A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing

Background: * The treatment of many cancers has been revolutionized through the use of monoclonal antibody immune checkpoint inhibitor drugs, particularly those that block the interaction of the anti-programmed death-ligand 1 (PD-L1) with the programmed death-1 (PD-1) receptor. * Atezolizumab was initially tested in a phase 1a multicenter, dose-escalation, and dose- expansion study (NCT01375842) which showed that the drug was well tolerated and produced clinical responses in a variety of tumors. * The initially approved atezolizumab regimen was 1,200 mg every 3 weeks, but 840 mg every 2 weeks was added based on the data from the TNBC trial (NCT01375842). This was taken further by Morrissey et al., who used population pharmacokinetic (PK) simulations to determine that dosing regimens of 840 mg every 2 weeks and 1,680 mg every 4 weeks are interchangeable with 1,200 every 3 weeks in terms of efficacy, leading the Food and Drug Administration (FDA) to expand the dosing regimens for atezolizumab. * The standard dosing regimens yield steady-state concentrations greater than 10-fold above the stated minimum effective concentration of 6 microg/mL, to ensure adequate exposure for all patients, including patients that may experience lower exposure due to the incidence of anti-drug-antibodies (ADA). Atezolizumab exhibits a flat exposure- response relationship. Objective: -To test the feasibility of reducing drug exposure while maintaining plasma drug concentration at or above the expected target trough value during a 16-week study period by using a method for therapeutic drug monitoring of atezolizumab. Eligibility: * Age \>= 18 years old. * Participants with a locally advanced or metastatic cancer whose NCI Licensed Independent Practitioner (LIP) determined they are candidates for treatment with atezolizumab, either alone or in combination with other FDA-approved drug(s). * Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2. * Adequate organ and marrow function. Design: * This is a phase I feasibility study of a therapeutic drug monitoring (TDM)-based method for atezolizumab dosing. * The participants will start with FDA approved dose and frequency of atezolizumab (840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks) selected by their treating physician for the first two doses of the drug per standard of care. * After the second dose, starting at 3rd dose, the dose of the drug will be switched to 840 mg and will be used going forward in the trial in all participants. * Prior to each dose a trough will be drawn which will be by the population PK model to predict the timing of the next dose to maintain the atezolizumab target trough for each participant specifically. This will be repeated for the first 16 weeks of treatment. -After 16 weeks of treatment, the timing of the next dose to maintain the atezolizumab target trough for each participant will be monitored and adjusted (if necessary) every 3 months for each participant until 2 years.