Abstract PS4-07-17: Results of the Dose-Expansion Cohort of a Phase 1 Trial of Intratumoral HER2- and HER3-Primed Dendritic Cells Injections for the Treatment of Early-Stage TNBC and HR Low Positive Breast Cancer.DecipHER trial

Abstract Background: Patients (pts) with breast cancer (BC) harboring low expression of hormone receptors (HR) and human epidermal growth factor receptor-2 (HER2) have poorer outcomes compared to other subsets of BC. Results from the KEYNOTE-522 trial showed that activation of the immune system using a PD1/PD-L1-targeted approach leads to clinically meaningful improvement in the outcomes of patients with these high-risk tumors. Dendritic cells (DCs) are antigen presenting cells which are pivotal for robust cytotoxic responses via broader activation of the adaptive immune system against tumor-associated antigens. Methods: DecipHER is a dose-escalation, dose-expansion phase 1 trial designed to assess the safety and the preliminary efficacy of autologous, HER2- and HER3-primed DCs in combination with KEYNOTE 522 regimen. Pts with clinical stage cT1cN1/2 or cT2-4cN0-2, HR 20%, HER2-negative BCs are eligible. Patients with inflammatory BC and uncontrolled immune-mediated diseases are excluded. After collection through apheresis, autologous DCs are primed ex vivo against 6 HER2 and 8 HER3 immunogenic peptides. Pts receive alternating ultrasound-guided intratumoral HER2 and HER3 DCs injections administered twice a week for 8 doses starting 2 weeks prior to neoadjuvant therapy with KEYNOTE 522 regimen. The dose-escalation phase of the study had a classic 3+3 design (ie, DL1-3 10-20, 30-50, 80-100 million, n=12). Additionally, 12 pts were treated at the maximum tolerated dose (MTD) of 80-100 million in the dose-expansion cohort. Endpoints included the absolute risk of adverse events, complete pathological response rate (PCR) and recurrence-free survival. Tumor tissue, blood and stool samples were collected for correlative analyses. Herein we report the safety results of the dose-expansion cohort ; 6 pts treated at DL3 were added for analysis of PCR. Results: A total 12 patients were enrolled into the dose-expansion cohort between 06/2024 and 09/2024. The median age in years was 53.5 (32-76) and 16.7% of pts were black; 33.3% had HER2-low, 16.7% had grade 3, 22.2% had T3 and 61.1% had N1 BCs.All patients received all planned vaccines. Grades 1 and 2 AEs that were at least possibly related to DCs (risk ≥10%) were fever (58.3%), chills (50%), pain (33.3%), headache (25%) fatigue (16.7%) and nausea (16.7%). No DC-associated grade ≥ 3 AEs were observed. None of the toxicities met the definition of DLT. Four pts had an SAE (i. bronchitis, ii. febrile neutropenia, iii. pulmonary embolism and iv. bilateral lower extremity weakness at weeks 13, 18, 22 and 14; respectively). One immune-related AEs was observed, hypothyroidism (1 pt). PCR was observed in 77.8% of the pts and it was observed at higher frequency among pts with T2 vs T3 tumors (92.3 vs 50%). Conclusion: Intratumoral DCs in combination with standard neoadjuvant chemotherapy and pembrolizumab showed preliminary efficacy and were well tolerated in pts with high-risk HR 20%, HER2-negative BC. This trial is ongoing to further assess the event-free survival of this novel treatment; correlative analyses will follow. The study is open at H. Lee Moffitt Cancer Center. Clinical trial information : NCT05504707 Funding : Shulas’ foundation. Citation Format: R. Costa, A. Soyano, A. Armaghani, N. Abdo, S. Wallace-Morrison, M. Al-Jumayli, L. Loftus, E. Abraham, J. Whiting, Q. Mo, Z. Jameel, T. O'Connor, K. Dvir, S. Hoover, J. Kiluk, M. Lee, C. Laronga, N. Khakpour, H. Han, H. Soliman, B. Czerniecki. Results of the Dose-Expansion Cohort of a Phase 1 Trial of Intratumoral HER2- and HER3-Primed Dendritic Cells Injections for the Treatment of Early-Stage TNBC and HR Low Positive Breast Cancer.DecipHER trial 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 PS4-07-17.