Given the relevance of the CDK4/6 pathway in PDAC, the preclinical activity of CDK4/6 inhibition in PDAC models, including in KRAS mutant pancreatic cancer cell lines,19 acceptable safety and tolerability, and the unmet medical need for refractory PDAC, this study aimed to explore the safety, efficacy, and pharmacokinetics (PK) of abemaciclib monotherapy and in combination with agents targeting PI3K/mTOR or TGFβ pathways compared to standard of care (SOC) chemotherapy in second‐ or third‐line treatment of patients with metastatic PDAC. The gene discussed is TGFB1; the disease is familial pancreatic carcinoma.