Phase 1 LP-118 dual BCL-2/BCL-XL inhibitor with ponatinib + blinatumomab in Ph+ ALL

This Phase 1, Wake Forest University Health Sciences–sponsored study tests whether adding LP-118 (an oral small-molecule inhibitor of the anti‑apoptotic proteins BCL-2 and BCL-XL) can be safely combined with a modern frontline regimen for newly diagnosed Philadelphia chromosome/BCR::ABL1–positive, CD19+ B‑cell acute lymphoblastic leukemia (ALL). Patients receive fixed-dose ponatinib (a multi-kinase tyrosine kinase inhibitor that potently targets BCR::ABL1, including many resistance mutations), dexamethasone (a glucocorticoid lympholytic steroid), methotrexate (a folate antagonist that blocks DNA synthesis), and blinatumomab (a CD19×CD3 bispecific T‑cell engager), with LP-118 dose-escalated and administered only during the Induction II course. The goal is to define safety/tolerability and a recommended LP-118 dose while looking for early efficacy signals (depth of remission/MRD clearance). The scientific angle is exploiting apoptosis priming (BCL-2/BCL-XL blockade) on top of potent BCR::ABL1 suppression plus CD19-directed immunotherapy—potentially deepening remissions without adding intensive multi-agent chemotherapy. Today’s care for adult Ph+ B‑ALL is a TKI (often ponatinib) combined with steroids and blinatumomab, with CNS prophylaxis and selective transplant depending on response risk and MRD.