This guidance provides recommendations to clinical investigators and sponsors regarding the inclusion of patients who have not received available therapy (commonly referred to as existing treatment options) for their cancer in clinical trials of drugs and biological products for the treatment of cancer in the non-curative setting. For the purpose of this guidance, non-curative is generally defined as 1) unresectable, locally advanced, or metastatic disease in solid tumors or 2) hematologic malignancies with unfavorable long-term overall survival.