A phase 2 randomized study of modakafusp alfa as a single agent in patients with relapsed/refractory multiple myeloma.

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.