WOKVAC Phase I Study Marks Progress Toward Breast Cancer Interception

The Cancer Vaccine Institute (CVI) is advancing the emerging field of cancer research, developing vaccines to intercept cancer before it becomes invasive. We have developed WOKVAC, a DNA-based vaccine designed to target three proteins - HER2, IGFBP-2, and IGF-1R - highly expressed in most Ductal Carcinoma In Situ (DCIS), a preinvasive form of breast cancer. Although not immediately life-threatening, 20% of DCIS lesions may progress to invasive cancer. Patients diagnosed with DCIS often receive surgery and radiation, exposing patients to health risks. Vaccine-generated immunity may be a less invasive and less toxic alternative to treating precancerous lesions such as DCIS.

We published the results of a Phase I trial testing safety and immunogenicity of WOKVAC in non-metastatic breast cancer in the Journal for ImmunoTherapy of Cancer. The study, conducted at the University of Washington and the University of Wisconsin, recruited 32 patients with non-metastatic, hormone receptor positive or triple negative breast cancer with no evidence of disease who received one of three doses of the vaccine (150, 300, or 600 µg) once a month for three months. Participants were then followed for five years for long-term toxicity.

Findings from this study demonstrate that the vaccine is safe, well tolerated, and generates strong, durable type I immune responses. The intermediate dose (300 µg) was the best dose - it had long-term persistence of immunity after vaccination and will be used in Phase II clinical trials of WOKVAC. CVI researchers also compared T‑cells from patients who responded to the vaccine with T‑cells from those who did not. They found that responders’ T‑cells showed gene‑expression patterns linked to stronger overall “immune fitness,” pointing to a potential biological explanation for why some patients benefit more than others.

Prior to this publication, WOKVAC was also tested in a Phase II multi-center clinical trial led by CVI collaborators at the Moffitt Cancer Center, in which patients with high risk non-metastatic HER2+ breast cancer received either WOKVAC or DC1, a dendritic-cell vaccine. Results from the Phase II study presented at the 2025 San Antonio Breast Cancer Symposium demonstrated recurrence-free survival across both vaccine groups of about 95% at three years and 90% at five years. Among patients who also received T-DM1, a standard HER2-targeted therapy now widely used after surgery, recurrence-free survival was even higher - about 96% at both 3 and 5 years. Immune monitoring showed that both vaccines doubled HER2-specific immune activity one year after vaccination.

Taken together, these studies demonstrate that WOKVAC is safe and produces robust, long‑lasting anti‑cancer T-cell responses. The encouraging recurrence‑free survival seen in the Phase II trial, combined with the vaccine’s ability to target proteins abundant in DCIS, positions WOKVAC as a promising candidate for intercepting breast cancer before it becomes invasive.

WOKVAC is also currently being tested in a Phase II neoadjuvant study for earlier-stage HER2-positive breast cancer. Additional Phase II trials are planned to further assess its efficacy in patients with DCIS, with the goal of intercepting invasive breast cancer before it develops.

Study Authors: Sasha E Stanton, Denise L Cecil, Howard H Bailey, Ying Liu, William R Gwin, Andrew L Colveler, John B Liao, Kari B Wisinski, Lisa Barroilhet, KyungMann Kim, Thomas C Havighurst, Katina DeShong, Kyleigh Twaroski, Jennifer S Childs, Eileen Diamond, Margaret Wojtowicz, Brandy M Heckman-Stoddard, Mary L Disis

Read the full publication here: https://jitc.bmj.com/content/14/5/e014314 

Stanton et al WOKVAC.pdf

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