EU Approves Tislelizumab for High-Risk NSCLC Patients

The European Commission has granted approval for tislelizumab (Tevimbra) to be used in combination with platinum-containing chemotherapy as neoadjuvant therapy for adult patients with resectable non-small cell lung cancer (NSCLC) at high risk of recurrence. This decision also allows for subsequent tislelizumab monotherapy as adjuvant therapy.

This regulatory milestone is supported by data from the phase 3 RATIONALE-315 trial (NCT04379635), which demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) when compared to chemotherapy plus placebo. The full results from this study are set to be unveiled in September 2025 at the IASLC World Conference on Lung Cancer.

Dr. Mariano Provencio, head of the Medical Oncology Department at Hospital Universitario Puerta de Hierro and professor at Universidad Autónoma de Madrid, emphasized the importance of this approval. “Patients with resectable NSCLC still face alarmingly high recurrence rates,” he stated. “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.”

Data from an interim analysis of RATIONALE-315 indicated that patients who received tislelizumab experienced a significant enhancement in event-free survival (EFS) compared to those who received a placebo (HR, 0.56; 95% CI, 0.40-0.79; 1-sided P = .0003). Furthermore, the combination of tislelizumab and chemotherapy resulted in a major pathological response (MPR) rate of 56.2%, compared to 15.0% for chemotherapy plus placebo, marking a difference of 41.1% (95% CI, 33.2%-49.1%; P < .0001). The rates of pathological complete response (pCR) were also significantly higher at 40.7% for tislelizumab versus 5.7% for the placebo group (difference, 35.0%; 95% CI, 27.9%-42.1%; P < .0001). Regarding safety, the trial noted that 72.1% of patients in the tislelizumab arm experienced grade 3 or higher treatment-related adverse effects (TRAEs) compared to 66.4% in the placebo arm. Serious TRAEs occurred in 15.5% of patients receiving tislelizumab versus 8.0% in the placebo group. The most frequently reported grade 3/4 TRAEs in the tislelizumab group included decreased neutrophil count and decreased white blood cell count, affecting at least 10% of patients. The randomized, double-blind, placebo-controlled study involved participants aged 18 years and older with histologically confirmed stage II or IIIA NSCLC. Key inclusion criteria included confirmed eligibility for R0 resection, measurable disease per RECIST 1.1 criteria, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Those who had received prior treatment for their lung cancer or who harbored known EGFR mutations or ALK translocations were excluded from the trial. Patients were randomly assigned to receive either tislelizumab alongside cisplatin or carboplatin and paclitaxel or pemetrexed as neoadjuvant therapy, followed by tislelizumab as adjuvant therapy, or to a control group receiving a placebo with the same chemotherapy regimen. The trial's dual primary endpoints were MPR rate and EFS, while secondary endpoints included OS, pCR rate, objective response rate, disease-free survival, safety, and quality of life. Dr. Mark Lanasa, chief medical officer of Solid Tumors at BeOne Medicines, remarked on the significance of these findings. “Delivering a statistically significant OS benefit—a critical endpoint in oncology studies—alongside the EC’s approval of tislelizumab in perioperative resectable NSCLC marks a pivotal moment for patients and physicians,” he stated. “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.”