As of Oct 2021, 30 pts had received modakafusp alfa 1.5 mg/kg Q4W. The median number of prior lines was 7 (range 3–16); 90% of pts were refractory to an anti-CD38 monoclonal antibody (mAb), while 37% were exposed to an anti-B-cell maturation agent (BCMA). Grade (G) 3–4 treatment-emergent adverse events (TEAEs) were reported in 25 pts (83%); the most frequent G3–4 TEAEs were neutropenia in 19 (63%), thrombocytopenia in 13 (43%), leukopenia in 12 (40%), anemia in 9 (30%), and decreased lymphocyte count in 9 (30%) pts. As reported previously, 1 pt in the 1.5 mg/kg Q4W cohort had a G3 bleeding event, while 3 pts had G3 infections. Among all pts, the ORR was 40% (complete response, 7%; very good partial response, 20%; partial response, 13%); among anti-CD38 mAb-refractory and anti BMCA-exposed pts, the ORR was 37% and 27%, respectively. Median progression-free survival was 6 mos and median duration of response had not been reached (Kaplan-Meier estimate, 91% at 6 mos). Based on pooled available data for the Q3W and Q4W cohorts (all doses) within the escalation and expansion phases, there was a strong trend for a dose-exposure-response relationship for ORR, with the apparent inflection point at 1.5 mg/kg Q4W dosing. No apparent relationship between dose-exposure-response and G3/4 thrombocytopenia or neutropenia was observed across all doses, whereas a correlation between dose-exposure-response and incidence of infusion-related reactions across the 0.4–6 mg/kg Q3W and Q4W dosing cohorts was found. There was an apparent non-linear (more than dose proportional) increase in exposure in the dose range of 0.1–3 mg/kg with a geometric mean terminal half-life of 13 hours in serum for modakafusp alfa 1.5 mg/kg. Based on the available data, 14% and 60% of pts were ADA positive at baseline and post-treatment, respectively.