etentamig intravenous (ABBV-383 IV) / AbbVie - LARVOL DELTA

Hematotoxicity and immune deficits with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma (ASH 2025) - "Among NHL cohorts, the BsAb distribution was: 7 glofitamab, 6 mosunetuzumab, 5 epcoritamab, and 4 odronextamab. Among MM cohorts, 6 received teclistamab, 3 talquetamab, 1 teclistamab and talquetamab, 2 elranatamab, 2 linvoseltamab and 1 etentamig (ABBV-383)... Cytopenias affect a substantial proportion of patients treated with BsAbs, particularly in MM and in NHL with combination regimes. These findings support the need for systematic hematologic monitoring, IG surveillance and tailored pre-emptive strategies to mitigate infection risk.This study represents the first and most comprehensive meta-analysis of hematotoxicity and immune deficits with BsAbs, establishing a benchmark across clinical settings."

Retrospective data • Review • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia

Ultra-sensitive detection of clonal m-protein by mass spectrometry enhances detection of residual disease: Results from A phase 1 study of etentamig monotherapy in patients with relapsed or refractory multiple myeloma (ASH 2025) - P1/2 | "Using MS-based clonotypic peptide detection, rapid and deep decline in serum M-proteinlevels was observed in RRMM patients treated with etentamig. Strong concordance was observedbetween MS M-protein levels and IMWG response, including in patients achieving MRD-negative CR at<10-5 and 10-6 thresholds. Non-invasive and ultra-sensitive M-protein detection is feasible in MM and mayserve as a key biomarker for enhancing the detection of residual disease in the future."

Clinical • IO biomarker • Monotherapy • P1 data • Residual disease • Hematological Malignancies • Multiple Myeloma

Validation of the high-risk consensus genomic staging system in the era of bispecific antibodies: Role of NGS and cytogenetic reclassification (ASH 2025) - "The median age at treatment initiation was 61 years (IQR 55–68), and 56.1% were male.Bispecific antibodies administered included teclistamab (27.6%), linvoseltamab (22.4%), talquetamab(21.4%), etentamig (14.3%), and elranatamab (12.2%).The most frequent high-risk cytogenetic alteration was 1q gain (38.8%), followed by del(17p) (21.4%),monoallelic del(1p32) (14.3%), t(4; 14) (11.2%), and t(14; 16) (3.1%). The revised IMWG-IMS high-risk genomic classification improved risk stratification over classic criteria ina large cohort of patients treated with bispecific antibodies. Even among heavily pretreated high-riskpatients, the updated classification more accurately identified those with poorer outcomes. Thesefindings support incorporating next-generation sequencing and refined cytogenetic definitions forprognostic assessment and treatment decisions in this patient population."

Next-generation sequencing • Hematological Malignancies • Multiple Myeloma • SDC1 • TP53

Impact of prior BCMA-targeted therapy on CAR-T expansion and host T-cell phenotypes in patients with Relapsed/Refractory multiple myeloma receiving BCMA CAR-T therapy (ASH 2025) - P1 | "TheBCMA CAR-Ts for RRMM were either ciltacabtagene autoleucel (ciltacel) given as standard of care, orthrough an investigator-initiated trial of a UCSF-manufactured BCMA-directed CAR-T for triple-classrefractory MM (NCT05577000)...Group 2 of collectionswere 3 RRMM patients receiving BCMA-directed CAR-T with prior BCMA-targeted therapy (anti-BCMAexposed group), which included idecabtagene vicleucel, belantamab mafadotin, teclistamab, and aninvestigational BCMA-directed bispecific T cell engager (TNB-383B, TeneoBio)...Prior BCMA-targeted therapy exposure may impact the host immune setpoint and downstreamresponses to subsequent BCMA-directed CAR-T therapy, including a shift from self-renewing non-CARhost T cell populations towards effector phenotypes, and impaired CAR-T expansion after CAR-T infusion.Further clinical follow up and correlative analysis to be presented will elucidate whether these immunefeatures of prior BCMA-targeted therapy are related to clinical..."

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • CD8 • CXCR4 • PTPRC

Phase 1/2 dose escalation and expansion study of etentamig in patients with relapsed or refractory light chain amyloidosis (ASH 2025) - P1/2, P3 | "Thirty-three percent have received a prior stem celltransplant and 50% previously received the regimen of daratumumab with cyclophosphamide,bortezomib, and dexamethasone in combination. Additional dose-level datawill be presented at the time of the meeting. All pts remain in ongoing follow-up and evaluation, and thestudy will begin the dose expansion (EXP) portion after dose selection."

Clinical • P1/2 data • Amyloidosis • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Multiple Myeloma • Neutropenia • Thrombocytopenia

Correlative biomarker analyses of etentamig in patients with Relapsed/Refractory multiple myeloma (RRMM) at optimal dose support its potential to maximize T-cell activity with rapid and transient proinflammatory cytokine responses (ASH 2025) - P1, P1/2 | "A modified dexamethasone premedication scheduleof 2 mg/60 mg Q4W cohort for C1 resulted in significantly reduced baseline levels of IL-6 and keymacrophage-associated cytokine/chemokines (eg, monocyte chemoattractant protein-1 and macrophageinflammatory protein-3 beta). Along treatment cycles, respondersmaintained their T-cell fitness, high clonality, and low T-cell exhaustion levels. Frequency of baselineCD4+ or CD8+ T-cell exhaustion (programmed cell death receptor 1+/ T cell immunoglobulin and mucin-domain containing-3 +) did not impact clinical response at optimal dose level of 2 mg/60 mg Q4Wetentamig.ConclusionsResponses to etentamig were independent of baseline sBCMA levels and resulted in rapid and transientproinflammatory cytokine production that promoted robust T-cell redistribution, activation, andproliferation indicating that the optimal dose of etentamig (2 mg/60 mg Q4W) maximizes its clinicalpotential as a convenient, safe, and effective therapy..."

Biomarker • Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • CCL19 • CCL2 • CD4 • CD8 • CXCL8 • IL10 • IL6 • TNFA

A Phase 2/3, multicenter, randomized, open-label study evaluating the efficacy and safety of etentamig and daratumumab compared to daratumumab, lenalidomide, and dexamethasone in frailer transplant-ineligible patients with newly diagnosed multiple myeloma (ASH 2025) - P2/3 | "Triplet or quadruplet regimens, such asdaratumumab, lenalidomide, and dexamethasone (DRd) or anti-CD38 monoclonal antibodies +bortezomib, lenalidomide, and dexamethasone are considered standard of care (SoC) in transplant-ineligible (TI) patients...The studywill include patients with an International Myeloma Working Group (IMWG) Myeloma Frailty Index Scoreof ≥1 (intermediate-fitness to frail).In the Phase 2 part of the study, patients will be randomized to receive 1 of 3 dose levels of etentamig (IV)every 4 weeks (Q4W) with 1800 mg of daratumumab (subcutaneous) every week (cycles 1–2), Day 1 andDay 15 (cycles 3–6), and Q4W (cycle 7+)...InPhase 3, measurable residual disease negativity (10−5 threshold) and progression-free survival are dualprimary endpoints. Approximately 54 sites across the United States, Canada, Japan, France, Norway, andSpain will participate in Phase 2, and additional countries contributing approximately 101 sites will beadded for Phase 3."

Clinical • P2/3 data • Hematological Malignancies • Multiple Myeloma • Transplantation

Restarting etentamig therapy after dosing delays or interruptions: Population pharmacokinetics (PopPK) and PK/PD simulations and supporting clinical data (ASH 2025) - P1, P1/2 | "The longest dosing delay observed was 68 days(~10 weeks) after a Cycle 3 dose, and six subjects had dose delays ranging from 27-35 days on or afterCycle 2. In all these cases, treatment was restarted with the full dose (60 mg) without any episode of CRS.PopPK simulations, IL-6 predictions and observed clinical data are collectively supportive of no reprimingin patients with dosing delays or interruptions lasting 16 weeks or less.ConclusionsBased on our popPK and PK/PD simulations and supportive clinical data, patients with dose delayslasting ≤16 weeks following treatment with etentamig full dose are not needed to restart the step-updose."

Clinical data • PK/PD data • Hematological Malignancies • Inflammation • Multiple Myeloma • IL6

T-cell engager activity of etentamig (BCMA x CD3) is potentiated by daratumumab in preclinical models of multiple myeloma (ASH 2025) - P1 | "Recentfindings from a Phase 1b, open-label, dose-escalation and expansion trial (NCT05259839) showed thatetentamig in combination with daratumumab, a CD38 monoclonal antibody, and dexamethasonedemonstrated promising activity in heavily pre-treated relapsed/refractory multiple myeloma (RRMM)(Blood 2024; 144(Supplement 1):496). We show that daratumumab enhances anti-tumor activity of etentamig by i) augmenting direct anti-tumor activity, ii) depleting immune regulatory and dysfunctional T cell populations, and iii) modulatingthe immunosuppressive bone marrow microenvironment (eg, IDO reduction). Collectively, our findingssupport the continued investigation of etentamig in combination with daratumumab in patients withMM."

IO biomarker • Preclinical • Hematological Malignancies • Immune Modulation • Immunology • Multiple Myeloma • CD8 • ENTPD1 • FOXP3 • ICOS • IL2RA • PD-1

Etentamig plus pomalidomide-dexamethasone combination therapy in relapsed or refractory multiple myeloma: A phase 1b dose-escalation and safety expansion study (ASH 2025) - P1, P1/2 | "Arm A evaluated etentamig in combination with POM+DEX in pts after≥3 prior lines of therapy (LoT), including the IMiD lenalidomide, a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody (mAB). Preliminary data are promising and suggest etentamig in combination with POM+DEX istolerable with robust efficacy (ORR and ≥VGPR: 81% and 72%, respectively) in pts with ≥3 prior LoT(median LoT = 4). In this heavily pretreated population, median PFS was not reached with a median followup of 18 months, suggesting prolonged disease control with etentamig in combination with POM+DEX.Overall, these data support further exploration of the regimen in a randomized Phase 3 study."

Clinical • Combination therapy • P1 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Influenza • Multiple Myeloma • Neutropenia • Pneumonia • Renal Disease • Respiratory Diseases

Etentamig (Bispecific T-Cell Engager) in R/R MM and AL (PRNewswire) - "Preliminary data from the dose escalation portion of the study (n=82) highlight that etentamig in combination with POM+DEX achieved an ORR of 81% and a very good partial response or better (≥VGPR) of 72% at median follow-up of 23 months (range: 1-33 months). In this heavily pretreated population, duration of response (DoR) were not reached at time of analysis. Most common grade 3/4 AEs were neutropenia (78%), anemia (28%) and thrombocytopenia (22%); Overall, these data support further exploration of the regimen in a randomized Phase 3 study; Additional preliminary data from the dose escalation study with etentamig monotherapy in R/R light chain AL will be showcased as an oral presentation. (NCT06158854)."

P1 data • P1/2 data • Amyloidosis • Multiple Myeloma

A Study to Assess Adverse Events of Intravenously (IV) Infused ABBV-383 in Adult Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=180 | Recruiting | Sponsor: AbbVie | Trial completion date: Mar 2027 ➔ Aug 2029 | Trial primary completion date: Mar 2027 ➔ Aug 2029

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

Pharmacokinetics and Immunogenicity of Abbv-383, a B-Cell Maturation Antigen (BCMA) × CD3 Bispecific T-Cell-Redirecting Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2023) - P1/2 | "Overall, sBCMA impacted (reduced) the ‘free’ ABBV-383 (pharmacologically active component) PK exposures only, with pronounced effect at lower doses and the effect is consistent with understanding of treatment dependent sBCMA dynamics over time. Determination of both ‘total’ and ‘free’ ABBV-383 serum concentrations allowed to demonstrate such underlying impact of sBCMA on PK."

Clinical • PK/PD data • Hematological Malignancies • Multiple Myeloma • Oncology

Bivalent BCMA Binding and Low Affinity CD3 T-Cell Engagement By Abbv-383 Drives Sustained Activation with Reduced T-Cell Exhaustion in Preclinical Models of Multiple Myeloma (ASH 2023) - "High avidity BCMA binding coupled to low affinity T-cell engagement distinguishes the resulting mechanism of action for ABBV-383 in MM. Here, we show that the presence of bivalent-BCMA reduced the negative impact of soluble BCMA, reduced inflammatory cytokine production, and dampened the emergence of TOX+ CD8+ T-cells indicating that ABBV-383 structure maximizes its clinical potential as a safe and effective MM therapy."

IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • CD8 • CTLA4 • LAG3 • PD-1

Pooled Analysis on Bispecific Antibody-Related Toxicities in Multiple Myeloma (ASH 2023) - "BsAb included in our study were the following: Teclistamab, Elranatamab, REGN-5458, AMG420, AMG701, CC-93269, TNB-383B, Linvoseltamab, Talquetamab, and Cevostamab. The use of BsAbs in MM has demonstrated remarkable efficacy; however, these have been linked to a unique adverse event profile. Our results showed that non-BCMA bsAb were associated less hematotoxicity (combined grade 3-4 events and hypogammaglobulinemia), whereas BCMA bsAb were associated with less CRS rates. This is important information for treatment selection and mitigation strategy development aiming to optimize patient outcomes."

Retrospective data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

MODULE 4: Bispecific Antibodies in the Treatment of MM (ASH 2023) - "Supported by AbbVie Inc, GSK, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Karyopharm Therapeutics, Legend Biotech, Regeneron Pharmaceuticals Inc, and Sanofi. Similarities and differences in the cellular targets and mechanisms of action among bispecific antibodies for MM Antitumor activity observed with teclistamab in the Phase I/II MajesTEC-1 study leading to its recent FDA approval for R/R MM; optimal incorporation into the treatment paradigm Rate, depth and duration of response observed with elranatamab in the pivotal Phase II MagnetisMM-3 trial for patients with R/R MM; FDA approval and current clinical role Key findings with other promising anti-BCMA bispecific antibody constructions, such as alnuctamab, linvoseltamab and ABBV-383, for heavily pretreated MM Available efficacy and safety findings with non-BCMA-targeted bispecific antibodies for MM, such as talquetamab, cevostamab and RG6234; FDA approval of talquetamab for patients with R/R MM..."

Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Mantle Cell Lymphoma • Oncology

Updated Safety and Efficacy Results of Abbv-383, a BCMA x CD3 Bispecific T-Cell Redirecting Antibody, in a First-in-Human Phase 1 Study in Patients with Relapsed/Refractory Multiple Myeloma (ASH 2023) - P1/2 | "At 40 mg and 60 mg, ABBV-383 monotherapy yielded deep and durable responses with mPFS of 13.7 mo and 11.2 mo, and 12-month DOR of 70% and 66% (mDOR NR in pts with ≥CR), respectively. These results in heavily pretreated RRMM pts support further clinical evaluation."

Clinical • First-in-human • IO biomarker • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Nephrology • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • CD4 • CD69 • CD8 • CXCL8 • IFNG • IL6 • TNFA

Exposure-Response (ER) and Pharmacokinetic/Pharmacodynamic (PK/PD) Analyses for Optimal Step-up Dose (SUD) Selection to Improve Cytokine Release Syndrome (CRS) Safety Profile of Abbv-383 in Patients with Relapsed or Refractory Multiple Myeloma (RRMM) (ASH 2024) - P1, P1/2 | "ABBV-383 monotherapy has shown promising activity and improved CRS safety profile with modified dexamethasone (Dex) premedication in patients (pts) with RRMM (NCT03933735; Rodriguez et al., JCO 2024; 42[suppl 16] : 7531). The CRS PK/PD predictions indicated that implementation of 2-SUDs provide minimal additional or no improvement in CRS safety profile compared to 1-SUD. Overall, the 1-SUD dosing regimen of 2 mg with modified premedication prior to the full dose of 60 mg Q4W showed promising results and can be considered for future evaluation and studies."

Clinical • Cytokine release syndrome • PK/PD data • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • IL6

A Phase 1b Study of Step-up Dosing with ABBV-383, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Patients with Relapsed or Refractory Multiple Myeloma (ASH 2024) - P1, P1/2 | "Introduction of a modified dexamethasone (Dex) premedication (premed) schedule in cycle (C) 1 lowered incidence and severity of CRS (43% overall; 5% grade ≥2) vs pts treated with low Dex (71% overall; 20% grade ≥2) (JCO 2024; 42[suppl 16] : 7531)...In the DE, 7 (30%) pts experienced CRS; 1 (4%) pt experienced grade 2 CRS, there were no grade ≥3 events, and only 2 (9%) pts received tocilizumab to treat CRS...Conclusions Introduction of 1 SUD of 2 mg on D1 followed by full dose of 60 mg on D4 in C1 combined with modification to the Dex premed schedule reduced the incidence and severity of CRS in pts with RRMM, further optimizing the safety profile of ABBV-383. Preliminary efficacy data show early and high response rates, consistent with outcomes from other ABBV-383 studies."

Clinical • P1 data • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • CD8 • IL6

ABBV-383 Plus Daratumumab-Dexamethasone in Relapsed or Refractory Multiple Myeloma: A Phase 1b Dose-Escalation and Safety Expansion Study (ASH 2024) - P1, P1/2 | "Conclusion Preliminary data suggest ABBV-383 in combination with Dd is tolerable. Overall rates of CRS were low and early response rates were promising in the investigated population of heavily pretreated pts with MM."

Clinical • P1 data • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Immunoglobulin Light Chain (AL) Amyloidosis Receiving Etentamig (ABBV-383) as an Intravenous (IV) Infusion (clinicaltrials.gov) - P1/2 | N=76 | Recruiting | Sponsor: AbbVie | Trial primary completion date: Dec 2025 ➔ Oct 2026

Adverse events • Trial primary completion date • Amyloidosis

Etentamig Shows Manageable Safety and Low Severe Infection Risk in RRMM (Pharmacy Times) - "Pooled data from 2 phase 1 trials show that etentamig (ABBV-383; AbbVie Inc) has a manageable safety profile and low incidence of grades 3 and 4 infection in patients with relapsed/refractory multiple myeloma (RRMM)...All-grade infections occurred in 99 patients (68%), most commonly upper respiratory infections (n = 26; 18%) and pneumonia (n = 25; 17%). Grade 3 and 4 infections were observed in 32 patients (22%), with pneumonia (n = 18; 12%) and sepsis (n = 7; 5%) most frequent. Infections led to dose interruptions in 48 patients (41%) and discontinuations in 6 patients (4%)."

Adverse events • Retrospective data • Multiple Myeloma

Infection Rate Profile of Etentamig Monotherapy in Patients with Relapsed/refractory Multiple Myeloma (IMS 2025) - P1, P1/2 | "Etentamig demonstrated a manageable infection profile. Low incidence of Grade 3/4 infections suggests low-affinity CD3 binding may improve the toxicity profile of etentamig. Pts with RRMM should receive appropriate screening, prophylaxis, and be carefully monitored at frequent intervals for effective management of infections."

Clinical • Monotherapy • Cytomegalovirus Infection • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock

AbbVie's etentamig and research pipeline demonstrate a commitment to innovation and functional cure for patients with multiple myeloma (IMS 2025) - No abstract available

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Future on Bispecifics and Antibody-Drug Conjugates (SOHO 2025) - "The pivotal phase 1/2 MajesTEC-1 trial and the MagnetisMM trials led to the US Food and Drug Administration (FDA) approval of teclistamab and elranatamab, respectively, both of which target surface B-cell maturation antigen (BCMA) on MM cells. A third approved BsAb, talquetamab, has efficacy against another antigen, G protein-coupled receptor family C group 5 member D (GPRC5D), as evidenced in the MonumenTAL-1 trial...These include BCMA-targeting linvoseltamab as well as ABBV-383, which features a distinct bivalent BCMA-binding domain and a low-affinity CD3-binding domain in a unique 2+1 design. A third MM antigen, Fc receptor-like 5 (FcRH5), is targetable by the BsAb cevostamab. Several other BsAbs engage CD38, the target of daratumumab and isatuximab...The ongoing phase 3 MajesTEC-7 study is assessing the combination of teclistamab, daratumumab, and lenalidomide versus daratumumab, lenalidomide, and dexamethasone for newly diagnosed patients who are ineligible for, or..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • GZMB • SDC1 • SLAMF7