Histologically or cytologically confirmed pancreatic adenocarcinoma with metastasis, who had obtained a best response of at least stable disease (SD) or a partial response (PR) for a period of 2 months with no further shrinkage of ≥ 30% on scan on their first line of chemotherapy for their advanced metastatic disease. Note: Patients that have had prior chemotherapy as adjuvant or neoadjuvant therapy are permitted. 4. Have a performance status of 0 or 1 on the ECOG performance scale. 5. Able to submit an archival tumor specimen (primary or metastatic site) and a discussion is documented with trial investigator at screening that patient will consider providing tissue from a newly obtained core or excisional biopsy of a tumor lesion at baseline and a second biopsy 9 weeks after starting trial treatment, unless tumor is considered inaccessible or biopsy is otherwise considered not in the patients’ best interest. Participation in this trial is not contingent on patient consenting to optional tumor biopsies.
Histologically or cytologically confirmed pancreatic adenocarcinoma with metastasis, who had obtained a best response of at least stable disease (SD) or a partial response (PR) for a period of 2 months with no further shrinkage of ≥ 30% on scan on their first line of chemotherapy for their advanced metastatic disease.
Histologically the first hallmarks of the disease can be detected by 3 months of age, when Cln7Δex2 mice present with AFSM in the hippocampus, cerebral cortex, cerebellum, thalamus and olfactory bulb (Xxxxxxxxxxxx et al., 2016). SCMAS accumulation has been identified by 3 months of age mainly in neurons of the hippocampus, the Purkinje cell layer and granule cell layer of the cerebellum, layer V and VI of the cerebellar cortex and the thalamus, but not in the granule cell layer of the dentate gyrus (Xxxxxxxxxxxx et al., 2016). SCMAS has also been detected in cardiac muscles, the kidney and the liver in Cln7Δex2 mice. Both saposin D and SCMAS were detected within the accumulated AFSM in Cln7Δex2 mice. By 9 months of age Cln7Δex2 mice displayed brain atrophy of the olfactory bulb, cerebral cortex and cerebellum as measured by MRI scanning (Xxxxxxxxxxxx et al., 2016). At end stage disease, by 10 months of age, the mice did not display loss of Purkinje cells in the cerebellum. Astrocytosis was detected in various brain regions, including the hippocampus, cerebral cortex and thalamus by 5 months of age and became progressively worse over time in Cln7Δex2 mice (Xxxxxxxxxxxx et al., 2016). Subsequent microglial activation was detected by 7 months of age in all brain regions of Cln7Δex2 mice, albeit at a less severe level than the astrocytosis. Levels of cathepsins were significantly increased by 5 months of age in both microglia and neurons, but not astrocytes (Xxxxxxxxxxxx et al., 2016). Cln7Δex2 mice also displayed pronounced degeneration of rod photoreceptor cells, reactive astrocytosis and microglial activation, accumulation of SCMAS and saposin D in the retina, resulting in severe retinal degeneration (Xxxxxxxxx et al., 2016).
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