Abstract PS3-10-26: Long-term outcomes of two her2 vaccines to prevent recurrence in patients with her-2 positive early stage breast cancer

Abstract Background: Patients (pts) with residual invasive disease following neoadjuvant therapy for HER2-positive early stage breast cancer (EBC) have an increased risk of recurrences compared to pts with a complete pathologic response (pCR). It also has been observed that pts who do not achieve a pCR have low or absent anti-HER-2 CD4 Th1 responses. We hypothesize that boosting anti-HER-2 CD4 Th1 response using vaccines is safe, induces anti-tumor immunity in HER2-positive breast cancer and reduces the risk of recurrence. We conducted a multi-center, phase 2, randomized study to determine the safety, immunogenicity and recurrence free survival of two HER2 vaccines (multivalent anti-oncodriver DNA vaccine (WOKVAC) or HER-2-pulsed dendritic cell vaccine (DC1)). Methods: Pts with HER2-positive EBC were eligible if they had residual invasive disease at surgery after receiving neoadjuvant chemotherapy plus HER2-targeted therapy. Pts were randomly assigned in a 1:1 ratio, stratified by residual cancer burden (RCB) (1+2 vs 3) to receive adjuvant HER2 vaccination with either DC1 or WOKVAC. For the initial vaccination phase, DC1 was delivered via US guided inguinal lymph node administration, weekly x 6 weeks and WOKVAC was given intradermally on weeks 1, 4, and 7. Booster vaccines were given at months 6, 9 and 12. The primary end points were the safety and immunogenicity of each vaccine and the secondary end point was recurrence-free survival (RFS). Exploratory analyses include the assessment of prognostic and predictive biomarkers including circulating tumor cells, serum HER2 levels, and others immune correlative biomarkers. Here we report the immune response and updated long-term outcome data. Results: 110 eligible pts (55 WOKVAC vs 55 DC1) were accrued from 2/2018 to 12/2022 from 7 academic institutions and received at least one dose of treatment. Most pts had clinical stage II/III 56/35 (83%) and 50% had node positive disease at diagnosis. 82% had hormone receptor positive disease. 37/38/8 patients had RCB 1/2/3. For patients with unknown RCB status, ypTNM was used to randomize (yp stage I/II/III=13/13/1 pts). 70.9% received adjuvant trastuzumab emtansine (T-DM1) following FDA approval in 2019. Most treatment related adverse events (TRAE) were grade 1 and 2 (previously reported). Eleven pts (6 in DC1 and 5 in WOKVAC) had recurrence with a median follow-up of 51.8 months. Of those 2/6 patients in the DC1 arm developed brain metastasis shortly after study enrollment during the induction phase. Of the remaining 9 pts with recurrence, 1 had a new primary cancer, 3 had local recurrence and 5 had distant recurrence. Three pts died from recurrent disease. RFS was 94.5% and 90.5% at 3 and 5 years respectively. Among pts who received adjuvant T-DM1, RFS was 95.9% at 3 and 5 years. HER2 immune response measured by ELISPOT (N=80) following vaccination demonstrated an average two-fold increase across both treatment groups at 12 months. Conclusion: Both DC1 and WOKVAC HER2 vaccines were well tolerated without significant toxicities. Both HER2 vaccines were immunogenic and associated with persistence of immunity at 12 months follow up. Our results (RFS) compare favorably with the KATHERINE trial suggesting potential additional benefit of adjuvant vaccines for these high-risk pts populations. Several studies are ongoing to evaluate the addition of neoadjuvant DC1 and WOKVAC to HER2 targeted therapies. (NCT 05325632/04329065) ClinicalTrials.gov Identifier: NCT03384914 Citation Format: H. S. Han, A. Aldrich, R. Weslowski, C. Fisher, S. Gandhi, W. R. Gwin III, M. Kowzun, K. Gogineri, H. Soliman, R. Costa, H. Liu, J. Whiting, M. Schell, M. L. Disis, B. Czerniecki. Long-term outcomes of two her2 vaccines to prevent recurrence in patients with her-2 positive early stage breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-10-26.