Phase I Trial of MK2 Inhibitor in Combination With mFOLFIRINOX for Untreated Metastatic Pancreatic Ductal Adenocarcinoma
The investigators hypothesize that MK2 inhibition may improve efficacy of mFOLFIRINOX chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC).
• Histologically or cytologically confirmed pancreatic ductal adenocarcinoma with no prior systemic treatment for advanced or metastatic disease. Patients with mixed cytology in their tumors such as adeno-squamous, mixed neuroendocrine-carcinoma are permitted if the portion of adenocarcinoma is predominant. Prior adjuvant/neoadjuvant therapy (including FOLFIRINOX or mFOLFIRINOX regimens) is allowed if progression occurred ≥ 12 months from the last dose of that therapy.
• Dose escalation: Diagnosis of advanced inoperable or metastatic disease, where mFOLFIRINOX (or classical FOLFIRINOX) is deemed a suitable option per the treating physician.
• Dose expansion: Diagnosis of metastatic disease, where mFOLFIRINOX (or classical FOLFIRINOX) is deemed a suitable option per the treating physician.
• Measurable disease by RECIST 1.1.
• At least 18 years of age
• ECOG performance status ≤ 1.
• Adequate bone marrow and organ function as defined below:
‣ Absolute neutrophil count ≥ 1.5 K/cumm
⁃ Platelets ≥ 100 K/cumm without transfusion within 2 weeks prior to C1D1
⁃ Hemoglobin ≥ 9.0 g/dL without transfusion within 2 weeks prior to C1D1
⁃ Total bilirubin ≤ 1.5 x IULN
⁃ AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN, unless there are liver metastases in which case AST and ALT ≤ 5.0 x IULN
⁃ Creatinine clearance \> 50 mL/min by Cockcroft-Gault
• Baseline EKG with QTcF ≤ 460 ms.
• Women of childbearing potential and men who are heterosexually active must agree to use adequate contraception as specified in the protocol. Contraception should continue for 1 month following last dose of zunsemetinib, 6 months following last dose of irinotecan, 9 months following last dose of oxaliplatin, and/or 3 months following last dose of fluorouracil. Should a woman (or the female partner of a male participant) become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).