Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 1

Phase 1b Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Other Cancer Treatments for Patients With Relapsed/Refractory Multiple Myeloma

NCT ID: NCT05137054Sponsor: Regeneron PharmaceuticalsLast updated: 2026-01-22

Summary

This study is researching an experimental drug called linvoseltamab in combination with other drugs for the treatment of a blood cancer called multiple myeloma. Linvoseltamab has previously been studied as a single agent (without other cancer treatments) in participants with multiple myeloma that returned after prior therapies and needed to be treated again. In the initial study, some participants treated with linvoseltamab had improvement of their myeloma, including complete responses (no evidence of myeloma in their bodies). This study is the first time linvoseltamab will be combined with other cancer therapies. The main goal is to understand if linvoseltamab can be given safely with other cancer treatments, and if so, what dose of linvoseltamab should be used for each combination. The study is looking at several other research questions, including: * How many participants treated with linvoseltamab in combination with each of the other cancer treatments have improvement of their multiple myeloma * What side effects may happen from taking linvoseltamab together with another cancer treatment * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)

Arms & interventions

  • DrugLinvoseltamab

    Linvoseltamab is administered by intravenous (IV) infusion

  • DrugDaratumumab

    Daratumumab is administered by IV infusion and/or subcutaneous (SC) injection; SC injection may be used after a minimum of 2 cycles of IV administration at the investigator's discretion.

  • DrugCarfilzomib

    Carfilzomib is administered by IV infusion

  • DrugLenalidomide

    Lenalidomide is administered by mouth (PO) as a capsule

  • DrugBortezomib

    Bortezomib is administered by IV infusion or SC injection

  • DrugPomalidomide

    Pomalidomide is administered by mouth (PO) as a capsule

  • DrugIsatuximab

    Isatuximab is administered by IV infusion

  • DrugFianlimab

    Fianlimab is administered by IV infusion

  • DrugCemiplimab

    Cemiplimab is administered by IV infusion

  • DrugNirogacestat

    Nirogacestat is administered by mouth (PO) as a tablet

  • DrugCevostamab

    Cevostamab is administered by IV infusion

Outcome measures

Primary

  • Incidence of pre-defined safety criteria or dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period

    Dose finding portion only

    Time frame: Up to 28 Days

  • Incidence of treatment-emergent adverse events (TEAEs)

    Time frame: Up to 5 Years

  • Severity of TEAEs

    Time frame: Up to 5 Years

  • Incidence of serious adverse events (SAEs)

    Time frame: Up to 5 Years

  • Severity of SAEs

    Time frame: Up to 5 Years

  • Incidence of adverse events of special interest (AESIs)

    Time frame: Up to 5 Years

  • Severity of AESIs

    Time frame: Up to 5 Years

  • Incidence of laboratory abnormalities

    ≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE v5.0\]

    Time frame: Up to 5 Years

Secondary

  • Objective response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria

    Time frame: Up to 5 Years

  • Duration of response (DOR) by IMWG criteria

    Time frame: Up to 5 Years

  • Progression-free survival (PFS) as measured by IMWG criteria

    Time frame: Up to 5 Years

  • Rate of minimal residual disease (MRD) negative status by IMWG criteria

    Time frame: Up to 5 Years

  • Concentrations of total linvoseltamab in serum over time

    Time frame: Up to 5 Years

  • Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab

    Time frame: Up to 5 Years

  • Overall Survival (OS)

    Time frame: Up to 5 Years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
General Key Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 2. Participants must have measurable disease as defined in the protocol according to International Myeloma Working Group (IMWG) consensus criteria 3. Adequate creatinine clearance, hematologic function and hepatic function, as defined in protocol 4. Life expectancy of at least 6 months. Cohort Specific Inclusion Criteria: For cohorts 1-6, each participant must have RRMM with progression following at least 3 lines of therapy, or at least 2 lines of therapy and either prior exposure to at least 1 anti-CD38 antibody, 1 immunomodulatory imide drug (IMiD) and 1 proteasome inhibitor (PI), or double-refractory to 1 PI and 1 IMiD, or the combination of 1 PI and 1 IMiD. Cohort 1: Prior treatment with daratumumab is allowed if previously tolerated. However, participants enrolled in the expansion portion cannot be refractory to an anti-CD38 antibody containing regimen. In addition, all participants must have at least a 6-month washout from prior anti-CD38 antibody therapy. Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the approved full dose. Carfilzomib-refractory participants may enroll in the dose finding portion provided they are triple-class refractory (PI, IMiD, anti-CD38 antibody). However, participants enrolled in the dose expansion portion cannot be refractory to carfilzomib. In addition, all participants must have at least a 6-month washout from prior carfilzomib therapy. Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the approved full dose. However, a participant cannot be refractory to any combination regimen that included 25 mg of lenalidomide. In addition, participants must have at least a 6-month washout from any prior lenalidomide therapy (including maintenance therapy). Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the approved full dose. Bortezomib-refractory participants may enroll in the dose finding portion provided they are triple-class refractory (PI, IMiD, anti-CD38 antibody). However, participants enrolled in the dose expansion portion cannot be refractory to bortezomib. In addition, all participants must have at least a 6-month washout from prior bortezomib therapy. Cohort 5: Prior treatment with pomalidomide is allowed if previously tolerated at the approved full dose. Additionally, participants must undergo at least a 6-month washout following prior pomalidomide therapy before enrollment. Cohort 6: Prior treatment with isatuximab is allowed if previously tolerated. Additionally, participants must undergo at least a 3-month washout following prior anti-CD38 antibody therapy before enrollment. Cohort 7 and 8: RRMM with progressive disease and received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1IMiD, and 1 PI or triple-class refractory disease (anti-CD38 antibody, IMiD, PI). Cohort 9: Progressive RRMM in participants with triple-class refractory disease (anti-CD38 antibody, IMiD, PI) after at least 3 lines of therapy Cohort 10: Progressive RRMM after at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, and 1 PI. General Key Exclusion Criteria: 1. Diagnosis of plasma cell leukemia, primary light-chain amyloidosis (excluding myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 2. Participants with known MM brain lesions or meningeal involvement 3. Treatment with any systemic anti-myeloma therapy within 5 half-lives or within 21 days prior to first administration of study drug regimen, whichever is shorter 4. History of allogeneic and autologous stem cell transplantation, as described in the protocol 5. Unless stated otherwise in a specific sub-protocol, prior treatment with a T cell-based immunotherapy directed against BCMA bispecific antibodies and bispecific T-cell engagers (BiTEs), and BCMA chimeric antigen receptor (CAR) T cells (Note: BCMA antibody-drug conjugates are not excluded) 6. History of progressive multifocal leukoencephalopathy, neurodegenerative condition or central nervous system (CNS) movement disorder or participants with a history of seizure within 12 months prior to study enrollment are excluded 7. Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential 8. Cardiac ejection fraction \<40% by echocardiogram (Echo) or multigated acquisition (MUGA) scan. Cohort Specific Exclusion Criteria: Cohort 2: 1\. Dose expansion: Prior treatment with a B-cell maturation antigen (BCMA) -directed CAR T-cell therapy will not be exclusionary if completed at least 12 weeks prior to first study treatment Cohort 3: 1\. Known malabsorption syndrome or pre-existing gastrointestinal (GI) condition that may impair absorption of lenalidomide; delivery of lenalidomide via nasogastric tube or gastrostomy tube is not allowed. Cohort 4: 1\. Peripheral neuropathy grade ≥2 Cohort 5: 1\. Known malabsorption syndrome or pre-existing GI conditions that may impair absorption of pomalidomide; delivery of pomalidomide via nasogastric tube or gastrostomy tube is not allowed. Cohort 7: 1. Prior treatment with anti-lymphocyte activation gene 3 (LAG-3) agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-programmed cell death protein 1 (PD-1) antibodies is permitted, as described in the protocol. 2. Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol. 3. Prior solid organ transplant. 4. History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies. Cohort 8: 1. Prior treatment with anti-PD-1 or anti-PD-L1 agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies is permitted, as described in the protocol. 2. Encephalitis or meningitis in the year prior to enrollment. 3. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to enrollment. 4. Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol. 5. Prior solid organ transplant. 6. History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies. Cohort 9: 1. Abnormal QT interval corrected by Fridericia's formula (QTcF), as described in the protocol 2. Use of concomitant medications that are known to prolong the QT/QTcF interval including Class Ia and Class III antiarrhythmics at the time of informed consent 3. Ongoing use or anticipated use of food or drugs that are known strong/moderate cytochrome P450 (CYP)3A4 inhibitors, or strong CYP3A inducers within 14 days prior to first dose of nirogacestat 4. Known malabsorption syndrome or existing gastrointestinal GI condition that may impair absorption of nirogacestat; delivery of nirogacestat via nasogastric tube or gastrostomy tube is not allowed. Cohort 10: 1. Known or suspected active Epstein-Barr virus (EBV) infection. 2. Known history of Hemophagocytic lymphohistiocytosis/Macrophage activation syndrome (HLH/MAS). 3. Prior treatment with cevostamab or another agent with the same target \[Fragment crystallizable receptor-like 5 (FcRH5)\]. NOTE: Other protocol defined inclusion/exclusion criteria apply

Study locations (13)

Scripps Clinic Torrey Pines

La Jolla, California, 92037

Recruiting

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30004

Recruiting

Indiana University Health Simon Cancer Center

Indianapolis, Indiana, 46202

Recruiting

Dana Farber/Harvard Cancer Center

Boston, Massachusetts, 02215

Recruiting

Karmanos Cancer Institute

Detroit, Michigan, 48201

Recruiting

Mayo Clinic

Rochester, Minnesota, 55905

Recruiting

Weill Cornell Medicine/New York Presbyterian Hospital

New York, New York, 10021

Recruiting

New York Presbyterian Hospital Columbia University Medical Center

New York, New York, 10032

Recruiting

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599

Recruiting

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157

Recruiting

The Ohio State University James Cancer Hospital

Columbus, Ohio, 43210

Recruiting

University of Texas Southwestern

Dallas, Texas, 75390

Recruiting

VA Puget Sound Health Care System

Seattle, Washington, 98108

Recruiting