Safety and efficacy of loading-dose thymosin α1 in patients with advanced and refractory solid tumors with lower absolute T lymphocyte.

e14543 Background: Nowadays immune checkpoint inhibitors (ICIs) has been reshaping the paradigm of cancer therapy, including various refractory advanced solid tumors. Many studies have shown that low baseline peripheral blood-based immune cells, such as lymphocytes, was one of the most relevant parameters associated with immunotherapy efficacy and prognosis. Thymosin a1, a synthetic polypeptide, has been demonstrated to increase the number of peripheral lymphocytes, especially T cells in patients with solid malignancies. In this current study, we aimed to evaluate the efficacy of loading-dose thymosin a1 (Ta-1) on peripheral lymphocytes and subpopulations in advanced solid tumors and identify how it affects the clinical outcome. Methods: Participants with confirmed the number of peripheral blood-based CD3 + T cells less than 0.5 ´ 10 9 /L, advanced solid tumors that had progressed after standard treatment, or intolerance were enrolled. In this study, those received 3.2mg thymosin α1 subcutaneously in a daily loading dose for 7 days, and the peripheral blood immune indexes were detected on the ninth day. Afterwards, these patients were decided whether to receive radiotherapy and PD-(L)1 inhibitor based on the clinician’s judgement. The primary endpoint was overall survival (OS) and the secondary endpoint were treatment-related adverse events and a panel of circulating lymphocytic subpopulations. Results: As of the cutoff date of February 6 th , 2023, a total of 27 patients were enrolled.The median age of them was 61 years old (range: 39-78). Twenty-two patients (81.5%) had poor ECOG performance status of 2 and 3. Eight (29.6%) patients had received at least 3 prior lines of systematic treatments. Most patients (19, 70.3%) had 2 or more metastatic sites. After treated daily with 3.2mg Ta-1 for 7 days, twenty-four patients (88.9%) were subsequently received radiotherapy and PD-(L)1 inhibitors. By data cut-off, median duration of follow-up was 19.2 months (95%CI: 6.2 to NA;), and median OS was 19.6 months (95%CI: 6.6 to 27.2). We found that peripheral CD3 + T cells, CD3 + CD4 + T cells, CD3 + CD8 + T cells, and natural killer (NK) cells were significantly increased after Ta-1 treatment. In an attempt to identify whether the increasing number of lymphocytes after Ta-1 treatment affects the clinical outcome, we compared the subgroup with increasing rate≥30 with that < 30%, which showed a trend of longer median OS in ≥30 subgroup than < 30% (19.6 months vs 3.9 months). No Grade ≥3 treatment-related adverse events occurred in all enrolled patients when treated with loading-dose Ta-1. Conclusions: In this study, we demonstrated that a daily loading-dose Tα-1 treatment increased the number of peripheral lymphocytic subpopulations, and this effect appears to benefit survival outcomes, shedding new light for patients with advanced or refractory solid tumors when initiated ICI treatment.