Sotorasib Combined With First-line Chemotherapy for Advanced Pancreatic Adenocarcinoma

Inclusion Criteria: 1\) Willing and able to provide informed consent. 2) Men or women aged ≥ 18 years old. 3) Using effective contraceptive measures or sexual abstinence during the treatment, up to 7 days after the last dose of sotorasib, for at least 6 months after the last dose of gem/nab-P and for 15 months after the last dose of mFOLFIRINOX for woman of childbearing age and 12 months after stopping mFOLFIRINOX for men: * Female of childbearing potential using a highly effective method of contraception (i.e., a method with less than 1% failure rate \[e.g., sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner\]) * Male agreeing to use condoms or having a partner who is using a highly efficient method of contraception as described above 4) Pathologically confirmed treatment-naïve of locally advanced or metastatic pancreatic adenocarcinoma harboring KRAS p.G12C mutation assessed by means of a IVDR compliant test) 5) Measurable disease per RECIST 1.1 criteria. 6) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 7) Life expectancy \> 3 months, in the opinion of the investigator. 8) Adequate hematologic, renal and hepatic organ function, defined as the following within 10 days prior study inclusion: * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility) * Hemoglobin ≥ 9.0 g/dL (without transfusion within 2 weeks of laboratory test used to determine eligibility) * Platelet count ≥ 100 x 109/L (without transfusion within 2 weeks of laboratory test used to determine eligibility) * Aspartate aminotransferase (AST) and ALT ≤ 2.5 times the upper limit of normal (ULN) or ≤5 times if liver metastasis * Serum bilirubin ≤ 1.5 x ULN * International normalized ratio (INR) ≤ 1.5 x ULN. Prothrombin time (PT) ≤ 1.5 x ULN may be used instead of INR for sites whose laboratory do not report INR * Creatinine clearance ≥ 30 mL/min (estimated by Cockcroft-Gault equation) 9) Ability to take oral medications and willing to record daily adherence to investigational product. Exclusion Criteria: 1. Patients with resectable or borderline resectable pancreatic cancer. 2. Known history or positive viral test for human immunodeficiency virus (HIV). 3. Peripheral sensory neuropathy. 4 )Proven complete dihydropyrimidine dehydrogenase (DPD) deficiency for patients that will be treated with mFOLFIRINOX. 5\) Poor nutritional status (albumin \<3 g/L or weight loss \>10% during the last 4 weeks). 6\) Patients with known active hepatitis (i.e., Hepatitis B or C) * Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible * Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA 7) Female: currently pregnant or breast-feeding or who plan to breastfeed while on study though 7 additional days after the last dose of sotorasib and for at least 6 months afterwards after the last dose of gem/nab-P or 15 months after the last dose of mFOLFIRINOX. 8\) Myocardial infarction within 6 months of study Day 1, symptomatic congestive heart failure (New York Heart Association \> class II), unstable angina, or cardiac arrhythmia requiring medication 9) Prior anti-tumor treatment for metastatic or locally advanced pancreatic adenocarcinoma\*. Prior chemotherapy or radiotherapy in the adjuvant or neoadjuvant setting is acceptable if received \> 6 months prior to study enrolment \*If initiation of treatment is deemed urgent by the investigator, patients can receive 1st month of Standard of Care (SoC) gem/nab-P (1 cycle) or FOLFIRINOX (2 cycles) during screening. This first month of gem/nab-P or FOLFIRINOX is not a requirement of the study and is not part of this clinical study 10) Active infection requiring antibiotics within 1 weeks of study enrollment. 11) Other malignancy unless curatively treated with no evidence of disease for ≥2 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, and/or ductal carcinoma in situ. 12\) Significant gastrointestinal disorder that results in significant malabsorption, requirement for IV alimentation, or inability to take oral medication. 13\) History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis. 14\) Presence of any condition that, in the opinion of the investigator, renders the patient at high risk from treatment complications or might affect the interpretation of the results of the study. 15\) Significant uncontrolled concomitant disease that could affect compliance with protocol procedures or interpretation of results or that pose a risk to patient safety, in the opinion of the investigator. 16\) Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly. Patients with PleurX catheters or intraperitoneal drainage catheters in place may be considered for the study with Medical Monitor approval. 17\) Major surgery within 4 weeks of study Day 1 18) Prior/concomitant therapy: * Previous treatment with a KRASG12C inhibitor * Use of warfarin. Other anticoagulation may be allowed * Use of known cytochrome P450 (CYP) 3A4 sensitive substrates and P-glycoprotein (P-gp) substrates (with a narrow therapeutic window), within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer, prior to study Day 1 (see examples of sensitive substrates and P-glycoprotein substrates in Appendix A) except for those investigational treatments administered as part of the study scheme that will be subject to specific PK analysis. * Use of strong inducers of CYP3A4 (including herbal supplements such as St John's wort) within 14 days or 5 half-lives (whichever is longer) prior to study Day 1 (see examples of strong inducers of CYP3A4 in Appendix A) * Live attenuated vaccines (against yellow fever, chickenpox, shingles, measles, mumps, rubella, tuberculosis, rotavirus and influenza), within 30 days prior of the first dose of study treatment. * Brivudine-based treatments within 4 weeks before treatment with 5-fluorouracil. 19) Patient has known sensitivity to any of the products or components to be administered during the study. 20\) History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion.