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

Not Recruiting

Trial ID: NCT03214250


The main purposes of this study are to learn how effective the study drug combinations are in treating patients with metastatic pancreatic adenocarcinoma. The drug combinations are APX005M+Nivolumab+Gemcitabine+nab-Paclitaxel, or APX005M+Gemcitabine+nab-Paclitaxel.

Official Title

Open-label, Multicenter, Phase 1b/2 Clinical Study to Evaluate the Safety and Efficacy of CD40 Agonistic Monoclonal Antibody (APX005M) Administered Together With Gemcitabine and Nab-Paclitaxel With or Without PD-1 Blocking Antibody (Nivolumab) in Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma

Stanford Investigator(s)

George A. Fisher Jr.
George A. Fisher Jr.

Colleen Haas Chair in the School of Medicine


Inclusion Criteria:

   1. Subject has histologically or cytologically documented diagnosis of pancreatic
   adenocarcinoma with metastatic disease. Locally advanced subjects are not eligible.

   2. Subject must have measureable disease by RECIST 1.1.

   3. Subjects must be age 18 years or older.

   4. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of
   0 or 1.

   5. Subjects must have the following laboratory values at screening within 2 weeks of the
   first dose of investigational agents:

      - Absolute neutrophil count (ANC) ≥1.5 x 109/L (in absence of growth factor

      - Platelet count ≥150 x 109/L

      - Hemoglobin ≥9 g/dL(without transfusion support)

      - Serum creatinine ≤1.5 mg/dL, and creatinine clearance ≥ 50 ml/min as measured by
      Cockcroft and Gault formula

      - Aspartate aminotransferase (AST) and ALT ≤2.5 x upper limit of normal (ULN)

      - Total bilirubin ≤1.5 x ULN, except in subjects with documented Gilbert's
      Syndrome, who must have a total bilirubin ≤3 x ULN

   6. Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum or
   urine) within the 7 days prior to study drug administration, and within the 3 days
   before the first study drug administration, or a negative pregnancy test within the 24
   hours before the first study drug administration.

   7. WOCBP and male subjects who are sexually active with WOCBP must agree to use 2 highly
   effective methods of contraception (including a physical barrier) before the first
   dose of study drugs, during the study, and for 5 months for women and 7 months for men
   following the last dose of study drug.

   8. Subjects must have the ability to understand and willingness to sign a written
   informed consent document.

Exclusion Criteria:

   1. Subject must not have received any prior treatment, including chemotherapy, biological
   therapy, or targeted therapy for metastatic pancreatic adenocarcinoma, with the
   following exceptions and notes:

      1. Subjects who have received prior adjuvant therapy for pancreatic adenocarcinoma
      are eligible if neoadjuvant and adjuvant therapy (including chemotherapy and/or
      radiotherapy) was fully completed more than 4 months before the start of study
      treatment. In this case, prior Gem and/or NP is allowable

      2. Prior resection surgery is allowable.

      3. Patients initially diagnosed with locally advanced pancreatic cancer who have
      undergone chemotherapy then resection and were with no evidence of disease are
      eligible if metastatic relapse of disease has occurred and if the last dose of
      chemotherapy was more than 4 months before the data of study entry.

   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

   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

   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

   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

      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)

   a. Subjects with known or suspected leptomeningeal disease or cord compression are not

13. Subjects must not have had major surgery as determined by the PI within 4 weeks before
   the first dose of investigational agent.

14. Subjects must not have received another investigational agent within the shorter of 4
   weeks or 5 half-lives before the first dose of investigational agent.

15. Subjects must not have received a live attenuated vaccine within 28 days before the
   first dose of investigational agent, and subjects, if enrolled, should not receive
   live vaccines during the study or for 180 days after the last dose of investigational

16. Females who are pregnant or lactating or who intend to become pregnant during
   participation in the study are not eligible to participate.

17. Subjects who are of reproductive potential who refuse to use effective methods of
   birth control during the course of participation of the study and within 5 month for
   women and 7 months for men of the last dose of investigational agent are ineligible to
   participate in the study.

18. Subjects who have any clinically significant psychiatric, social, or medical condition
   that, in the opinion of the investigator, could increase the subject's risk, interfere
   with protocol adherence, or affect the subject's ability to give informed consent are
   ineligible to participate in the study.


drug: APX005M

drug: Nivolumab

drug: Nab-Paclitaxel

drug: Gemcitabine

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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