OA-05: Efficacy of forimtamig, a GPRC5DxCD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): analysis of patient- and disease-related factors associated with responses

Introduction: Forimtamig, a GPRC5DxCD3 T-cell-engaging bispecific antibody (BsAb), is currently being evaluated in patients (pts) with RRMM. In a first-in-human Phase 1a dose-escalation study (BP42233; NCT04557150), forimtamig induced deep and durable responses in heavily pre-treated pts and had a safety profile consistent with its MOA and target expression (Carlo-Stella et al. ASH 2022). We evaluated clinical responses in high-risk subgroups.

Methods: Eligible pts had RRMM and ≥1 prior line(s) of therapy (LOT), and were refractory to a PI and an IMiD. Pts received forimtamig target doses of 0.018–10mg either IV or SC with prior administration of 2 step doses. Efficacy was evaluated in the following subgroups: age ≥65 years, >4 prior LOT, triple-class and penta-drug refractory disease, prior BCMA-targeted therapy, high-risk cytogenetics (del(17p), t(4;14), t(14;16)), 1q21 gain (irrespective of other high-risk aberrations), ISS disease Stage III at baseline, high tumor burden (>median sBCMA at baseline), and presence of soft tissue plasmacytoma (bone-based and extramedullary). The primary endpoint was objective response rate (ORR) assessed per IMWG criteria.

Results: As of January 25, 2023, 120 pts in the efficacy-evaluable population had received forimtamig during the dose escalation. Median age was 63 years, and median time from diagnosis to enrollment was 6.2 years (range: 0.4–30.7). ORR across all dose levels was 66.7% (very good partial response or better: 54.2%), with a median duration of response of 12.2 months (range: 0.03–20.8) and 61.3% of responders with ongoing responses at cut-off. High ORRs were observed across all risk groups. ORRs in pts aged ≥65 years (n=52) and in pts with >4 LOT (n=49) were 71.2% and 63.3%, respectively. Pts with high-risk cytogenetics (n=33) had an ORR of 63.4%, while those with 1q21 gain (n=15) had an ORR of 86.7%. ORRs in pts with triple-class (n=81) and penta-drug (n=45) refractory disease were 60.5% and 57.8%, respectively. Twenty-nine pts had received prior BCMA-targeted therapy (n=19 with antibody-drug conjugates [ADCs], n=5 with BsAbs, and n=5 with CAR T-cells, including n=3 with ADCs and BsAbs or CAR T-cells). ORRs were 51.2% in all pts, 47.4% in ADC, 42.9% in BsAb, and 66.7% in CAR T-cell. ORRs in pts with ISS disease Stage III (n=24) and extramedullary disease (n=28), factors known to be of prognostic relevance for T-cell-directed therapy, were 70.8% and 50.0%, respectively. Levels of sBCMA, a potential novel biomarker for tumor load and disease monitoring, above (n=54) and below (n=55) the median at baseline (327 ng/ml) were associated with ORRs of 55.6% and 80.0%, respectively.

Conclusions: Forimtamig induced objective responses in all subgroups and showed high clinical activity in pts with high-risk features that are known to be clinically relevant in T-cell-directed therapy. Optimization of the forimtamig dose and schedule is ongoing, as well as evaluation of long-term treatment benefit, including in pts with high-risk disease.