Safety and Efficacy of APX005M With Gemcitabine and Nab-Paclitaxel With or Without Nivolumab in Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma

Inclusion Criteria

• •2. Prior resection surgery is allowable.
• •2. Subjects must not have another active invasive malignancy, with the following exceptions and notes:
• •1. History of a non-invasive malignancy, such as cervical cancer in situ, non-melanomatous carcinoma of the skin, in situ melanoma, or ductal carcinoma in situ of the breast, is allowed.
• •2. History of malignancy that is in complete remission after treatment with curative intent is allowed.
• •3. No current or history of a hematologic malignancy is allowed, including subjects who have undergone a bone marrow transplant.
• •3. History of clinically significant sensitivity or allergy to monoclonal antibodies, their excipients, or intravenous gamma globulin
• •4. Previous exposure to CD40, PD-1, PD-L1, CTLA-4 antibodies or any other immunomodulatory agent
• •5. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease
• •6. Subjects must not have a known or suspected history of an autoimmune disorder, including but not limited to inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of investigational agent, except for the following.
• •a. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders such as vitiligo, or alopecia not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are eligible.
• •7. Subjects must not have an uncontrolled intercurrent illness, including an ongoing or active infection, current pneumonitis, symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina, uncontrolled hypertension, cardiac arrhythmia, interstitial lung disease, active coagulopathy, or uncontrolled diabetes.
• •8. Subjects must not have a history of myocardial infarction within 6 months or a history of arterial thromboembolic event within 3 months of the first dose of investigational agent.
• •9. Subjects must not have a history of human immunodeficiency virus, hepatitis B, or hepatitis C, except for the following:
• •1. subjects with anti-hepatitis B core antibody but with undetectable HBV DNA and negative for HBsAg
• •2. subjects with resolved or treated HCV (i.e. HCV antibody positive but undetectable HCV RNA)
• •10. Subjects must not have a history of primary immunodeficiency.
• •11. Subjects must not receive concurrent or prior use of an immunosuppressive agent within 14 days of the first dose of investigational agent, with the following exceptions and notes:
• •1. Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted. Steroids as anti-emetics for chemotherapy are not allowed.
• •2. Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted.
• •3. Subjects with a condition with anticipated use of systemic steroids above the equivalent of 10 mg prednisone are excluded.
• •12. Subjects must not have a history of clinically manifested central nervous system (CNS) metastases.