Tislelizumab Prolongs PFS in Recurrent or Metastatic Nasopharyngeal Cancer

Tislelizumab, an anti-PD-1 antibody combined with gemcitabine and cisplatin demonstrated improvement in progression-free survival (PFS) compared with chemotherapy as first-line treatment of patients with recurrent or metastatic nasopharyngeal cancer, meeting the primary end point of the phase 3 RATIONALE 309 trial, according to a press release by BeiGene, Ltd.

Findings from the interim analysis of the trial also showed that tislelizumab had a safety profile consistent with prior known risks of the agent. No new safety signals were observed in the study. Full results from the interim analysis will be presented at an upcoming medical conference.

“We are excited to see a clinically meaningful improvement in progression-free survival in our Phase 3 trial for tislelizumab plus chemotherapy in patients with [nasopharyngeal cancer]. This is our fifth positive phase 3 readout for tislelizumab, which we are developing broadly as a potentially differentiated anti-PD-1 antibody,” said Yong (Ben) Ben, MD, chief medical officer, Immuno-Oncology, BeiGene, in a statement.

The study enrolled 263 patients with recurrent or metastatic nasopharyngeal cancer to assess the safety and efficacy of tislelizumab. The secondary end points explored in the study include overall survival, duration of response, overall response rate, PFS by investigator assessment, and PFS after the next line of treatment as assessed by the investigator.

Patients in the study were randomized 1:1 to receive tislelizumab 200 mg administered intravenously (IV) once every 3 weeks with gemcitabine mg/m², administered as an IV infusion within 30 minutes and cisplatin 80 mg/m², administered as an IV infusion over 4 hours in the experimental arm. The control was treated with matching doses of gemcitabine and cisplatin.

Those with histologically or cytologically confirmed recurrent or metastatic nasopharyngeal cancer were eligible for the study if they were between the ages of 18 to 75 years, had fresh or archival tissue for biopsy, an ECOG performance status of 1 or lower, and measurable disease per RECIST 1.1. The study excluded those with local recurrence suitable for curative surgery or radiotherapy, who received any approved systemic anticancer therapy,palliative radiotherapy for bone metastases, immunotherapy, or therapies targeting PD-1 or PD-L1. Patients with active leptomeningeal disease, autoimmune disease, or an active malignancy that occurred within 2 years were excluded from the study also.

Tislelizumab is intended to limit the amount of binging to FcyR macrophages. Preclinical research around the agent showed its ability to promote anti-tumor activity and kill effector T cells. Tislelizumab has been granted 3 biologics license applications in China for the frontline treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, the second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy, and for the treatment of patients with previously treated unresectable hepatocellular carcinoma.

To future explore the capabilities of tislelizumab, 17 clinical trials have been initiated in China and globally. Thirteen of the tislelizumab trials are in phase 3.

_Reference:

_{BeiGene announces positive topline results from phase 3 trial of tislelizumab in combination with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer. News release. May 21, 2021. Accessed May 21, 2021. https://bit.ly/3oBfcEN}