FDA Accepts Tislelizumab BLA for Advanced Gastric and GEJ Cancers

Gastric stomach cancer cells closeup view 3d illustration: © LASZLO - stock.adobe.com

• The biologics license application of tiselizumab (Tevimbra), an anti-PD-1 monoclonal antibody, plus chemotherapy for the first-line treatment of gastric or gastroesophageal junction (GEJ) cancer has been accepted by the FDA.
• The filing is supported by findings from the phase 3 RATIONALE-305 trial (NCT03777657) where tislelizumab plus chemotherapy demonstrated a 20% reduction in the risk of disease progression or death.
• The Prescription Drug User Fee Act (PDUFA) target action date is expected in December 2024.

The FDA has accepted the biologics license application of tislelizumab, an anti-PD-1 monoclonal antibody, combined with fluoropyrimidine- and platinum-containing chemotherapy for the treatment of patients with newly diagnosed, locally advanced or metastatic gastric and GEJ adenocarcinoma.¹ A PDUFA target action date of December 2024 is anticipated.

“There is an urgent need for new treatment options for gastric cancer, which is often diagnosed at the advanced or metastatic stage,” said Mark Lanasa, MD, PhD, chief medical officer, solid tumors at BeiGene, in a press release. “In clinical trials, [tislelizumab] has demonstrated its potential to improve survival for patients with gastric and gastroesophageal junction cancer. This FDA acceptance brings us one step closer to delivering on a new treatment option for patients who often face poor prognoses.”

About RATIONALE-305

The application is based on findings from the global phase 3 RATIONALE-305 trial, which met its primary end point of overall survival (OS). The median OS was 15.0 months for patients treated with tiselizumab plus chemotherapy vs 12.9 months for patients treated with placebo plus chemotherapy (HR, 0.80; 95% CI, 0.70-0.92; P =.0011).

Tislelizumab plus chemotherapy also demonstrated a higher overall response rate (47.3% vs 40.5%) and median duration of response (8.6 months vs 7.2 months) compared with placebo plus chemotherapy.¹ Further, the median progression-free survival was 6.9 months in the tislelizumab arm vs 6.2 months in the placebo arm (HR, 0.78; 95% CI, 0.67-0.90).²

The safety profile of the drug combination was manageable and in line with what has been previously reported of the individual agents.¹ In the tislelizumab arm, 53.8% of patients experienced grade 3 or higher treatment-related adverse events (TRAEs) compared with 49.8% in the placebo arm. The most common TRAEs of any grade were nausea, decreased appetite, decreased platelet count, decreased neutrophil count, vomiting, and anemia.

The European Commission recently approved tislelizumab for the treatment of patients with advanced or metastatic esophageal squamous cell carcinoma who have received prior chemotherapy. The FDA is reviewing applications for tislelizumab in the same intent-to-treat population, as well as for the first-line treatment of patients with esophageal squamous cell carcinoma.

REFERENCES:

1. BeiGene’s biologics license application for Tevimbra (tislelizumab) for first-line gastric or gastroesophageal junction cancers accepted by FDA. News release. BeiGene, Ltd. February 27, 2024. Accessed February 27, 2024. http://tinyurl.com/2bfxky4j

2. BeiGene announces late-breaking data at ESMO showing tislelizumab plus chemotherapy significantly improved overall survival at final analysis in first-line advanced gastric or gastroesophageal junction adenocarcinoma. News release. BeiGene, Ltd. Updated October 17, 2023. Accessed February 27, 2024. https://tinyurl.com/e3wnm6vz