A lymph-node-targeting vaccine activated immune responses in 67% of patients with KRAS-mutated pancreatic and colorectal cancers during UCLA Health's phase 1 AMPLIFY 201 trial, priming T-cells to recognize tumor mutations beyond the intended KRAS target. The trial addresses a decades-old gap: KRAS mutations have been "undruggable" outside the rare G12C subtype, leaving most patients without targeted options.

KRAS mutations drive roughly one-quarter of all human cancers; in the United States, they appear in 85–90% of pancreatic cancers and 35–40% of colorectal cancers, yet few targeted therapies exist. The mutations lock growth-regulating proteins into an "on" position. Tumors expand unchecked. Chemotherapy and immunotherapy often fail after first-line treatment.

Researchers at UCLA Health's Jonsson Cancer Center delivered vaccine doses directly into lymph nodes—tissues where immune cells gather and learn to identify threats—then tracked blood samples for T-cell activity against KRAS and other tumor-associated mutations. Patients generated responses not only to KRAS but also to additional cancer signatures, demonstrating that the vaccine primed the immune system to recognize a wider mutation array. All doses were tolerated without serious adverse events.

However, the data confirm the vaccine triggers measurable immune responses; they do not yet demonstrate tumor shrinkage, survival extension, or symptom relief. Phase 1 trials assess safety and biological activity in small patient groups. Larger phase 2 and phase 3 trials are required to establish clinical benefit.

The research team will expand enrollment to measure whether immune activity translates into patient outcomes over the next several years, determining whether this approach earns regulatory consideration. Patients interested in trial participation can consult oncologists about eligibility for future AMPLIFY phases.