Traditional treatments like chemotherapy and immunotherapy are conventionally administered intravenously or orally. As a results, they are not effective since only a small amount of drug reaches the tumor, while the rest spread all over the body causing unwanted side effects. Because of this, researchers are exploring drug delivery directly into the tumor to increase its effectiveness and avoid side effects. However, this approach requires repeated injections because the drugs leak out of the tumor rapidly, which is harmful to healthy surrounding tissues. To solve this problem, we developed a tiny device called the ‘biodegradable intratumoral drug-eluting seed’ (bNDES). This device is smaller than a grain of rice and inserted into the tumor in a one-time minimally invasive manner using an existing clinical tool. Upon intratumoral insertion, the bNDES slowly releases drugs directly into the tumor over a long period, avoiding the need for repeated injections. Because the bNDES is composed of biodegradable materials used in clinically approved medications, they naturally dissolve safely in the body after completing their function, eliminating the need for surgical removal. In this study, we will use the bNDES to deliver a combination of five different immunotherapy drugs, each of which targets different parts of the immune system. These five drugs work together to activate the body’s immune system to attack the tumor. Normally, delivering these drugs at once would be dangerous and not possible clinically because of the severe, and possibly fatal, side effects. With the bNDES, we avoid the risks by releasing these drugs directly into the tumor in small, controlled amounts steadily over time. We will test the effectiveness of the bNDES in pancreatic cancer, one of the deadliest types of cancer. This cancer is challenging to treat because the tumor is surrounded by tough fibrous tissue that makes it difficult for drugs to reach the cancer cells. We will use a preclinical model of pancreatic cancer to test two main aims: (1) assess the efficacy and safety of bNDES-delivered immunotherapeutic combinations and (2) evaluate immune mechanisms of synergistic immunotherapeutic combinations delivered intratumorally via the bNDES. We will measure the success of these aims by evaluating how well the tumor is controlled or eliminated, how the immune environment in the tumor changes, and how much toxicity, if any, occurs. Building on our previous findings, we aim to show that the bNDES is versatile and can be used for different types of cancers and drugs. The bNDES is a universal, unique and unconventional approach to cancer treatment, with fewer side effects and better results.