Background: TNBC, which is characterized by a lack of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) overexpression, is associated with a poor prognosis. In combination with gem or carbo/bevacizumab, nab-P has demonstrated high response rates as first-line treatment for mTNBC. tnAcity (triple-negative Albumin-bound paclitaxel combination international treatment study) is a phase 2/3 trial evaluating the efficacy and safety profiles of 2 nab-P combination regimens (with gem or carbo) as first-line treatment for mTNBC, using gem/carbo as a control. Methods: The phase 2 portion of the study will evaluate 240 patients (pts), randomized 1:1:1 (stratified by disease-free interval [DFI]: ≤ 1 y vs > 1 y) to nab-P 125 mg/m² plus gem 1000 mg/m², nab-P 125 mg/m² plus carbo area under the curve (AUC) 2, or the control regimen of gem 1000 mg/m² plus carbo AUC 2, all given days 1 and 8 of a 21-day cycle. Eligibility criteria include measurable mTNBC (defined as ER and PgR in < 1% of tumor cell nuclei and HER2 IHC 0 or 1+ or 2+ and FISH-negative); no prior chemotherapy for metastatic disease; prior adjuvant/neoadjuvant anthracycline use required if indicated; adjuvant/neoadjuvant treatment with a taxane, platinum, or gem is permitted if completed ≥ 12 months prior to randomization; ECOG performance status ≤ 1; peripheral neuropathy grade < 2; and absence of brain metastases. The primary objective of the phase 2 portion is to identify the nab-P combination arm to be evaluated in the phase 3 study by a ranking algorithm of 5 efficacy and safety parameters. In the phase 3 portion, 550 pts will be randomized 1:1 (stratified by DFI [≤ 1 y vs > 1 y] and prior taxane use) to the nab-P combination arm selected from the phase 2 portion or to the control arm. The primary endpoint of the phase 3 portion is PFS by independent radiological assessment; secondary endpoints include ORR, OS, disease control rate, duration of response, and safety. Biomarker and circulating tumor cell analyses will also be performed. As of the submission deadline, 21 patients have been randomized. Clinical trial information: NCT01881230.