Tislelizumab Plus Chemotherapy as First-Line Tx Improves PFS for Nasopharyngeal Cancer

Doctor examines patient
Doctor examining neck of patient
The phase 3 RATIONALE 309 trial evaluated the efficacy and safety of tislelizumab plus chemotherapy in 263 adults with recurrent or metastatic nasopharyngeal cancer (RM-NPC).

Treatment with tislelizumab in combination with chemotherapy demonstrated prolonged progression-free survival (PFS) as first-line treatment for recurrent or metastatic nasopharyngeal cancer (RM-NPC), according to the results from the phase 3 RATIONALE 309 trial presented at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress 2021.

Tislelizumab is an investigational humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. The RATIONALE 309 trial (ClinicalTrials.gov Identifier: NCT03924986) evaluated the efficacy and safety of tislelizumab plus chemotherapy in 263 adults with RM-NPC. Patients were randomly assigned 1:1 to receive either tislelizumab 200mg intravenously plus gemcitabine and cisplatin or placebo plus gemcitabine and cisplatin. The primary endpoint was PFS, as assessed by the Independent Review Committee (IRC). Key secondary endpoints included overall response rate (ORR) and duration of response (DoR). 

As of March 26, 2021, results after a median follow-up of 10 months showed that treatment with tislelizumab plus chemotherapy achieved the following improvements compared with chemotherapy alone, respectively:

  • IRC-assessed median PFS: 9.2 months (95% CI, 7.6-10.1) vs 7.4 months (95% CI, 5.6-7.5), with a stratified hazard ratio of 0.52 (95% CI, 0.38-0.73; stratified log-rank P <.0001);
  • Investigator-assessed median PFS: 9.8 months (95% CI, 7.8-11.9) vs 7.6 months (95% CI, 6.6-7.8), with a stratified hazard ratio of 0.54 (95% CI, 0.38-0.76);
  • PFS benefit was consistent in most subgroups, including disease status, baseline liver metastases, and gender;
  • ORR and complete response rate: 69.5% and 16.0% vs 55.3% and 6.8%, as assessed by IRC; and
  • Median DoR: 8.5 months (95% CI, 6.5-not evaluable) vs 6.1 months (95% CI, 4.7-6.2), as assessed by IRC.

The safety profile of tislelizumab plus chemotherapy was manageable with the most treatment-emergent adverse events (incidence greater than or equal to 20%) being anemia, decreased white blood cell count, decreased neutrophil count, nausea, decreased platelet count, decreased appetite, vomiting, constipation, leukopenia, neutropenia, rash, hypothyroidism, increased alanine aminotransferase (ALT), hyponatremia, increased blood creatinine, increased aspartate aminotransferase (AST), malaise, and pyrexia.

“In the RATIONALE 309 trial, the addition of tislelizumab to chemotherapy significantly prolonged PFS for previously untreated patients with RM-NPC, an aggressive head and neck cancer prevalent in Asia, with consistent survival benefit across patient subgroups. Safety results in both arms remained similar to known risks and no new safety signals were identified. The promising results support the potential of tislelizumab in combination with chemotherapy as a new standard of care in China for the first-line treatment of RM-NPC,” commented Yunpeng Yang, MD, Professor at Sun Yat-sen University Cancer Center and principal investigator of the study.


BeiGene presents results from phase 3 trial of tislelizumab in nasopharyngeal cancer at ESMO Immuno-Oncology Congress 2021. News release. BeiGene. Accessed December 10, 2021. https://www.businesswire.com/news/home/20211210005022/en/BeiGene-Presents-Results-from-Phase-3-Trial-of-Tislelizumab-in-Nasopharyngeal-Cancer-at-ESMO-Immuno-Oncology-Congress-2021