Pancreatic Cancer

Pancreatic cancer is almost always fatal. Patients diagnosed with pancreatic cancer often have a poorer prognosis compared with other cancers in part because early detection is difficult. Although there has been progress in the last few decades in treating pancreatic cancer and there are new agents available, there still is only a limited benefit from any of these agents for the average patient.

Masitinib is currently investigated in non-resectable locally advanced or metastatic pancreatic cancer, restricted to patients with cancer related pain.

Masitinib differentiates from registered drugs both in terms of administration (oral administration) and eligibility criteria (less restrictive eligibility criteria).

In recognition of the critical need for new treatments, masitinib received orphan drug designation for pancreatic cancer from both the European Medicine Agency (EMA) and the U.S. Food and Drug Administration (FDA).

The number of patients targeted by masitinib amounts to 20,000 to 40,000 in Europe and in the US.

In this study, patients with unresectable, locally advanced or metastatic pancreatic cancer received oral masitinib combined with standard gemcitabine. The primary endpoint of median Time To Progression (TTP) was 6.4 months (95% CI [2.7–11.7]). Median Overall Survival (OS) was 7.1 months (95% CI [4.8–17.0]).

These results of masitinib combined with gemcitabine, with extended survival and median TTP that supported initiation of a phase 3 trial, have been published.

AB Science completed a first phase 2/3 study to compare efficacy and safety of masitinib in combination with gemcitabine, to placebo in combination with gemcitabine, in treatment of patients with advanced/metastatic pancreatic cancer.

Despite, the median Overall Survival (OS) for the overall population was similar for both treatment-arms, ex-post analysis showed that masitinib in combination with gemcitabine extended the OS in the patients with cancer pain sub-population, representing 45% of the overall population. In this pain subgroup, patients treated with masitinib plus gemcitabine had a median OS of 8.0 months [95% CI (5.8; 11.5)] compared with a median OS of 5.4 months [95% CI (3.7; 8.3)] for the placebo plus gemcitabine treatment-arm, an OS gain of + 2.6 months.

Therefore, this phase 2/3 study enabled identification of a subgroup based on the level of pain (marker of mast cell activation) at baseline where survival was statistically increased. Results have been published in the Annal of Oncology.

AB Science completed a confirmatory Phase 3 study evaluating masitinib in first line pancreatic cancer patients with pain. The primary endpoint of the study was overall survival (OS).

The study met its primary endpoint with significant OS increase (+1.8 months median, p=0.007, below 2.5%) in population with locally advanced tumors, which represents a reduction in risk of death of 54% for masitinib-treated patients relative to control.

Secondary analysis in progression free survival (+1.8 months, p=0.039) was consistent with survival results, and masitinib reduced pain, supporting the rationale for targeting this population having pain at baseline.

The safety of masitinib 6.0 mg/kg/day in combination with gemcitabine compared favorably to that of gemcitabine as a single agent, with fewer adverse event and severe adverse events reported in the masitinib arm as compared with the control arm.

No survival benefit detected in the overall population including both locally advanced and metastatic pancreatic cancer, suggesting that masitinib treatment should be initiated early in the course of the disease, prior to metastasis.