P1/2, N=30, Not yet recruiting, Daiichi Sankyo Inc.

P1/2, N=420, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

P1/2, N=134, Recruiting, Debiopharm International SA | Not yet recruiting --> Recruiting

P1/2, N=134, Not yet recruiting, Debiopharm International SA

Anti-IL6 antibody tocilizumab improved the ADC's cytotoxic activity in CD37+ cells...Adding idelalisib or venetoclax overcame resistance in the resistant derivative and improved the cytotoxic activity in the parental cells. In conclusion, targeting B-cell lymphoma with the naratuximab emtansine showed vigorous anti-tumor activity as a single agent, which was also observed in models bearing genetic lesions associated with inferior outcomes, such as MYC translocations and TP53 inactivation or R-CHOP resistance. Resistant DLBCL models identified active combinations of naratuximab emtansine with drugs targeting IL6, PI3Kδ, and BCL2.

Our work revealed that the clinically relevant anti-CD37 antibody drug conjugate (ADC) Debio 1562 (αCD37-DM1) is highly cytotoxic to AML blasts, but not normal hematopoietic stem cells. We found that αCD37-DM1 improved clinical outcomes and overall survival in multiple in vivo models of AML. Together, these data demonstrate that targeting CD37 with an ADC such as αCD37-DM1 is a feasible and promising therapeutic option for the treatment of AML.

Rituximab (RTX) plus chemotherapy (R-CHOP) applied as a first-line therapy for lymphoma leads to a relapse in approximately 40% of the patients...Importantly, even a major downregulation in CD37 levels does not hamper the efficacy of CD37-directed chimeric antigen receptor (CAR) T cells. In summary, we present here a novel mechanism of CD37 regulation with further implications for the use of anti-CD37 immunotherapies.

For those patients, CAR-T cells offers an attractive therapeutic option, as illustrated by the recent clinical trial combining CD19 CAR-T cells with ibrutinib... Targeting CD37 via CAR-T cells is a promising therapeutic option for CLL patients and an attractive alternative to CD19-directed CAR-based therapies. Further in vivo studies are warranted.

DL analysis of the co-expression and spatial arrangement of CD37 and CD20 positive cells in pre-treatment biopsies of DLBCL patients could potentially be used as a predictive biomarker for a response to a combination treatment of naratuximab emtansine and rituximab in DLBCL, and may improve patient stratification for further clinical trials.

DL analysis of the co-expression and spatial arrangement of CD37 and CD20 in pre-treatment biopsies of DLBCL patients could potentially be used as a predictive biomarker for a response to a combination treatment of anti-CD37 and anti-CD20 drugs in DLBCL, and may improve patient stratification for further clinical trials.