As of data cut-off (June 10, 2021), 68 pts were treated with REGN5458 in the dose escalation cohort with full doses ranging from 3–400 mg. The median age at enrollment was 64 years (range, 41‒81) and 20.6% pts were ≥75 years. As per Revised International Staging System, stage was 1, 2 or 3 in 14.7%, 60.3% and 23.5% of pts respectively. Pts had a median of 5 prior lines of systemic therapy (range, 2–17) with the majority of pts (51.5%) being penta-refractory (see Table). The median duration of follow-up was 2.4 months (range, 0.1–20.8).

Treatment-emergent adverse events (TEAE) were reported in 66 pts (97.1%), and Grade (Gr) ≥3 TEAEs in 52 (76.5%) pts. The most frequent TEAEs were fatigue in 29 pts (42.6%), Gr 1/2 in 26 pts (38.2%), Gr 3 in 3 pts (4.4%); cytokine release syndrome (CRS) in 26 pts (38.2%), CRS was Gr 1 in 23 pts (33.8%) and Gr 2 in 3 pts (4.4%). No pt had Gr ≥3 CRS or discontinued treatment due to CRS. There were no Gr ≥3 neurotoxicity events. Nausea was reported in 22 pts (32.4%). The severity of nausea was Gr 1 in 23.5% of pts and Gr 2 in 8.8% of pts.

Treatment-related adverse events (TRAE) were reported in 56 patients (82.4%). The most frequent hematologic TRAE was neutropenia in 11 pts (16.2%), with Gr ≥3 severity in 9 of these pts (13.2%). The most frequent non-hematologic TRAEs were CRS (38.2%) and fatigue (20.6%). The safety profile was consistent across all dose levels, and there was no correlation between CRS and the full dose of REGN5458.

Responses were observed at all dose levels. Amongst pts treated at the 96 and 200 mg dose levels, the response rate was 73.3% (11/15). Across all dose levels, 92.6% (n=25) of all responders achieved at least a very good partial response and 48.1% (n=13) of responders had a complete response (CR) or stringent CR. Pts without extramedullary plasmacytomas (EMP) responded more frequently than those with EMP. The Kaplan–Meier estimated median DOR was not reached and the probability of DOR ≥8 months was 92.1% (95% confidence interval: 72.1, 98.0), with responses ongoing up to 19 months at the latest data cut-off.

Disease response was not impacted by level of BCMA expression in the core biopsy, as assessed by immunohistochemistry.

Results indicated that 95% (n = 18) of 19 patients who responded to treatment experienced a very good partial response (VGPR) or better and 42% achieved a complete response (CR) or a stringent CR (sCR).

At a median follow-up of 2.6 months, patients who received the agent at a dose of 3 mg, 6 mg, or 12 mg (n = 24; dosing levels [DL] 1-3) experienced an overall response rate (ORR) of 29.2%; 20.9% of these responders experienced a CR or sCR, while 4.2% had VGPR or better and 4.2% achieved a partial response (PR).

The ORR was higher among those who received REGN5458 at a dose of 24 mg or 48 mg (n = 17; DL 4-5), at 41.2%, with 11.8% of patients collectively experiencing a CR (11.8%)/sCR (5.9%) and 23.5% of patients achieving a VGPR. Patients who received 96 mg (n = 8; DL 6), the highest dose of the antibody evaluated on the trial, experienced the highest ORR, at 62.5%; all of these patients had a VGPR.

Results were presented today at the American Society of Hematology (ASH) Annual Meeting from the first two dose groups (3 mg and 6 mg weekly doses).

• Patients had a median of seven lines of prior systemic therapy, and all had failed CD38 antibody treatment.
• Responses were observed in 4 of 7 (57%) patients, including 3 of 4 (75%) in the 6 mg dose group.
• In the 6 mg dose group, 2 patients (50%) were also minimal residual disease (MRD) negative, meaning that no cancer cells were detectable in their bone marrow.