Tislelizumab/Chemotherapy Earns EU Approval in Nasopharyngeal Carcinoma

"The approval of [tislelizumab] combined with chemotherapy in Europe marks an important advancement for people with recurrent or metastatic [NPC]—a rare and challenging disease,” according to Lisa Licitra, MD.

The European Commission has approved tislelizumab-jsgr (Tevimbra) plus cisplatin and gemcitabine as frontline treatment for adults with recurrent or metastatic nasopharyngeal carcinoma (NPC) not amenable to curative surgery or radiation, according to a press release from the developer, BeOne Medicines.1

Supporting data for the approval in the EU came from the phase 3 RATIONALE-309 trial (NCT03924986), in which investigators evaluated tislelizumab/chemotherapy vs placebo/chemotherapy among 263 patients with treatment-naïve NPC. Data from the first prespecified interim analysis showed that the median progression-free survival (PFS) was 9.2 months in the tislelizumab arm compared with 7.4 months in the placebo arm. Treatment with the tislelizumab combination reduced the risk of progressive disease or death by 48%, reaching the trial’s primary end point across the intent-to-treat (ITT) population (HR, 0.52; 95% CI, 0.38-0.73; P <.0001).

After an additional 12 months of follow-up, data highlighted efficacy outcomes with the tislelizumab combination that were comparable with those observed in the interim analysis. Here, the median overall survival (OS) was 45.3 months vs 31.8 months in the tislelizumab and placebo arms, respectively.

Investigators identified no new safety signals in the RATIONALE-309 trial, as tislelizumab plus chemotherapy appeared to be well tolerated. In a pooled safety analysis including over 3900 patients who received tislelizumab alone (n = 1952) or with chemotherapy (n = 1950) at the approved dosing regimen, the most common grade 3/4 adverse effects (AEs) associated with the combination included neutropenia, anemia, and thrombocytopenia.

“The approval of [tislelizumab] combined with chemotherapy in Europe marks an important advancement for people with recurrent or metastatic [NPC]—a rare and challenging disease,” Lisa Licitra, MD, chief of the Head and Neck Cancer Medical Oncology Department at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, stated in the press release.1 “Thanks to the compelling results from the RATIONALE-309 study, we now have a powerful new treatment that not only delays disease progression but also helps patients live longer. This approval brings new hope and a clinically proven option to patients who urgently need better care.”

Developers designed tislelizumab as a humanized immunoglobulin G4 anti–PD-1 monoclonal antibody with high affinity and binding specificity against PD-1. The agent works to minimize binding to Fc-gamma on macrophages, thereby aiding the body’s immune system to detect and target tumors.

In the multicenter, double-blind, randomized phase 3 RATIONALE-309 trial, patients were randomly assigned to receive tislelizumab at 200 mg intravenously every 3 weeks or matched placebo in combination with gemcitabine and cisplatin.2 Investigators administered gemcitabine at 1 g/m2 intravenously on days 1 and 8 of each cycle plus cisplatin at 80 mg/m2 intravenously on day 1 of each cycle for 4 to 6 cycles.

The trial’s primary end point was PFS per independent review committee (IRC) assessment. Secondary end points included overall response rate per IRC evaluation, duration of response, OS, investigator-assessed PFS, PFS after next line of therapy, quality of life, and incidence of AEs.

Patients 18 to 75 years old with histologically or cytologically confirmed, recurrent, or metastatic NPC were eligible for enrollment on the trial. Other eligibility criteria included having an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST v1.1 guidelines, and no prior therapy for recurrent or metastatic disease.

Those with locally recurrent disease suitable for curative radiotherapy or surgery, receipt of any approved systemic anticancer therapy within 28 days of beginning study treatment, or active autoimmune disease or history of autoimmune diseases that may have relapsed were ineligible to enroll on the trial.

References

1. European Commission approves TEVIMBRA® in combination with chemotherapy as a first-line treatment for nasopharyngeal carcinoma. News release. BeOne Medicines Ltd. July 10, 2025. Accessed July 11, 2025. https://tinyurl.com/2ebufkrj
2. Tislelizumab combined with chemotherapy versus chemotherapy alone in recurrent or metastatic nasopharyngeal cancer (NPC) (RATIONALE-309). ClinicalTrials.gov. Updated January 31, 2025. Accessed July 11, 2025. https://tinyurl.com/y89p4nsp