Clinical Trials /

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

NCT03214250

Description:

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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: PICI0002
  • SECONDARY ID: UPCC 11217
  • NCT ID: NCT03214250

Conditions

  • Metastatic Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
APX005MGem/NP/APX005M
NivolumabOpdivoGem/NP/nivolumab
Nab-PaclitaxelAbraxaneGem/NP/nivolumab
GemcitabineGemzarGem/NP/nivolumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Gem/NP/nivolumabExperimentalGemcitabine+Nab-Paclitaxel+nivolumab
  • Nivolumab
  • Nab-Paclitaxel
  • Gemcitabine
Gem/NP/APX005MExperimentalGemcitabine+Nab-Paclitaxel+APX005M
  • APX005M
  • Nab-Paclitaxel
  • Gemcitabine
Gem/NP/nivolumab/APX005MExperimentalGemcitabine+Nab-Paclitaxel+nivolumab+APX005M
  • APX005M
  • Nivolumab
  • Nab-Paclitaxel
  • Gemcitabine

Eligibility Criteria

        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
                  support)

               -  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
             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.

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

         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
             agent.

         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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Time Frame:up to 6 month
Safety Issue:
Description:Phase 1b Primary Safety Outcome

Secondary Outcome Measures

Measure:Objective response rate (ORR) as determined by RECIST criteria
Time Frame:up to 6 month
Safety Issue:
Description:Phase 1b and Phase 2 Secondary Efficacy Outcome
Measure:Duration of response (DOR) defined as time from first documentation of response (complete response [CR] or partial response [PR]) to first documentation of progressive disease
Time Frame:up to 6 month
Safety Issue:
Description:Phase 1b and Phase 2 Secondary Efficacy Outcome
Measure:Disease control rate (DCR) is defined as the proportion of subjects who achieve a CR or PR or SD
Time Frame:up to 6 month
Safety Issue:
Description:Phase 2 Secondary Efficacy Outcome
Measure:Progression free survival (PFS) defined as the time from initiation of study therapy to date of first documented progression of disease, date of death due to any cause or date of most recent subject contact which documented progression free status
Time Frame:up to 6 month
Safety Issue:
Description:Phase 2 Secondary Efficacy Outcome

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Parker Institute for Cancer Immunotherapy

Trial Keywords

  • Nivolumab
  • APX005M
  • previously untreated metastatic pancreatic adenocarcinoma
  • Gemcitabine
  • nab-Paclitaxel

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