Results: As of May 9, 2024, 104 pts were enrolled in Cohorts A, C, and D; 28 pts received MeziVd (Cohort A) and 27 pts received MeziKd (Cohort C) in the dose-escalation cohorts. Median (range) age was 65.5 (46–86) and 68 (41–76) years (y), median time since diagnosis was 4.8 (1.9–17.1) and 5.4 (0.7–15.7) y, median number of prior regimens was 3 (2–4) and 2 (2–4), 24 (85.7%) and 24 (88.9%) pts were refractory to IMiD agents, and 14 (50.0%) and 14 (51.9%) to PIs, respectively. Median follow-up was 13.6 (MeziVd) and 15.2 months (mo) (MeziKd); 3 (10.7%) and 5 (18.5%) pts continue on treatment, with 12.5 and 12 median cycles received, and PD being the main reason for discontinuation (64.3% and 48.1%), respectively.

In the dose-escalation cohorts, the most common grade 3/4 treatment-emergent adverse events (TEAEs) were neutropenia (35.7%), thrombocytopenia (21.4%), and infections (17.9%) with MeziVd; and neutropenia (44.4%) and infections (33.3%) with MeziKd. Grade 3/4 non-hematologic TEAEs, including rash and diarrhea, were low or absent. MEZI dose reductions due to TEAEs were needed in 7 (25.0%) and 8 (29.6%) pts. The overall response rate (ORR) was 75.0% (21/28 pts) and 85.2% (23/27 pts), with ≥ very good partial responses (VGPR) in 39.3% and 44.4% pts. Median (95% CI) duration of response (DOR) was 10.9 (8.1–18.7) and 11.9 (6.4–NA) mo and median (95% CI) progression-free survival (PFS) was 11.8 (9.0–18.0) and 13.5 (8.4–19.7) mo, respectively.

As of May 9, 2024, 49 pts received MeziVd in the Cohort D dose-expansion cohort. Median age was 64 (43–83) y, median time since diagnosis was 4.2 (0.9–20.5) y, and median number of prior regimens was 1 (1–3). Overall, 31 (63.3%) pts were refractory to IMiD agents, and 8 (16.3%) to PIs. Median follow-up was 18.3 mo; 9 (18.4%) pts continue on treatment, with 15 median cycles received. Discontinuations were mainly due to PD (53.1%).

The most common grade 3/4 TEAEs were neutropenia (63.3%), infections (32.7%), and thrombocytopenia (26.5%); grade 3/4 non-hematologic TEAEs remained low or absent. MEZI dose reductions due to TEAEs were needed in 18 (36.7%) pts. ORR was 85.7% (42/49 pts) with ≥ VGPR in 63.3% of pts; median DOR was 19.4 (9.7–NA) mo, median PFS was 17.5 (9.4–24.0) mo.

MEZI exposure increased in a dose-linear manner over the dose range, and exposures were similar when comparing pts treated with MeziVd and MeziKd. MEZI showed pharmacodynamic activity with BORT or CFZ across all doses tested, with 1.0 mg MEZI inducing the greatest pharmacodynamic effects including substrate degradation and T-cell proliferation, supporting the use of 1.0 mg MEZI in combination with PIs.

Conclusions: With longer follow-up, MeziVd and MeziKd in RRMM confirmed promising efficacy and a manageable safety profile at all dose levels tested, with no cumulative toxicity and low grade 3/4 non-hematologic TEAEs (including rash and diarrhea). These results informed ongoing and planned phase 3 trials. Updated data will be presented at the meeting.