Phase 1b samuraciclib trial tests CDK7 inhibitor transcription/cell-cycle blockade in basal PDAC

This single-institution, single-arm, open-label Phase 1b window-of-opportunity study evaluates whether samuraciclib (CT7001)—an oral small-molecule CDK7 inhibitor that disrupts transcriptional CDK activity and cell-cycle control—changes tumor biology and shows early activity in localized “basal” pancreatic ductal adenocarcinoma. Patients with resectable, borderline resectable, or locally advanced disease without metastases receive samuraciclib by mouth once daily for 14 days, positioned before planned chemotherapy and/or surgery, with on-study research EUS/FNB plus CT imaging and blood collection. The biomarker-defined population is basal PDAC (GATA6-negative and HMGA2-positive by IHC, with positivity defined as >10% tumor epithelial nuclei), a subgroup associated with worse outcomes and reduced benefit from gemcitabine-based adjuvant therapy in published cohorts (HMGA2+/GATA6− was the poor-prognosis group). Commercially, the key angle is using a short, pre-treatment “window” to rapidly learn whether CDK7 inhibition meaningfully perturbs basal PDAC programs, potentially enabling biomarker-driven development. Today’s care for localized PDAC is surgery when feasible plus perioperative multi-agent chemotherapy (commonly modified FOLFIRINOX; alternatives include gemcitabine-based regimens), with chemoradiation selectively used for borderline/locally advanced cases.