AstraZeneca Plc reported two positive outcomes and one negative outcome for three Phase 3 lung cancer trials on 17 August. The trials were all testing treatments for non-small cell lung cancer, the most prevalent type, which makes up about 85% of all lung cancers globally, according to the World Health Organization. The largest trial, which was testing a dual checkpoint inhibitor bispecific antibody, failed to show efficacy. However the two other studies, targeting cancers with specific genetic mutations, achieved statistically significant and clinically meaningful results.
The largest study, eVOLVE-Lung02, enrolled 895 patients across 25 countries and was part of the company’s strategy to improve treatments for lung cancer patients whose tumours have a low expression of programmed death ligand 1 (PD-L1). This is a protein that regulates the body’s immune response to disease. In a cancer setting, PD-L1 is the target for many immunotherapies. However low expression can limit success. The trial investigated volrustomig, a bispecific antibody, in combination with chemotherapy compared with pembrolizumab and chemotherapy. The company stopped the study early on the advice of the independent data monitoring committee for lack of efficacy.
By comparison, on the same day, the company reported positive data for two other Phase 3 lung cancer trials. The first, DESTINY-Lung04, was a test of Enhertu (trastuzumab), a widely prescribed antibody-drug conjugate for multiple cancers, in a new indication – HER2-mutant advanced non-small cell lung cancer. The trial enrolled 454 patients across sites in Asia, Europe and North America in order to find out whether Enhertu could produce better outcomes for patients than the standard of care – chemotherapy with pembrolizumab.
The results showed a statistically significant improvement in progression-free survival in a first-line setting. This supports “the potential for Enhertu to move earlier in the treatment of HER2-mutant non-small cell lung cancer,” Susan Galbraith, of head of oncology haematology R&D at AstraZeneca, said in a prepared statement. This positive outcome was matched in a third trial, SAFFRON, which tested AstraZeneca’s lung cancer drug Tagrisso (osimertinib), with the kinase inhibitor Orpathys (savolitinib). Orpathys was approved in China in 2021and developed by HUTCHMED (China) Ltd. The trial enrolled 338 patients with epidermal growth factor receptor mutated non-small cell lung cancer.
They also had overexpression of MET, a cell surface receptor and mechanism of resistance. The investigational treatment was compared with chemotherapy. Patients who enrolled in the trial had experienced a progression of their disease after prior treatment with Tagrisso. The results showed improvements in both progression-free and overall survival. In a statement, Dr Galbraith said that “by combining Orpathys and Tagrisso, with its established efficacy, safety profile and central nervous system protection, we aim to deliver the first biomarker-directed, all-oral option in this setting to patients across the globe.”
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