Plerixafor and Cemiplimab for the Treatment of Metastatic Pancreatic Cancer

Inclusion Criteria

• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Have histologically- or cytologically-proven ductal adenocarcinoma of the pancreas
• Have metastatic disease
• Have documented radiographic disease progression at the time of study enrollment, after previous systemic chemotherapy given in a neoadjuvant, adjuvant, locally advanced or metastatic setting
• 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
• Life expectancy of greater than 3 months
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,000/mcL
• Platelets >= 90 x 10^3/uL
• Hemoglobin >= 8.0 g/dL
• Total bilirubin =< 1.5 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 glutamate pyruvate transaminase [SGPT]) =< 3.0 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 >= 3.0 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 enrollment for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 4 weeks (duration of ovulatory cycle) for a total of 5 months post treatment completion * Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion * 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

• Patient has a known history or evidence of brain metastases
• Patient who has had chemotherapy, radiation, or biological cancer therapy within 14 days prior to the first dose of study drug
• Patient has received an 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
• Patients who have had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement
• Patients who have received any prophylactic vaccine within 14 days of first dose of study drug or received a live vaccine within 30 days of planned start of study therapy
• Patients with a history of prior treatment with an anti-CXCR4 agent
• Currently using any chronic systemic steroids (at doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy (steroid premedication for contrast is allowed)
• Patients receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of study drug administration. Use of such agents while on study is also prohibited
• History of severe hypersensitivity reaction to any monoclonal antibody. Exceptions may be approved by protocol chair if the patient has subsequently tolerated an antibody
• Evidence of clinical or radiographic ascites. Trace or small amounts of radiographic ascites may be approved by the protocol chair
• History of clinically significant and/or malignant pleural effusion
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Subjects with active autoimmune disease. Subjects with Graves or Hashimoto’s disease, vitiligo, type I diabetes mellitus, psoriasis or other conditions not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects with autoimmune conditions requiring systemic treatment in the past may be approved by the protocol chair
• Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Exceptions can be approved by the protocol chair if loss of the graft is not a clinical concern. 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) 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
• Have received a diagnosis of human immunodeficiency virus (HIV), hepatitis B (hep B surface antigen [sAg] negative permitted) or hepatitis C (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 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 is pregnant or breastfeeding
• Have rapidly progressing disease, as judged by the investigator (e.g., rapid progression through prior treatment[s])
• History of significant, recurrent, unexplained postural hypotension in the last 6 months