Perioperative Tislelizumab Wins EU Approval for Resectable NSCLC at High Risk of Recurrence

The European Commission (EC) has approved tislelizumab (Tevimbra) in combination with platinum-containing chemotherapy as neoadjuvant therapy, followed by tislelizumab monotherapy as adjuvant therapy, for adult patients with resectable non–small cell lung cancer (NSCLC) at high risk of recurrence.1

The regulatory decision was backed by data from the phase 3 RATIONALE-315 trial (NCT04379635), which showed that the tislelizumab regimen generated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with chemotherapy plus placebo. Full data from the study will be presented in September at the 2025 IASLC World Conference on Lung Cancer.

“Patients with resectable NSCLC still face alarmingly high recurrence rates,” Mariano Provencio, MD, PhD, head of the Medical Oncology Department at Hospital Universitario Puerta de Hierro and professor at Universidad Autónoma de Madrid, stated in a news release. “The RATIONALE-315 results confirm that starting tislelizumab in the neoadjuvant phase, and continuing after surgery, has proven to be a powerful approach to improve outcomes for these patients. Now, with approval in the EU, we have a clinically validated new treatment option in the perioperative setting.”

Previously reported data from an interim analysis of RATIONALE-315 showed that patients treated in the tislelizumab arm experienced a statistically significant improvement in event-free survival (EFS) compared with those treated in the placebo arm (HR, 0.56; 95% CI, 0.40-0.79; 1-sided P = .0003).1,2

Additionally, tislelizumab plus chemotherapy generated a statistically significant and clinically meaningful improvement in major pathological response (MPR) rate at 56.2% vs 15.0% with chemotherapy plus placebo (difference, 41.1%; 95% CI, 33.2%-49.1%; P < .0001). The pathological complete response (pCR) rates were 40.7% and 5.7%, respectively (difference, 35.0%; 95% CI, 27.9%-42.1%; P < .0001).

Regarding safety, grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 72.1% of patients in the tislelizumab arm vs 66.4% of patients in the placebo arm. The rates of serious TRAEs were 15.5% and 8.0%, respectively. The most common grade 3/4 TRAEs reported in at least 10% of patients in the experimental arm included decreased neutrophil count and decreased white blood cell count.

RATIONALE-315 Background

The randomized, double-blind, placebo-controlled study enrolled patients at least 18 years of age with histologically confirmed stage II or IIIA NSCLC who had confirmed eligibility for R0 resection.3 Other key inclusion criteria comprised measurable disease per RECIST 1.1 criteria and an ECOG performance status of 0 or 1.

Investigators excluded patients who received any prior therapy for their current lung cancer, including chemotherapy, or radiotherapy, or harbored known EGFR mutations or ALK translocations.

Patients were randomly assigned 1:1 to receive tislelizumab plus cisplatin or carboplatin and paclitaxel or pemetrexed as neoadjuvant therapy, followed by tislelizumab as adjuvant therapy; or placebo plus the same chemotherapy regimen in the neoadjuvant setting, followed by placebo monotherapy in the adjuvant setting.

MPR rate and EFS served as the trial’s dual primary end points. Secondary end points included OS, pCR rate, objective response rate, disease-free survival, safety, and quality of life.

“Delivering a statistically significant OS benefit—a critical end point in oncology studies—alongside the EC’s approval of [tislelizumab] in perioperative resectable NSCLC marks a pivotal moment for patients and physicians,” Mark Lanasa, MD, PhD, chief medical officer of Solid Tumors at BeOne Medicines, said in a news release.1 “As only the second PD-1 inhibitor to demonstrate an OS benefit in this setting, [tislelizumab] is poised to reshape lung cancer treatment in Europe.”

References

1. 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 August 27, 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
2. BeOne Medicines receives positive CHMP opinion for Tevimbra in neoadjuvant/adjuvant NSCLC treatment. News release. BeOne Medicines. July 28, 2025. Accessed August 27, 2025. https://ir.beonemedicines.com/news/beone-medicines-receives-positive-chmp-opinion-for-tevimbrar-in-neoadjuvantadjuvant-nsclc-treatment/a97f721c-af0c-439c-a2b5-a0e7d29eefa2
3. Comparing the efficacy and safety of a new additional treatment with tislelizumab in non-small cell lung cancer (NSCLC). ClinicalTrials.gov. Updated April 15, 2025. Accessed August 27, 2025. https://clinicaltrials.gov/study/NCT04379635