ParadigMM-1B phase I/Ib: Pavurutamab monotherapy for triple-class RRMM

Results from the phase I/Ib monotherapy portion of ParadigMM-1B (NCT03287908), a phase I/Ib/II, multicenter, nonrandomized, open-label dose-exploration and dose-confirmation study evaluating pavurutamab in adults with triple-class relapsed/refractory multiple myeloma (RRMM), were published in Blood by Lee et al. In total, 172 patients received ≥1 dose, of which 73 received the recommended phase II dose (RP2D; 18,000 µg). The primary endpoint was safety, including dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and treatment-related adverse events (TRAEs).

Key data: DLTs occurred in 11% of evaluable patients (n = 109), with none observed at the RP2D of 18,000 µg. Grade ≥3 TEAEs occurred in 94.2% of patients. Grade 3 CRS was reported in 8.1% of patients overall and 4.1% at the RP2D. Infections were reported in 70.9%, including Grade 3/4 in 30.8% and Grade 5/fatal in 4.1%. The overall response rate (ORR) was 46.5% overall, increasing to 65.8% at the RP2D, where 60.3% of patients achieved ≥very good partial response or better (≥VGPR). At a median follow-up of 17.2 months, the median duration of response (DoR) was 36.6 months (95% confidence interval [CI], 22.3–not estimable [NE]) overall and was not reached at the RP2D. Median progression-free survival (PFS) was 5.5 months (95% CI, 2.8–10.1) overall and 16.8 months (95% CI, 5.0–NE) at the RP2D.

Key learning: Pavurutamab monotherapy showed clinically meaningful activity with no DLTs observed at the RP2D in triple-class RRMM, supporting the potential of B-cell maturation antigen (BCMA)-directed T-cell engager therapy in this population. Proactive CRS and infection risk mitigation remain important considerations.