European Commission Approves Tislelizumab for Neoadjuvant/Adjuvant NSCLC

The European Commission has granted marketing authorization for tislelizumab (Tevimbra) in combination with platinum-containing chemotherapy for the neoadjuvant treatment of resectable non–small cell lung cancer (NSCLC) in adults at high risk of recurrence.¹ The approval also includes subsequent tislelizumab monotherapy for adjuvant treatment.

This represents a significant advancement in the curative-intent setting for NSCLC, providing a new therapeutic option for a patient population with a high unmet need for improved outcomes. The decision is based on the robust data from the phase 3 RATIONALE-315 clinical trial (NCT04379635), which demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit.

Efficacy and Trial Data

The RATIONALE-315 trial was a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of tislelizumab in this specific setting.

Data published in The Lancet Respiratory Medicine earlier this year showed that, with a median trial follow-up of 38.5 months, the tislelizumab-based regimen showed a statistically significant and clinically meaningful benefit in OS vs the chemotherapy/placebo arm (HR, 0.65; 95% CI, 0.45–0.93; 1-sided P =.0093).² The significant event-free survival (EFS) benefit previously reported with tislelizumab vs chemotherapy/placebo was sustained in this analysis (HR, 0.58; 95% CI, 0.43–0.79), and this improvement was consistent across both independent review committee and investigator assessments. OS and EFS benefits were observed across major subgroups, regardless of PD-L1 expression, disease stage, and histology.

“Delivering a statistically significant overall survival benefit—a critical [end point] in oncology studies—alongside the European Commission’s approval of [tislelizumab] in perioperative resectable NSCLC marks a pivotal moment for patients and physicians,” said Mark Lanasa, MD, PhD, chief medical officer, Solid Tumors at BeOne, in a press 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.”

More data from this trial will be presented as a late-breaking abstract at the IASLC 2025 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain, September 6 to 9, 2025.

Safety Profile and Tolerability

The safety profile of tislelizumab observed in the RATIONALE-315 trial was consistent with previously reported findings for the drug. No new safety signals were identified. The most frequent grade 3 or 4 treatment-related adverse events were hematological, specifically decreased neutrophil and white blood cell counts, which are common with platinum-based chemotherapy. Other adverse events were manageable with standard supportive care. This consistent safety profile is critical for a regimen intended for a curative setting, where maintaining patient quality of life and tolerability to complete the full course of treatment is paramount. Clinicians should be vigilant in monitoring for and managing potential immune-related adverse events, a known class effect of PD-1 inhibitors.

Clinical Implications

This approval provides oncologists in Europe with a new, evidence-based strategy to improve long-term outcomes for patients with resectable NSCLC. The demonstration of an OS benefit is particularly noteworthy, as it moves beyond traditional end points like EFS to show a definitive impact on patient survival. The regimen offers a comprehensive approach, combining neoadjuvant therapy to downstage the tumor and eradicate micrometastases before surgery, followed by adjuvant therapy to consolidate the response and further reduce the risk of recurrence. This dual-phase approach capitalizes on the benefits of both local and systemic control. The ability of the regimen to improve outcomes regardless of PD-L1 status is also a significant advantage, simplifying treatment decisions and potentially expanding the eligible patient population beyond those with high PD-L1 expression.

FAQs

What is tislelizumab (Tevimbra), and what has it been approved for in Europe?

Tislelizumab (Tevimbra) is a PD-1 inhibitor that has been granted marketing authorization by the European Commission. It is approved for use in combination with platinum-containing chemotherapy for the neoadjuvant treatment of resectable non–small cell lung cancer (NSCLC) in adult patients who are at high risk of recurrence. The approval also extends to subsequent tislelizumab monotherapy for adjuvant treatment.

What is the significance of this approval for patients with NSCLC?

This approval represents a significant advancement in the curative-intent setting for NSCLC. It provides a new therapeutic option for a patient population with a high unmet need for improved outcomes. As only the second PD-1 inhibitor to demonstrate an overall survival (OS) benefit in this setting, tislelizumab is poised to reshape lung cancer treatment in Europe by offering a comprehensive, dual-phase approach to improve long-term outcomes.

What clinical trial data supports the approval of tislelizumab?

The approval is based on robust data from the phase 3 RATIONALE-315 clinical trial. This randomized, double-blind, placebo-controlled study demonstrated a statistically significant and clinically meaningful OS benefit for the tislelizumab-based regimen compared with the chemotherapy/placebo arm (HR, 0.65; 95% CI, 0.45–0.93; 1-sided P =.0093). The trial also sustained the previously reported significant event-free survival (EFS) benefit (HR, 0.58; 95% CI, 0.43–0.79). These benefits were consistent across major subgroups, irrespective of PD-L1 expression, disease stage, and histology.

What is the safety profile of tislelizumab?

The safety profile of tislelizumab observed in the RATIONALE-315 trial was consistent with previously reported findings for the drug, with no new safety signals identified. The most frequent grade 3 or 4 treatment-related adverse events were hematological, specifically decreased neutrophil and white blood cell counts, which are common with platinum-based chemotherapy. Other adverse events were manageable with standard supportive care. Clinicians should be vigilant in monitoring for and managing potential immune-related adverse events, a known class effect of PD-1 inhibitors.

How does tislelizumab work in the context of NSCLC treatment?

Tislelizumab is used in a perioperative setting, meaning both before and after surgery. It combines neoadjuvant therapy (before surgery) with platinum-containing chemotherapy to help downstage the tumor and eradicate micrometastases. This is followed by adjuvant tislelizumab monotherapy (after surgery) to consolidate the response and further reduce the risk of recurrence. This dual-phase approach leverages both local and systemic control to improve patient outcomes.

REFERENCES:

1. European Commission Approves TEVIMBRA® as Neoadjuvant/Adjuvant NSCLC Treatment Ahead of Late-Breaking Data Presentation at WCLC 2025. News release. August 27, 2025. Accessed August 27, 2025. https://tinyurl.com/yvc64ybe

2. Yue D, Wang W, Liu H, et al. Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomized clinical trial. Lancet Respir Med. 2025;13(2):119-129.