GLP-1 RA Plus SOC Treatment in First-line, Metastatic Pancreatic, Colorectal, or Hepatocellular Cancer

The United States is facing a growing epidemic of obesity and type 2 diabetes, with over 42% of adults now classified as obese and nearly 20% of children affected by obesity. This rise has been driven by a combination of poor dietary habits, sedentary lifestyles, and social and economic factors that limit access to healthy food and healthcare. Type 2 diabetes, closely linked to obesity, affects more than 37 million Americans, with an additional 96 million adults estimated to have prediabetes. These conditions not only contribute to significant personal health burdens but also cost the U.S. economy over $370 billion annually. Disparities are evident, with higher rates among Black, Hispanic, Native American, low-income, and rural populations, largely due to systemic barriers and social determinants of health. In response, public health initiatives have promoted better nutrition, physical activity, and early intervention programs. New medications, such as GLP-1 receptor agonists, offer promising tools for weight loss and diabetes management, though their accessibility remains limited by cost and insurance coverage. Prescription data show GLP 1 RA use has exploded in recent years. For example, GLP 1 prescribing volume in the U.S. roughly tripled from early 2020 to late 2022, and annual spending jumped from $13.7 billion in 2018 to $71.7 billion by 2023 (a 62% increase in just 2022-23). Semaglutide products (Ozempic/WEGOVY) still account for the largest share of use, but Lilly's tirzepatide (Mounjaro/Zepbound) has gained market share rapidly. Uptake is broadening across age groups. Surveys indicate \~19% of adults ages 50-64 and 8% of those ≥65 have tried GLP 1 drugs (mainly for diabetes) and prescribing to adolescents with obesity surged \~300% in 2023 (albeit reaching only \~0.5% of obese youth). Looking ahead, analysts project continued robust growth. One forecast estimates U.S. GLP 1 weight loss drug sales rising from about $10 B in 2024 to \~$37 B by 2030 (≈19% CAGR). Globally, GLP 1 market revenue (diabetes + obesity) could approach $130 B by 2030, with the leading agents (semaglutide and tirzepatide lines) alone generating on the order of $100 B by decade's end. This outlook reflects expanding approved uses (e.g. heart disease, potential NASH indications) and large unmet need (only \~10-12% of U.S. adults have used GLP 1s despite over half of adults being overweight or obese). Taken together, the data indicate an unprecedented growth trajectory for GLP 1 RAs, with rapid year over year prescription gains and forecasts of very high revenues and market dominance through 2030. Similarly, pancreatic cancer and hepatocellular carcinoma are also associated with modifiable risk factors including obesity, dietary factors, and diabetes. Consequently, there is a growing number of patients diagnosed with GI cancers who are also simultaneously being treated with GLP-1 RAs. To date, no clinical trial data exists to establish safety and/or feasibility with use of GLP-1 RAs during chemotherapy in the metastatic setting. This highlights an unmet need to investigate the safety of GLP-1 RA use during chemotherapy treatment for patients with metastatic colorectal cancer, pancreatic cancer, and hepatocellular carcinoma. Furthermore, emerging evidence supports investigation of GLP-1 RAs on metabolic modulation, insulin resistance reduction, and potential anti-inflammatory effects from GLP-1 RAs in oncology settings. Both cancer types may benefit from adjunctive metabolic therapy, particularly in patients at risk of sarcopenia, cachexia, or insulin resistance. This trial aims to investigate the safety, tolerability, and efficacy of GLP-1 receptor agonist treatment in combination with standard of care (SOC) chemotherapy in patients with metastatic pancreatic, colorectal, or hepatocellular cancers in the first-line setting.