CHMP Recommends EU Approval of Frontline Tislelizumab/Chemo for Metastatic Nasopharyngeal Carcinoma

Metastatic Nasopharyngeal Carcinoma

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The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of tislelizumab (Tevimbra) in combination with gemcitabine and cisplatin for the first-line treatment of adult patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) that is not amenable to curative surgery or radiotherapy.1

The recommendation is supported by findings from the phase 3 RATIONALE-309 trial (NCT03924986), a randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of tislelizumab plus gemcitabine and cisplatin in this patient population.

At the time of the prespecified interim analysis, tislelizumab plus chemotherapy significantly improved progression-free survival (PFS) compared with chemotherapy alone. In the intent-to-treat (ITT) population, the hazard ratio for PFS was 0.52 (95% CI, 0.38-0.73; P < .0001), translating to a 48% reduction in the risk of disease progression or death. The median PFS was 9.2 months in the tislelizumab arm vs 7.4 months in the placebo arm.

An updated analysis showed continued benefit in overall survival (OS), with a median OS of 45.3 months for patients treated with tislelizumab plus chemotherapy compared with 31.8 months for those receiving placebo plus chemotherapy.

“Chemotherapy has been the standard treatment for metastatic NPC; however, distant metastasis continues to be a significant cause of treatment failure and death, making new treatment options essential,” professor Lisa Licitra, chief of the Head and Neck Cancer Medical Oncology Department at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, stated in a news release. “Results from the RATIONALE-309 study support the robust clinical benefit of [tislelizumab] plus chemotherapy, which has the potential to significantly reduce the risk of disease progression or death for patients with recurrent or metastatic NPC.”

RATIONALE-309 Trial Design

RATIONALE-309 enrolled adult patients aged 18 to 75 years with histologically or cytologically confirmed recurrent or metastatic NPC who were treatment naive in the advanced disease setting.2 Patients were enrolled across multiple international centers.

Eligible patients were required to have at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and the ability to provide fresh or archival tumor tissue for biomarker assessment. Archival tissue had to be collected within 2 years prior to screening; otherwise, a baseline biopsy was mandated. Key exclusion criteria included receipt of prior systemic anticancer therapy within 28 days of study treatment, prior treatment with PD-1/PD-L1 inhibitors, active leptomeningeal disease, uncontrolled and untreated brain metastases, autoimmune disease with relapse risk, and locally recurrent disease amenable to curative surgery or radiotherapy.

Patients were randomly assigned to receive tislelizumab or placebo in combination with gemcitabine and cisplatin. Tislelizumab was administered at the approved dosing schedule, and treatment continued according to protocol-defined criteria.

The primary end point of the trial was PFS in the ITT population. Key secondary end points included overall response rate, duration of response, OS, PFS after next line of treatment, quality-of-life outcomes, and safety.

Safety Findings

In the tislelizumab/chemotherapy arm, grade 3 /4 neutropenia occurred in more than 2% of patients, as did anemia, thrombocytopenia, hyponatremia, and hypokalemia.1 Grade 3/4 fatigue, pneumonia, lymphopenia, rash, and decreased appetite were also reported at a frequency of more than 2%. Elevations in liver enzyme levels, including grade 3/4 increases in aspartate aminotransferase and alanine aminotransferase levels, also occurred in more than 2% of patients in the combination arm.

“Today’s announcement marks a second positive CHMP opinion for [tislelizumab] in 2025, signifying the potential to expand into yet another disease area in the European Union [EU] and to support even more patients living with cancer,” Mark Lanasa, MD, PhD, chief medical officer of Solid Tumors at BeiGene, added in the news release. “As the foundation of our solid tumor portfolio, we are encouraged by [tislelizumab’s] momentum in achieving more than 100 regulatory approvals for a range of cancer indications across the world, including major markets such as the United States, the EU, China, and Japan, demonstrating the strength of evidence across a range of indications.”

References

1. BeiGene receives positive CHMP opinion for TEVIMBRA as a first-line treatment for nasopharyngeal cancer. News release. BeiGene. May 27, 2025. Accessed May 27, 2025. https://ir.beonemedicines.com/news/beigene-receives-positive-chmp-opinion-for-tevimbrar-as-a-first-line-treatment-for-nasopharyngeal-cancer/6df997d9-f05c-4ddf-ae91-d4f2129355c1
2. Tislelizumab combined with chemotherapy versus chemotherapy alone in recurrent or metastatic nasopharyngeal cancer (NPC) (RATIONALE-309). ClinicalTrials.gov. Updated January 31, 2025. Accessed May 27, 2025. https://clinicaltrials.gov/study/NCT03924986