Nivolumab with or without Cabiralizumab for the Treatment of Resectable Biliary Tract Cancer

Inclusion Criteria

• Have histologically confirmed biliary tract cancer that is considered resectable by a hepatobiliary surgeon
• Be willing and able to provide written informed consent/assent for the trial
• 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 principal investigator)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale at study entry
• Absolute neutrophil count (ANC) >= 1,500 mcL (within 7 days of treatment initiation)
• Platelets >= 100,000/mcL (within 7 days of treatment initiation)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (within 7 days of treatment initiation)
• Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (within 7 days of treatment initiation) (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) * Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (expect participants with Gilbert's syndrome who must have normal direct bilirubin) (within 7 days of treatment initiation) * Note: Hyperbilirubinemia secondary to tumor-associated extrahepatic biliary obstruction is allowed
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X ULN (within 7 days of treatment initiation)
• Albumin > 3.0 gm/dL (within 7 days of treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 7 days of treatment initiation)
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 7 days of treatment initiation)
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 24 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the case of a positive human chorionic gonadotropin (HCG) test, a transvaginal ultrasound must be used to confirm lack of pregnancy
• Female subjects of childbearing potential should be willing to use highly effective methods: hormonal contraception or IUD (intra-uterine device or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy

Exclusion Criteria

• Receiving, or previously received any chemotherapy or radiation therapy for biliary tract cancer
• Has an active, known, or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Grave’s disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll after discussing with the Bristol-Myers Squibb (BMS) medical monitor. Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease * Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study treatment is permitted
• Previous malignancies (except non-melanoma skin cancers, and in situ bladder, gastric, colorectal, endometrial, cervical/dysplasia, melanoma, or breast cancers) unless complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period
• Has ever had prior therapy involving anti-PD-1, anti-PD-L1, or anti-CSF-1R antibody (or any other antibody targeting T cell co-regulatory pathways)
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis
• Has evidence of an uncontrolled, active infection requiring parenteral anti-bacterial, antiviral or anti-fungal therapy =< 7 days prior to administration of study medication
• Has received a blood transfusion within 72 hours prior to first dose of study drug administration
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Major surgery within 4 weeks prior to initiation of study treatment
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Has received non-oncology vaccine therapies for prevention of infectious diseases (e.g., human papillomavirus vaccine) within 4 weeks of study drug administration. The inactivated seasonal influenza vaccine can be given to patients before treatment and while on therapy without restriction. Influenza vaccines containing live virus or other clinically indicated vaccinations for infectious diseases (i.e., pneumovax, varicella, etc) may be permitted, but must be discussed with the investigational new drug (IND) sponsor and may require a study drug washout period prior to and after administration of vaccine
• Has a history of allergy to study treatments or any of its components of the study arm that the participant is enrolling
• Has uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: * Myocardial infarction or stroke/transient ischemic attack within the past 6 months * Uncontrolled angina within the past 3 months * Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes) * History of other clinically significant heart disease (e.g., cardiomyopathy, congestive heart failure with New York Heart Association functional classification III to IV, pericarditis, significant pericardial effusion, or myocarditis) * Cardiovascular disease-related requirement for daily supplemental oxygen therapy
• Has any of the following conditions specific to cabiralizumab administration: * Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum creatine kinase (CK) levels * Concomitant use of statins while on study. However, a patient using statins for over 3 months prior to study drug administration and in stable status without CK rise may be permitted to enroll * Known history of sensitivity to infusions containing Tween 20 (polysorbate 20) and Tween 80 (polysorbate 80)