Pancreatic cancer is the third leading cause of cancer-related deaths in the United States, with a five-year survival rate of 13%. Survival remains low in part because most patients are diagnosed at an advanced stage, when treatment options are limited. For patients with early, localized tumors, surgery, often combined with chemotherapy, offers the only potential cure. Yet more than 80% of these patients experience recurrence, highlighting the urgent need for new strategies.
Over the last decade, immunotherapies have revolutionized the treatment of cancers such as melanoma and lung cancer. These therapies harness the body’s own immune system to detect and destroy tumor cells. Unfortunately, pancreatic cancer has been largely resistant to this approach.
A recent, early-stage clinical trial, AMPLIFY-201, has shown promising results in reducing relapse by treating patients with a cancer vaccine after surgery. The phase I clinical trial was co-led by Dr. Zev Wainberg, a gastrointestinal medical oncologist at the UCLA Agi Hirshberg Center for Pancreatic Diseases. Dr. Wainberg has also presented on advances in chemotherapy at the Agi Hirshberg Symposium on Pancreatic Cancer.
The study enrolled patients with pancreatic cancer or colorectal cancer (CRC) who had undergone surgery but still showed minimal residual disease (MRD). MRD is when no tumors are visible on scans but tumor cells or elevated biomarkers such as CA19-9 are detectable in the blood. Patients in the trial received the ELI-002 2P vaccine, which contains small peptides designed to train the immune system’s T cells to identify and destroy the remaining tumor cells to prevent relapse.
Unlike many cancer vaccines that are personalized for each patient after the tumor has been biopsied and sequenced, ELI-002 2P is an “off-the-shelf” treatment. The vaccine used peptides to activate T cells to identify mutant versions of a protein called KRAS. Mutated KRAS is a driver mutation for 50% of all colorectal cancers and more than 90% of pancreatic ductal adenocarcinomas (PDACs) tumors. The vaccine specifically targets two specific KRAS mutations, G12D and G12R, which have been found in a high percentage of tumors. This shared vulnerability allows one standardized vaccine to be used across many patients.
The vaccine’s design is also novel. Each peptide is linked to a lipophilic tail that binds albumin, a protein in the blood. The albumin allows the peptides to “hitchhike” directly to lymph nodes, where T cells are activated. The peptides, along with an adjuvant, get taken up by dendritic cells, which present the peptides and prime T cells for attack. Once activated, these T cells circulate through the body, ready to recognize and eliminate cancer cells harboring KRAS mutations.
In the AMPLIFY-201 trial, 25 patients with pancreatic or colorectal cancer received six vaccine doses over eight weeks, followed by a rest period, then four booster doses. The vaccine was well tolerated: nearly half of patients reported only mild side effects such as fatigue, injection-site soreness, or muscle pain. Importantly, no patients experienced serious immune-related toxicities such as Cytokine Release Syndrome (CRS). CRS is an acute systemic inflammatory response characterized by fever and multiple organ dysfunction.
The immune responses were striking. After more than 19 months of follow-up, 68% of patients developed KRAS-specific T cell responses linked to reductions in circulating tumor DNA. Of these patients, 11 have shown no evidence of new tumor growth on imaging, and six achieved complete clearance of tumor biomarkers. Even more promising, many patients had T cells that recognized additional tumor proteins beyond the KRAS mutations targeted by the vaccine, a phenomenon called epitope spreading, that further broadens their immune defense against cancer cells.
While larger studies are needed, these early results suggest that cancer vaccines, both “off-the-shelf” and personalized, may finally offer a way to reduce relapse rates for pancreatic cancer patients after surgery. For a disease long resistant to immunotherapy, AMPLIFY-201 represents a hopeful advance and an important step toward more durable outcomes.
