The purpose of this research study is to learn more about a new combination of drugs being
given to treat pancreatic cancer. The drugs being tested are BMS-813160, nivolumab,
gemcitabine, and nab-paclitaxel. The investigators will be looking at both the side effects
and the way the disease responds to treatment.
- Histologically or cytologically confirmed locally advanced or borderline resectable
pancreatic ductal adenocarcinoma. Patients with clinical suspicion of pancreatic
adenocarcinoma can be enrolled for pre-treatment biopsy, and must be histologically
confirmed to have adenocarcinoma before being treated on study. Patients with squamous
carcinoma, adenosquamous carcinoma or neuroendocrine tumor will be excluded. Tumor
Biopsy can be omitted, if deemed by PI and treatment physician, that it may incur
immediate, excessive health risks to patients. This determination (rationale and
discussion with PI and treating physician) should be clearly documented in the
screening visit notes.
- Measurable disease defined as lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI.
- At least 18 years of age.
- ECOG performance status ≤ 1
- Normal bone marrow and organ function as defined below:
- Leukocytes ≥ 2,000/mcL
- Absolute neutrophil count ≥ 1,500/mcl
- Hemoglobin ≥ 8.5 g/dL
- Platelets ≥ 100,000/mcl
- Total bilirubin ≤ 1.5 x IULN (except participants with Gilbert's Syndrome who
must have normal direct bilirubin)
- AST(SGOT)/ALT(SGPT) ≤ 3 x IULN
- Serum albumin ≥ 3g/dL
- Creatinine ≤ 1.5 x IULN OR creatinine clearance ≥ 40 mL/min by Cockcroft-Gault
for patients with creatinine levels above institutional normal
- Women of childbearing potential and men must agree to use at least two forms of
contraception (hormonal, barrier method of birth control, abstinence, and must include
barrier method) prior to study entry, for the duration of study participation, and
through 5 months (for women) or 7 months (for men) after the last dose of treatment on
this study. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she must inform her treating physician immediately.
- Able to understand and willing to sign an IRB approved written informed consent
- 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 [NCI CTCAE] v5.0) or baseline before administration of study
treatment. Participants with toxicities attributed to prior anti-cancer therapy that
are not expected to resolve and result in long lasting sequelae, such as neuropathy
after platinum-based therapy, are permitted to enroll.
- Prior exposure to chemotherapy or radiation for the disease to be treated on this
trial not allowed.
- Previous malignancies (except non-melanoma skin cancers, and in situ bladder, gastric,
colorectal, endometrial, cervical/dysplasia, melanoma, or breast cancers) unless a
complete remission was achieved at least 2 years prior to study entry AND no
additional therapy is required during the study period. Other active malignancy
requiring concurrent intervention
- Currently receiving any other investigational agents, or exposure to any
investigational drug or placebo within 4 weeks of study treatment
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to BMS-813160, nivolumab, gemcitabine, paclitaxel,
nab-paclitaxel, or other agents used in the study.
- Prior exposure to anti-PD-1, anti-PD-L1, CCR2/5, or anti-CTLA4 antibodies.
- Taking immunomodulatory agents (including steroids and NSAIDs). A wash-out period of
at least 4 weeks or 5 half-lives, whichever is shorter, is required for patients
receiving immunomodulatory agents at the time of enrollment.
Note: daily use of low dose aspirin (e.g. 81 mg PO QD) is not considered an
immunomodulatory agent and patients are still eligible for enrollment despite taking such
medication at a low dose
- Participants with 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 Principal Investigator
- Participants with a condition requiring systemic treatment with either corticosteroids
(> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within
14 days of study treatment 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.
- History of allogeneic organ or stem cell transplant.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry and again within 24 hours prior to first
- Known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive)
or known active hepatitis C virus (by PCR).
- Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome. Anti-retroviral agents are known to have potential
adverse pharmacokinetic interactions with nivolumab and/or BMS-813160. IN addition,
patients not on anti-retroviral agents, regardless of HIV viral load, are at increased
risk of lethal infections with marrow-suppressive therapy including chemotherapy.
Testing for HIV must be performed at sites mandated by local requirements.
- Requires continued use of warfarin for anticoagulation and cannot stop warfarin or be
safely switched to another anticoagulant.
- Current or recent (within 3 months of study treatment administration) gastrointestinal
disease or conditions that could interfere with the swallowing or absorption of study
medication or inability to tolerate oral medication.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring parenteral anti-bacterial, anti-viral, or anti-fungal therapy ≤ 7
days prior to administration of study medication; immunosuppression; autoimmune
conditions; underlying pulmonary disease; or psychiatric illness/social situations
that would limit compliance with study requirements.
- Interstitial lung disease that is symptomatic or may interfere with the detection or
management of suspected treatment-related pulmonary toxicity.
- 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
- Uncontrolled angina within the past 3 months
- Any history of clinically significant arrhythmias (such as ventricular
tachycardia, ventricular fibrillation, or Torsades de pointes)
- QT interval corrected for heart rate using Fridericia's formula (QTcF)
prolongation > 480 msec
- History of other clinically significant heart disease (e.g. cardiomyopathy,
congestive heart failure with NYHA functional classification III-IV,
pericarditis, significant pericardial effusion, or myocarditis)
- Major surgery within 28 days prior to the first study treatment. Participants must
have recovered from the effects of major surgery or significant traumatic injury at
least 14 days before the first dose of study treatment.
- Concurrent use of medications/food which may interfere with BMS-813160 including any
strong inhibitors or inducers of CYP3A4 or P-gp is not allowed. These include but are
not limited to Class I antiarrhythmics (eg, quinidine, procainamide, dysopiramide,
lidocaine, phenytoin, mexiletine, tocainide, flecainide, propafenone, moricizine),
Grapefruit and Seville oranges.