SPR1020: a Promising PARP1-Selective Inhibitor in Advanced Solid Tumors (Including mCRPC)

A  first-in-human Phase 1/2 trial of SPR1020, a highly selective PARP1 inhibitor, dosed its inaugural patient, igniting hope for patients with advanced solid tumors harboring DNA repair deficiencies. This open-label, multicenter study employs a classic 3+3 dose-escalation design to pinpoint the recommended Phase II dose or maximum tolerated dose, transitioning seamlessly into expansion cohorts tailored to high-need malignancies like BRCA-mutated breast, ovarian, prostate, and pancreatic cancers.
​What sets SPR1020 apart is its laser-focused inhibition of PARP1 (the key enzyme exploited by tumors with homologous recombination repair (HRR) defects) while sparing PARP2 to sidestep the severe blood count crashes plaguing broader-spectrum PARP inhibitors such as olaparib or niraparib. Preclinical models underscore this precision: potent synthetic lethality against HRD cells, brain penetration for metastatic disease, and a cleaner safety profile that could extend therapy duration and patient quality of life.

Clinical trial.