Age ≥18 years.
A fresh pre-treatment and on-treatment tumor biopsy must be provided for biomarker analysis. Participants must have a tumor that can be biopsied at an acceptable clinical risk as judged by the investigator to be eligible. An unsuccessful fresh tumor biopsy at screening will not exclude participants from receiving study treatment. The biopsy must be a core biopsy, an excisional biopsy, or a surgical specimen. Archival biopsies at screening are allowed if obtained ≤3 months prior to the first dose and meet tissue requirements as described in the laboratory manual, provided no intervening systemic anti-cancer treatment was administered within that period.
Histological confirmation of pancreatic adenocarcinoma with metastatic disease.
ECOG Performance Status (PS) 0 or 1.
Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Initial diagnosis of metastatic disease (as per American Joint Committee on Cancer 8th Edition [AJCC 2017]).
Electrocardiogram (ECG) without any clinically significant findings (QT interval corrected by Fridericia’s formula (QTcF) ≤450 msec and no known arrhythmias) and per the investigator’s assessment.
The following laboratory values obtained ≤15 days prior to registration:
Hemoglobin ≥9.0 g/dL (transfusion to achieve this level is not permitted within 2 weeks of first study treatment administration)
White blood cells (WBC) ≥2000/μL
Absolute neutrophil count (ANC) ≥1500/mm3 (stable off any growth factor within 4 weeks of first study treatment administration)
Platelet count ≥100,000/mm3 (transfusion to achieve this level is not permitted within 2 weeks of first study treatment administration)
Total bilirubin ≤ 1.5 x ULN, except in patients with documented Gilbert’s syndrome, who must have a total bilirubin ≤ 3 x ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 institution’s upper limit of normal (ULN) for patients with no concurrent liver metastases, OR ≤ 5.0 x institution’s ULN for patients with concurrent liver metastases
PT/INR/aPTT ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy
Calculated creatinine clearance ≥40 ml/min using the Cockcroft-Gault formula below: See Protocol
Negative pregnancy test done ≤8 days prior to registration, for persons of childbearing potential only.
Provide written informed consent.
Ability to complete questionnaire(s) by themselves or with assistance.
Willingness to provide mandatory blood specimens for correlative research (see Section 14.0).
Willingness to provide mandatory tissue specimens for correlative research (see Section 17.0).
Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
Willing to follow the requirements of the {Revlimid®/Pomalyst®} REMS program
Any of the following because this study involves an agent that has known genotoxic mutagenic and teratogenic effects:
Failure to recover from any adverse events related to any of the following therapies received prior to registration:
Minor surgical or interventional procedure
Major surgical procedure other than diagnostic surgery, within 4 weeks prior to registration.
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
Uncontrolled intercurrent illness including, but not limited to:
ongoing or active infection
symptomatic congestive heart failure ≤ 6 months before registration
unstable angina pectoris ≤ 6 months before registration
cardiac arrhythmia
coronary stenting or myocardial infarction ≤1 prior to registration
dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
psychiatric illness/social situations that would limit compliance with study requirements
Known historical or active infection with hepatitis B, or active infection with
hepatitis C (note that subjects with hepatitis C who have been clinically cured, defined as persistent absence of hepatitis C ribonucleic acid (RNA) detected by polymerase chain reaction (PCR) test in serum 12 weeks after completing antiviral treatment, are eligible for this study)
Active infection or an unexplained fever >38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumour fever may be enrolled), which in the investigator’s opinion might compromise the subject’s participation in the study or affect the study outcome.
Major surgery, other than diagnostic surgery, within 4 weeks prior to registration
Interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
Peripheral artery disease (e.g. claudication, Leo Buerger's disease).
Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma.
Known human immunodeficiency virus (HIV) positive with an acquired immune deficiency syndrome (AIDS)-defining opportunistic infection within the last year, or a current CD4 count <350 cells/μL. Participants with HIV are eligible if:
They have received antiretroviral therapy for ≥4 weeks prior to the first dose of study treatment, as clinically indicated, while enrolled on study.
They continue on antiretroviral therapy as clinically indicated while enrolled on study.
CD4 counts and viral load are monitored per standard of care by a local health care provider.
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
Other active malignancy ≤5 years prior to registration
EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (hormonal therapy, immunotherapy, chemotherapy, radiation) for their cancer.
History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
Prior treatment of pancreatic cancer in the metastatic setting with surgery,radiotherapy, chemotherapy or investigational therapy:
Documented serum albumin <3 g/dL within 7 days prior to registration.
Known history of central nervous system (CNS) metastases.
History of any prior chemotherapy, radiation therapy, immunotherapy, biologic ('targeted') therapy, or investigational therapy for pancreas adenocarcinoma. Palliative radiotherapy and placement of biliary stent/tube is permitted.
Steroids administered post-radiation therapy tapered to ≤ 10 mg prednisone (or equivalent) before starting study treatment.
Active, known, or suspected autoimmune disease (type 1 diabetes mellitus,hypothyroidism only requiring hormone replacement)
Systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) within 14 days or other immunosuppressive medications within 30 days of the first dose of study treatment.
Prior therapy with anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-CCR8 antibody.
Malignant disease other than that being treated in this study. Note: Participants with any of the following additional malignancies are not excluded:
Malignancies with negligible risk of metastases or death (e.g., risk of death or
metastases <5% at 5 years) that were treated with curative intent and have not recurred within the past 2 years prior to Study Day 1
Completely resected basal cell or squamous cell skin cancers, CIS of the cervix, or ductal CIS of the breast.
Malignancies considered to be indolent and never having required therapy.
Malignancies treated with hormonal therapy alone.
Receipt of an allogeneic tissue/solid organ transplant.
Any other clinically significant disease or comorbidity that may adversely affect the safe delivery of treatment within this trial or may limit compliance with study requirements in the opinion of the Investigator.
Known hypersensitivity to BMS-986340 or its metabolites and/or excipients and known hypersensitivity to any component of the regimens, their metabolites and/or excipients being used in the combination therapy cohorts for which the participant is being considered.
Unwillingness to follow study related procedures.
Inability to provide informed consent.