Final Analysis of Perioperative Tislelizumab Plus Chemotherapy Shows Sustained OS and EFS Improvement in Resectable NSCLC

Perioperative tislelizumab-jsgr (Tevimbra) in combination with platinum-doublet chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared with placebo plus chemotherapy in patients with resectable non–small cell lung cancer (NSCLC), according to findings from the final analysis of the phase 3 RATIONALE-315 trial (NCT04379635) presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer.¹

In all treated patients, perioperative tislelizumab plus chemotherapy demonstrated a 35% reduction in the risk of death compared with placebo plus chemotherapy (HR, 0.65; 95% CI, 0.45-0.93; P = .009). Median OS was not reached ([NR] 95% CI, not estimable [NE]-NE) in either arm, with 48-month OS rates of 72.3% for tislelizumab vs 62.2% for placebo. Improvements in event-free survival (EFS) were also observed (HR, 0.58; 95% CI, 0.43-0.79). Median EFS was NR (95% CI, 50.3 months-NE) in the tislelizumab arm compared with 30.6 months (95% CI, 16.6-45.3) in the placebo arm, with 48-month EFS rates of 61.2% and 41.1%, respectively.

“These findings [showed] a clinically meaningful and statistically significant benefit in OS and a clinically meaningful sustained improvement in EFS. Improvements in EFS and OS were consistent across all subgroups,” lead study author Dongsheng Yue, MD, associate professor at Tianjin Medical University Cancer Institute and Hospital in Tianjin, China, explained in a live presentation of the data.

How Was RATIONALE-315 Structured to Evaluate Perioperative Tislelizumab in NSCLC?

On August 27, 2025, the European Commission approved tislelizumab in combination with platinum-containing chemotherapy as neoadjuvant therapy, followed by tislelizumab monotherapy as adjuvant therapy, for adult patients with resectable NSCLC at high risk of recurrence, based on findings from RATIONALE-315.2

The trial evaluated perioperative tislelizumab in patients with resectable stage II to IIIA NSCLC.1 Eligible patients had an ECOG performance status of 0 or 1, were candidates for R0 surgical resection, and had EGFR/ALK wild-type tumors. Patients were stratified by histology (squamous vs nonsquamous), disease stage (II vs IIIA), and PD-L1 tumor cell expression level (<1% vs ≥1%).

Participants were randomly assigned to receive either 200 mg of neoadjuvant tislelizumab intravenously every 3 weeks plus platinum-doublet chemotherapy for 3 to 4 cycles, followed by surgery and 400 mg of adjuvant tislelizumab every 6 weeks for up to 8 cycles, or matched placebo plus platinum-doublet chemotherapy in the neoadjuvant setting followed by placebo after surgery in the adjuvant setting. Chemotherapy regimens consisted of cisplatin or carboplatin with paclitaxel for squamous histology, or cisplatin/carboplatin with pemetrexed for nonsquamous disease.

The trial’s primary end points included blinded independent pathologic review (BIPR)–assessed major pathologic response and EFS. Secondary end points included BIPR-assessed pathologic complete response, as well as OS, objective response rate, disease-free survival per blinded independent central review, investigator-assessed EFS, and safety.

What Was the Safety Profile of the Regimen With Updated Follow-Up?

The most common treatment-related adverse effects (TRAEs) in the tislelizumab and placebo arms, respectively, were decreased neutrophil count (any grade, 78.8% vs 78.3%; grade ≥3, 61.5% vs 59.3%) and decreased white blood cell count (any grade, 63.3% vs 67.3%; grade ≥3, 16.8% vs 14.2%).

TRAEs occurred in nearly all patients in both arms (99.1% with tislelizumab vs 99.6% with placebo). Grade 3 or higher TRAEs were reported in 73.0% of patients in the tislelizumab arm compared with 67.3% in the placebo arm. Serious TRAEs occurred in 15.5% vs 8.8% of patients, respectively. TRAEs led to treatment discontinuation in 12.8% of patients in the tislelizumab arm vs 9.3% of those in the placebo arm; TRAEs leading to dose modification occurred in 39.4% vs 32.3% of patients, respectively.

Immune-mediated adverse effects (imAEs) were reported in 40.3% of patients in the tislelizumab arm vs 18.1% in the placebo arm. Grade 3 or higher imAEs occurred in 9.3% vs 3.1% of patients, respectively. Treatment discontinuation due to imAEs was required in 5.8% of patients receiving tislelizumab, and 12.8% required dose modification. Systemic corticosteroids for imAEs were administered in 14.6% of patients in the tislelizumab arm.

“Perioperative tislelizumab plus platinum-based doublet chemotherapy was well tolerated with no new safety concerns. This final data further supports perioperative tislelizumab plus platinum-based doublet chemotherapy as an efficacious and well-tolerated treatment option for patients,” Yue concluded.

References

1. Yue D, Wang W, Liu H, et al. Perioperative tislelizumab for resectable non-small cell lung cancer: final analysis of RATIONALE-315. Presented at: International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer; September 6-10, 2025; Barcelona, Spain. MA04.08.
2. European Commission approves Tevimbra as neoadjuvant/adjuvant NSCLC treatment ahead of late-breaking data presentation at WCLC 2025. News release. BeOne Medicines. August 27, 2025. Accessed September 8, 2025. https://ir.beonemedicines.com/news/european-commission-approves-tevimbrar-as-neoadjuvantadjuvant-nsclc-treatment-ahead-of-late-breaking-data-presentation-at-wclc/0d7553af-93d0-4616-a02b-ac223e497bca