A phase 2 randomized study of modakafusp alfa as a single agent in patients with relapsed/refractory multiple myeloma
Mené sur 147 patients atteints d'un myélome multiple réfractaire ou récidivant, cet essai randomisé de phase II détermine la dose maximale tolérée du modakafusp alfa en monothérapie (une immunocytokine ciblant CD38) puis évalue son efficacité du point de vue du taux de réponse globale, après l'échec de plusieurs lignes thérapeutiques (nombre médian de thérapies antérieures : 6)
Modakafusp alfa is a first-in-class immunocytokine directing interferon-α to CD38-positive cells. Our previous phase 1/2 trial identified two potential phase 2 doses of modakafusp alfa in patients with relapsed/refractory multiple myeloma (RRMM): 1.5 or 3 mg/kg every 4 weeks (Q4W). The overall response rate (ORR) among 30 patients treated at 1.5 mg/kg was 43%. This phase 2 dose optimization study (NCT03215030) randomized 147 patients with triple-class refractory disease and ≥3 prior lines of therapy 1:1 to modakafusp alfa 120 mg (n = 71) or 240 mg (n = 75) Q4W (fixed-dose equivalents of 1.5 and 3 mg/kg Q4W). Patients had received a median of 6 prior lines of therapy; 66% were penta-exposed and 45% anti-BCMA-exposed. Modakafusp alfa development was discontinued for strategic reasons by the sponsor and the study was terminated early. At median follow-ups of 7.3 and 7.6 months in the 120 and 240 mg arms, ORRs were 32% and 41%; median progression-free survival was 4.1 and 5.3 months, respectively. ORRs were higher in patients who had not received prior-BCMA therapy (46% vs 29%). The most common treatment-related adverse events (TEAEs) in the 120 and 240 mg arms were thrombocytopenia (75% and 84%; grade ≥3, 55% and 61%) and neutropenia (68% and 73%; grade ≥3, 56% and 68%); 90% and 96% of patients experienced grade ≥3 TEAEs; 39% and 44% experienced serious TEAEs. Pharmacokinetic studies showed a ~2-fold greater exposure with 240 vs 120 mg. Our results confirm the efficacy of single-agent modakafusp alfa in patients with RRMM.
Blood , article en libre accès 2025