AB Science announces that confirmatory Phase 3 study AB12005 with masitinib in first line pancreatic cancer with pain was successful - Seite 4

The study enrolled 383 patients (randomization 2:1 between masitinib and placebo) with i) histologically or cytologically confirmed adenocarcinoma of the pancreas, unresectable locally advanced or metastatic stage, ii) pain related to the disease (Visual Analogue Scale > 20 mm or opioid analgesics at a dose ≥ 1 mg/kg/day), and iii) chemotherapy naïve for the advanced/metastatic disease. 92 patients had unresectable locally advanced with pain criteria.

Efficacy analysis was performed in the modified intent-to-treat (mITT) population, which included all randomized patients who took at least one dose of study treatment (masitinib/placebo) and with pain criteria (VAS > 20 and/or patients treated with opioid analgesics dose ≥ 1 mg/kg/day at baseline). There was a difference of 4 patients between the ITT population and the mITT population, with 1 patient receiving no study treatment and 3 patients without pain criteria.

Rationale for developing masitinib in patients with pancreatic cancer with pain

A first phase 2/3 study (AB07012) enabled the identification of a subgroup based on the level of pain at baseline where survival was statistically increased (+2.6 months, p=0.012, Hazard Ratio=0.62). Pain intensity was assessed via a visual analog scale (VAS) at baseline. This linear scale provides a visual representation of pain as perceived by the patient. Pain intensity was represented by a 100 mm long, continuous line free of any internal reference marks. One extremity indicated an absence of pain (0-value) and the other extremity indicated very severe pain (100-value). The VAS threshold for the ‘pain’ subgroup was set to VAS ≥20 mm, which is consistent with established precedent from the scientific literature [3-6]. 

There is evidence from the scientific literature in support of biological plausibility for the observed masitinib treatment-effect in patients with baseline pain (VAS ≥ 20). The presence of pain in pancreatic cancer is thought to flag an increased mast cell activity within the tumor microenvironment, which promotes disease progression. Masitinib’s highly selective inhibition of mast cell activation is expected to be of therapeutic benefit by modulating mast cell related remodeling of the tumor microenvironment.