 PurposeAims: Over 50 oral agents in pill form are currently on the market, with projections that in three years, 25 of cancer treatment will be delivered in pill form with patients assuming responsibility for self-management at home. For oral agents to achieve a therapeutically effective level for cancer treatment, patients must strictly adhere to the regimen. Adherence to oral cancer agents is often less than 80, which may be inadequate for treating the cancer. The aim of this study is to refine and determine the feasibility and preliminary efficacy of an intervention entitled ADHERE that uses motivational interviewing MI to elicit reasons to adhere and brief cognitive behavioral therapy CBT as a mechanism for goal-oriented systematic patient education PE to promote adherence and symptom management among cancer patients prescribed oral agents. Significance: This study targets a challenging clinical problem among patients with a life-threatening disease, assisting them in adhering to and completing their cancer treatment, impacting symptoms, quality of life, and longevity. Framework: The Motivation and Behavior Skills Model guides this work. The model asserts even a well informed or highly motivated patient will have difficulty achieving and sustaining optimal adherence if they lack the skills required to acquire or self-manage or feel incapable of performing such behaviors. Main Variables: Adherence and symptom severity. Methods: This practice-based study will be conducted using a 4-week intervention ADHERE to promote adherence and symptom management in patients newly prescribed oral agents in two phases. Phase 1 will use a single-subject-design to consecutively enrolling 5-patients from a cancer center over 4-weeks and investigators will use an iterative process to refine ADHERE in a practice-based setting. Phase 2 will use an 8-week quasi-experimental sequential design, enrolling 60-patients 30 intervention 30 control from 2-cancer centers to examine feasibility and preliminary efficacy of a 4-week ADHERE intervention and follow-up for 4-weeks to assess adherence and symptom management. Descriptive statistics will be provided as appropriate for all data collected, and 95 confidence intervals will be provided by using exact method for outcome variables, such as: the proportion of patients who are enrolled to participate in the study among those who are recruited; the proportion of ADHERE received by the patient over the four-week time period; and the proportion of patients who report high satisfaction with ADHERE. Exploratory analysis of efficacy as measured weekly by proportion of pills taken compared to what was prescribed. Implications: This study has the potential to have a transformative impact on oral agent adherence by developing an advanced practice registered nurse-led strategy to promote adherence among the increasing number of cancer patients who receive their cancer treatment in pill form. This intervention will lead to standardized care for patients newly prescribed oral agents. Results of this study will be used to inform the development of an R01 application to conduct a larger randomized trial to test the efficacy of this innovative intervention. 