513 Background: Addition of pembrolizumab to anthracycline-taxane-platinum chemotherapy improves pathologic complete response (pCR) and event free survival (EFS) in TNBC. Aim of this study was to assess the efficacy of the anthracycline free neoadjuvant regimen of pembrolizumab plus carboplatin plus docetaxel (Cb+D) in TNBC. Methods: In this multicenter study, eligible patients with stage I-III TNBC received carboplatin (AUC 6) + docetaxel (75 mg/m²) + pembrolizumab (200 mg) every 21 days x 6 cycles. The primary endpoint was pCR (no evidence of invasive tumor in breast and axilla). Secondary endpoints were residual cancer burden (RCB), EFS, toxicity, and immune response biomarkers. RNA isolated from pretreatment tumor tissue was subjected to next generation sequencing. Samples were classified as DNA Damage Immune Response (DDIR) signature and DetermaIO signature positive/negative using predefined cutoffs. Evaluation of stromal tumor infiltrating lymphocytes (sTILs) was performed using standard criteria. Results: 117 patients were enrolled from September 2018 to January 2022. 18% were African American, 39% had node positive disease, 88% had stage II/III disease and 15% had ER/PR 1-10%. Pathologic response information is available for 105 patients. pCR and RCB 0+1 rates were 60% (95% CI 51%-70%) and 71% (95% CI 62%-80%), respectively. Treatment related adverse events led to discontinuation of any trial drug in 12% of patients. Immune adverse events were observed in 28% of patients (Grade ≥3=6%). 47% of patients had sTILs ≥30%, 48% were DetermaIO positive, and 61% DDIR positive. The table describes the impact of these biomarkers on pCR and RCB. The areas under the prediction curve (AUC) for pCR were 0.660, 0.709, and 0.719 for DDIR, sTILs, and DetermaIO respectively. At a median follow up of 21 months, 2-year EFS is 88% in all patients; 98% in pCR group and 82% in no pCR group. Conclusions: Neoadjuvant pembrolizumab plus Cb+D regimen yields pCR of 60% and 2-year EFS of 88% in the absence of adjuvant pembrolizumab. The regimen was well tolerated, and no new toxicity signals were noted. Immune enrichment identified by sTILs or DetermaIO signature was associated with high pCR rates approaching or exceeding 80%. PD-L1 and additional biomarker analyses are ongoing. Clinical trial information: NCT03639948. [Table: see text]