ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study

Prior treatment

• The patient has received chemotherapy as adjuvant therapy for locally advanced disease, resectable or borderline resectable.
• Patient has received previous abdominal radiotherapy, (with the exception of analgesic radiotherapy that was not performed on target lesions).
• Patients previously treated with an inhibitor of the PI3K/Akt/mTOR pathway by a systemic route.

Other illness

• Patients has only locally advanced disease, resectable or borderline resectable.
• History of chronic diarrhea or inflammatory disease of the colon or rectum, or occlusion or sub-occlusion not resolved under symptomatic treatment
• Patient has active Hepatitis B or C, human immunodeficiency virus (HIV) or Covid-19 infection with non-controlled disease according to the treating physician.

Lab values

• Patient is pregnant or in lactation period. High sensitivity pregnancy test (urine or serum) to be performed within 7 days before study treatment starts.
• Patient had myocardial infarction within ≤ 6 months prior to study entry, LVEF \<50%, symptomatic congestive heart failure (New York Heart Association \> class II), unstable angina pectoris, or unstable cardiac arrhythmia requiring medication.
• Patients with any other medical conditions (such as psychiatric illness, cardiovascular disease, infectious diseases, abnormal physical examination or laboratory findings) that in the opinion of the investigator may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.

Other

• Patients with any histology other than carcinoma, adenocarcinoma or ductal adenocarcinoma (such as squamous cell, acinar cell, medullary, colloid, neuroendocrine, etc)
• 12-lead ECG with clinically relevant abnormality or showing a QTcF \>450 ms, PR \>210 ms, or QRS \>120 ms at screening.
• Patients unable to provide informed consent like those under administrative or legal supervision

• Histologically or cytologically confirmed carcinoma, adenocarcinoma or ductal adenocarcinoma of the pancreas.
• Confirmed metastatic disease
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 guidelines with at least one "target lesion" to be used to assess response. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Age, older than 18 years old
• Adequate hematologic function, measured as:
  • absolute neutrophil count ≥ 1.5x109/L
  • platelet count ≥ 100x109/L without transfusion support
  • hemoglobin ≥ 10 g/dL
• Total bilirubin ≤ 1.5 x ULN
• Albumin ≥ 3.3 g/dL
• AST (SGOT) and ALT (SGPT) ≤ 2.5 times x upper limit of normal (≤ 5 times the ULN in patients with evidence of liver metastases)
• Alkaline phosphatase ≤ 2.5 times ULN (≤5 times the ULN in patients with evidence of liver metastases)
• Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2
• Only for Phase II patients. If available, a sample of tumor tissue or cytology (either archival or new tumor biopsy) for biomarker analyses. The most recently collected tumor tissue sample should be provided.
• Contraception: All premenopausal female patients must use contraception. Male patients and their female partners (if fertile), must use contraception as well. In both cases, contraception means two forms of highly effective contraception during the study and for a period of 6 months following the last administration of the study drug.
• Willing and able to provide informed consent
• Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol.