71TiPA randomized, phase 3 trial with anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) versus placebo for patients with early stage NSCLC after resection and completion of standard adjuvant therapy (EORTC/ETOP 1416-PEARLS)

Background: In the last 5 years no major advances have been made in the treatment of early stage NSCLC. Checkpoint inhibitors have shown promising clinical efficacy in advanced, refractory non-small cell lung cancer (NSCLC), but they have not yet been explored in the adjuvant setting. PEARLS (NCT02504372) is international, triple-blinded, placebo-controlled, randomized phase III trial to compare pembrolizumab versus placebo after complete resection of stage IB (T ≥ 4 cm), II and IIIA NSCLC, followed by standard adjuvant chemotherapy, if appropriate as per local guidelines, in patients who have signed the informed consent. Trial design: Eligible patients are those with completely resected stage IB (T ≥ 4 cm), II and IIIA NSCLC that have or have not received adjuvant platinum-based chemotherapy and whose PD-L1 status is known: negative (TPS=0%) versus weak positive (TPS = 1-49%) versus strong positive (TPS≥50%). Co-primary endpoints are disease-free survival in the PD-L1 strong positive subgroup and in the overall population. An HR = 0.78 is targeted for the whole population with 640 disease free survival events from a sample size of 1380 randomized patients. Secondary endpoints include disease-free survival in the PD-L1 positive subgroup, overall survival in each subpopulation and in the overall population, lung cancer specific survival, and safety and tolerability. The exploratory endpoints will assess pharmacokinetics, immunogenicity, quality of life and potential biomarkers of treatment response. Recruitment started in January 2016 and is currently ongoing. As of November 17, 2016, among the 102 randomized patients so far, 44 (43.1%), 32 (31.4%) and 26 (25.5%) patients have negative, weak positive and strong positive PD-L1 status respectively. Clinical trial identification: (EudraCT number 2015-000575-27) (NCT02504372) Legal entity responsible for the study: MSD EORTC, ETOP Funding: MSD Disclosure: All authors have declared no conflicts of interest.