Modakafusp Alfa Demonstrates Antitumor Activity Among Patients With Relapsed/Refractory Multiple Myeloma
Modakafusp alfa demonstrated promising antitumor activity and immune activation among patients with relapsed/refractory (R/R) multiple myeloma (MM) who have been heavily pretreated, according to results from a phase 1/2 trial published in Blood.
Modakafusp alfa is an immunocytokine, consists of 2 attenuated interferon alfa-2b molecules fused to an anti-CD38 IgG4 antibody which targets delivery to CD38+ immune and myeloma cells, yielding immune activation and antitumor activity.
Researchers conducted an open-label, phase ½ trial to evaluate the safety, tolerability, and efficacy of modakafusp alfa in a heavily pretreated patient population. Dose escalation included 10 dosing regimens across 13 cohorts. The primary end points were safety in the escalation phase and overall response rate (ORR) in dose expansion.
The trial enrolled 106 patients with R/R MM, of which 37 patients were treated with modakafusp alfa at 1.5 mg/kg Q4W (30) or 3 mg/kg Q4W (7) as the maximum tolerated dose. Among all patients, the median number of prior lines of therapy was 6.5 and the median age was 64.5 years.
Among the 30 patients treated at 1.5 mg/kg Q4W, the ORR was 43.3 (95% confidence interval [CI], 25.5 to 62.6). The median time to response after beginning treatment was 1.1 months, median duration of response was 15.1 months (95% CI, 7.1 to 26.1), and median progression-free survival was 5.7 months (95% CI, 1.2 to 14.0). For patients treated at 3 mg/kg Q4W, the ORR was slightly lower (42.9%), and the median duration of response was 10.2 months (95% CI, 7.9 to not reached).
In terms of safety, grade ≥3 adverse events occurred in 93.3% of patients, most commonly neutropenia (66.7%) and thrombocytopenia (46.7%). Infections occurred in 26.7% of patients, with grade 3 infections in 16.7%.
Researchers also observed an increase in peripheral natural killer cells and CD8 T cells, along with increased interferon-associated cytokine production.
Overall, modakafusp alfa demonstrated immune activation and antitumor activity.
“The immune stimulatory effects of modakafusp alfa, along with its manageable toxicity profile, monthly administration, and distinct CD38 binding epitope, suggest a potential for combination with a wide range of antimyeloma therapies including IMiDs, PIs, anti-CD38 antibodies, and T-cell–redirecting therapies,” concluded the researchers.
“The association between modakafusp alfa–induced immune stimulation and myeloma response remains to be determined and presents a unique opportunity to elucidate the role of the immune system in oncologic disease,” they explained. “The single-agent activity warrants continued exploration of modakafusp alfa for the treatment of MM.”
Source:
Vogl DT, Shebli Atrash, Holstein SA, et al. Targeted interferon therapy with modakafusp alfa for relapsed or refractory multiple myeloma. Blood. Published online February 27, 2025. doi: 10.1182/blood.2024026124
