IV, Subcutaneous Forimtamig Induces Effective, High Response Rates in Relapsed/Refractory Multiple Myeloma

Article

The findings, according to the lead study author, demonstrate that treatment with forimtamig delivered intravenously or subcutaneously may elicit long-term responses in patients with relapsed or refractory multiple myeloma.

Treatment with an investigational T-cell engaging bispecific antibody that was administered subcutaneously or intravenously (IV) resulted in significant response rates among a group of patients with relapsed or refractory multiple myeloma, according to updated results from a phase 1 dose-escalation study presented at 2022 American Society of Hematology Annual Meeting.

The agent, forimtamig, may also elicit long-term treatment responses lasting for at least a median of 10 months, according to the findings.

The trial comprised 108 patients who were administered study drug either intravenously (n = 51; median age, 62 years [range, 27-78]; 54.9% male) or subcutaneously (n = 57; median age, 63 years [range, 46-79]; 50.9% male).

To be enrolled, patients must have presented with relapsed/refractory multiple myeloma and underwent prior treatment with an immunomodulatory agent and a proteosome inhibitor. They also qualified for enrollment if there were no established therapies for their disease, or appropriate or tolerable treatments available.

However, patients were permitted to have previously been treated with CAR T-cell therapies, as well as antibody drug conjugates and bispecific antibodies.

Forimtamig, a GPRC5DxCD3 T-cell engaging bispecific antibody, was administered to patients on a once every 2 weeks schedule for 1 year. The primary end point was to determine the maximum tolerated dose, as well as the recommended phase 2 dose and safety. Additional end points included pharmacokinetics and pharmacodynamics, as well as the immunogenicity and efficacy of the drug.

The median time from initial myeloma diagnosis was 7 years (range, 1.8-24.7) for patients within the IV arm and 5.9 years (range, 0.7-19.0) for the subcutaneous arm. Those in the IV treatment cohort previously received a median of 5 treatments (range, 2-15) compared with a median of 4 in the subcutaneous group (range, 2-14).

More than half of each treatment arm experienced a grade 3/4 adverse effect (AE) following the use of study drug delivered intravenously (68.6%) or subcutaneous forimtamig (73.7%).

Patients in the IV cohort were more likely to experience a serious AE (68.8%) than those who received treatment subcutaneously (61.4%). The occurrence of cytokine release syndrome (CRS) was common in both treatment the IV (82.4%) and subcutaneous (78.9%) arms. However, almost all (97.8%) CRS events were resolved by data cut-off.

Both forms of forimtamig were effective. The overall response rate was 71.4% among those treated with IV forimtamig and 63.6% in those who received study drug subcutaneously.

Of note, the lead study author, Carmelo Carlo-Stella, MD, PhD, section chief of Lymphoid Malignancies and Cancer Therapeutics at Humanitas Clinical and Research Center—IRCCS in Italy, highlighted the duration of response in both arms.

In the IV arm, the median duration of response was 10.8 months (range, 0.0-17.6). As for the subcutaneous arm, patients derived a median duration of response of 12.5 months (range, 1.2-12.5).

As of Oct. 21, 2022, 23 of 35 patients in the IV arm continued demonstrating a treatment response. That response continued in 25 of 35 patients in the subcutaneous cohort.

Carlo-Stella concluded and explained that ongoing studies are evaluating ways to optimize both the subcutaneous and intravenous dosing of forimtamig.

Reference

Carlo-Stella C, Mazza R, Manier S, et al. RG6234, a GPRC5DxCD3 T-cell engaging bispecific antibody, is highly active in patients (pts) with relapsed/refractory multiple myeloma (RRMM): updated intravenous (IV) and first subcutaneous (SC) results from a phase 1 dose-escalation study. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana. Abstract 161.

Recent Videos
4 experts are featured in this series.
Cytokine release syndrome was primarily low or intermediate in severity, with no grade 5 instances reported among those with diffuse large B-cell lymphoma.
3 experts in this video
3 experts in this video
Safety results from a phase 2 trial show that most toxicities with durvalumab treatment were manageable and low or intermediate in severity.
Updated results from the 1b/2 ELEVATE study elucidate synergizing effects observed with elacestrant plus targeted therapies in ER+/HER2– breast cancer.
Patients with ESR1+, ER+/HER2– breast cancer resistant to chemotherapy may benefit from combination therapy with elacestrant.
3 experts in this video
Related Content