FDA Accepts BLA for Tislelizumab/Chemo in Gastric/GEJ Adenocarcinoma

The FDA has set a Prescription Drug User Fee Act for December 2024 for its decision on approving tislelizumab in locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.

The FDA has accepted a biologics license application (BLA) for tislelizumab (Tevimbra) plus fluoropyrimidine- and platinum-based chemotherapy as a treatment for those with locally advanced or metastatic gastric or gastroesophageal (GEJ) junction adenocarcinoma, according to a press release from BeiGene, the developers of tislelizumab.¹

The regulatory agency has set a Prescription Drug User Fee Act for December 2024 for its decision on approving tislelizumab in the aforementioned indication.

“There is an urgent need for new treatment options for gastric cancer, which is often diagnosed at the advanced or metastatic stage,” Mark Lanasa, MD, PhD, chief medical officer of Solid Tumors at BeiGene, said in the press release.¹ “In clinical trials, [tislelizumab] has demonstrated its potential to improve survival for patients with gastric and [GEJ] cancer. This FDA acceptance brings us one step closer to delivering on a new treatment option for patients who often [have] poor prognoses.”

Supporting data for the BLA came from the double-blind, placebo-controlled phase 3 RATIONALE 305 trial (NCT03777657). Investigators previously presented final analysis findings from the intent-to-treat (ITT) population of the trial as part of a late-breaking oral presentation at the 2023 European Society for Medical Oncology Congress (ESMO).

Among 997 evaluable patients, data highlighted a median overall survival (OS) of 15.0 months with tislelizumab plus chemotherapy vs 12.9 months with placebo plus chemotherapy (HR, 0.80; 95% CI, 0.70-0.92; P = .0011). The objective response rate (ORR) in each respective arm was 47.3% vs 40.5%, and the median duration of response (DOR) was 8.6 months vs 7.2 months. Investigators reported a median progression-free survival (PFS) of 6.9 months with the tislelizumab-based combination vs 6.2 months with chemotherapy alone (HR, 0.78; 95% CI, 0.67-0.90).

Grade 3 or higher treatment-related adverse effects (TRAEs) affected 53.8% of patients in the tislelizumab arm compared with 49.8% of those in the placebo arm. Common high-grade toxicities included nausea, decreased appetite, platelet count decreases, neutrophil count decreases, vomiting, and anemia. Investigators concluded that the safety profile of tislelizumab plus chemotherapy in the RATIONALE 305 trial was comparable with prior reports of anti–PD-1 antibodies.

“The data from the RATIONALE 305 study suggest that tislelizumab plus chemotherapy represents a potential new first-line treatment option for patients with advanced [gastric or GEJ adenocarcinoma] regardless of PD-L1 expression status,” principal investigator Rui-Hua Xu, MD, PhD, director of the Cancer Control Center of Sun Yat-sen University, said in a press release on these findings.² “Tislelizumab plus chemotherapy provided significant and clinically meaningful [OS] benefit versus chemotherapy in all [randomly assigned] patients with previously untreated, HER2-negative advanced [gastric or gastroesophageal adenocarcinoma].”

In the RATIONALE 305 trial, patients were randomly assigned to receive tislelizumab intravenously at 200 mg on day 1 of each 21-day cycle or matched placebo plus chemotherapy. Oxaliplatin/capecitabine (Xeloda) or cisplatin/5-fluorouracil combinations were administered as backbone chemotherapy.

The trial’s primary end point was OS. Secondary end points included PFS, ORR, DOR, safety, and quality of life.

Patients 18 years and older with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma and no prior systemic therapy for their disease were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1 within 7 days of study entry and adequate organ function.

In China, the National Medical Products Administration approved tislelizumab plus chemotherapy for patients with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma with high PD-L1 expression in February 2023.³ Supporting data for the approval came from the RATIONALE 305 trial.

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/ymbdbm58
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. BeiGene, Ltd. October 17, 2023. Accessed February 27, 2024. http://tinyurl.com/9rcjx4ye
3. BeiGene receives 10th approval for PD-1 inhibitor tislelizumab in China. News release. BeiGene, Ltd. February 24, 2023. Accessed February 27, 2024. https://bit.ly/3SBpZ0Q