Therapeutic: tislelizumab for oncology

20-May-2022

With three main subtypes (adenocarcinoma, squamous cell carcinoma and large cell), non-small cell lung cancer is the predominant form of lung cancer

Despite advances in treatment, survival rates remain poor, with only a quarter of patients whose disease has reached stage 3b surviving for 5 years. The figure drops to 10% in stage 4a disease and just 1% for stage 4b.

Oesophageal squamous cell cancer, meanwhile, is the most common type of oesophageal cancer, but treatment options remain limited for those who have progressed after first-line therapy. New therapy options are clearly necessary.

One such drug is tislelizumab, a humanised monoclonal antibody that was designed to bind to the cell surface receptor PD-1, which plays a role in downregulating the immune system and preventing the activation of T-cells.1

The IgG4 anti-PD-1 antibody was designed by scientists at BeiGene in Beijing, China, and is being commercialised in collaboration with Novartis. Its point of difference from the PD-1 antibodies that have already reached the market is the fact that it has an engineered Fc region that preclinical data suggest should minimise negative interactions with other immune cells.

As well as lung cancer, its potential in a range of other solid tumours, including oesophageal and blood cancers, is being evaluated.

Numerous Phase III trials have been run and reported. For example, in an open label Phase III trial comparing the antibody to chemotherapy, 512 patients with advanced or metastatic oesophageal squamous cell carcinoma who had progressed after first-line systemic therapy were given 200 mg of tislelizumab intravenously once every 3 weeks, or chemotherapy with paclitaxel, docetaxel or irinotaxel, as chosen by the investigator.2

At final analysis, after 410 deaths had taken place, the overall survival in all patients with the antibody was 8.6 months, compared with 6.3 months with chemotherapy alone. The objective response rate with the antibody was 20.3% compared with 9.8% with chemotherapy, and fewer subjects in the tislelizumab group experienced grade 3 or higher treatment-related adverse events.

In another randomised Phase III trial, its effects in combination with chemotherapy were evaluated in 355 patients with advanced squamous NSCLC.3 Subjects were given the antibody in combination with carboplatin plus paclitaxel or carboplatin plus nab-paclitaxel, or the carboplatin/paclitaxel combination alone.

Global health status and quality of life scores improved for both of the combinations compared with the chemotherapy only arm at both weeks 6 and 12. These patients also had a reduction in most lung cancer-specific symptoms. A further open label Phase III trial involved 332 NSCLC patients who were given the antibody plus either carboplatin or cisplatin plus pemetrexed every 3 weeks, or chemotherapy alone.4

After a median follow-up period of 9.8 months, progression-free survival of 9.7 months with the antibody was significantly longer than the 7.6 months with chemotherapy alone. Response rates were higher and the response duration longer with the combination too. The most common grade 3 or higher adverse events were neutropenia and leukopenia, and were associated with the chemotherapy.

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References

  1. Y. Hong, et al., FEBS Open Biol. 11, 782 (2021).
  2. L. Shen, et al., J. Clin. Oncol. (2022): online ahead of print (doi:10.1200/JCO.21.01926).
  3. J. Wang, et al., Cancer Treat. Res. Commun. (2021): online ahead of print (doi: 10.1016/j.ctarc.2021.100501).
  4. S. Lu, et al., J. Thorac. Oncol. 16, 1512 (2021).

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