Abstract Background: Currently, a four-chemotherapy drug regimen (plus pembrolizumab if stage II-III), is frequently used as neoadjuvant strategy for triple-negative breast cancer (TNBC). Theses regimens are associated with high toxicity rates, and, given the heterogeneity of the disease, some patients may achieve favorable outcomes with less intensive treatment strategies. In this context, high levels of tumor-infiltrating lymphocytes (TILs) have been identified as a marker of excellent prognosis. Additionally, radiologic response can assist in treatment decision-making, allowing escalation only for patients with inadequate response, thereby optimizing therapy. The DespaTIL study investigates a biomarker-driven de-escalation approach to neoadjuvant chemotherapy (NAC) in early-stage TNBC. Methods: DespaTIL is a multicenter, single-arm, investigator-initiated phase II trial evaluating a de-escalated NAC strategy in patients with stage I TNBC with any level of TILs, or stage II TNBC with ≥50% stromal TILs. All patients receive four cycles of carboplatin and a taxane. Radiologic response is assessed via breast magnetic resonance imaging after cycle 4. Patients achieving a radiologic complete response proceed to surgery. Those without a radiologic complete response are escalated to four additional cycles of anthracycline and cyclophosphamide (AC), with or without pembrolizumab at the physician's discretion. Eligible participants are patients with HER2-negative invasive breast carcinoma, estrogen receptor and progesterone receptor expression 10%, and one of the following: (1) clinical stage T1c N0 M0 with any TIL level; or (2) clinical stage T2 N0 M0 with TILs ≥50%. A total of 40 patients will be enrolled. The primary endpoint is pathologic complete response (pCR) following four cycles of carboplatin and taxane. Secondary endpoints include the correlation between radiologic and pathologic response, residual cancer burden (RCB), event-free survival (EFS), overall survival (OS), and subgroup analyses by disease stage. Patient enrollment is expected to begin in the second half of 2025. Citation Format: R. C. Bonadio, R. Barroso-Sousa, J. Bines, C. dos Anjos, D. Assad-Suzuki, G. Tiburzio, L. Testa. Despatil study: a phase II trial of de-escalated neoadjuvant chemotherapy for early-stage triple-negative breast cancer guided by tumor-infiltrating lymphocytes (TILs) and radiologic response 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 PS5-09-08.
Bonadio et al. (2026) studied this question.