Safety Study of Nivolumab With Nab-Paclitaxel Plus or Minus Gemcitabine in Pancreatic Cancer, Nab-Paclitaxel / Carboplatin in Stage IIIB/IV Non-Small Cell Lung Cancer or Nab-Paclitaxel in Recurrent Metastatic Breast Cancer

Inclusion Criteria

• Subject is male or female, ≥ 18 years old at the time of signing the informed consent form (ICF).
• Subject has a confirmed diagnosis of advanced unresectable solid tumors in the target subject population within the parameters mentioned:
• Pancreatic Cancer
• Subject has a definitive histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas. Subjects with islet cell neoplasms are excluded.
• nab-Paclitaxel and Nivolumab: Subjects must have received 1 prior systemic chemotherapy regimen for locally advanced or metastatic disease.
• nab-Paclitaxel + Nivolumab and nab-paclitaxel, Gemcitabine and Nivolumab: Subjects must have received no previous systemic chemotherapy or investigational therapy for the treatment of pancreatic adenocarcinoma, including neo-adjuvant or adjuvant therapy, with the exception of prior treatment administered as a radiosensitizer concomitant with radiotherapy in the adjuvant setting. In this case, ≥ 6 months must have elapsed since completion of the last dose and no lingering toxicities may be present. Initial diagnosis of metastatic disease must have occurred ≤ 6 weeks prior to randomization in the study.
• Non-small Cell Lung Cancer (NSCLC):
• Subject has definitive histologically or cytologically confirmed Stage IIIB or IV NSCLC.
• Subjects must have received no previous chemotherapy or investigational therapy for the treatment of metastatic disease. Adjuvant, neo-adjuvant chemotherapy or chemoradiotherapy is permitted providing cytotoxic chemotherapy was completed > 12 months prior to randomization, without disease recurrence or progression during those 12 months.
• Metastatic Breast Cancer: Human Epidermal Growth Factor Receptor 2 - negative (HER2(-)) recurrent Metastatic Breast Cancer:
• Subject has a definitive histologically or cytologically confirmed diagnosis of HER2(-) metastatic breast cancer.
• Subject has received zero to one prior cytotoxic chemotherapy regimen for metastatic disease, regardless of prior targeted therapy (eg. everolimus, palbociclib or lapatinib), biologic (eg. trastuzumab) or hormonal therapy treatment (eg. aromatase inhibitors, selective estrogen receptor modulators, or estrogen receptor down-regulators).
• If subject has received solvent-based paclitaxel (TAXOL) or docetaxel as adjuvant chemotherapy, subject must not have relapsed with breast cancer within 12 months of completing said therapy.
• Suitable candidate for single agent nab-paclitaxel as assessed by the investigator.
• Subject has measurable disease according to RECIST 1.1. 4. Archival formalin-fixed, paraffin-embedded tumor sample collected within 90 days prior to subject consent available or subject has biopsiable metastatic lesion and is willing to undergo biopsy .
• Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Subject has no other malignancy within 5 years, except non-melanoma skin cancer, cervical intraepithelial neoplasia, or in-situ cervical cancer or incidental histological finding of prostate cancer (TNM stage of T1a or T1b); all treatments of which should have been completed 6 months prior to signing ICF.
• Subject has the following laboratory values at screening:
• WBCs ≥ 2000/uL,
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L,
• Hemoglobin (Hgb) ≥ 90 g/L,
• Platelets (plt) ≥ 100 x 109/L,
• Potassium within normal range, or correctable with supplements,
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 3.0 x ULN if liver tumor is present,
• Serum total bilirubin ≤ 1.5 x ULN (except in subjects with Gilbert's who may have serum bilirubin < 3.0 x ULN),
• Serum creatinine ≤ 1.5 x ULN, or 24-hr clearance ≥ 60 mL/min,
• Normal coagulation [prothrombin time and partial thromboplastin time within normal limits (±15%)].
• Subject has resting baseline oxygen saturation by pulse oximetry of ≥ 92% at rest.
• Females of child-bearing potential (defined as a sexually mature woman who: 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or, 2) has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 consecutive months) must: a. Agree in writing to use two forms of medical doctor-approved contraception throughout the study (without interruptions while on study treatment) and subsequently for 23 weeks5 months. b. Have a negative serum pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of β hCG) at screening and 24 hours prior to the start of any IP and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy.
• Male subjects agree in writing to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 7 months following IP discontinuation, even if he has undergone a successful vasectomy.
• Subject or his/her legally authorized representative or guardian understands and voluntarily signs an informed consent document prior to any study related assessments/procedures are conducted (except as noted in Section 6).
• Subject is able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria

• Subject has a history of allergy or hypersensitivity to any study drugs or their excipients.
• Subject has had prior therapy with T-cell immune modulating antibodies, including anti-CTLA-4, anti-PD-1 or anti-PD-L1.
• Subject has symptomatic brain metastases, spinal cord compression, or intractable back pain due to compression of destructive mass.
• Subject has active, known or suspected autoimmune disease, including systemic lupus erythematodes, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa or auto-immune hepatitis. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Subject is currently receiving or requires treatment with immunosuppressive agents or immunosuppressive doses of systemic corticosteroids (unless used to treat drug-related adverse events).Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption), and some uses of systemic corticosteroids are permitted as per Section 9.1.
• Subject has any peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events ) Grade 2 at randomization/enrollment.
• Subject has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies. Any lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Subject has a high cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year.
• Subject has unstable angina, a significant cardiac arrhythmia, or New York Heart Association Class 3 or 4 congestive heart failure.
• Subject has a history of peripheral artery disease (eg, claudication, Leo Buerger's disease).
• Subject has had major surgery, other than diagnostic surgery, within 4 weeks prior to treatment in study.
• Subject has known acute or chronic pancreatitis.
• Subject has persistent diarrhea, malabsorption, or known sub-acute bowel obstruction ≥ NCI CTCAE Grade 2, despite medical management.
• Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Subject has any history of testing positive for Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency disorder (AIDS).
• Subject has active hepatitis B or C. Subject with hepatitis in medical history may be eligible if infection considered cleared, ie core Ab+, surface Ab+, surface Ag- for hep B and Ab+/DNA- for hep C.
• Subject is pregnant or breast-feeding. Women must not breast-feed until at 5 months after completion of study participation..
• Subject is currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug.
• Subject is currently using or use within 6 months of illicit drugs.
• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Subject has any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Subject has any condition that confounds the ability to interpret data from the study.