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

Inclusion Criteria

• •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.
• •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.