Efficacy and safety from the phase 1/2 MonumenTAL-1 study of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma: Analyses at an extended median follow-up.

7528 Background: Talquetamab (Tal) is the first and only approved anti-GPRC5D bispecific antibody (BsAb) for relapsed/refractory multiple myeloma (RRMM). In previous results from the phase 1/2 MonumenTAL-1 study (CCO Jan 2024; median follow-up [mFU] 20–30 mo), Tal elicited deep, durable responses with low discontinuation rates. We report efficacy and ongoing safety from MonumenTAL-1 at an extended mFU of 30–38 mo, the longest mFU for any anti-GPRC5D agent. Methods: Patients (pts) were intolerant to or progressed on established therapies (phase 1, NCT03399799) or had ≥3 prior lines of therapy (LOT), including ≥1 PI, ≥1 IMiD, and ≥1 anti-CD38 mAb (phase 2, NCT04634552). Pts received recommended phase 2 doses (RP2D) of SC Tal 0.4 mg/kg weekly (QW) or 0.8 mg/kg every other week (Q2W), with step-up doses. Results: As of Sept 2024, mFU was 38.2, 31.2, and 30.3 mo in the QW (n=143), Q2W (n=154), and prior T-cell redirection (TCR; n=78, received either RP2D) cohorts, respectively. Across cohorts, overall response rate (ORR; 67–74%) was unchanged vs previous results. Median duration of response (mDOR) and median progression-free survival (mPFS) continued to demonstrate superior outcomes in the Q2W vs QW cohort (mDOR 17.5 vs 9.5 mo; mPFS 11.2 vs 7.5 mo). In the prior TCR cohort, mDOR was reached with longer mFU (19.2 mo), and mPFS was 7.7 mo. In the QW, Q2W, and prior TCR cohorts, median overall survival (OS) was 34.0 mo, not reached, and 28.3 mo (36-mo OS rates: 49%, 61%, and 45%), respectively (Q2W data not mature). In pts with <4 vs ≥4 prior LOT, ORR was higher (85% vs 72%), but responses were less durable (mDOR 6.8 vs 10.8 mo) in the QW cohort, whereas ORR was similar (71% vs 69%), but responses were more durable (mDOR 20.7 vs 16.8 mo) in the Q2W cohort. As previously reported, most common adverse events (AE) were CRS and GPRC5D-associated (oral and dermatologic) AEs, and most common grade 3/4 AEs were cytopenias. No new discontinuations occurred due to oral or dermatologic GPRC5D-associated AEs and no new discontinuations occurred due to weight loss. In QW, Q2W, and prior TCR cohorts, respectively, any-grade infections occurred in 61%, 71%, and 78% of pts; grade 3/4 infections (23%, 21%, 26%) were mostly limited to early treatment cycles. A new safety signal, ataxia/balance disorders, was recently identified in association with Tal and had low prevalence in MonumenTAL-1. Dose reduction and discontinuation rates due to AEs remained low. No pts died due to Tal-related AEs. Conclusions: At an extended mFU, high ORRs elicited by Tal were durable and led to promising 36-mo OS rates (45–61%). The safety profile was consistent with previous results and continued to show lower risk of high-grade infections relative to approved anti-BCMA BsAbs, potentially contributing to the OS benefit seen in pts receiving Tal. Clinical trial information: NCT03399799 / NCT04634552 .