At data cut-off (April 2022), 100 pts had been treated with modakafusp; 56 pts in dose escalation and 44 pts in expansion cohorts. During dose escalation, dose-limiting toxicities were reported with QW and Q2W dosing schedules. In the Q4W dosing schedule, the maximum tolerated dose (MTD) of modakafusp was exceeded at 6 mg/kg due to a grade (G) 3 infusion-related reaction (IRR) in 1 pt and a prolonged thrombocytopenia and neutropenia in 1 pt; the MTD was therefore determined as 3 mg/kg Q4W. During dose escalation, PRs were reported with 0.1 mg/kg and 0.4 mg/kg QW (n=1 each), an unconfirmed VGPR was observed with 0.4 mg/kg Q3W, and PRs (n=3) and a CR (n=1) were reported with 1.5–6 mg/kg Q4W.

During expansion, of 8 pts receiving modakafusp 0.4 mg/kg Q3W, 5 had SD and 3 had PD. Of 3 pts in the 0.4 mg/kg Q3W + dex cohort, 2 had SD and 1 had PD.

Among 30 pts treated with modakafusp 1.5 mg/kg Q4W (5 in dose escalation and 25 in expansion), the ORR was 43% (Table), median time to response was 1.2 months, and median duration of response was not reached (range 1.0–18.9 months). Median progression-free survival was 5.7 months (95% confidence interval 1.2–15.9). At 1.5 mg/kg Q4W, G≥3 treatment-emergent adverse events (TEAEs) occurred in 26 (87%) pts, including neutropenia (n=19, 63% [G4 n=9, 30%]), thrombocytopenia (n=14, 47% [G4 n=6, 20%]), and lymphopenia (n=11, 37% [G4 n=7, 23%]); 3 (10%) pts had G3 infections, and 1 (3%) pt had a G3 bleeding event. Except for 1 report of G4 hyperuricemia, there were no G4 non-hematological TEAEs; IRRs occurred in 11 pts (37% [G3 n=1, 3%]).

Of 8 pts treated with modakafusp 1.5 mg/kg Q4W + dex, 1 pt had a VGPR and 1 pt had SD (1 pt was not evaluable and 5 pts had no post-baseline response assessment). At 1.5 mg/kg Q4W + dex, G≥3 TEAEs occurred in 7 (88%) pts, including thrombocytopenia (n=4, 50% [G4 n=1, 13%]), anemia (n=2, 25%), lymphopenia (n=2, 25% [G4 n=1, 13%]), pneumonia (n=2, 25%), and neutropenia (n=1, 13%). IRRs occurred in 2 pts (25%, none G≥3).

Of 4 pts treated at 1.5 mg/kg Q4W with MRD samples collected at screening and suspected CR, 1 pt was MRD– at 10-5. Preliminary analysis showed no correlation between CD38 receptor density on peripheral blood immune cells and clinical response. Further evaluation to explore the association between clinical response and CD38 receptor density on MM cells within BMAs is underway.