On 27 April, Novartis published a press release stating that the Phase III pivotal RATIONALE 306 trial of its investigational immunotherapy tislelizumab + chemotherapy in 649 patients with previously untreated, advanced oesophagal squamous cell carcinoma (ESCC) met its primary endpoint of overall survival (OS) at interim analysis. Novartis aims to submit these results to the US Food and Drug Administration (FDA), but if tislelizumab is approved, it could face stiff competition from Bristol-Myers Squibb’s (BMS) combination therapies of Opdivo (nivolumab) + chemotherapy and Opdivo + Yervoy (ipilimumab) in this setting.
The inner lining of the oesophagus is made up of squamous cells in which ESCC can develop, constituting 30% of all oesophagal cancers. It is estimated that 20,640 patients will be diagnosed with ESCC this year, which would make up around 1% of all cancer diagnoses in the US. Around 16,410 patients will die from ESCC in the US this year, and one in 125 men and one in 417 women will develop this cancer in their lifetime.
The five-year survival rate for patients with localised ESCC is 46%, but for patients with distant, metastatic ESCC, this figure drops to 5%. In the US, systemic treatments are composed mainly of immune checkpoint inhibitors (ICIs) alongside chemotherapy. Tislelizumab is an anti-programmed cell death protein (PD)-1 ICI that has shown positive results in a myriad of solid tumours in the RATIONALE trial program.
Tislelizumab has been making strides towards market approval for the treatment of patients with ESCC in the second-line setting, Novartis’ lead indication for this drug. In February this year, Novartis entered a $2.2bn licensing agreement with Chinese biotechnology company BeiGene, the developer of tislelizumab, to develop, manufacture and commercialise the drug in North America and several countries in Europe and Asia, excluding China.
On 18 April, BeiGene obtained approval from the China National Medical Products Administration (NMPA) to treat patients with ESCC with tislelizumab in the second-line setting based on positive data from the RATIONALE 302 trial. The FDA and European Medicines Agency (EMA) are also currently reviewing tislelizumab as a therapy in this setting, with the FDA expected to make a decision on 12 July. Tislelizumab and chemotherapy have also been hypothesised to improve OS in patients with ESCC in the first-line setting.
Novel data from the multi-regional, Phase III RATIONALE 306 study shows that tislelizumab + chemotherapy significantly improves OS in patients with previously untreated unresectable, locally advanced, recurrent or metastatic ESCC compared to chemotherapy alone. Jeff Legos, Novartis’ executive vice-president and global head of oncology and haematology development, said the company plans to discuss these data with health authorities and continue to expand its tislelizumab clinical development programme.
Novartis will collaborate with BeiGene to present this data at an upcoming medical meeting, which could be presented as late-breaking trial data at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Tislelizumab is, however, expected to be up against tough competition in this indication.
Earlier this year, BMS’ Opdivo + fluoropyrimidine-based and platinum-based chemotherapy received approval from the European Commission (EC) for the treatment of patients with ESCC in the first-line setting, and this combination therapy is currently being reviewed by the FDA. The EC has also approved Opdivo + Yervoy in this setting. With patients tending to prioritise brand familiarity when agents have the same modality, tislelizumab may struggle to compete in the US and European markets against two of the most well-known oncology drugs.