Efficacy and safety of talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): Updated results from MonumenTAL-1.

• DOI: 10.1200/jco.2022.40.16_suppl.8015
• Publication Date: 2022-06-06T17:16:22Z
• Authors: Monique C. Minnema; Amrita Y. Krishnan; Jesus G. Berdeja; Albert Oriol Roca...; Niels W.C.J. van ...; Paula Rodríguez-O...; Daniel Morillo; Maria-Victoria Ma...; Luciano J. Costa; Jo Caers; Deeksha Vishwamitra; Joanne Ma; Shiyi Yang; Brandi Hilder; Jaszianne A. Tolbert; Jenna D. Goldberg; Ajai Chari
• Keywords: Tolerability; Cytokine Release Syndrome

8015 Background: G protein-coupled receptor family C group 5 member D (GPRC5D), which has limited expression in normal human tissue but is highly expressed on malignant plasma cells, a promising target for multiple myeloma (MM) immunotherapy. Talquetamab (JNJ-64407564) first-in-class, bispecific IgG4 antibody that binds to both GPRC5D and CD3 receptors, mediating T-cell–activated lysis of GPRC5D+ MM cells. Here we report updated results with additional patients (pts) longer follow-up from MonumenTAL-1, phase 1 trial talquetamab RRMM (NCT03399799). Methods: Eligible pts had or were intolerant standard therapies; prior B-cell maturation antigen-directed therapies permitted. The primary objectives identify the recommended 2 doses (RP2Ds) (part 1) assess safety tolerability at RP2Ds 2). Collective safety, efficacy, PK, PD data supported talquetamab: 405 μg/kg SC QW (n = 30) 800 Q2W 44). Step-up dosing was used mitigate against severe cytokine release syndrome (CRS); required premedications step-up first full dose talquetamab. Adverse events (AEs) graded by CTCAE v4.03 CRS per Lee et al 2014 criteria. Investigators assessed responses International Myeloma Working Group Results: As Jan 17, 2022, μg/kg/800 groups, respectively, received median 6 /5 lines therapy, 100%/98% triple-class (TC) exposed, 77%/75% TC refractory. Median (range) 11.7 (1.0–21.2)/4.2 (0.7–13.7) months. Most AEs grade 2. most common cytopenias CRS. Cytopenias (including neutropenia [67%/36%; 3/4: 53%/23%]) reversible, mostly confined cycle 1–2 doses, generally resolved within week. Infections occurred 47%/34% (grade 7%/9%) pts. (77%/80%; 3: 3%/0%) during dosing. Skin-related nail disorder 83%/75% (most commonly skin exfoliation: 37%/39% [all 2]). Dysgeusia (63%/57%) mild managed adjustments. overall response rates response-evaluable 70% (21/30 pts)/64% (28/44 pts); very good partial better rate: 57%/52%; time confirmed (range): 0.9 (0.2–3.8)/1.2 (0.3–6.8) duration will be reported. No died due drug-related AEs. PK profiles appear comparable. Conclusions: These show have comparable pharmacokinetic confirm as novel, first-in-class therapy efficacy heavily pretreated pt population. Clinical information: NCT03399799.