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A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Patients With Multiple Myeloma That is Resistant to Current Standard of Care Treatments

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: NCT05137054
Recruitment Status : Recruiting
First Posted : November 30, 2021
Last Update Posted : April 12, 2024
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

The 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 your blood at different times
  • Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Linvoseltamab Drug: Daratumumab Drug: Carfilzomib Drug: Lenalidomide Drug: Bortezomib Drug: Pomalidomide Drug: Isatuximab Drug: Fianlimab Drug: Cemiplimab Drug: Nirogacestat Phase 1

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 317 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Other Cancer Treatments for Patients With Relapsed/Refractory Multiple Myeloma
Actual Study Start Date : August 17, 2022
Estimated Primary Completion Date : January 13, 2027
Estimated Study Completion Date : August 7, 2032

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Cohort 1: Linvoseltamab + Daratumumab
Linvoseltamab + Daratumumab
Drug: Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Other Name: REGN5458

Drug: Daratumumab
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.
Other Name: Darzalex®; Darzalex Faspro™

Experimental: Cohort 2: Linvolseltamab + Carfilzomib
Linvoseltamab + Carfilzomib
Drug: Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Other Name: REGN5458

Drug: Carfilzomib
Carfilzomib is administered by IV infusion
Other Name: Kyprolis®

Experimental: Cohort 3: Linvoseltamab + Lenalidomide
Linvoseltamab + Lenalidomide
Drug: Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Other Name: REGN5458

Drug: Lenalidomide
Lenalidomide is administered by mouth (PO) as a capsule
Other Name: Revlimid®

Experimental: Cohort 4: Linvoseltamab + Bortezomib
Linvoseltamab + Bortezomib
Drug: Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Other Name: REGN5458

Drug: Bortezomib
Bortezomib is administered by IV infusion or SC injection
Other Name: Velcade®

Experimental: Cohort 5: Linvoseltamab + Pomalidomide
Linvoseltamab + Pomalidomide
Drug: Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Other Name: REGN5458

Drug: Pomalidomide
Pomalidomide is administered by mouth (PO) as a capsule
Other Name: Imnovid, Pomalyst®

Experimental: Cohort 6: Linvoseltamab + Isatuximab
Linvoseltamab + Isatuximab
Drug: Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Other Name: REGN5458

Drug: Isatuximab
Isatuximab is administered by IV infusion
Other Name: Sarclisa®

Experimental: Cohort 7: Linvoseltamab + Fianlimab
Linvoseltamab + Fianlimab
Drug: Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Other Name: REGN5458

Drug: Fianlimab
Fianlimab is administered by IV infusion
Other Name: REGN3767

Experimental: Cohort 8: Linvoseltamab + Cemiplimab
Linvoseltamab + Cemiplimab
Drug: Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Other Name: REGN5458

Drug: Cemiplimab
Cemiplimab is administered by IV infusion
Other Name: LIBTAYO

Experimental: Cohort 9: Linvoseltamab + Nirogacestat
Linvoseltamab + Nirogacestat
Drug: Nirogacestat
Nirogacestat is administered by mouth (PO) as a tablet
Other Name: PF-03084014




Primary Outcome Measures :
  1. Incidence of pre-defined safety criteria or dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period [ Time Frame: Up to 28 Days ]
    Dose finding portion only

  2. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 5 Years ]
  3. Severity of TEAEs [ Time Frame: Up to 5 Years ]
  4. Incidence of serious adverse events (SAEs) [ Time Frame: Up to 5 Years ]
  5. Severity of SAEs [ Time Frame: Up to 5 Years ]
  6. Incidence of adverse events of special interest (AESIs) [ Time Frame: Up to 5 Years ]
  7. Severity of AESIs [ Time Frame: Up to 5 Years ]
  8. Incidence of laboratory abnormalities [ Time Frame: Up to 5 Years ]
    ≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE v5.0]


Secondary Outcome Measures :
  1. Objective response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria [ Time Frame: Up to 5 Years ]
  2. Duration of response (DOR) by IMWG criteria [ Time Frame: Up to 5 Years ]
  3. Progression-free survival (PFS) as measured by IMWG criteria [ Time Frame: Up to 5 Years ]
  4. Rate of minimal residual disease (MRD) negative status by IMWG criteria [ Time Frame: Up to 5 Years ]
  5. Concentrations of total linvoseltamab in serum over time [ Time Frame: Up to 5 Years ]
  6. Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab [ Time Frame: Up to 5 Years ]
  7. Overall Survival (OS) [ Time Frame: Up to 5 Years ]


Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 the below cohorts, 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 one of the following:

  • 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: each participant must have progressive RRMM and the following:

  • Received at least 3 lines of therapy and
  • Triple-class refractory disease (anti-CD38 antibody, IMiD, 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 stem cell transplantation, or autologous stem cell transplantation within 12 weeks of the start of study drug regimen
  5. Unless stated otherwise in a specific sub-protocol, prior treatment with BCMA-directed immunotherapies, including 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 3:

1. Known malabsorption syndrome or pre-existing gastrointestinal (GI) conditions that may impair absorption of lenalidomide (eg, gastric bypass, lap band, or other gastric procedures that would alter absorption); 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 (eg, gastric bypass, lap band, or other gastric procedures that would alter absorption); 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 conditions that may impair absorption of nirogacestat (eg, gastric bypass, lap band, or other gastric procedures that would alter absorption); delivery of nirogacestat via nasogastric tube or gastrostomy tube is not allowed.

NOTE: Other protocol defined inclusion/exclusion criteria apply


Information from the National Library of Medicine

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): NCT05137054


Contacts
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Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
Show Show 32 study locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05137054    
Other Study ID Numbers: R5458-ONC-2012
2020-004638-39 ( EudraCT Number )
First Posted: November 30, 2021    Key Record Dates
Last Update Posted: April 12, 2024
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
Relapsed/Refractory Multiple Myeloma (RRMM)
B-cell maturation antigen (BCMA)
Anti-CD3 monoclonal antibodies (mAbs)
Additional relevant MeSH terms:
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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
Lenalidomide
Pomalidomide
Bortezomib
Daratumumab
Cemiplimab
Nirogacestat
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Immunological
Gamma Secretase Inhibitors and Modulators
Enzyme Inhibitors