Multiple Myeloma
Conditions
Keywords
Relapsed/Refractory Multiple Myeloma (RRMM), B-cell maturation antigen (BCMA), Anti-CD3 monoclonal antibodies (mAbs)
Brief 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)
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
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of pre-defined safety criteria or dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period | Up to 28 Days | Dose finding portion only |
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 5 Years | — |
| Severity of TEAEs | Up to 5 Years | — |
| Incidence of serious adverse events (SAEs) | Up to 5 Years | — |
| Severity of SAEs | Up to 5 Years | — |
| Incidence of adverse events of special interest (AESIs) | Up to 5 Years | — |
| Severity of AESIs | Up to 5 Years | — |
| Incidence of laboratory abnormalities | Up to 5 Years | ≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE v5.0\] |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria | Up to 5 Years |
| Duration of response (DOR) by IMWG criteria | Up to 5 Years |
| Progression-free survival (PFS) as measured by IMWG criteria | Up to 5 Years |
| Rate of minimal residual disease (MRD) negative status by IMWG criteria | Up to 5 Years |
| Concentrations of total linvoseltamab in serum over time | Up to 5 Years |
| Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab | Up to 5 Years |
| Overall Survival (OS) | Up to 5 Years |
Countries
France, Greece, Israel, Spain, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed