{
  "abstract": "Background: Bispecific antibodies (BsAbs) have begun to transform outcomes in relapsed/refractory multiple myeloma (RRMM). Emerging data suggest that targeting two MM antigens with T-cell redirection may overcome tumor heterogeneity and acquired resistance to further improve clinical outcomes. JNJ-5322 is a next-generation trispecific antibody dually targeting BCMA and GPRC5D via T-cell redirection, comprising novel binding domains, including low affinity CD3, selected in vitro to enhance on-tumor effects and reduce off-tumor impact. Aims: We report the first results from an ongoing phase 1 study of JNJ-5322 (NCT05652335). Methods: Dose escalation/expansion cohorts enrolled measurable RRMM patients previously exposed to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody. Escalating fixed Q2W or Q4W SC doses (0.4–300 mg) were explored, including 100 mg Q4W, the putative recommended phase 2 dose (RP2D). Patients received 1 step-up dose (SUD) of 5 mg prior to receiving the 100 mg Q4W dose, allowing faster full dose initiation and attenuation of cytokine release syndrome (CRS) risk. Adverse events (AEs) were graded by CTCAE v5.0; CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Overall response rate (ORR) was assessed by IMWG criteria. Results: As of Jan 15, 2025, 126 patients received JNJ-5322 (36 at 100 mg Q4W); median follow-up (mFU) was 8.2 months. Median age 64 years; median 4 prior lines of therapy; 100% triple-class exposed (56% refractory); 31% high-risk cytogenetics; 23% had prior anti-BCMA/-GPRC5D therapy (77% naïve). The putative RP2D was identified as 100 mg Q4W. Overall, 99% of patients had ≥1 AE, most commonly CRS (59%; all grade 1 [45%]/2 [14%]; no grade ≥3), nail AEs (grade 1/2 56%), taste AEs (grade 1/2 56%), neutropenia (48%; grade 3/4 41%), and non-rash skin AEs (47%; grade 3/4 1%). Overall, 16% of patients had weight decreases (no grade ≥3), 16% had rashes (no grade ≥3), 2% had ICANS (all grade 1), and 75% had infections (grade 3/4 28%). Five patients had dose-limiting toxicities. Four patients died due to AEs. In response-evaluable patients, ORR was 86% (75% ≥VGPR) at the RP2D (n=36), and 73% (66% ≥VGPR) overall (n=124). ORR was 100% (89% ≥VGPR) at the RP2D among patients naïve to anti-BCMA/-GPRC5D therapies (n=27), and all patients remain in response (mFU 8.5 months). Median time to first response was 1.2 months. Conclusions: In the largest data set for a next-generation dual antigen T-cell redirecting trispecific antibody, the first clinical data for JNJ-5322 showed a 100% ORR at the putative RP2D in anti-BCMA/-GPRC5D naïve patients, with convenient Q4W dosing. Tolerability appeared improved, including lower incidence and severity of GPRC5D-associated AEs vs anti-GPRC5D BsAbs and manageable grade 3/4 infection rates. CRS was mostly grade 1 (no grade ≥ 3 CRS) using 1 SUD. First data with JNJ-5322 suggest a paradigm shift, offering ORRs similar to CAR-Ts but as an off-the-shelf therapy intended for outpatient dosing.",
  "abstract_shown": true,
  "affiliations": [
    "Clinical Research Facility, National Institute for Health Research University College London Hospitals NHS Foundation Trust, London, United Kingdom",
    "Centre Hospitalier Universitaire de Nantes, Nantes, France",
    "CHU de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, Université de Toulouse, Université Paul Sabatier, Service d'Hématologie, Toulouse, France",
    "Division of Hematology and Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium",
    "Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Spain",
    "Department of Hematology, Ghent University Hospital, Ghent, Belgium",
    "Department of Hematology, CHU de Liège, Liège, Belgium",
    "University Medical Center Utrecht, Utrecht, Netherlands; 9The Royal Marsden, NHS Trust, London, United Kingdom",
    "The Royal Marsden, NHS Trust, LondonUnited Kingdom",
    "Johnson & Johnson Brazil, São Paulo, SP, Brazil",
    "University of Texas, MD Anderson Cancer Center, Houston, TX, United States",
    "Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States",
    "Colorado Blood Cancer Institute, Sarah Cannon Research Institute, Denver, CO, United States",
    "Icahn School of Medicine at Mount Sinai, New York, NY, United States",
    "City of Hope National Medical Center, Duarte, CA, United States",
    "Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France",
    "Department of Hematology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain",
    "University Medical Center Groningen, Groningen, Netherlands - Netherlands",
    "Memorial Sloan Kettering Cancer Center, New York, NY, United States",
    "Department of Hematology, Levine Cancer Institute Atrium Health, Charlotte, NC, United States",
    "Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States",
    "Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan",
    "Johnson & Johnson, Spring House, PA, States",
    "Enliven Therapeutics, Boulder, CO, United States",
    "24University Hospital of Salamanca/IBSAL/CIC/CIBERONC, Salamanca, Spain",
    "Clínica Universidad de Navarra, CIMA, CIBERONC, IDISNA, Pamplona, Spain",
    "Division of Hematology, START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain",
    "Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 36,
  "authors": [
    {
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        0
      ],
      "name": "Rakesh POPAT"
    },
    {
      "affs": [
        1
      ],
      "name": "Cyrille TOUZEAU"
    },
    {
      "affs": [
        2
      ],
      "name": "Aurore PERROT"
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    {
      "affs": [
        3
      ],
      "name": "Sébastien ANGUILLE"
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    {
      "affs": [
        4
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      "name": "Albert ORIOL"
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    {
      "affs": [
        5
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      "name": "Nicolas KINT"
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    {
      "affs": [
        6
      ],
      "name": "Jo CAERS"
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    {
      "affs": [
        7
      ],
      "name": "Monique C MINNEMA"
    },
    {
      "affs": [
        8
      ],
      "name": "Martin KAISER"
    },
    {
      "affs": [
        9
      ],
      "name": "Tiago MACHADO"
    },
    {
      "affs": [
        10
      ],
      "name": "Hans LEE"
    },
    {
      "affs": [
        11
      ],
      "name": "Alfred GARFALL"
    },
    {
      "affs": [
        12
      ],
      "name": "Jeffrey MATOUS"
    },
    {
      "affs": [
        13
      ],
      "name": "Larysa SANCHEZ"
    },
    {
      "affs": [
        14
      ],
      "name": "Azra BOROGOVAC"
    },
    {
      "affs": [
        15
      ],
      "name": "Lionel KARLIN"
    },
    {
      "affs": [
        16
      ],
      "name": "Laura ROSINOL"
    },
    {
      "affs": [
        17
      ],
      "name": "Wilfried ROELOFFZEN"
    },
    {
      "affs": [
        18
      ],
      "name": "Saad USMANI"
    },
    {
      "affs": [
        19
      ],
      "name": "Cindy VARGA"
    },
    {
      "affs": [
        20
      ],
      "name": "Darren PAN"
    },
    {
      "affs": [
        21
      ],
      "name": "Tadao ISHIDA"
    },
    {
      "affs": [
        22
      ],
      "name": "Pansy MINNICK"
    },
    {
      "affs": [
        23
      ],
      "name": "Damiette SMIT"
    },
    {
      "affs": [
        22
      ],
      "name": "Nikki DASKALAKIS"
    },
    {
      "affs": [
        22
      ],
      "name": "Thomas PRIOR"
    },
    {
      "affs": [
        22
      ],
      "name": "Maria KREVVATA"
    },
    {
      "affs": [
        22
      ],
      "name": "Ashley NGUYEN"
    },
    {
      "affs": [
        22
      ],
      "name": "Brandi HILDER"
    },
    {
      "affs": [
        22
      ],
      "name": "Daniel JONATHAN"
    },
    {
      "affs": [
        22
      ],
      "name": "Joseph WEIDMAN"
    },
    {
      "affs": [
        22
      ],
      "name": "Sangmin LEE"
    },
    {
      "affs": [
        24
      ],
      "name": "Maria-victoria MATEOS"
    },
    {
      "affs": [
        25
      ],
      "name": "Paula RODRIGUEZ-OTERO"
    },
    {
      "affs": [
        26
      ],
      "name": "Gala VEGA"
    },
    {
      "affs": [
        27
      ],
      "name": "Niels VAN DE DONK"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7shj9vtqrge2b.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107871",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926016184",
  "id": "7shj9vtqrge2b",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107871",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2720|Multiple Myeloma Research and Treatments"
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  "openalex": "W7223128839",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2531137926016184/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/7shj9vtqrge2b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:31Z",
      "native_id": "34bf99b86c1d4b8ea152fbbd507f2287",
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      "url": "https://doi.org/10.1016/j.htct.2026.107871"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC633-647.5",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "FIRST-IN-HUMAN STUDY OF JNJ-79635322 (JNJ-5322), A NOVEL, NEXT-GENERATION TRISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL PHASE 1 RESULTS",
  "title_text": "FIRST-IN-HUMAN STUDY OF JNJ-79635322 (JNJ-5322), A NOVEL, NEXT-GENERATION TRISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL PHASE 1 RESULTS",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:31Z",
  "url": "https://research.draconitic.com/paper/7shj9vtqrge2b",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}