epratuzumab-cys-tesirine (ADCT-602)

Combining ADCT-602 + pacritinib was beneficial in ADCT-602-resistant cells. Chidamide increased CD22 expression on B-cell tumor surfaces, increasing ADCT-602 activity. These data support clinical testing of ADCT-602 in R/R B-ALL (NCT03698552) and CD22-positive hematological cancers.

P1/2, N=65, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

P1/2, N=65, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

The median age was 39 years (range, 21-82) and pts had received a median of 5 (range, 2-9) prior therapies [inotuzumab ozogamicin 12/21 (57%); blinatumomab 18/21 (86%); venetoclax 12/21 (57%)]. In this phase 1 study in pts with very heavily pretreated R/R B-ALL with a median of 5 prior lines of therapy and high baseline bone marrow tumor burden, single-agent ADCT-602 was well tolerated with one pt with DLT noted at the 50µg/kg weekly dose level. Notably, all 3 pts treated at this dose level had evidence of clinical activity with 2/3 pts achieving MRD negative CR. Due to 1 pt with DLT at this dose level, this cohort is being expanded to treat 3 additional pts.

P1/2, N=65, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022

The median age was 39.5 years (range, 22-82) and pts had received a median of 5 (range, 2-7) prior therapies [inotuzumab ozogamicin 10/14 (71%); blinatumomab 13/14 (93%); venetoclax 10/14 (71%); CD19 CAR 5/14 (36%)]. In this Phase 1 study in pts with very heavily pretreated R/R B-ALL with a median of 5 prior lines of therapy and high baseline bone marrow tumor burden, single-agent ADCT-602 was well tolerated with no DLTs noted. Two pts achieved MRD-negative remission. Dose escalation in the weekly schedule continues and 2 additional dose levels (40µg/kg weekly and 50µg/kg weekly) are planned.

ADCT-602 is an antibody drug conjugate (ADC) composed of Emab-C220, an engineered version of the anti-CD22 humanized IgG1 antibody epratuzumab, site-specifically conjugated to SG3249, which includes the DNA minor groove crosslinking pyrrolobenzodiazepine (PBD) dimer SG3199 linked to the antibody via a protease-cleavable linker (Zammarchi et al, ASH 2016). Expression signatures and other features (MZL or DHT DLBCL histology), but not the expression levels of its target, were associated with different sensitivity to the ADC. Our data supports the clinical evaluation of ADCT-602 in patients with B-cell lymphoma in addition to B-ALL.