556 Background: Pembro has shown efficacy and acceptable safety in pts with previously treated metastatic TNBC. The phase Ib KEYNOTE-173 study (NCT02622074) evaluated pembro + chemo as neoadjuvant therapy for locally advanced TNBC. We present cohorts A and B. Methods: Women aged ≥18 y with locally advanced, nonmetastatic TNBC; ECOG PS 0/1; and no prior chemo, targeted therapy, or immunotherapy within 12 mo were eligible. Dosing in A was single-dose pembro followed by 4 cycles of pembro Q3W + nab-paclitaxel (Np) weekly followed by 4 cycles of pembro + doxorubicin + cyclophosphamide Q3W. Dosing in B was the same as in A but with carboplatin Q3W added to pembro + Np. Concentrations were pembro 200 mg; doxorubicin 60 mg/m2; cyclophosphamide 600 mg/m2; Np 125 mg/m2 in A, 100 mg/m2 in B; and carboplatin AUC 6 (1 cycle = 21 d). DLTs were assessed at cycles 1-3 and 6-7. Dose levels were deemed toxic if ≥3 of the first 6 pts or ≥4 of 10 pts had DLTs. Surgery was 3-6 wk after treatment completion/discontinuation. Primary end points were safety and recommended phase 2 dose of pembro combined with chemo. Key efficacy end points were pathological CR (pCR) rate, defined as ypT0/Tis, ypN0, and ypT0 ypN0, and ORR (RECIST v1.1, investigator). pCR analyses included all pts. Results: By Jan 6, 2017, 10 pts were in each cohort. Median age was 53 y (range 32-71); most pts had invasive ductal histology (90%), primary tumor stage ≥T2 (90%), and nodal involvement (75%). DLTs (myelosuppression) occurred in 7 pts (3 in A, 4 in B) and were unrelated to pembro. Gr 3-4 treatment-related AEs (TRAEs) occurred in 8 pts in A and 10 pts in B; none were fatal. One pt in A and 2 pts in B discontinued for a TRAE (2 ALT elevations with pembro; 1 DVT with chemo). Overall ORR (CR+PR) before surgery was 80% (90% CI, 49-96) in A and 100% (90% CI, 74-100) in B. ypT0/Tis pCR rate was 70% (90% CI, 39-91) in A and 100% (90% CI, 74-100) in B; ypT0 ypN0 pCR rate was 50% (90% CI, 22-78) in A and 90% (90% CI, 61-100) in B; and yT0/Tis ypN0 pCR rate was 60% (90% CI, 30-85) in A and 90% (90% CI, 61-100) in B. Conclusions: Preliminary data suggest that pembro + chemo as neoadjuvant therapy for TNBC results in manageable toxicity and promising antitumor activity. Clinical trial information: NCT02622074.