Study of Sotorasib Combined With Chemotherapy for Second Line Treatment of Pancreas Cancer

Inclusion Criteria: Subject must meet all of the following applicable inclusion criteria to participate in this study: * Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. * Age ≥ 18 years at the time of consent. * ECOG Performance Status of 0-1 within 14 days prior to registration. * Histological or cytological confirmation of pancreatic cancer per AJCC, 8th edition. * Unresectable or metastatic pancreatic cancer. * Measurable disease according to RECIST 1.1 within 28 days prior to registration. * KRAS p. G12C mutation by CLIA certified molecular testing of tumor biopsy or blood based circulating tumor DNA. NOTE: patients must have KRAS p.G12C molecularly confirmed previously or have archived tissue sent for testing and/or undergo biopsy confirming KRAS p.G12C mutation prior to enrollment. * Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration: * Hematological * Absolute Neutrophil Count (ANC): ≥ 1.5 x 109/L * Hemoglobin (Hgb): ≥ 9 g/dL; Transfusion permitted within 1 week * Platelet Count (Plt): ≥ 100 x 109/L * Renal * Calculated creatinine clearance1: ≥ 50 mL/min * Creatinine (Cr): ≤ 1.5 × upper limit of normal (ULN) * Hepatic * Bilirubin: ≤ 1.5 × upper limit of normal (ULN) * Aspartate aminotransferase (AST) : ≤ 2.5 × ULN; if liver metastases are present, ≤ 5 x ULN * Alanine aminotransferase (ALT): ≤ 2.5 × ULN; if liver metastases are present, ≤ 5 x ULN * Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT): ≤ 1.5 × ULN; this would not apply to patient's on anti-coagulation therapy (which is permitted on study; EXCEPT Warfarin) * Progression of disease after first line chemotherapy or recurrent disease either during or \< 6 months after last dose of systemic therapy administered for curative intent. * Prior cancer treatment (including investigational agents) must be completed at least 2 weeks prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia or neuropathy) to Grade ≤ 1 or baseline. * Life expectancy \> 3 months in the opinion of the investigator. * Therapeutic or palliative radiation \>/= 2 weeks from registration is allowed provided subject has recovered from all reversible acute toxic effects to Grade \</= 1 or baseline. * Ability to take oral medications. * Females of childbearing potential with a male partner able to father a child must have a negative pregnancy test within 7 days prior to registration. See protocol for definition of childbearing potential. * Females of childbearing potential with a male partner able to father a child and male participants able to father a child who have a female partner of childbearing potential must be willing to abstain from heterosexual intercourse or to use effective method(s) of contraception as outlined in protocol. * As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. Exclusion Criteria: Subjects meeting any of the criteria below may not participate in the study: * Receipt of two or more lines of chemotherapy. NOTE: Adjuvant or neoadjuvant therapy would be counted as one line of therapy if recurrence or development of metastatic disease occurred within 6 months of last dose of adjuvant/neoadjuvant therapy. * Previous treatment with a KRASG12C inhibitor. * Patient unable to receive nal-IRI/5FU/LV or GEM/nab-paclitaxel as second line chemotherapy for pancreatic cancer. * Grade 2 or higher neuropathy preventing treatment with abraxane containing regimen. * History of pneumonitis and/or interstitial lung disease (ILD). * Active brain metastases and/or carcinomatous meningitis from non-brain tumors. NOTE: Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study Day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade ≤ 2; b) on stable doses of dexamethasone, if applicable; and c) follow-up magnetic resonance imaging (MRI) performed within 28 days shows no new lesions appearing. * Active infection requiring antibiotics within 1 week of enrollment. * Cardiac dysfunction: * Myocardial Infarction within 6 months of enrollment * NYHA \> class II CHF * unstable angina * arrhythmia requiring medication * QTc \> 470msec. * Has a known history of Hepatitis B or C. NOTE: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. NOTE: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. * Has a known history of Human Immunodeficiency Virus (HIV) infection. NOTE: Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed if they are stable and have been on treatment for ≥ 4 weeks prior to first dose of study drug(s). Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy. Testing not required.no testing for HIV is required unless mandated by local health authority. * Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial. * History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥ 2 years. * Surgery within 28 days of enrollment. * Known dihydropyrimidine dehydrogenase deficiency. * Use of known CYP3A4 and P-gp sensitive 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 that was not reviewed and approved by the principal investigator. * 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 that was not reviewed and approved by the principal investigator. * Female subjects who are breastfeeding or who plan to breastfeed while on study and through the timeframe as described in protocol (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). Male participants who plan to donate sperm while on study and through the timeframe as described in protocol. * Use of warfarin. NOTE: use of low molecular weight heparin (LMWH) are permitted. * Acid reducing agents including proton pump inhibitors (PPIs) and H2 receptor antagonists. Alternative agents to acid reducing agents are permitted. If an acid-reducing agent cannot be avoided, administer sotorasib 4 hours before or 10 hours after acid-reducing agent use.