alnuctamab (CC-93269) / BMS - LARVOL DELTA

Alnuctamab (ALNUC; BMS-986349; CC-93269), a B-Cell Maturation Antigen (BCMA) x CD3 T-Cell Engager (TCE), in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from a Phase 1 First-in-Human Clinical Study (ASH 2022) - P1 | "All CRS events were limited to grade 1 (21 pts; 45%) or grade 2 (4 pts; 9%); 20 pts received ≥ 1 concomitant medication for CRS, including tocilizumab (n = 12) and/or corticosteroids (n = 8). SC ALNUC exhibited promising dose-dependent antitumor activity with a high proportion of MRD responses. Enrollment in the phase 1 study is ongoing and updated data will be presented."

Clinical • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology

Alnuctamab, a bivalent B-cell maturation antigen-targeting T cell engager for patients with relapsed or refractory multiple myeloma: results from a phase 1, first-in-human study. (PubMed, Leukemia) - "These results support improved safety of SC versus IV, and corroborate a step-up dosing strategy to mitigate CRS. Importantly, a schedule that de-intensifies over time provides favorable toxicity that may be applicable to other bispecific engagers."

First-in-human • Journal • P1 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology

Mezigdomide reverses T-cell exhaustion through degradation of IKZF1/IKZF3 and reinvigoration of cytokine production pathways. (PubMed, Blood) - "Mezigdomide treatment in exhausted T cells results in decreased expression of exhaustion-related markers, increased proinflammatory cytokine expression, and enhanced target cell killing with Alnuctamab, a B-cell maturation antigen (BCMA) targeting TCE. This study provides crucial mechanistic insights into the roles of IKZF1/IKZF3 in T cell exhaustion, supporting the rationale for combining mezigdomide with TCEs to enhance therapeutic outcomes in MM."

IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Targeted Protein Degradation • CRBN • IKZF1 • IKZF3

A Study to Evaluate Alnuctamab in Combination With Mezigdomide in Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: Celgene | N=156 ➔ 4 | Active, not recruiting ➔ Terminated; Business objectives have changed

Enrollment change • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=250 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Celgene | Active, not recruiting ➔ Recruiting

Enrollment open • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Celgene | Active, not recruiting ➔ Recruiting | N=19 ➔ 120

Enrollment change • Enrollment open • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=220 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Celgene | N=135 ➔ 220

Enrollment change • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=183 | Terminated | Sponsor: Celgene | Active, not recruiting ➔ Terminated; Business objectives have changed

First-in-human • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=135 | Recruiting | Sponsor: Celgene | Trial completion date: Nov 2023 ➔ Nov 2026 | Trial primary completion date: Oct 2023 ➔ Oct 2026

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=115 | Recruiting | Sponsor: Celgene | Trial completion date: Jun 2022 ➔ Nov 2023 | Trial primary completion date: Jul 2021 ➔ Oct 2023

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=250 | Active, not recruiting | Sponsor: Celgene | Trial completion date: Aug 2029 ➔ Mar 2025 | Trial primary completion date: Jun 2029 ➔ Mar 2025

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting | N=125 ➔ 19

Enrollment change • Enrollment closed • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Celgene | Trial completion date: Nov 2026 ➔ Aug 2027 | Trial primary completion date: Oct 2026 ➔ Jul 2027

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=250 | Recruiting | Sponsor: Celgene | Trial completion date:Aug 2027 ➔ Aug 2029 | Trial primary completion date: Jul 2027 ➔ Jun 2029

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=250 | Recruiting | Sponsor: Celgene | Trial completion date: Aug 2027 ➔ Aug 2029 | Trial primary completion date: Jul 2027 ➔ Jun 2029

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=115 | Recruiting | Sponsor: Celgene | Active, not recruiting ➔ Recruiting

Enrollment open • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=250 | Recruiting | Sponsor: Celgene | Trial completion date: Aug 2029 ➔ Aug 2027 | Trial primary completion date: Jun 2029 ➔ Jul 2027

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=120 | Not yet recruiting | Sponsor: Celgene

First-in-human • New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Alnuctamab, a bivalent B-cell maturation antigen-targeting T cell engager for patients with relapsed or refractory multiple myeloma: results from a phase 1, first-in-human study (Nature) - "Ninety-five patients received ALNUC SC; at data cutoff, 44.2% remained on treatment and median follow-up was 8.0 months. The recommended phase 2 dose was 30 mg. The most common treatment emergent adverse events (any grade/grade 3/4) were CRS (57.9%/0%), and neutropenia (53.7%/43.2%). Infections were also frequent (64.2%/14.7%). ORR was 58.9% for all ALNUC SC-treated patients and 71.4% for the 30-mg cohort; 47/95 (49.5%) were measurable residual disease (MRD) negative. Overall, the safety and efficacy of ALNUC SC were comparable to other BCMA-targeted therapies."

First-in-human • P1 data • Multiple Myeloma

Alnuctamab for Refractory SLE (LATTE Study) (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Safety and Efficacy of Anti-B-cell Maturation Antigen (Anti-BCMA) Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Clinical Trials. (PubMed, Cureus) - "AMG-420, AMG-701, elranatamab, REGN5458, teclistamab (Tec), alnuctamab (ALNUC), and ABBV-383 are the seven anti-BCMA-CD3 bispecific Abs currently being assessed in clinical trials as monotherapy and in combination with immunomodulators/proteasome inhibitors against RRMM. Our analysis of the trials revealed that bispecific Abs showed efficacy in RRMM, with CRS and hematologic toxicities being the most common adverse events, mostly low-grade and manageable. Based on the promising efficacy and safety of BCMA targeting bispecific Abs, these drugs are emerging as a new therapeutic option for patients with advanced and RRMM."

Journal • Review • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

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