PRESS RELEASE
RESULTS FROM MASITINIB STUDY AB12005 IN PANCREATIC CANCER SELECTED FOR PRESENTATION AT THE ASCO ANNUAL MEETING
The 2021 ASCO Annual Meeting, taking place online
Joël Ezenfis, Head of the
Presentation details are as follows:
- Session Title: Poster Discussion Session, Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
- On-Demand Session Release Date and Time:
June 04, 2021 , 3;00PM (CEST) - Presentation Title: Masitinib plus gemcitabine as first-line treatment of pancreatic cancer with pain: Results from phase 3 study AB12005
- Authors:
Joel Ezenfis , Julien Taiëb andOlivier Hermine for theAB12005 Study Group
The full abstract will be published in the 2021 ASCO Annual Meeting Proceedings (a supplement to
Joël Ezenfis said: “These results from study AB12005 are welcome news in the fight against pancreatic cancer. Masitinib, an oral tyrosine kinase inhibitor that targets inflammatory cells associated with a pro-tumoral immune response, improved prognosis for unresectable, locally advanced pancreatic ductal adenocarcinoma patients with pain”.
Study AB12005 was a placebo controlled, randomized (2:1) trial, evaluating oral masitinib (6 mg/kg/d) plus gemcitabine (1000 mg/m²) in chemo-naïve unresectable locally advanced pancreatic cancer (LAPC) or metastatic with pain criteria (defined as visual analog scale of pain intensity >20 or patient taking an opioid analgesics dose ≥1 mg/kg/d).
The study was successful if the difference in median OS (primary endpoint) relative to control, reached a 2.5% level of statistical significance for either the predefined LAPC subgroup (n=92) or the overall population (n=379).
Highlights from the presentation include:
- Masitinib plus gemcitabine confers a meaningful overall survival benefit of +1.8 months relative to the control arm, corresponding to a significant 54% reduced risk of death (p=0.005) in LAPC patients with pain.
- No survival benefit was seen for the overall study population, which included metastatic patients.
- Survival response rate were consistent with overall survival results.
- Masitinib plus gemcitabine increased median progression free survival (PFS) by 3.6 months, corresponding to a significant 54% reduced risk of disease progression (p=0.004) in LAPC patients with pain.
- Toxicities were manageable with similar rates of severe and serious adverse events relative to control.
- AB12005 results are confirmatory for positive benefit/risk in unresectable locally advanced pancreatic cancer with pain.
- Findings provide further clinical evidence associating mast cells with pancreatic cancer.
AB12005 Study Design
Study AB12005 was a randomized, placebo-controlled, phase 3 study of masitinib in first-line treatment of unresectable locally advanced or metastatic pancreatic cancer patients with pain at baseline or taking opioids.
The pre-specified primary endpoint was overall survival. The primary analysis was pre-specified both in the overall population and also in patients with unresectable locally advanced tumors, with alpha spending split at a 2.5% level of significance between the overall population (2.5%) and locally advanced subgroup (2.5%). The distinction between unresectable locally advanced or metastatic disease status was a stratification factor, thereby ensuring that treatment-arms were unbiased for this known prognostic factor. Secondary endpoints included progression free survival according to central RECIST criteria and change in pain from baseline.
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. 89 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,
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.
About pancreatic cancer
The estimated prevalence of people living with pancreatic cancer is 21 per 100,000 [5]. At the time of diagnosis, most patients with pancreatic ductal adenocarcinoma present with locally advanced or metastatic disease and only 10-20% of cases are candidates for curative surgery. Median overall survival is between 6 to 7 months and 1-year survival rates range between 17 to 25% [6;7]. As such, population with unresectable pancreatic cancer in first line is around 100,000 in the EU and 60,000 in the
From the first Phase 3 study AB07012 [8] and literature [9], around 50% of patients with pancreatic cancer had pain intensity (VAS > 20) and 25% to 50% of pancreatic cancer patients are patients with unresectable locally advanced tumors.
Reference
[1] Khazaie K, Blatner NR, Khan MW, et al. The significant role of mast cells in cancer. Cancer Metastasis Rev.
[2] Theoharides TC. Mast cells and pancreatic cancer. N Engl J Med.
[3] Maltby S, Khazaie K, McNagny KM. Mast cells in tumor growth: angiogenesis, tissue remodelling and immune-modulation. Biochim Biophys Acta.
[4] Christy AL, Brown MA. The multitasking mast cell: positive and negative roles in the progression of autoimmunity. J Immunol.
[5]
[6] Heinemann V, et al. BMC Cancer. 2008;8:82.
[7] Von Hoff DD, et al. N Engl J Med.
[8] Deplanque 2015, Ann Oncol. doi: 10.1093/annonc/mdv133. http://annonc.oxfordjournals.org/content/26/6/1194
[9] Balaban EP, et al. Locally Advanced Unresectable Pancreatic Cancer:
About masitinib
Masitinib is a new orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can be developed in a large number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system. In oncology due to its immunotherapy effect, masitinib can have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and microglia and consequently the inhibition of the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases and the degeneration of these diseases.
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Attachment
- CP Pancreatic ASCO2021 VEng VF
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