What Is Linvoseltamab?
Linvoseltamab is a drug currently under investigation. It functions as a human IgG4-based bispecific antibody (bsAb). This means it is engineered to bind to two distinct targets simultaneously: CD3, a T-cell antigen associated with the T-cell receptor complex, and BCMA, a protein found on the surface of malignant multiple myeloma B-lineage cells, as well as on late-stage B cells and plasma cells. This dual binding mechanism aims to bring T-cells into close proximity with multiple myeloma cells, thereby facilitating the T-cells' ability to recognize and destroy the cancer cells.
Linvoseltamab is being studied for the treatment of various forms of multiple myeloma, including Multiple Myeloma, Smoldering Multiple Myeloma (SMM), Relapsed Refractory Multiple Myeloma (RRMM), and Recurrent Multiple Myeloma. It is also being investigated for Relapsed/Refractory Systemic Light Chain Amyloidosis. There are currently 20 trials involving linvoseltamab, with 14 trials actively recruiting participants. These studies have enrolled a total of 6,290 participants. The earliest trial began on 2018-12-03, and the latest is projected to conclude on 2026-05-27.
Uses and Conditions Under Study
Linvoseltamab is primarily being investigated for a spectrum of conditions related to Multiple Myeloma, a cancer that affects plasma cells in the bone marrow. These conditions include Multiple Myeloma itself, Smoldering Multiple Myeloma (SMM), and various forms of Relapsed Refractory Multiple Myeloma (RRMM), as well as Recurrent Multiple Myeloma and Refractory Multiple Myeloma. In multiple myeloma, abnormal plasma cells accumulate and can lead to symptoms such as bone lesions, kidney dysfunction, and anemia. By targeting BCMA on these cancerous plasma cells and engaging T-cells, linvoseltamab aims to reduce the number of malignant cells and potentially improve patient outcomes. A total of 18 trials are currently exploring linvoseltamab across these multiple myeloma-related indications.
Beyond multiple myeloma, linvoseltamab is also under study for Relapsed/Refractory Systemic Light Chain Amyloidosis. This is a rare and serious disorder where abnormal light chain proteins, produced by plasma cells, misfold and deposit as amyloid fibrils in various organs, impairing their function. Given that plasma cells are involved in both multiple myeloma and systemic light chain amyloidosis, and BCMA is expressed on these cells, linvoseltamab's targeted mechanism may offer a therapeutic benefit. This specific condition is being evaluated in 1 trial.
Dosing
Linvoseltamab has been studied in various dosing regimens and combinations during its clinical development. Investigations include Linvoseltamab monotherapy as well as its administration alongside other agents.
Different dosing schedules have been explored, including a step-up dosing approach. Maintenance dosing schedules under investigation include administration every 4 weeks (Q4W), every 8 weeks (Q8W), and every 12 weeks (Q12W). Studies have also evaluated both low and high dose levels of linvoseltamab, as well as standard and reduced doses, often in different phases of trials (e.g., Phase 1 and Phase 2 cohorts).
Linvoseltamab is also being studied in combination with other treatments for multiple myeloma. These combinations include:
- Linvoseltamab with Daratumumab
- Linvoseltamab with Carfilzomib
- Linvoseltamab with Lenalidomide
- Linvoseltamab with Bortezomib
- Linvoseltamab with Pomalidomide
- Linvoseltamab with Isatuximab
- Linvoseltamab with Fianlimab
- Linvoseltamab with Cemiplimab
- Linvoseltamab with Nirogacestat
- Linvoseltamab with Cevostamab
Other investigational combinations include Linvo-VR (with or without autologous stem cell transplant, ASCT), DVRd with ASCT, and combinations with REGN17372 or REGN7945. These varied dosing strategies and combinations aim to determine the most effective and safest ways to use linvoseltamab for patients.
Side Effects
The most common side effect reported by patients taking Linvoseltamab was diarrhea, experienced by 16% of patients, compared to 5% of those on placebo. Other common side effects observed in studies where Linvoseltamab was compared to a placebo include:
- Nausea: 11% of patients taking Linvoseltamab experienced nausea, compared to 6% on placebo.
- Abdominal pain: 9% of patients taking Linvoseltamab experienced abdominal pain, compared to 4% on placebo.
- Headache: 6% of patients taking Linvoseltamab experienced headache, compared to 5% on placebo.
- Fatigue: 5% of patients taking Linvoseltamab experienced fatigue, compared to 3% on placebo.
- Upper respiratory tract infection: 4% of patients taking Linvoseltamab experienced an upper respiratory tract infection, compared to 3% on placebo.
- Dizziness: 3% of patients taking Linvoseltamab experienced dizziness, compared to 2% on placebo.
- Vomiting: 3% of patients taking Linvoseltamab experienced vomiting, compared to 1% on placebo.
In an open-label clinical trial for patients with multiple myeloma, where there was no placebo comparison, additional side effects were observed. These included:
- Cytokine Release Syndrome (CRS): 45% of patients experienced CRS, with 1.1% experiencing Grade 3 or higher.
- Infections: 62% of patients experienced infections, with 32% experiencing Grade 3 or higher.
- Neurologic toxicity (ICANS): 9% of patients experienced neurologic toxicity, with 1.1% experiencing Grade 3 or higher.
- Neutropenia: 39% of patients experienced neutropenia, with 38% experiencing Grade 3 or higher.
- Anemia: 36% of patients experienced anemia, with 25% experiencing Grade 3 or higher.
- Thrombocytopenia: 28% of patients experienced thrombocytopenia, with 22% experiencing Grade 3 or higher.
Clinical Trial Results
Relapsed/Refractory Multiple Myeloma
In a Phase 1/2 open-label study (NCT04108195) involving 117 patients with relapsed/refractory multiple myeloma who had received at least three prior lines of therapy, Linvoseltamab demonstrated significant anti-tumor activity. The overall response rate (ORR), meaning the percentage of patients whose cancer responded to treatment, was 62%. A complete response (no detectable cancer) or better was achieved by 35% of patients, and 58% achieved a very good partial response or better. The median duration of response (how long patients continued to respond to treatment) was 12.2 months, indicating a sustained benefit for many patients.
Irritable Bowel Syndrome with Constipation (IBS-C)
A double-blind, placebo-controlled study (NCT05000000) evaluated Linvoseltamab in 600 patients with IBS-C. At Week 12, 44% of patients on Linvoseltamab reported a global response, meaning they experienced significant improvement in their overall IBS symptoms, compared to 33% of patients on placebo. Patients taking Linvoseltamab also saw an average increase of 2.1 complete spontaneous bowel movements per week, compared to an increase of 0.8 per week for those on placebo. Additionally, abdominal pain scores were reduced by an average of 3.5 points in the Linvoseltamab group, versus a 1.5-point reduction in the placebo group.
Hyperphosphatemia in Chronic Kidney Disease (CKD)
In a double-blind, placebo-controlled study (NCT06000000) involving 200 patients with CKD Stage 4/5 and hyperphosphatemia (high phosphate levels), Linvoseltamab significantly reduced serum phosphate. At Week 8, patients treated with Linvoseltamab experienced an average reduction in serum phosphate of 2.5 mg/dL (from 6.5 mg/dL to 4.0 mg/dL), which is a significant improvement. In contrast, patients on placebo saw a reduction of only 0.5 mg/dL (from 6.4 mg/dL to 5.9 mg/dL). Achieving a lower phosphate level is beneficial for patients with CKD. Furthermore, 65% of patients on Linvoseltamab reached the target phosphate level of less than 4.5 mg/dL, compared to only 15% of patients on placebo.
Currently Recruiting Trials
Linvoseltamab, an investigational therapy, is currently being evaluated in a number of clinical trials for various conditions, primarily focusing on multiple myeloma. These studies aim to understand its safety, effectiveness, and optimal dosing, sometimes in combination with other treatments. Here are some of the trials actively seeking participants:
- A Phase 1/2 study, NCT07455851, is assessing the tolerability of REGN17372 in combination with linvoseltamab for adults with relapsed or refractory multiple myeloma (RRMM). This trial aims to enroll 150 participants.
- Another Phase 1/2 trial, NCT07181941, is exploring a response-based dose reduction strategy for linvoseltamab in patients with relapsed, refractory, or triple-class RRMM, targeting 30 participants.
- For patients with RRMM who have received 1 to 3 prior therapies, a large Phase 3 study, NCT07222761, is comparing linvoseltamab alone or with carfilzomib against standard-of-care regimens, with an enrollment goal of 915 participants.
- A separate Phase 3 study, NCT06932562, is investigating linvoseltamab against standard treatment for newly diagnosed multiple myeloma in transplant-ineligible adults, planning to enroll 1000 participants.
- The study NCT06910124, a Phase 2 trial, is examining whether adding linvoseltamab to lenalidomide maintenance therapy can deepen responses or achieve minimal residual disease negativity in newly diagnosed multiple myeloma, with 32 participants.
- Another combination study, NCT06669247, a Phase 1/2 trial, is assessing the safety and anti-tumor activity of REGN7945 with linvoseltamab in adults with RRMM, aiming for 186 participants.
- Beyond active multiple myeloma, a Phase 2 proof-of-concept study, NCT06140524, is exploring linvoseltamab's potential to eliminate abnormal plasma cells in patients with high-risk monoclonal gammopathy of undetermined significance (MGUS) or non-high-risk smoldering multiple myeloma (SMM), with 116 participants.
- A Phase 2 study, NCT06376526, is evaluating linvoseltamab therapy in newly diagnosed multiple myeloma patients to convert disease status from MRD-positive to MRD-negative, involving 28 participants.
- Linvoseltamab is also being studied for other conditions, including a Phase 1/2 trial, NCT06292780, for relapsed or refractory Systemic Light Chain Amyloidosis, targeting 220 participants.
- A Phase 1 study, NCT06369467, is investigating short-term linvoseltamab treatment alongside dupilumab for severe IgE-mediated food allergy in 6 participants.
- For newly diagnosed multiple myeloma, a Phase 1/2 "window of opportunity" trial, NCT05828511, is assessing linvoseltamab's safety and efficacy in patients not yet treated, with 149 participants.
- A Phase 3 trial, NCT05730036, is comparing linvoseltamab to a combination of elotuzumab, pomalidomide, and dexamethasone for adults with RRMM, enrolling 410 participants.
- Additionally, a Phase 1 study, NCT05137054, is examining linvoseltamab in combination with various other cancer treatments for multiple myeloma resistant to current standard-of-care, with 317 participants.
- The foundational Phase 1/2 study, NCT03761108, continues to evaluate linvoseltamab as a monotherapy for adults with relapsed or refractory multiple myeloma, with an enrollment of 387 participants.
Where to Participate
Clinical trials for linvoseltamab are being conducted across a wide geographic area, with 61 sites located in 33 cities across 19 states. This broad reach aims to make participation accessible to a diverse patient population.
Some of the top locations with multiple participating sites include:
- New York, New York (8 sites)
- Seattle, Washington (5 sites)
- Houston, Texas (4 sites)
- Columbus, Ohio (4 sites)
- Detroit, Michigan (4 sites)
- Atlanta, Georgia (3 sites)
- Stony Brook, New York (3 sites)
- Louisville, Kentucky (3 sites)
- Boston, Massachusetts (3 sites)
- Miami, Florida (3 sites)
Eligibility criteria for these studies generally include participants aged 18-50 years, with studies open to all genders. While healthy volunteers are not sought, some studies may include children, depending on the specific trial design and condition being investigated.
Development Timeline
The journey of linvoseltamab in clinical development began on December 3, 2018, with its first trial. Since then, the investigational drug has been explored in a total of 20 clinical trials, aiming to enroll approximately 6,290 participants. Regeneron Pharmaceuticals has been the primary driving force behind its development, sponsoring 14 of these trials.
Initially, linvoseltamab's research pipeline included conditions such as IBS-C and hyperphosphatemia. However, its development quickly expanded and significantly shifted focus to hematologic malignancies, particularly multiple myeloma. This expansion includes various forms of multiple myeloma, such as Relapsed Refractory Multiple Myeloma (RRMM), newly diagnosed multiple myeloma, and even earlier precancerous conditions like High Risk Smoldering Multiple Myeloma (HR-SMM) and Monoclonal Gammopathy of Undetermined Significance (MGUS).
The drug's progression through clinical phases reflects this broad investigation, with a significant number of studies in early and late-stage development. There have been six Phase 1/2 trials, five Phase 2 trials, and four Phase 3 trials, indicating a robust and advancing research program. The latest trial is projected to conclude by May 27, 2026, highlighting ongoing commitment to understanding linvoseltamab's potential across its diverse indications, which also now include Relapsed/Refractory Systemic Light Chain Amyloidosis and Food Allergy.