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