Forimtamig Delivers Responses in Relapsed/Refractory Multiple Myeloma

Forimtamig monotherapy generated high overall response rates and durable responses in all subgroups of patients with relapsed/refractory multiple myeloma enrolled in a phase 1a dose-escalation trial (BP42233; NCT04557150), according to findings that were presented during the 20th International Myeloma Society Annual Meeting.¹

At a median duration of response (DOR) of 12.2 months (range, 0.03-20.8), the objective response rates (ORR) across all dose levels was 66.7% and a very good partial response (VGPR) rate of 54.2%.

“About 60% of patients responded, with the majority achieving a VGPR or better, with about a third of patients achieving a CR [complete response],” Simon J. Harrison, MBBS, MRCP, FRCPath, FRACP, PhD, director of the Centre of Excellence in Cellular Immunotherapy at the Peter MacCallum Cancer Centre in Melbourne, Australia, said during a presentation of the data.

A total of 169 patients were eligible if they received prior treatment with immunomodulatory imide drugs and proteasome inhibitors and had an ECOG performance status 0 or 1. Investigators also enrolled patients who were treated with chimeric antigen receptor (CAR) T cells, antibody-drug conjugates (ADCs), and bispecific antibodies.

Forimtamig was delivered either intravenously (n = 51; 0.18-10 mg) or subcutaneously (n = 122; 0.3-7.2 mg) once every 2 weeks. Cytokine release syndrome (CRS) mitigation measures included step-up dosing and corticosteroid premedication during cycle 1. Patients were hospitalized for CRS management and observation after dose 1 only, Harrison said.

The primary objectives were safety and tolerability, maximum tolerated dose, and to determine the recommended phase 2 dose. Secondary objectives included pharmacokinetic and pharmacodynamic measures, immunogenicity, and clinical activity.

“The study design involved step-up dosing on day 1 and day 8 with the first full dose given on day 15,” Harrison said.

The median age of the 169 patients was 63 years (range, 27-82) and the majority (55%) were male. Nearly 59% (58.6%) of patients had demonstrated high-risk cytogenetic tendencies and half (50.0%) had 1q21 gain/amplification, regardless of other high-risk aberrations.

“An interesting feature of this study is that patients with 1q gain or amplification seemed to be doing at least as well as standard patients, and may have done slightly better in terms of response rate,” Harrison noted.

The number of prior lines of treatment was 4 and 121 patients (71.6%) had 4 or more prior lines of therapy. About one-third of patients (33.7%) were penta-drug refractory and nearly double that percentage (66.3%) were triple-class refractory. About a quarter (25.4%) of patients had been treated with a prior BCMA-targeted therapy, 16.9% had been treated with an ADC, 10.2% had been treated with a bispecific antibody, and 5.4% received CAR T-cell therapy.

Investigators reported high ORRs across all subgroups, including those patients with high-risk cytogenetics and extramedullary disease.

Patients with prior BCMA-targeted therapy experience (n = 43) and baseline serum BCMA levels (n = 66), reported response rates of 47% and 46%, respectively, and were doing less well than other patients, Harrison said.

Among all patients, 61 patients (60.4%) had an ongoing response at data cut-off after a median follow-up of 10.2 months (range, 0.2-29.9).

“Overall, when DOR is analyzed, there isn’t anything to pick out as suggesting that patients are going to do less well, apart from the fact that BCMA-targeted therapy is associated with a slightly lower response of 9 months, compared with 14 months across the population,” Harrison said. “Most of the other subgroups showed more than 12 months’ DOR.”

Regarding safety, there were no new safety signals observed in terms of CRS, rash, or other on target events.

Forimtamig, a bispecific antibody, targets GPRC5D on plasma cells and CD3 on T cells. A prior phase 1 dose-escalation study presented at the 64th Annual American Society of Hematology Annual Meeting & Exposition confirmed the agent’s mechanism of action and potency.²

Harrison noted that the forimtamig development plan will continue exploring the agent as a monotherapy and in combination to identify the optimal patient outcomes. This will include intravenous and subcutaneous delivery methods.

References

1. Harrison SJ, Riley CH, Manier S, et al. 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. Presented at: International Myeloma Society 20th Annual Meeting and Exposition; September 27-30, 2023; Athens, Greece. Abstract OA-05
2. Dekhtiarenko I, Lelios I, Attig J, et al. Intravenous and subcutaneous administration of rg6234, a novel gprc5dxcd3 t-cell engaging bispecific antibody, is highly active in patients with relapsed/refractory multiple myeloma (RRMM): biomarker results from a phase I study. Blood. 2022;140(suppl 1):10137–10139. doi:10.1182/blood-2022-158146