P-023: Talquetamab, a G Protein–Coupled Receptor Family C Group 5 Member D × CD3 Bispecific Antibody, in Relapsed/Refractory Multiple Myeloma: Efficacy and Safety of Patient Subgroups from MonumenTAL-1

Introduction: Talquetamab (Tal) is a first-in-class GPRC5D×CD3 bispecific antibody that has shown >71% overall response rates (ORRs) and clinically manageable safety in patients (pts) with relapsed/refractory multiple myeloma (RRMM) in the MonumenTAL-1 study. We present subgroup analysis of the efficacy and safety of Tal in pts with disease and clinical features typically associated with poorer outcomes on established myeloma therapies.

Methods: MonumenTAL-1 (NCT03399799/NCT04634552) is an open-label, single arm, phase 1/2 trial in pts with RRMM. Safety and efficacy of pts treated at the recommended phase 2 doses of subcutaneous Tal at 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W) were previously reported. Pt subgroups assessed were age ≥75 years; high-risk cytogenetics [del(17p), t(4;14), and/or t(14;16)]; ISS stage III; renal impairment (baseline function ≤60 mL/min/1.73m2); triple-class refractory (to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody); and extramedullary disease (EMD; ≥1, including soft tissue plasmacytomas).

Results: As of Jan 17, 2023, 143 and 145 pts received Tal 0.4 mg/kg QW and 0.8 mg/kg Q2W, respectively. Of these, respectively, 106 (74.1%) and 100 (69.0%) were triple-class refractory; 21 (14.7%) and 32 (22.1%) were ≥75 years; 41 (28.7%) and 37 (25.5%) had high-risk cytogenetics; 28 (19.6%) and 35 (24.1%) were ISS III; 40 (28.0%) and 45 (31.0%) had renal impairment; and 33 (23.1%) and 37 (25.5%) had EMD. Median follow-up for the subgroups was consistent with their respective dose cohorts in the overall population (QW, 19 mo; Q2W, 13 mo). In the Q2W cohort, efficacy was consistent with the broader population (ORR, 72%; 9-mo DOR, 76%; 12-mo PFS, 54%; 12-mo OS, 77%) in the following subgroups: age ≥75 years (ORR, 75%; 9-mo DOR, 92%; 12-mo PFS, 71%; 12-mo OS, 83%), high-risk cytogenetics (ORR, 76%; 9-mo DOR, 78%; 12-mo PFS, 63%; 12-mo OS, 62%), triple-class refractory (ORR, 69%; 9-mo DOR, 73%; 12-mo PFS, 50%; 12-mo OS, 73%) and renal (ORR, 67%; 9-mo DOR, 64%; 12-mo PFS, 40%; 12-mo OS, 72%). Efficacy was lower in ISS III (ORR, 60%; 9-mo DOR, 61%; 12-mo PFS, 38%; 12-mo OS, 67%) and EMD (ORR, 43%; 9-mo DOR, 56%; 12-mo PFS, 27%; 12-mo OS, 65%) subgroups. Trends were similar in the QW cohort. The safety profile among subgroups in both cohorts was generally consistent with the overall population. Rates of discontinuation due to adverse events were higher than the overall population (QW and Q2W, 5–8%) in age ≥75 years (14.3%) and ISS III (10.7%) subgroups in the QW cohort and ISS III (14.3%) and renal (13.3%) subgroups in the Q2W cohort.

Conclusions: Most pts with traditional high-risk features experience clinical benefit with Tal monotherapy that is consistent with the overall study population. While responses were less consistent in EMD and ISS III subgroups, Tal still provided responses in over one-third and one-half of these pts, respectively.