poseltinib (HM71224)

Background: Despite the groundbreaking introduction of rituximab for the treatment of diffuse large B cell lymphoma (DLBCL), approximately 30% of the patients ultimately experience refractory / relapse (R/R) disease and so far myriads attempts to improve survival outcomes have not yielded firm positive results...To mitigate the risk of glofitamab associated cytokine release syndrome, obinutuzumab premedication and cycle 1 step-up dosing was implemented...One patient with a previous history of prior COVID19 infection after TNB-486 (CD19/CD3 bispecific) clinical trial, despite receiving vaccination prior to this study enrollment, experienced COVID19 reactivation after cycle 1... Glofitamab, poseltinib and lenalidomide (GPL) is promising combination for thetreatment of R/R DLBCL. (Table) Refractory, DLBCL, Bispecific

Building on our previous work on ibrutinib-based reversible covalent Bruton's tyrosine kinase (BTK) PROTACs, we explored a different irreversible BTK inhibitor poseltinib as the BTK binder for PROTAC development. We showed that PS-RC-1 potently induces degradation of IKZF1 and IKZF3 but not BTK or GSPT1, accounting for its toxicity in Mino cells. We further decreased the molecular size of PS-RC-1 by shrinking the BTK binding moiety and developed PS-2 as a potent BTK and IKZF1/3 triple degrader with high specificity.

P2, N=76, Recruiting, Seoul National University Hospital | Not yet recruiting --> Recruiting

P2, N=76, Not yet recruiting, Seoul National University Hospital