Abstract CT288: Phase 3, randomized, placebo-controlled study of stereotactic body radiotherapy (SBRT) with or without pembrolizumab in patients with inoperable stage I/IIA non-small-cell lung cancer (NSCLC): KEYNOTE-867
Authors: Jabbour Salma K. , Houghton Baerin , Robinson Andrew G. , Quantin Xavier , Wehler Thomas , Kowalski Dariusz , Ahn Myung-Ju , Erman Mustafa , Giaccone Giuseppe , Borghaei Hossein , McLean Jessica , Zhang Jin , Souza Fabricio , Decker Roy 
Published: September 2020

Abstract
Background: Anti-PD-(L)1-directed therapy following radiotherapy or following concurrent chemoradiation is associated with significantly longer PFS and OS in patients with advanced or metastatic NSCLC, including those with locally advanced inoperable tumors. KEYNOTE-867 (NCT03924869) evaluates the efficacy and safety of SBRT with or without pembrolizumab in patients with inoperable stage I/IIA NSCLC. Trial Design: In this phase 3, randomized, placebo-controlled study, approximately 530 adult patients with previously untreated, medically inoperable, histologically/cytologically confirmed stage I/IIA NSCLC are randomized 1:1 to receive thoracic SBRT to primary tumors for ≤2 wk (Table) and either pembrolizumab 200 mg or placebo every 3 wk for 17 cycles (approximately 1 year) or until disease recurrence, development of unacceptable AEs, SBRT not started for any reason, or study withdrawal. Randomization is stratified by disease stage (I/IIA), ECOG PS (0-1/2), and geographic region (East Asia/other). Imaging assessment by blinded independent central review (BICR) occurs at 12 wk (≥10 wk after SBRT completion), followed by every 16 wk for 3 y, and then every 6 mo. Primary endpoints are event-free survival (EFS) by BICR and OS. Secondary endpoints include time to death or distant metastases and safety; exploratory endpoints are time to subsequent treatment, disease-specific survival, and time to recurrence/progression on subsequent line of therapy. AEs are monitored throughout the trial until 30 d after last dose (90 for serious AEs) and graded according to NCI CTCAE version 4.0. EFS and OS are analyzed by the nonparametric Kaplan-Meier method, treatment differences by stratified log-rank test, and hazard ratios by stratified Cox proportional hazard model with Efron's method of tie handling. Enrollment started on June 17, 2019, at 131 sites.
Table.Stereotactic Body Radiotherapy RegimenUnit Dose Strength(s)Peripheral tumors3×15 Gy or 3×18 Gy fractions (preferred regimens); 4×12 Gy or 5×10 Gy fractions (acceptable regimens)Tumors abutting the chest wall4×12 Gy fractions or 5×10 Gy fractionsCentral tumors5×10 Gy fractions
Citation Format: Salma K. Jabbour, Baerin Houghton, Andrew G. Robinson, Xavier Quantin, Thomas Wehler, Dariusz Kowalski, Myung-Ju Ahn, Mustafa Erman, Giuseppe Giaccone, Hossein Borghaei, Jessica McLean, Jin Zhang, Fabricio Souza, Roy Decker. Phase 3, randomized, placebo-controlled study of stereotactic body radiotherapy (SBRT) with or without pembrolizumab in patients with inoperable stage I/IIA non-small-cell lung cancer (NSCLC): KEYNOTE-867 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT288.