Abstract 1196: Peripheral immune analyses correlate with clinical outcome: A phase II trial of nivolumab, capecitabine, or the combination in patients with triple negative breast cancer

Abstract Introduction: Patients with triple negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy have a higher risk of recurrence and worse outcomes than patients achieving pathologic complete response. Here, we report on immune correlates from the OXEL study (NCT03487666), an open label randomized phase II trial in TNBC patients with residual disease following neoadjuvant chemotherapy, who were treated with post-neoadjuvant nivolumab (360 mg intravenously every 3 weeks, Arm A), capecitabine (1, 250 mg/m2 orally twice daily on days 1-14 of each 3-week cycle, Arm B), or the combination of nivolumab and capecitabine (Arm C). The primary endpoint was to assess the immunologic effects of nivolumab, capecitabine, or the combination. Methods: Peripheral blood mononuclear cells were evaluated at baseline and after 6 and 12 weeks of therapy in patients from Arm A (n=15), B (n=14), and C (n=13) by flow cytometry to identify 158 immune cell subsets. Peripheral immunoscores reflective of enhanced immune cell function were calculated to evaluate changes in the immune profile induced by each therapy, and the association between the immune profile at baseline and disease recurrence. Results: At 6 weeks versus baseline, an increase in immune cell function was seen in patients on Arms A+C compared to Arm B. Additional distinct immune subsets showed statistical changes after 6 and 12 weeks of therapy that were specific to each arm. At baseline, a higher peripheral immunoscore was associated with a lack of eventual disease recurrence in patients on Arm A or Arms A+C, but not for patients on Arm B. Patients on Arm A (p=0. 0003) or Arms A+C (p=0. 0085) with a peripheral immunoscore above the median also had a longer interval of disease-free survival than patients at or below the median; this association was not seen in Arm B. Distinct immune subsets at baseline also associated with development of recurrence in each arm; higher levels of naïve CD8+ T cells and HLA-DR+ Tregs and lower levels of NKp30+ NK and PD1+ NKT cells associated with recurrence in Arm A, while in Arm B, greater levels of intermediate and nonclassical monocytes associated with recurrence. In Arm C, higher frequencies of multiple Treg subsets were associated with recurrence. Conclusions: Patients receiving nivolumab, with or without capecitabine, showed enhanced immune cell function. A peripheral immunoscore based on the immune profile at baseline was associated with disease recurrence only in patients receiving immunotherapy. These data highlight the importance of assessing peripheral blood to reveal important immunologic phenomenon and potential associations with clinical outcome. Citation Format: Nicole J. Toney, Filipa Lynce, Candace Mainor, Claudine Isaacs, Jeffrey Schlom, Renee N. Donahue. Peripheral immune analyses correlate with clinical outcome: A phase II trial of nivolumab, capecitabine, or the combination in patients with triple negative breast cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 1196.