RATIONALE 001: Tislelizumab (BGB-A317) + concurrent chemoradiotherapy (cCRT) followed by tislelizumab monotherapy in patients (pts) with newly diagnosed locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC)
Authors: L. Paz-Ares, S. Senan, D. Planchard, L. Wang, A. Cheong, R. Slepetis, M.H. Nguyen, E.E. Vokes
Journal: Annals of Oncology (2019)

Background: In pts with locally advanced, unresectable, stage III NSCLC, cCRT is associated with better survival than radiotherapy (RT) alone, but 5-y survival remains poor. Immunotherapies targeting PD-1/PD-L1 may be synergistic with cCRT, improving outcomes. Tislelizumab, an anti–PD-1 antibody, showed clinical activity/tolerability in solid tumors, including NSCLC. RATIONALE 001 is a phase III, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of first-line tislelizumab + cCRT in pts with locally advanced, unresectable, stage III NSCLC. Trial design: RATIONALE 001 aims to answer important scientific questions by employing a 3-arm study design (840 pts randomized 1:1:1) to evaluate whether the timing of giving tislelizumab earlier upfront with cCRT in addition to consolidation will improve outcomes rather than giving the anti–PD-1 as consolidation only (Table). Both tislelizumab approaches (Arms 1 and 2) will each be compared to a global standard of care, cCRT alone. Chemotherapy will be investigator's choice (cisplatin + etoposide or carboplatin + paclitaxel). RT will be given in 2 Gy fractions (target dose of 60 Gy). Key eligibility: Locally advanced, unresectable, stage III NSCLC; stage III confirmed by FDG-PET and brain imaging; Eastern Cooperative Oncology Group performance status ≤ 1; and no prior anti–PD-1/PD-L1 therapy. PD-L1 expression assessment is not required prior to randomization. Primary endpoint: Progression-free survival. Secondary endpoints include overall survival (OS), OS at 24 mo, objective response rate, and safety. Blood and tumor biomarkers, including PD-L1 expression and tumor mutational burden, will be evaluated for correlations with clinical benefit.Table185TiPcCRT PhaseMonotherapy PhaseArm 1Tislelizumab + cCRTTislelizumabArm 2Placebo + cCRTTislelizumabArm 3Placebo + cCRTPlacebo Open table in a new tab Clinical trial identification: NCT03745222; EudraCT: 2018-001132-22. Legal entity responsible for the study: Celgene Corporation. Funding: Celgene Corporation. Disclosure: L. Paz-Ares: Honoraria: Lilly, MSD, BMS, Roche, Pharmamar, Merck, AstraZeneca, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex, Celgene, Amgen, Incyte, Pfizer; Board member: Genomica; Institutional financial interest: AstraZeneca, BMS, MSD. S. Senan: Grants/Research support: Varian Medical Systems; Advisory/Board member: Celgene, AstraZeneca; Honoraria: Varian Medical Systems, AstraZeneca. D. Planchard: Consulting, honoraria, travel and/or institutional: AZ, BMS, BI, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Onc, Peer CME, Roche; Institutional: Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. A. Cheong: Employment, stock holder: Celgene Europe Ltd. R. Slepetis: Employment, stock holder: Celgene. M.H. Nguyen: Employment, stock holder: Celgene Corporation. E.E. Vokes: Employment: University of Chicago; Grants/Research support: AbbVie; Consultant, honoraria: AbbVie, Amgen, AstraZeneca, Biolumina, BMS, Celgene, Eli Lilly, EMD Serono, Genentech, Merck, Novartis, Regeneron. All other authors have declared no conflicts of interest.