Second-Line Tislelizumab Demonstrates OS Benefit in Advanced Esophageal Squamous Cell Carcinoma

The primary end point of improvement in overall survival (OS) was met with the anti–PD-1 antibody tislelizumab (BGB-A317) compared with investigator’s choice of chemotherapy in patients with advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC) who have received prior systemic therapy. Topline results from the global phase 3 RATIONALE 302 trial (NCT03430843) were released in a press release from BeiGene showing a statistically significant and clinically meaningful improvement in overall survival in the intention-to-treat (ITT) population.

“Esophageal cancer represents a significant unmet medical need with rapid progression and high mortality. Recent years have seen a paradigm-shift in advanced ESCC treatment from chemotherapy and radiation to immunotherapy. The positive topline 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,” said lead investigator Lin Shen, MD, vice president of clinical oncology at Beijing Cancer Hospital, in a statement.

The safety profile was consistent with known risks for the agent. Findings from the trial will be shared with global health authorities and presented at an upcoming medical conference.

“We are excited to announce the improved overall survival 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,” stated Yong (Ben) Ben, MD, chief medical officer, Immuno-Oncology, BeiGene.

Tislelizumab is a humanized IgG4 anti–PD-1 monoclonal antibody designed to minimize binding to FcγR on macrophages.

RATIONALE 302 is randomized, open-label, multicenter global study that is exploring the safety and efficacy of tislelizumab in comparison with investigator’s choice of chemotherapy in patients with advanced unresectable or metastatic ESCC in the second-line setting. A total of 512 patients have been enrolled in the study from 11 countries across Asia, Europe, and North America.

Patients with tumor progression during or after first-line therapy for advanced unresectable or metastatic disease, measurable disease, an ECOG performance status of 0 or 1, and adequate end-organ function were eligible to enroll. Those with a history of gastrointestinal perforation and/or fistula, tumor invasion into organs near the esophagus, uncontrollable pleural effusion, prior malignancy, active brain or leptomeningeal metastasis, autoimmune disease, interstitial lung disease, cardiovascular risk factors, or HIV were excluded from the study.

Treatment in the experimental arm consisted of 200 mg intravenous tislelizumab given every 21 days. In the comparator arms, patients received either paclitaxel at 135 to 175 mg/m2 intravenously every 21 days or 80 to 100 mg/m2 intravenously every week, docetaxel at 75 mg/m2 intravenously, or irinotecan at 125 mg/m2 intravenously.

Secondary end points include OS in the PD-L1–positive patients, overall response rate, progression-free survival, duration of response, health-related quality of life, and safety.

“With our ongoing evaluation of tislelizumab across multiple tumor types, we are working to provide clinical evidence and bring this potentially differentiated anti–PD-1 antibody to far more patients around the world,” Ben added.

Tislelizumab is currently being investigated in 15 potentially registration-enabling clinical trials, including 2 other phase 3 trials in ESCC—one in combination with chemotherapy in the first-line setting (NCT03783442) and another with chemoradiotherapy versus chemoradiotherapy alone in patients with localized disease (NCT03957590). BeiGene also entered into an agreement this month with Novartis to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan; the agreement is expected to close in the first quarter of 2021.

_Reference

_{BeiGene Announces Positive Topline Results for Global Phase 3 Trial of Tislelizumab in Esophageal Squamous Cell Carcinoma. News release. January 27, 2021. Accessed January 28, 2021. https://bwnews.pr/3os0UV2}