Perioperative Tislelizumab Receives Positive CHMP Opinion for High-Risk Resectable NSCLC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of tislelizumab (Tevimbra) in combination with platinum-containing chemotherapy as neoadjuvant treatment and then continued as monotherapy as adjuvant treatment, for the treatment of adult patients with resectable non–small cell lung cancer (NSCLC) at high risk of recurrence.1

The positive CHMP opinion was based on data from the phase 3 RATIONALE-315 trial (NCT04379635), which showed that patients treated with tislelizumab plus chemotherapy prior to surgery experienced a major pathologic response (MPR) rate of 56.2% compared with 15.0% of patients treated 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).

Additionally, a statistically significant improvement was observed for event-free survival (EFS; HR, 0.56; 95% CI, 0.40-0.79; 1-sided P = .0003), and data trended in favor of the tislelizumab regimen for overall survival (OS; HR, 0.62; 95% CI, 0.39-0.98; 1-sided P = .0193).

Updated EFS and OS data from the pre-planned final analysis presented at an upcoming medical conference.

“Patients with resectable, early-stage NSCLC face an urgent challenge—despite surgery and current therapies, recurrence rates remain alarmingly high,” Mariano Provencio, MD, PhD, head of the Medical Oncology Department at Hospital Universitario Puerta de Hierro and professor at the Faculty of Medicine of Universidad Autonoma de Madrid in Spain, stated in a news release. “The significant clinical benefit observed in the RATIONALE-315 study has important implications for patients. If approved, perioperative tislelizumab will offer oncologists a powerful new option to improve outcomes and potentially alter the course of this difficult-to-treat disease.”

RATIONALE-315 Background

The randomized, placebo-controlled, double-blind study enrolled patients at least 18 years of age with histologically confirmed stage II or IIIA NSCLC and confirmed eligibility for R0 resection with curative intent.2 Patients were also required to have an ECOG performance status of 0 or 1 and measurable disease per RECIST 1.1 criteria.

Investigators excluded patients who received any prior therapy for their malignancy, including chemotherapy or radiotherapy; harbored known EGFR mutation or ALK gene translocations; had any condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to randomization; had active autoimmune diseases or history of autoimmune diseases that may relapse; or had a history of interstitial lung disease or non-infectious pneumonitis.

Patients were randomly assigned 1:1 to receive tislelizumab plus platinum-based doublet chemotherapy as neoadjuvant treatment, followed by tislelizumab as adjuvant therapy; or placebo plus platinum-based doublet chemotherapy as neoadjuvant treatment, followed by placebo as adjuvant therapy.1

EFS per blinded independent central review and MPR rate were the trial’s dual primary end points, which were met at the interim analyses in the study.1,2 Secondary end points included OS, pCR rate, objective response rate, disease-free survival, investigator-assessed EFS, safety, and quality of life.2

Safety Data

Findings from RATIONALE-315 showed that no new safety signals were reported.1 Grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 72.1% of patients in the tislelizumab arm compared with 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 comprised decreased neutrophil count and decreased white blood cell count. Additionally, the use of tislelizumab did not impact the feasibility or completeness of surgery.

“[Tislelizumab] is already approved in the European Union across multiple settings in NSCLC, the most common form of lung cancer, and this positive CHMP opinion expands its potential to help patients earlier in their treatment journey,” Mark Lanasa, MD, PhD, chief medical officer, Solid Tumors, at BeOne Medicines, stated in a news release. “As the foundational asset of our solid tumor portfolio, [tislelizumab] continues to demonstrate its strength and versatility across the continuum of care, bringing us closer to our goal of delivering more comprehensive and effective cancer treatment to more patients.”

References

1. BeOne Medicines receives positive CHMP opinion for Tevimbra in neoadjuvant/adjuvant NSCLC treatment. News release. BeOne Medicines. July 28, 2025. Accessed July 28, 2025. https://ir.beonemedicines.com/news/beone-medicines-receives-positive-chmp-opinion-for-tevimbrar-in-neoadjuvantadjuvant-nsclc-treatment/a97f721c-af0c-439c-a2b5-a0e7d29eefa2
2. 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 July 28, 2025. https://clinicaltrials.gov/study/NCT04379635