EC Approves Frontline Tislelizumab Plus Chemo for Advanced ESCC and Gastric/GEJ Cancer

Tislelizumab Plus Chemo for Advanced

Gastric/GEJ Cancer | Image Credit:

© Sebastian Kaulitzki – stock.adobe.com

The European Commission has approved tislelizumab (Tevimbra) in combination with chemotherapy for the first-line treatment of patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) and gastric or gastroesophageal junction (GEJ) adenocarcinoma.¹

The regulatory decision was supported by data from the phase 3 RATIONALE-306 (NCT03783442) and RATIONALE-305 (NCT03777657) trials in ESCC and gastric/GEJ adenocarcinoma, respectively.

“Patients diagnosed with advanced gastric and esophageal cancers confront median survival times measured in months, not years—highlighting the urgent need for more effective treatment options,” Florian Lordick, MD, PhD, professor of oncology and director of the University Cancer Center in Leipzig, Germany, stated in a news release. “The compelling data from the RATIONALE-305 and 306 trials underscore the unique clinical profile of tislelizumab and its potential to deliver meaningful improvements in outcomes for eligible patients, offering new hope where it’s needed most.”

Safety data supporting the approval were garnered from more than 2800 patients who received tislelizumab monotherapy (n = 1534) or in combination with chemotherapy (n = 1319) at the approved dosing. The most common grade 3/4 adverse effects reported in at least 2% of patients treated with tislelizumab plus chemotherapy included neutropenia, thrombocytopenia, anemia, fatigue, hypokalemia, hyponatremia, pneumonia, decreased appetite, rash, lymphopenia, increased alanine aminotransferase levels, increased aspartate aminotransferase levels, diarrhea, pneumonitis, and hepatitis.

RATIONALE-306 Data and Overview

Data from the, placebo-controlled, double-blind trial demonstrated that tislelizumab plus chemotherapy led to a statistically significant and clinically meaningful improvement in overall survival (OS) compared with placebo plus chemotherapy in the intention-to-treat population (HR; 0.66; 95% CI, 0.54-0.80; 1-sided P < .0001). Patients treated with the tislelizumab regimen experienced a median OS of 17.2 months compared with 10.6 months for those given the placebo regimen. In patients with a PD-L1 expression of at least 5%, the median OS was 19.1 months for the experimental arm vs 10.0 months for the control arm (HR, 0.62; 95% CI, 0.49-0.79).

The study enrolled patients at least 18 years of age with pathologically or histologically confirmed stage IV unresectable ESCC or unresectable, locally advanced recurrent or metastatic ESCC.² Patients who received prior platinum-based chemotherapy in the neoadjuvant or adjuvant settings were allowed to enroll if they had a treatment-free interval of at least 6 months.

Patients were randomly assigned to receive tislelizumab at 200 mg once every 3 weeks until disease progression, unacceptable toxicity, or patient withdrawal in combination with chemotherapy; or placebo plus chemotherapy.

OS served as the trial’s primary end point. Secondary end points included progression-free survival (PFS), objective response rate (ORR), OS in patients with PD-L1 expression of at least 10%, duration of response (DOR), quality of life (QOL), and safety.

RATIONALE-305 Findings and Design

In this, double-blind, placebo-controlled, global study, patients with advanced gastric/GEJ cancer treated with tislelizumab plus chemotherapy achieved a median OS of 15.0 months vs 12.9 months for those given placebo plus chemotherapy (HR; 0.80; 95% CI, 0.70-0.92; P = .0011).¹ In patients with a PD-L1 expression of at least 5%, the median OS was 16.4 months for the experimental regimen vs 12.8 months for the placebo regimen (HR; 0.71; 95% CI, 0.58-0.86).

The study included patients at least 18 years of age with locally advanced unresectable or metastatic gastric/GEJ cancer with histologically confirmed adenocarcinoma.³ Patients were not allowed to have prior systemic therapy in the locally advanced unresectable or metastatic settings. Prior neoadjuvant or adjuvant therapy was permitted if completed without recurrence or disease progression for at least 6 months following the final dose. An ECOG performance status 0 or 1 and adequate organ function were required.

Patients were randomly assigned to receive 200 mg of tislelizumab once every 3 weeks in combination with investigator’s choice of platinum-based chemotherapy; or placebo plus chemotherapy.

OS was the trial’s primary end point. Secondary end points included PFS, ORR, DOR, disease control rate, clinical benefit rate, time to response, QOL, and safety.

References

1. European Commission approves BeiGene’s Tevimbra for first-line treatment of advanced/metastatic esophageal squamous cell carcinoma and gastric or gastroesophageal junction cancer. News release. BeiGene. November 27, 2024. Accessed November 27, 2024. https://ir.beigene.com/news/european-commission-approves-beigene-s-tevimbra-for-first-line-treatment-of-advanced-metastatic-esophageal-squamous-cell-carcinoma-and/22ce8afc-1ba7-4525-82dd-058f6cfea63c/
2. A study of tislelizumab (BGB-A317) in combination with chemotherapy as first line treatment in participants with advanced esophageal squamous cell carcinoma. ClinicalTrials.gov. Updated October 26, 2024. Accessed November 27, 2024. https://clinicaltrials.gov/study/NCT03783442
3. Tislelizumab in combination with chemotherapy as first-line treatment in adults with inoperable, locally advanced or metastatic gastric, or gastroesophageal junction carcinoma. ClinicalTrials.gov. Updated October 26, 2024. Accessed November 27, 2024. https://clinicaltrials.gov/study/NCT03777657