Optimizing Ancillary Therapies With Immune Checkpoint Inhibitors for Solid Tumors (OAT ICI)

There are multiple reports of ancillary drugs impacting the efficacy of immune checkpoint inhibitor therapy. However, there are no prospective studies evaluating the potential benefit of optimizing multiple ancillary therapies in a prospective study. To address this gap in knowledge the approach is to compare two groups; the first group is a prospective interventional population consisting of 98 solid tumor patients who have radiologically measurable cancer which are scheduled to receive immunotherapy as part of the participant's cancer treatment. Enrolled patients will be asked to avoid daily acetaminophen and the use of cannabis/THC/CBD. The participants will also be prescribed aspirin 162 mg (2 x 81 mg baby aspirin) and loratadine 10 mg to be taken once daily for 126 days. Collectively, optimizing these 4 drugs is called the OAT protocol. Once the prospective patient enrollment is complete, a historical control will be created to match patients based on their cancer, the treatment regimen, line of therapy, performance status, and age. The control group will not have received the OAT protocol optimization. The primary endpoint of the trial will be response rate at 18 weeks. Other efficacy endpoints include progression free survival and overall survival at 12 months. Safety and toxicity endpoints include those associated with aspirin and loratadine as well as the rate of immune-related adverse events. The study will also capture drug discontinuation, including ICI therapy as a measure of toxicity. Lastly, the study will explore the efficacy of the OAT protocol in different populations based on disease, smoking status, genetics, and cytokines. The hypothesis is that optimizing these therapies will increase response rates by at least 15% compared to the controls.

Inclusion criteria

• Solid tumor patients with measurable disease. Including patients with early stage and advanced stage cancer.
• Patients who are to get neoadjuvant or induction therapy prior to planned surgery or radiation are included if definitive therapy is planned to occur at least 18 weeks after ICI initiation.
• Treatment plan includes an immune checkpoint inhibitor (PD1 or PD-L1 inhibitor) as standard of care. Standard of care will be determined by referring to the NCCN guidelines. For rare situations where a disease is not found in the NCCN guideline, the treatment must be considered standard of care at the MCC.
• ECOG Performance Status 0-3.
• Life expectancy of at least 3 months.
• Adequate hematologic, renal and hepatic function based on institutional standards.
• Must be willing to stop/not start daily acetaminophen during the study period
• Must be willing to stop/not start THC-containing agent (e.g., medical or recreational marijuana, CBD) during the study period
• Patients willing to take a second-generation antihistamine (loratadine) and an NSAID (aspirin). Patients already taking a daily antihistamine and/or NSAID can participate and will continue the class of drug already being taken
• Ability to understand and the willingness to follow study procedures, including urine testing for THC.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

• Contraindication to immunotherapy, aspirin, or loratadine (including patients on blood thinners or antiplatelet agents that pose a high risk of bleeding based on the treating oncologist's opinion)
• History of allergic reactions attributed to loratadine or aspirin (true allergy, not intolerance)
• Known immunocompromised patients; defined as disease or drug related. This includes solid organ transplant patients, patients with active human immunodeficiency virus (detectable disease within the last 60 days), and those with autoimmune diseases on immune modulating drugs (disease modifying agents or steroids at a prednisone equivalent dose > 10 mg daily).
• Early-stage disease patients who are scheduled for definitive therapy in less than 126 days from treatment initiation
• Patients must not have had prior ICIs for advanced disease except as neoadjuvant + adjuvant therapy. Patients with recurrence after definitive therapy may have had prior ICIs for earlier stage disease if it was > 6 months since the last dose.
• Patients on an interventional cancer study
• History or evidence of any other clinically significant condition that, in the opinion of the investigator or treating physician, would pose a risk to subject safety or interfere with study procedures, evaluation or completion