A lack of effective therapies in the advanced stages of pancreatic cancer makes it one of the most difficult oncology indications to manage, resulting in high mortality rates. Considerable clinical development efforts have been focused on identifying drugs with novel mechanisms of action that target complex host-tumour interactions. Therapies aimed at modifying the immune system are currently the focus of R&D strategies that GlobalData anticipates will shape the future treatment of pancreatic cancer. Among these pipeline agents is AB Science’s Masiviera (masitinib), an orally administered tyrosine kinase inhibitor. Masiviera is designed to selectively target mast cells and macrophages through the inhibition of c-Kit, Lyn, Fyn, and macrophage colony-stimulating factor receptor-1 (MCSFR-1) kinases, which are critical components of the tumour microenvironment. These kinases promote angiogenesis and tumour growth and also contribute to tumorigenesis by suppression of the immune response.

Scientific literature and results from early phase clinical trials suggest there may be a survival benefit in late-stage advanced / metastatic patients who are treated with masitinib. The presence of pain in pancreatic cancer is considered to indicate increased mast cell activity within the tumour microenvironment, which promotes disease progression. Masitinib’s mast cell activation is expected to offer therapeutic benefit by modulating mast cell-related remodelling of the tumour microenvironment.

To assess the effects of Masiviera in patients with locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma, AB Science designed AB12005 (NCT03766295), a randomised, placebo-controlled, Phase III study in the first-line setting to compare the efficacy and safety of Masiviera at a dosing of 6mg / kg per day in combination with gemcitabine versus placebo in combination with gemcitabine. On 4 December, AB Science announced that Masiviera in combination with gemcitabine met its primary endpoint to demonstrate statistically significant overall survival relative to the comparator arm (with a median overall survival of 13 months in the masitinib arm versus 11.2 months in the control group, and a median progression-free survival of 7.4 months in the masitinib arm versus 5.6 months in the control group. The risk of death was reduced by 54% for masitinib-treated patients.

Dr Joël Ezenfis, the principal coordinating investigator of the study, said: “We are very pleased that this study is successful. The increase of 1.8 months in median overall survival for masitinib-treated patients is clinically relevant, as this population of patients suffers from a condition with very limited treatment options and the survival rate has remained stubbornly poor despite decades of clinical studies.”

Achieving the study’s primary endpoint is a major milestone for AB Science, as is its successes in other indications, including positive Phase III results from a clinical trial evaluating Masiviera in mild to moderate Alzheimer’s disease. The company has plans to submit a Marketing Authorization Application for Masiviera in the first-line treatment of locally advanced unresectable and metastatic patients with pain to the FDA. With Masiviera’s forecast launch in 2022, GlobalData expects that the treatment paradigm for patients in the first-line setting will evolve, and the market will show substantial growth over the next several years. For more information, see GlobalData’s upcoming Pancreatic Cancer Opportunity Analysis and Forecast from 2019–2029 report, which discusses Masiviera and several other key pipeline agents in development for pancreatic cancer.