Background: NSCLC is often diagnosed at an advanced stage, conferring a poor prognosis. The current standard of care for first-line treatment comprises platinum-based regimens. Veliparib is a potent, orally bioavailable PARP1/2 inhibitor that can delay DNA repair following damage induced by chemotherapeutic agents. In preclinical tumor models, veliparib has been shown to enhance antitumor activity of carboplatin, and phase 1 data show that it can be safely combined with carboplatin and paclitaxel. A phase 2 study indicated favorable efficacy for veliparib plus carboplatin and paclitaxel vs placebo plus carboplatin and paclitaxel in the subgroup of patients with Sq NSCLC (Ramalingam et al. Ann Oncol 2014;25(Suppl 4):1234P). Based on these results, this phase 3 pivotal trial has been initiated. Methods: This is a randomized, double blind, multicenter, phase 3 trial (NCT02106546). Patients ( ≥ 18 years) who have received no prior chemotherapy or chemoradiotherapy for advanced/metastatic Sq NSCLC are randomized 1:1 to oral veliparib (120 mg) or placebo, twice daily on Days −2 through 5 (7 consecutive days) of 21-day cycles. Randomization is stratified by tumor extent, smoking history, ECOG performance status, and geographic region. All patients receive carboplatin (AUC 6 mg/mL/min i.v.) and paclitaxel (200 mg/m² i.v.) on Day 1 of each 21-day cycle. Treatment continues for a maximum of 6 cycles, or until radiographic progression or unacceptable toxicity. The primary study objective is to determine if the addition of veliparib to carboplatin and paclitaxel improves overall survival, compared with placebo plus carboplatin and paclitaxel. Secondary objectives are to assess progression-free survival and objective response rate. Duration of overall response, safety, tolerability, ECOG performance status, and quality of life are also evaluated. Sites from 37 countries are planned for trial participation. Recruitment began in Apr 2014 and900 patients are planned for enrollment.Clinical trial information: NCT02106546