NeoTRACT: Phase II trial of neoadjuvant tumor infiltrating lymphocyte- and response-adapted chemoimmunotherapy for triple-negative breast cancer (TNBC).

TPS629 Background: Neoadjuvant chemoimmunotherapy is recommended for patients with high risk early stage TNBC. The 5 drug KEYNOTE-522 neoadjuvant chemoimmunotherapy regimen involves 5-6 months of treatment and is associated with suboptimal treatment completion due to toxicity. Approaches to deescalate chemoimmunotherapy without compromising outcomes for patients with highly chemosensitive disease are needed. Stromal tumor infiltrating lymphocyte (sTIL) enrichment is positively associated with pathologic complete response (pCR) in TNBC and may be useful to identify patients for whom de-escalation of neoadjuvant chemoimmunotherapy might be acceptable. NeoTRACT trial investigates deescalating neoadjuvant chemoimmunotherapy based on degree of pretreatment sTIL enrichment. We hypothesize that baseline immune upregulation assessed by sTILs can guide neoadjuvant treatment optimization in TNBC patients. Specifically, in patients with immune enriched TNBC (sTILs ≥30%), short anthracycline free taxane–platinum chemoimmunotherapy will yield high pCR rate. Methods: NeoTRACT is an ongoing open label phase II trial for patients with previously untreated TNM stage I (T>1cm)–III TNBC. TNBC is defined as estrogen and progesterone receptor ≤10% and HER2 negative per ASCO/CAP criteria. Patients with T4 or N3 breast cancer are excluded. Patients must have adequate organ function and no contraindication to pembrolizumab. All participants initiate carboplatin (AUC 6) + docetaxel (75mg/m2) + pembrolizumab (200mg) (CbD+P) every 21 days. After registration, sTILs are evaluated centrally on pretreatment H&E core needle biopsy slide using standard criteria. Participants are assigned to three neoadjuvant treatment regimens (A, B, or C) based on sTIL enrichment. Regimen A (sTILs ≥30%) includes four cycles CbD+P. All participants assigned to regimen A undergo breast MRI after four cycles: those with complete MRI response proceed to breast surgery; those with less than complete MRI response receive two additional cycles of CbD+P. Regimen B (sTILs 5-29%) includes six cycles of CbD+P. Regimen C (sTILs <5%) includes four cycles of CbD+P followed by four cycles of doxorubicin (60mg/m2) + cyclophosphamide (600mg/m2) + P (200mg) (AC+P). All patients undergo surgery after completing the assigned neoadjuvant regimen. Breast/axillary surgery, adjuvant systemic therapy, and radiotherapy are recommended per standard of care. pCR is defined as absence of residual invasive disease in breast and axilla. Primary endpoint is pCR rate among participants with ≥30% sTILs. Secondary endpoints include residual cancer burden (RCB) rates in patients with ≥30% sTILs, pCR and RCB rates in patients with 5-29% and <5% sTILs, and event free and overall survival for all patients. As of January 2024, 45 of 139 participants have been enrolled. Clinical trial information: NCT05645380 .