Efficacy And Safety Of Talquetamab, A Gprc5d×cd3 Bispecific
Background:Talquetamab (tal) is the first bispecific antibody targeting the novel antigen, GPRC5D, approved in the US andEU for treatment of patients (pts) with relapsed/refractory multiple myeloma (RRMM). Approval was based ondata from the MonumenTAL-1 study demonstrating high overall response rates (ORRs; >71% at therecommended phase 2 doses [RP2Ds] of tal) in pts with RRMM. Pts from China were not included in the initialMonumenTAL-1 study results.Aims:We report the first analysis of efficacy and safety of tal from the China cohort in phase 2 of the MonumenTAL-1study.
Methods:MonumenTAL-1 is a first-in-human, phase 1/2, open-label, multicenter study of tal monotherapy in pts withRRMM. Phase 1 identified 2 RP2Ds, 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W), whichwere further assessed in phase 2. Chinese pts were enrolled in phase 2 (Feb 2022–Feb 2023) and received tal0.4 mg/kg QW or 0.8 mg/kg Q2W. Eligible pts had received ≥3 prior lines of therapy (LOT), including ≥1proteasome inhibitor, ≥1 immunomodulatory drug, and ≥1 anti-CD38 monoclonal antibody, and had not beenexposed to T-cell redirection therapies. The primary endpoint of phase 2 was ORR. CRS and ICANS were gradedby ASTCT criteria; all other AEs were graded by CTCAE v4.03. Response was assessed per IMWG criteria. Dataare reported for the 0.4 mg/kg QW China cohort; data for the 0.8 mg/kg Q2W China cohort will mature laterand will be presented at the meeting.
Results:As of Jan 24, 2024, 29 Chinese pts received tal 0.4 mg/kg QW. Median age was 63 years, and most pts weremale (72.4%). Median prior LOT was 4 (range, 3–9). Half of pts (51.7%) were triple-class refractory and 10.3%were penta-refractory. Two pts (6.9%) had International Staging System stage III disease, 6 (20.7%) hadextramedullary disease (EMD), and 10 (of 27, 37.0%) had high-risk cytogenetics, defined as del(17p), t(4;14), ort(14;16). ORR was 69.0%, and 58.6% and 37.9% of pts had ≥VGPR and ≥CR, respectively. Median time to firstresponse was 1.3 mo. Consistent ORR was observed in clinically relevant subgroups, except pts with EMD,although subgroup numbers were small.