European Commission approval for tislelizumab as treatment for non-small cell lung cancer

“Tislelizumab is foundational for BeiGene’s solid tumor portfolio and has demonstrated its potential across multiple tumor types, including NSCLC, in which there remains a significant unmet need at all stages of the disease,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. “Today’s EC authorization marks the second in the region for tislelizumab, with both NSCLC and locally advanced or metastatic esophageal squamous cell carcinoma now approved in the European Union. Second-line use in ESCC was also approved just weeks ago by the FDA, putting us well on our way to fulfilling our commitment to bring this innovative therapy to many more patients around the world.”

“Non-small cell lung cancer remains one of the most common and deadly cancers in Europe, with 50% of patients diagnosed already progressed to advanced stages, making it difficult to treat,” said Luis Paz-Ares, M.D., Ph.D., Head of the Medical Oncology Service at the Hospital Universitario 12 de Octubre, Madrid. “Across three Phase III studies, tislelizumab has been shown to improve outcomes for patients with certain types of NSCLC, providing a new option for those facing the disease.”

Tislelizumab was approved for these NSCLC indications under the brand name Tizveni. BeiGene plans to combine the NSCLC indications with the second-line ESCC indication under the brand name Tevimbra, which will launch in the first EU countries later in 2024. Tevimbra is approved in the U.S. and EU for advanced or metastatic ESCC after prior chemotherapy and is under review by the European Medicines Agency and the FDA as a first-line treatment for patients with unresectable, recurrent, locally advanced or metastatic ESCC and for first-line gastric or gastroesophageal junction cancers.

The EC approval is based on the results from three Phase III studies in the RATIONALE program that enrolled 1,499 patients: i. RATIONALE 307 (NCT03594747) is an open-label, randomized Phase III trial that enrolled 360 patients with advanced squamous NSCLC. The study met its primary endpoint, with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in progression free survival (PFS), as well as higher objective response rates and a manageable safety/tolerability profile, regardless of PD-L1 expression. The most common grade greater than 3 treatment emergent adverse events (TEAEs) were decreased neutrophil levels, neutropenia and leukopenia. See full study results published in JAMA Oncology. ii. RATIONALE 304 (NCT03663205) is an open-label, randomized Phase III trial that enrolled 334 patients with locally advanced or metastatic non-squamous NSCLC. The study met its primary endpoint, with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in PFS compared to chemotherapy (HR: 0.65 [95% CI: 0.47-0.91]; P=0.0054) along with higher response rates and longer response duration. The most common grade greater than 3 TEAEs were associated with chemotherapy and included neutropenia and leukopenia. See full study results published in the Journal of Thoracic Oncology. iii. RATIONALE 303 (NCT03358875) is an open-label, randomized Phase III trial with tislelizumab versus docetaxel that enrolled 805 patients with advanced NSCLC who progressed on prior platinum-based chemotherapy. The study met its primary endpoint, with second- or third-line tislelizumab resulting in statistically significant and clinically meaningful improvement in overall survival compared with docetaxel in the intent-to-treat population (HR: 0.66 [95% CI: 0.56-0.79]; P<0.0001), regardless of pd-l1 expression. the most commonly reported grade greater than than 3 teaes were pneumonia, anemia and dyspnea. see full study results published in the journal of thoracic oncology.

See- ORIGINAL ARTICLE | NON-SMALL CELL LUNG CANCER| VOLUME 18, ISSUE 1, P93-105, JANUARY 2023. "Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase III, Open-Label, Randomized Controlled Trial",. Caicun Zhou, MD, Dingzhi Huang, MD, Yun Fan, MD, Songzi Li, PhD, Cunjing Yu, PhD, Gareth Rivalland, MD, Open Access Published: September 28, 2022 DOI:https://doi.org/10.1016/j.jtho.2022.09.217.

See-"Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non–Small-Cell Lung Cancer":"- A Phase III Randomized Clinical Trial" Jie Wang, MD, PhD; Shun Lu, MD, PhD; Xinmin Yu, Ph.,; et al JAMA Oncol. 2021;7(5):709-717. doi:10.1001/jamaoncol.2021.0366.

See- ORIGINAL ARTICLE | NON- SMALL CELL LUNG CANCER| VOLUME 16, ISSUE 9, P1512-1522, SEPTEMBER 2021PDF [1 MB]. "Tislelizumab Plus Chemotherapy as"; First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase III Trial Shun Lu, MD, PhD, Jie Wang, MD, PhD, Yan Yu, PhD, Yuanyuan Bao, MS ,Liang Liang, PhD , Mengzhao Wang, MD, PhD Open Access.Published:May 21, 2021DOI:https://doi.org/10.1016/j.jtho.2021.05.005.