Multicenter phase 1 trial of XmAb 18968 for relapsed or refractory acute myeloid leukemia or T-cell acute lymphoblastic leukemia

The transmembrane glycoprotein CD38 is highly expressed in acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL). XmAb 18968 is a novel CD38-CD3 bispecific T-cell engager with Fc domain modified to reduce non-selective activation of effector cells. A multicenter phase 1 trial in the USA evaluated outcomes with XmAb 18968 in adult patients with relapsed/refractory (R/R) AML (n=13) and T-ALL (n=9). The median age was 63 years (range 31-77). Prior lines of therapy (median 3, range 1-8) included venetoclax (77.3%), allogeneic hematopoietic cell transplantation (22.7%), CD7 CAR-T cell therapy and daratumumab (11.1%). Grade ≥ 3 adverse events included anemia (14%), neutropenia (18%), and thrombocytopenia (14%). No grade ≥ 3 cytokine release syndrome or neurotoxicity were observed. Overall, 11 AML and 6 ALL patients completed at least one cycle of therapy.Among the RR AML patients, two (18%) achieved MRD negative complete remission, and one (9%) achieved partial remission. Among the RR T-ALL patients, four (66%) achieved meaningful improvement in disease burden, with one (16%) clearance of MRD. Median overall survival was 8.5 months in AML and 8.7 months in T-ALL. The authors conclude that XmAb 18968 is safe and tolerable with encouraging preliminary efficacy.