This is a single-center, randomized, open-label clinical trial designed to evaluate the impact of low-dose olanzapine on weight loss, appetite, and nutritional outcomes in patients with gastric cancer receiving neoadjuvant chemotherapy. Eligible patients will be randomized to receive olanzapine 2.5 mg orally once daily (QD) in addition to standard neoadjuvant chemotherapy, beginning prior to initiation of chemotherapy and continuing until surgical resection. Patients will otherwise receive standard-of-care (SOC) oncologic treatment, with no alterations to chemotherapy regimens or surgical management. The study is designed to prospectively assess whether olanzapine improves appetite, mitigates weight loss, and enhances nutritional status and quality of life (QoL) during neoadjuvant therapy. This study will be conducted at the University of Illinois Cancer Center (UICC) as a single-site investigator-initiated trial, with an anticipated accrual of 26 participants over 2 years.

Inclusion Criteria:

• Age ≥ 18 years of age at time of consent
• Eastern Cooperative Oncology Group (ECOG) score of 0-2
• Histologically confirmed gastric adenocarcinoma, documented by biopsy.
• Planned to receive neoadjuvant chemotherapy followed by surgical resection, as determined by the treating oncologist.
• Demonstrates adequate organ function. All screening labs are to be obtained within 30 days prior to registration.
• Able to provide written informed consent and HIPAA authorization for release of personal health information, via an approved UIC Institutional Review Board informed consent form and HIPAA authorization. If a subject is unable to consent, a Legally Authorized Representative (LAR) may provide consent on their behalf.
• Women of childbearing potential must not be pregnant or breastfeeding. A negative serum or urine pregnancy test is required per institutional practice guidelines.
• As determined at the discretion of the enrolling physician or protocol designee, the ability of the subject to understand and comply with study procedures for the entire length of the study

Exclusion Criteria:

• Active infection requiring systemic therapy
• Uncontrolled HIV/AIDS or active viral hepatitis
• Pregnant or nursing
• Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this investigational regimen, as determined by the treating medical oncologist.
• Patients with a feeding tube (e.g., gastrostomy or jejunostomy) receive their primary source of nutritional intake via enteral tube feeding at the time of enrollment.
• Any mental or medical condition that prevents the patient from giving informed consent or participating in the trial.
• Other major comorbidity, as determined by the study PI