Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) is a family of proteins that plays important roles in multiple cellular processes, including single-strand DNA breaks, which if left unrepaired, leads to double-strand breaks (DSB) during DNA replication. The DSB can be repaired either through error-free homologous recombination (HR) or error-prone non-homology end joining. In HR deficient cancer cells with mutations on HR genes such as BRCA1, BRCA2 or partner and localizer of BRCA2 (PALB2), DSB cannot be efficiently and correctly repaired, resulting in cell death. Viable cells, on the other hand, have normal HR and do not replicate as often as cancer cells; thus they can survive PARP inhibition. PARP inhibitors are being actively developed worldwide as promising anti-tumor therapeutics. The current trial will be conducted in participants with advanced solid tumors for whom satisfactory treatments are not yet available.~In the dose-escalation phase, patients will be enrolled sequentially into the 8 dose levels of SHR3162 designated in this study(3-6 patients per cohort). One to two sentinel participants in Cohort 1 who will be treated and closely monitored for 24 hours. If no adverse effects are noted during the 24-hour period, dosing of further participants in the cohort may continue.~In the dose expansion part of the study, up to 12 additional participants will be enrolled at the MTD.
This is an open-label, multicenter, non-randomized, dose-escalation phase 1 trial to evaluate the safety and tolerability of SHR3162 in participants with advanced solid tumors.