Abstract PS4-06-11: Initial Results from Correlative Analysis of a Single Arm Phase 2 Study of Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women with Hormone Receptor-Negative, HER2-Negative Early Stage/Resectable Breast Cancer

Abstract Background: Triple negative breast cancer (TNBC) is a biologically distinct subtype with a high risk of early relapse, particularly in patients with residual disease following neoadjuvant chemotherapy (NAC). Failure to achieve a complete response may reflect underlying immune evasion mechanisms, including upregulation of immune checkpoints such as programmed cell death protein 1 (PD-1), which impair effective T cell-mediated antitumor responses. Cryoablation (cryo) can stimulate T-cell priming and reduce MDSCs to overcome resistance to immune checkpoint inhibition (ICI). Preclinical and early clinical data suggest that the combination of cryo with ICI may synergistically improve immune activation. We conducted a multi-center, single arm, phase 2 study to evaluate the impact of cryo with standard-of-care pembrolizumab (pembro) in women with residual TNBC after taxane-based neoadjuvant chemotherapy (NAC), a group at high risk of early relapse (NCT03546686). Methods: Eligible women are ≥18y, with ER 10%, PR 10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. Patients underwent percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and receive peri-operative pembro per standard-of-care. Peripheral blood was collected pre- and post-cryo, and flow cytometry was performed on paired peripheral blood mononuclear cells (PBMCs) from an initial cohort (n = 5) to identify changes in immune response. Results: Post-cryo, we observed an overall trend in the decrease of PD1-positive T cells and myeloid cells. PD1+CD8+ T cells decreased by 2.9-fold, PD1+CD4+ T cells decreased by 4.6-fold and PD1+CD3- decreased by 6.3-fold. Notably, we observed a decrease in CD11b+CD3- MDSCs by 14.92-fold. Additional exploratory correlative studies on tumor and blood, including tumor infiltrating lymphocytes and tumor PD-1 IHC, are ongoing to fully characterize the immunologic impact of the intervention and to explore predictors of efficacy. Conclusion: These initial results suggest that the addition of cryo to pembro may act synergistically to reduce the overall immunosuppressive immune environment, potentially resulting in improved immunity in patients with high-risk residual TNBC. Funding sources: Susan G. Komen, B-SEARCH, Conquer Cancer Foundation, Breast Cancer Research Foundation, Boston Scientific. Citation Format: S. Bhandari, A. Alhalwani, I. Terrazas, R. Sridharan, S. Rice, H. L. McArthur, I. S. Chan. Initial Results from Correlative Analysis of a Single Arm Phase 2 Study of Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women with Hormone Receptor-Negative, HER2-Negative Early Stage/Resectable 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 PS4-06-11.