Tislelizumab Prolongs Survival in Advanced, Unresectable, or Metastatic ESCC

January 28, 2021 - The anti–PD-1 antibody tislelizumab was found to significantly improve overall survival compared with investigator’s choice of chemotherapy in the treatment of patients with advanced, unresectable, or metastatic esophageal squamous cell carcinoma.

The anti–PD-1 antibody tislelizumab (BGB-A317) was found to significantly improve overall survival (OS) compared with investigator’s choice of chemotherapy in the treatment of patients with advanced, unresectable, or metastatic esophageal squamous cell carcinoma (ESCC), meeting the primary end point of the phase 3 RATIONALE-302 trial (NCT03430843).1

Specifically, the agent was shown to lead to a statistically significant and clinically meaningful OS improvement over chemotherapy in the intent-to-treat (ITT) population. Moreover, the toxicity profile of the immunotherapy proved to be consistent with what has previously been reported.

The findings from the trial will be shared with health authorities on a global scale and are anticipated to be presented at an upcoming medical meeting, according to BeiGene, Ltd.

“We are excited to announce the improved OS observed in another phase 3 trial for tislelizumab when compared to chemotherapy standard of care. This is our fourth positive phase 3 readout for tislelizumab and the first from our large phase 3 program in gastrointestinal cancers that also include liver, stomach cancers as well as esophageal cancer,” Yong Ben, MD, chief medical officer, Immuno-Oncology at BeiGene, stated in a press release.

In the open-label, multicenter, global phase 3 trial, investigators set out to examine the safety and efficacy of tislelizumab versus investigator’s choice of chemotherapy in patients with advanced, unresectable, or metastatic ESCC who previously received systemic treatment.

To be eligible for enrollment, patients had to have histologically confirmed diagnosis of ESCC, tumor progression during or after frontline treatment for advanced unresectable or metastatic ESCC, at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0-1, and acceptable end-organ function.2

Patients who had previously received 2 or more systemic treatments for advanced or metastatic unresectable ESCC, had a history of gastrointestinal perforation and/or fistula or aorto-esophageal fistula within 6 months before randomization, experienced tumor invasion into organs located adjacent to the esophageal disease site, or previously received PD-1 or PD-L1 agents, were excluded.

The primary objective of the trial was OS in the ITT population, while key secondary objectives comprise OS in the PD-L1–positive subgroup, overall response rate, progression-free survival, duration of response, health-related quality of life, and safety.

The trial enrolled a total of 512 patients across 11 countries in Asia, Europe, and North America. Participants were randomized 1:1 to receive intravenous (IV) tislelizumab at a dose of 200 mg on day 1, every 21 days or investigator’s choice of chemotherapy. Those on the control arm received either IV paclitaxel at a dose of 135 mg/m2-175 mg/m2 on day 1, every 21 days or on a weekly schedule; IV docetaxel at a dose of 75 mg/m2 on day 1, every 21 days; or IV irinotecan at a dose of 125 mg/m2 on days 1 and 8, given every 21 days.

“The positive top-line results from the RATIONALE 302 trial demonstrated that tislelizumab may offer a new treatment option for those living with this devastating disease and bring hope to patients and their families,” Li Shen, MD, lead investigator of the trial and vice president of clinical oncology, at Beijing Cancer Hospital, added in the release.

Previously, the PD-1 inhibitor was also found to improve OS compared with docetaxel in the second- and third-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who experienced disease progression on platinum-based chemotherapy, meeting the primary end point of the phase 3 RATIONALE 303 trial (NCT03358875).3

In January 2021, the tislelizumab was granted an approval by the China National Medical Products Administration for use in combination with 2 chemotherapy regimens in the frontline treatment of patient with advanced squamous NSCLC. The decision was based on data from the phase 3 BGB-A317-307 trial (NCT03594747), which demonstrated that the combination resulted in improved PFS over chemotherapy alone in Chinese patients with advanced disease.

Specifically, the median PFS with tislelizumab plus paclitaxel/carboplatin in patient with a PD-L1 expression of less than 1% was 7.6 months compared with 5.5 months with paclitaxel/carboplatin alone (HR, 0.636; 95% CI, 0.368-1.101).4 When tislelizumab was combined with nab-paclitaxel (Abraxane) and carboplatin, the median PFS was 7.4 months (HR vs control, 0.692; 95% CI, 0.406-1.178).


  1. BeiGene announces positive topline results for global phase 3 trial of tislelizumab in esophageal squamous cell carcinoma. News release. BeiGene, Ltd. January 27, 2021. Accessed January 28, 2021. http://bit.ly/39qV6Hn.
  2. A study of tislelizumab (BGB-A317) versus chemotherapy as second line treatment in participants with advanced esophageal squamous cell carcinoma. ClinicalTrials.gov. Updated June 26, 2020. Accessed January 28, 2021. https://clinicaltrials.gov/ct2/show/NCT03430843.
  3. BeiGene announces that RATIONALE 303 trial of tislelizumab in non-small cell lung cancer met the primary endpoint of overall survival at interim analysis. News release. BeiGene, Ltd. November 17, 2020. January 28, 2021. https://bit.ly/3lGDLOb.
  4. Wang J, Yu X, Lu S, et al. Phase III study of tislelizumab plus chemotherapy vs chemotherapy alone as first-line (1L) treatment for advanced squamous non-small cell lung cancer (sq NSCLC). J Clin Oncol. 2020;28(suppl 15):9554. doi:10.1200/JCO.2020.38.15_suppl.9554