Lynozyfic (linvoseltamab-gcpt) / Regeneron, Sanofi - LARVOL DELTA

Multiple Myeloma Unpacked (ICML 2025) - P3 | "Several other phase II studies have explored the efficacy of triplet regimens incorporating Rd as a backbone, combined with agents such as elotuzumab [30], ixazomib [31], or carfilzomib [32] as well as quadruplet regimen including daratumumab and carfilzomib [33]...The landscape of induction treatment has evolved with the incorporation of the anti-CD38 monoclonal antibody daratumumab (D) into the triplet bortezomib-thalidomide-dexamethasone (VTd) and, more recently, bortezomib-lenalidomide-dexamethasone (VRd)...In transplant-ineligible patients, VRd [45], daratumumab-lenalidomide-dexamethasone (DRd) [46, 47] and daratumumab-bortezomib-melphalan-prednisone (DVMP) [48, 49] have been the standards of cares for years...The FDA approval of isatuximab-bortezomib-lenalidomide-dexamethasone (Isa-VRd), based on the results of the IMROZ study [38], which demonstrated the superiority of Isa-VRd over VRd in terms of MRD negativity and PFS, introduces a new SoC...Consequently,..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • Smoldering Multiple Myeloma • B2M • CRBN • CTCs • XPO1

Tocilizumab Prophylaxis for Patients with Multiple Myeloma Treated with Bispecific Antibodies. (PubMed, Blood Adv) - "For teclistamab, elranatamab, linvoseltamab and talquetamab individually, the CRS rate was 8.9%, 12.5%, 0%, and 13%. There were no grade 3 CRS events, and no additional doses of tocilizumab or corticosteroids were given for CRS. Our real-world evidence results suggest that tocilizumab may be effective as a preventative, rather than reactive, measure to prevent CRS without compromising efficacy."

Journal • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

Indirect Comparison of Linvoseltamab vs Teclistamab for the Treatment of Triple-Class Exposed Relapsed/Refractory Multiple Myeloma (Clin Lymphoma Myeloma Leuk) - "After matching (effective sample size = 83.0), linvoseltamab showed numerically longer duration of response (P = 0.100) and significantly longer progression-free survival (PFS, P = 0.004), overall survival (OS, P = 0.039), and time to next treatment (P = 0.028) than teclistamab based on hazard ratios. Linvoseltamab demonstrated numerically higher objective response rate, very good partial response or better, complete response or better (≥CR), and minimal residual disease–negativity (10-5 threshold) rates vs teclistamab based on odds ratios. Additional MAICs matching all prognostic factors available in both trials showed significantly longer PFS (P = 0.038) and OS (P = 0.039), significantly higher ≥CR (P = 0.043), and favorable trends for all other outcomes."

Retrospective data • Multiple Myeloma

Lynozyfic (linvoseltamab-gcpt) Receives FDA Accelerated Approval for Treatment of Relapsed or Refractory Multiple Myeloma (Regeneron Pharmaceuticals Press Release) - "Regeneron Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Lynozyfic (linvoseltamab-gcpt) to treat adult patients with relapsed or refractory (R/R) multiple myeloma (MM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti‑CD38 monoclonal antibody. Lynozyfic was granted accelerated approval based on response rate and durability of response in the LINKER-MM1 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial."

Accelerated approval • FDA approval • Multiple Myeloma

SYSTEMATIC REVIEW OF BISPECIFIC ANTIBODIES EFFICACY AND SAFETY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (EHA 2025) - "BCMA-targeting BsAbs include elranatamab (MagnetisMM-3, MagnetisMM-5, MagnetisMM-9), teclistamab (MajesTEC-1), and linvoseltamab (LINKER-MM1). BsAbs are a promising advancement in the treatment of R/RMM. Currently, three BsAbs - teclistamab (MajesTEC-1), talquetamab (MonumenTAL-1), and elranatamab (MagnetisMM-3)- have received accelerated FDA approval. However, BsAbs are associated with safety concerns, including cytokine release syndrome, hematologic toxicity, and an increased risk of infections."

Clinical • Review • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

LINVOSELTAMAB + BORTEZOMIB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL RESULTS FROM THE LINKER-MM2 TRIAL (EHA 2025) - P1 | "Dexamethasone premedication was limited to C0-1...One DLT occurred at DL2: Gr 3 cytomegalovirus colitis on day 48, which resolved with treatment delay and ganciclovir... LINVO + BTZ induced high response rates, with encouraging early DOR and PFS, in a population that was mostly PI-refractory. Safety was consistent with the known profile of each drug, and risk of Gr 3–5 infection was similar to LINVO monotherapy. These data will inform LINVO combination strategies for earlier LoT."

Clinical • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

LINVOSELTAMAB + CARFILZOMIB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL RESULTS FROM THE LINKER-MM2 TRIAL (EHA 2025) - P1 | "Dexamethasone premedication was limited to C0-1. LINVO + CFZ induced a high rate of deep and durable responses with a safety profile consistent with the individual drugs, supporting further development. Enrollment of patients receiving LINVO 200 mg in combination with CFZ is ongoing."

Clinical • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

EXPOSURE–RESPONSE ANALYSES OF VARIOUS EFFICACY AND SAFETY ENDPOINTS IN SUPPORT OF REGISTRATIONAL DOSE SELECTION OF LINVOSELTAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (EHA 2025) - P1/2 | "This E-R analysis identified a set of covariates that confirmed dose-related improvements in efficacy and safety, and demonstrated the influence of disease burden markers on these outcomes. This approach offers a data-driven, mechanistic insight into RRMM therapy and dose optimization. Overall, the E-R analyses support using the 200 over the 50 mg linvoseltamab dose after the step-up regimen."

Clinical • IO biomarker • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology

REAL-WORLD EFFECTIVENESS OF BELANTAMAB MAFODOTIN, BCMA-CD3 BISPECIFIC ANTIBODIES AND TALQUETAMAB IN PATIENTS WITH TRIPLE-CLASS-EXPOSED MULTIPLE MYELOMA. FIRST RESULTS FROM THE DANISH ABCD-STUDY. (EHA 2025) - "34 patients received BCMA-ADC belantamab mafodotin (belamaf), 59 patients received a BCMA-BsAb (49 teclistamab, 4 elranatamab, 6 linvoseltamab) and 19 patients received GPRC5D-BsAb talquetamab. Our study confirms the clinical activity of ABC-therapies in TCE patients in a real-world setting. We found that class-specific AEs for each respective drug were a frequent cause for reductions of dose and dose intensity. The retrospective nature, heterogeneous population and sample-size can explain the differences in effectiveness in our cohort compared to prospective clinical studies."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Keratitis • Multiple Myeloma • Neutropenia • Ocular Inflammation • Oncology • Ophthalmology • Respiratory Diseases

INDIRECT COMPARISON OF LINVOSELTAMAB VERSUS ELRANATAMAB FOR TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA (EHA 2025) - P1/2, P2 | "Compared with patients receiving elranatamab, patients receiving linvoseltamab demonstrated significantly higher ORR and ≥CR rate, numerically better ≥VGPR rate, and longer DOR, PFS, and OS, though the follow-up period was shorter. These results highlight the potential of linvoseltamab as a highly effective treatment option for patients with TCE RRMM."

Hematological Malignancies • Multiple Myeloma • Oncology

MASS SPECTROMETRY ENABLES PRECISE MONITORING OF BISPECIFIC ANTIBODY THERAPY IN MULTIPLE MYELOMA (EHA 2025) - "Therapeutic antibodies, including Elranatamab, Teclistamab, Talquetamab, and Linvoseltamab, were assessed in serum samples...Bispecific antibodies were detected in 11 serum samples (8 cases of Linvoseltamab and 3 cases of Teclistamab), while Daratumumab was also detected in 5 additional samples.Measurable residual disease (MRD) was assessed using next-generation flow (NGF) in bone marrow samples from 19 patients... Bispecific antibodies represent a good alternative for relapsed MM patients, achieving CR in at least 66% of patients. In addition, only one patient relapsed during the follow-up. MS enables accurate identification of bispecific antibodies in serum samples, ensuring no interference with MP quantification."

Hematological Malignancies • Multiple Myeloma • Oncology

LINKER-MM2: 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 (clinicaltrials.gov) - P1 | N=317 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jan 2033 ➔ Sep 2034 | Trial primary completion date: Mar 2027 ➔ Apr 2028

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

BCMA Bispecific Antibody Therapy for Post-BCMA CAR T-Cell Therapy Relapse (RECLAIM) (clinicaltrials.gov) - P2 | N=34 | Not yet recruiting | Sponsor: Medical College of Wisconsin

New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Linvoseltamab (LINVO) + bortezomib (BTZ) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): First results from the LINKER-MM2 trial. (ASCO 2025) - P1 | "Dexamethasone premedication was limited to C0–1...One DLT occurred at DL2 (Gr 3 CMV colitis on day 48; resolved with tx delay and ganciclovir)... LINVO + BTZ induced high response rates, with encouraging early DOR and PFS, in a population that was mostly PI-refractory. Safety was consistent with the known profile of each drug, and risk of Gr 3–5 infection was similar to LINVO monotherapy. These data will inform LINVO combination strategies for earlier LoT."

Clinical • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

Linvoseltamab (LINVO) + carfilzomib (CFZ) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial results from the LINKER-MM2 trial. (ASCO 2025) - P1 | "Dexamethasone premedication was limited to C0–1. LINVO + CFZ induced a high rate of deep and durable responses with a safety profile consistent with the individual drugs, supporting further development. Enrollment at 200 mg LINVO in combination with CFZ is ongoing."

Clinical • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

Indirect comparison of linvoseltamab versus elranatamab for triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). (ASCO 2025) - "Linvoseltamab demonstrated significantly higher ORR and ≥CR rate, numerically better ≥ VGPR rate, DOR, PFS, and OS compared with elranatamab, though the follow-up was shorter. These results highlight the potential of linvoseltamab as a highly effective treatment option for TCE RRMM. OR >1 or HR <1 favor linvoseltamab."

Hematological Malignancies • Multiple Myeloma • Oncology

LINVOSELTAMAB IN PATIENTS IDENTIFYING AS BLACK OR AFRICAN AMERICAN WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): RESULTS FROM LINKER-MM1 (COMy 2025) - No abstract available

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

CHARACTERIZATION OF LINVOSELTAMAB’S BCMA BINDING EPITOPE AND EFFICACY AGAINST BCMA MUTATIONS IN RELAPSED/REFRACTORY MUTLIPLE MYELOMA (COMy 2025) - No abstract available

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology

Linvoseltamab in patients with relapsed/refractory multiple myeloma (RRMM): longer follow-up and selected high-risk subgroup analyses of the LINKER-MM1 study (COMy 2025) - No abstract available

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Additional linvoseltamab combination with bortezomib showed promising clinical activity in R/R MM (GlobeNewswire) - P1b | N=317 | LINKER-MM2 (NCT05137054) | Sponsor: Regeneron Pharmaceuticals | "Among enrolled patients (n=24), 6 received linvoseltamab at 100 mg and 18 at 200 mg before initiating bortezomib. More than half were refractory to PIs, including 58% to carfilzomib and 13% to bortezomib. Of the 20 patients evaluable for efficacy and with a median duration of follow-up of 9 months, results across dose levels showed an 85% ORR (17 of 20 patients), with 50% (10 of 20 patients) achieving a CR. The most common TEAEs (>50%) of any grade and Grade ≥3 were CRS (58% and 0%), neutropenia (54% and 50%) and thrombocytopenia (54% and 37.5%). Four patients experienced ICANS (one Grade 1 and three Grade 2). Infections occurred in 75% of patients (Grade ≥3: 38%)."

P1 data • Multiple Myeloma

Linvoseltamab combined with carfilzomib showed strong responses in R/R MM (GlobeNewswire) - P1b | N=317 | LINKER-MM2 (NCT05137054) | Sponsor: Regeneron Pharmaceuticals | "With a median follow-up of 15 months, efficacy results across all dose levels showed a 90% objective response rate (ORR; 19 of 21 patients), with 76% (16 of 21 patients) achieving a complete response (CR). At 12 months, the estimated probability of maintaining a response was 87% (n=19; 95% confidence interval [CI]: 56% to 97%) and being progression-free was 83% (n=21; 95% CI: 55% to 94%). A registrational, randomized Phase 3 trial investigating this combination against standard-of-care in the same setting is planned. Among the 23 patients evaluable for safety, the most common treatment emergent adverse events (TEAEs; >50%) of any grade and Grade ≥3 were neutropenia (65% and 56.5%), cytokine release syndrome (CRS; 61% and 0%), diarrhea (52% and 4%) and thrombocytopenia (52% and 30%).

Cytokine release syndrome • P1 data • Multiple Myeloma

Use of an Independent Data Review Committee to Promote Best Practices for External Control Arms: A Case Study in Relapsed/Refractory Multiple Myeloma (ISPOR 2025) - P, P1/2 | " R5458-ONC-21101 (NCT05673967) is a global, non-interventional study examining RWD from patients with triple-class exposed or refractory MM initiating standard-of-care (SOC) treatment to contextualize results from the linvoseltamab (anti-BCMA×CD3 antibody) 200 mg cohort of the LINKER-MM1 phase 1/2 clinical trial (NCT03761108)... An IDRC provides impartial evaluation of data suitability for comparing clinical trial and RW SOC cohorts, minimizing biases and strengthening regulatory/health technology submissions. Selection of unbiased experts, and a predefined assessment process and charter, are essential to the IDRC’s successful implementation in RW studies."

Case study • Clinical • Review • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Short-Term Linvoseltamab Treatment on Top of Chronic Dupilumab Treatment for Adults With Severe Immunoglobulin E (IgE)-Mediated Food Allergy (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Oct 2025 ➔ Mar 2028 | Trial primary completion date: Oct 2025 ➔ Mar 2028

Trial completion date • Trial primary completion date • Allergy • Food Hypersensitivity • Immunology

Regeneron to Highlight Advances at ASCO with Phase 3 Adjuvant Libtayo (cemiplimab) CSCC Updates and Promising Early Blood Cancer Data with Linvoseltamab Combination (GlobeNewswire) - "Eighteen presentations will share the latest insights from ongoing research of approved and investigational treatment regimens across a range of difficult-to-treat cancers including non-melanoma and melanoma skin cancer, lung cancer, lymphoma and multiple myeloma...Notable presentations at ASCO on Regeneron’s oncology pipeline include detailed efficacy and safety findings from the Phase 3 C-POST trial evaluating the adjuvant use of the PD-1 inhibitor Libtayo in post-surgical high-risk cutaneous squamous cell carcinoma (CSCC). The results will be presented in an oral session on Saturday, May 31...Regeneron will debut results from two cohorts of the LINKER-MM2 trial...which will be featured in two rapid oral presentations on Monday, June 2...In addition, the results of a cooperative group study reporting on the primary analysis of a randomized Phase 2 trial of vidutolimod..."

Clinical data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

Lynozyfic (linvoseltamab) Approved in the European Union for the Treatment of Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - "Regeneron Pharmaceuticals, Inc...announced that the European Commission (EC) has granted conditional marketing approval of Lynozyfic (linvoseltamab) to treat adults with relapsed and refractory (R/R) multiple myeloma (MM). The indication is specific to those who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy....The EC approval is based on results from the pivotal LINKER-MM1 trial..."

EMA approval • Multiple Myeloma