort 2
High Dose of REGN5458/linvoseltamab IV monotherapy.
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Drug: Linvoseltamab
Administered by IV infusion and/or SC
Other Name: REGN5458 |
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Experimental: Linvoseltamab - Phase 2 - Cohort 3
Anti-interleukin (IL)-6 receptor (R) prophylactic therapy followed by high dose of IV dose of REGN5458 monotherapy. Note: Cohort 3 is not applicable for US. |
Drug: Linvoseltamab
Administered by IV infusion and/or SC
Other Name: REGN5458 |
- Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period [ Time Frame: Up to 28 days ]Phase 1 and Phase 2 for Japanese cohort only
- Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 5 years ]Phase 1 Note: Phase 1, part 2 is not applicable for US.
- Incidence and severity of adverse events of special interest (AESI) [ Time Frame: Up to 5 years ]Phase 1 Note: Phase 1, part 2 is not applicable for US.
- Concentrations of REGN5458 in serum over time [ Time Frame: Up to 5 years ]Phase 1, part 2 and Phase 2, for Japanese cohort only
- Objective response rate (ORR) as determined by an Independent Review Committee (IRC) [ Time Frame: Up to 5 years ]Phase 2, cohorts 1 and 2
- Incidence and severity of cytokine release syndrome (CRS) with REGN5458 [ Time Frame: Up to 5 years ]Phase 2, cohort 3 Note: Phase 2, Cohort 3 is not applicable for US.
- ORR of IV REGN5458 as assessed by investigator in patients who have progressed [ Time Frame: Up to 5 years ]Phase 2, cohort 3 Note: Phase 2, Cohort 3 is not applicable for US.
- Concentrations of REGN5458 in the serum over time [ Time Frame: Up to 5 years ]Phase 1 part 1 and Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
- Incidence over time of anti-drug antibodies (ADAs) to REGN5458 [ Time Frame: Up to 5 years ]Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.
- Titer of anti-drug antibodies (ADAs) to REGN5458 over time [ Time Frame: Up to 5 years ]Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.
- Incidence of neutralizing antibodies (Nab) to REGN5458 over time [ Time Frame: Up to 5 years ]Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.
- Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria [ Time Frame: Up to 5 years ]Phase 2, cohorts 1 and 2
- DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria [ Time Frame: Up to 5 years ]Phase 1 and Phase 2, cohorts 1 and 2 Note: Phase 1, part 2 is not applicable for US.
- Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria [ Time Frame: Up to 5 years ]Phase 2, cohorts 1 and 2
- PFS as determined by an investigator, measured using the IMWG criteria [ Time Frame: Up to 5 years ]Phase 1 and Phase 2, cohorts 1 and 2 Note: Phase 1, part 2 is not applicable for US.
- Rate of minimal residual disease (MRD) negative status using the IMWG criteria [ Time Frame: Up to 5 years ]Phase 1 Note: Phase 1, part 2 is not applicable for US.
- Rate of MRD negative status status [ Time Frame: Up to 5 years ]Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
- Overall survival (OS) [ Time Frame: Up to 5 years ]Phase 1 and Phase 2 Note: Phase 1, part 2 and Phase 2, Cohort 3 is not applicable for US.
- ORR as measured as determined by blinded IRC, as measured using the IMWG criteria [ Time Frame: Up to 5 years ]Phase 1, part 1 dose level 7 (DL7)
- ORR as determined by the investigator, measured using the IMWG criteria [ Time Frame: Up to 5 years ]Phase 1 and Phase 2, cohorts 1 and 2 Note: Phase 1, part 2 is not applicable for US.
- Effects of REGN5458 on health-related quality of life (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 ]
Phase 2
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."
Note: Phase 2, Cohort 3 is not applicable for US.
- 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 ]
Phase 2
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.
Note: Phase 2, Cohort 3 is not applicable for US.
- 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 ]
Phase 2
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.
Note: Phase 2, Cohort 3 is not applicable for US.
- Change in patient-reported global health status/QoL per EORTC QLQ-C30 [ Time Frame: Baseline up to Up to 5 years ]Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
- Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 [ Time Frame: Up to 5 years ]Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
- Effects of REGN5458 on general health status per EQ-5D-3L [ Time Frame: Up to 5 years ]Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
- Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30 [ Time Frame: Up to 5 years ]Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
- Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20 [ Time Frame: Up to 5 years ]Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
- Incidence and severity of TEAEs with REGN5458 [ Time Frame: Up to 5 years ]Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
- Incidence and severity of AESIs with REGN5458 [ Time Frame: Up to 5 years ]Phase 2 Note: Phase 2, Cohort 3 is not applicable for US.
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
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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, Part 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:
a. 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 b. 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 1, Part 2 (SC Administration): Patients with MM whose disease meets the following criteria:
a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. 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.
- Phase 2 (Cohorts 1 and 2):
Patients with MM whose disease meets the following criteria:
a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.
- Phase 2 (Cohort 3):
Patients with MM whose disease meets the following criteria:
- Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
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Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.
- Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.
AND, for ALL patients, if they have relapsed after a BCMA-directed CAR-T cellular therapy then:
• Treatment with a CAR-T must have been associated with a response of PR or better, and
• If CAR-T cellular therapy was the most recent prior therapy, excluding corticosteroids, then treatment must have been a minimum of 60 days prior to treatment with REGN5458.
Key Exclusion Criteria:
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1. 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) 2. Patients with known MM brain lesions or meningeal involvement -Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA) 3. Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs. Note: BCMA antibody-drug conjugates are not excludedand BCMA-directed CAR-T treatment is not excluded in Phase 2 Cohort 3.
4. History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment
Note 1: Other protocol defined inclusion / exclusion criteria apply Note 2: US enrollment completed
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
| Contact: Clinical Trial Administrator | 844-734-6643 | clinicaltrials@regeneron.com |
Show 38 study locations
| 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 9, 2024 |
| Last Verified: | December 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 |