Retifanlimab for the Treatment of Unresectable or Metastatic Pancreatic Cancer

Inclusion Criteria

• Have histologically- or cytologically-proven adenosquamous carcinoma of the pancreas by central pathologic review. Patients must have squamous component to be included. All pathology will be reviewed at the Johns Hopkins Department of Pathology
• Have unresectable or metastatic disease
• Must have received (or been intolerant to, ineligible for, or refused) at least 1 prior line of cytotoxic chemotherapy and received no more than 2 prior systemic treatments
• Presence of at least one lesion with measurable disease as defined by 10 mm in longest diameter for a soft tissue lesions or 15 mm in short axis for a lymph node by RECIST 1.1
• Patient’s acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• If human immunodeficiency virus (HIV)-positive, then all of the following criteria must also be met: CD4+ count >= 350/uL, undetectable viral load, and receiving highly active antiretroviral therapy
• Life expectancy of greater than 3 months
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 75 x 10^3/uL
• Hemoglobin >= 8.0 g/dL
• Total bilirubin =< upper limit of normal (ULN) except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x ULN
• Alkaline phosphatase =< 5.0 x ULN
• Creatinine =< 1.5 x ULN or creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula)
• Albumin >= 2.5 g/dL
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]). NOTE: If a patient has a positive or indeterminate serum or urine pregnancy test, then an ultrasound must be done to rule out pregnancy to enroll on trial. * WOCBP must agree to follow instructions for method(s) of contraception from the time of screening, through the duration of treatment with study drug plus 6 months after the last dose of study drug * Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception from the time of screening, through the duration of treatment with study drug plus 6 months after the last dose of study drug * At least one barrier method of contraception must be employed by all sexually active patients (male and female), regardless of other methods, to prevent the transfer of body fluids
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

• Patients with known high-frequency microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR) adenosquamous pancreatic cancer
• Patient has a known history or evidence of active brain/central nervous system (CNS) metastases. Patients with treated brain/CNS metastases by surgery or radiation who are not on steroid therapy for this indication and have a stable magnetic resonance imaging (MRI) brain for 3 months are eligible for the study
• Patient who has had chemotherapy, radiation, or biological cancer therapy within 14 days prior to the first dose of study drug. With the following caveats: 28 days for pelvic radiotherapy, 6 months for thoracic region radiotherapy that is > 30 Gy. Hormonal therapy in the setting of a second, hormone-sensitive malignancy not thought to have impact on longevity (i.e prostate cancer, early stage breast cancer) are allowed at the discretion of the principal investigator
• Patient has received an antineoplastic investigational agent or used an investigational device within 28 days of the first dose of study drug
• Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study. Exceptions are hormonal therapy in the setting of a second, hormone-sensitive malignancy not thought to have impact on longevity (i.e. prostate cancer, early stage breast cancer)
• Patients who have had major surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, port placement, etc.), celiac plexus block, biliary stent placement, etc.
• Patients who have received a live vaccine within 28 days prior to the first dose of study drug. Seasonal influenza vaccines for injection are generally killed virus and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed
• Patients with a history of prior treatment with immune checkpoint inhibitor therapy including anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, anti-OX40, and anti-LAG-3 antibodies
• Have used any systemic steroids within 14 days of study treatment
• History of severe hypersensitivity reaction to any monoclonal antibody
• Evidence of clinical or radiographic ascites. Trace or small amounts of radiographic ascites may be approved by the Investigational New Drug (IND) Sponsor
• Have clinically significant and/or malignant pleural effusion (pleural effusions that are not clinically significant are allowed, defined as no more than 25% fluid level of the corresponding hemithorax and stable fluid level [non-progressive] over at least 6 weeks documented radiographically)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of autoimmune disease requiring systemic immunosuppression within the last 2 years
• Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded
• All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE], version 5.0) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long-lasting sequelae, such as neuropathy after chemotherapy, are permitted to enroll
• Known active hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection, as defined by elevated transaminases with the following serology: positivity for HAV IgM antibody, hepatitis C antibody (anti-HCV), hepatitis B core antibody (anti-HBc) IgG or IgM, or hepatitis B surface antigen (HBsAg) (in the absence of serology suggesting prior immunization or achieve immunity). Patients who are hepatitis C antibody positive may be enrolled if they are confirmed with negative viral load at screening
• Patient has a pulse oximetry of =< 92% on room air
• Patient is on supplemental home oxygen
• Patient has an unhealed surgical wound or ulcer, or a bone fracture considered non-healing
• Patient has clinically significant heart disease (such as uncontrolled angina, myocardial infarction within the last 3 months or congestive heart failure of New York Heart Association III or IV)
• Patient is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements
• Patient is unwilling or unable to follow the study schedule for any reason
• Patient has history of non-infectious pneumonitis