Monthly Alternating NALIRIFOX and GnP in the First-Line Setting for Metastatic Pancreatic Ductal Adenocarcinoma

Inclusion criteria

Inclusion: * \>18 years of age * Histologically proven pancreatic ductal adenocarcinoma, poorly differentiated carcinoma, or adenosquamous carcinoma * Radiographic evidence of metastatic disease * At least 1 measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Metastatic relapse of previously resected pancreatic cancer is allowed provided the patient is more than 6 months from last SOC adjuvant treatment * ECOG PS 0-1 * Laboratory assessments within 14 days as indicated below: * Hemoglobin \> 9.0 g/dL (patients with hemoglobin \< 9 g/dL may be transfused prior to study enrollment) * Platelet count \> 100 x 10\^9/L * Absolute neutrophil count (ANC) \> 1.5 x 10\^9/L * Total bilirubin \< 3 x upper limit of normal (ULN) * Aspartate transaminase (AST) and alanine transaminase (ALT) \< 3 x ULN (if liver metastases are present, AST and ALT \< 5 x ULN is permitted. * Creatinine ≤1.5 ULN * Creatinine clearance \> 40 mL/min as calculated by Cockcroft-Gault formula * APTT (aPTT) ≤ 1.5 × ULN. For subjects receiving unfractionated heparin \< 2.5 × ULN, or within acceptable range considered by the investigator. * PT/INR INR ≤ 1.5 × ULN. For subjects receiving warfarin, 2.0 -3.0, or within acceptable range considered by the investigator. * Women of childbearing potential must be surgically sterile or postmenopausal or must have a negative pregnancy test (serum or urine) prior to study enrolment and must use effective barrier contraception or abstinence during the treatment period. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions and therefore are not considered effective for this study. Male patients must be surgically sterile or use effective contraception or abstinence during the treatment period. The definition of effective contraception will be based on investigator discretion. Female and male patients are advised to use effective contraceptives for at least 9 months after the last treatment dose. * Ability to understand and willing to sign informed consent form Exclusion: * A history of other disease, metabolic dysfunction, physical examination finding or clinical laboratory test result suspicious of a disease or condition which, in the opinion of the investigator, would compromise patient safety due to risk of treatment complications or could affect interpretation of the study results * Ampullary, acinar, squamous, and neuroendocrine histology * Presence of central nervous system metastases * Life expectancy \< 12 weeks * Pregnant or breastfeeding women * Prior neuropathy \> grade 1 as per CTCAE v5 * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. * Major surgery within 4 weeks prior to initiation of the study treatment, without full recovery * Any past chemotherapy delivered for metastatic pancreatic cancer * Known somatic or germline mutations in BRCA1, BRCA2, or PALB2 * Active second malignancy whose prognosis has a high likelihood of impacting survival * Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results. Patients also unwilling or unable to comply with study procedures and/or study visits, including long-term follow-up for survival.