Tislelizumab (BGB-A317) + concurrent chemoradiotherapy (cCRT) followed by tislelizumab monotherapy for newly diagnosed locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) in a phase III study (RATIONALE 001).

Abstract

TPS8574 Background: cCRT improves survival vs RT alone and is a global standard of care in patients (pts) with stage III NSCLC, but survival remains poor for these pts. Combining PD-1/PD-L1-targeting immunotherapies and cCRT may lead to synergistic activity and improved outcomes. Tislelizumab (anti–PD-1) demonstrated clinical activity and tolerability in solid tumors, including NSCLC. This phase III, randomized, double-blind, placebo-controlled study (RATIONALE 001) will evaluate efficacy and safety of tislelizumab + cCRT. Methods: Pts (N ≈ 840) will be randomized 1:1:1 in a 3-arm study design to evaluate whether the timing of giving tislelizumab earlier upfront with cCRT in addition to as consolidation (Arm 1) or giving tislelizumab as consolidation only (Arm 2) will improve outcomes vs cCRT alone (Arm 3; Table). RT will be given in 2 Gy fractions to a target dose of 60 Gy (30 fractions). Chemotherapy will be investigator’s choice of cisplatin + etoposide or carboplatin + paclitaxel. A safety analysis specific to the cisplatin + etoposide component of the cCRT + tislelizumab combination is planned. All sites must pass a radiation quality assurance review process. The primary endpoint is PFS. Secondary endpoints include ORR, OS, OS at 24 months, and safety. As an exploratory endpoint, blood and tumor biomarkers will be assessed for correlations with clinical benefit. With a one-sided α of 1.25%, a total of 580 PFS events are required to allow ≈ 90% power to detect a HR for progression or death of 0.7 for either pairwise comparison (Arm 1 vs Arm 3 or Arm 2 vs Arm 3). Key eligibility criteria are locally advanced, unresectable, stage III NSCLC; FDG-PET and brain imaging confirmation of stage III status; no prior treatment; and ECOG PS ≤ 1. PD-L1 expression assessment is not required prior to randomization. EudraCT number 2018-001132-22. Clinical trial information: NCT03745222. [Table: see text]