Clinical Trials /

MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study

NCT03611556

Description:

The objective of this study is to evaluate the safety, tolerability, and antitumor activity of oleclumab (MEDI9447) in combination with or without durvalumab plus chemotherapy in subjects with metastatic pancreatic cancer.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study
  • Official Title: A Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of Oleclumab (MEDI9447) With or Without Durvalumab in Combination With Chemotherapy in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: D6070C00005
  • SECONDARY ID: D6070C00005
  • NCT ID: NCT03611556

Conditions

  • Carcinoma
  • Metastatic Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
oleclumabMEDI9447Arm A2
durvalumabMEDI4736Arm A3
gemcitabineArm A1
nab-paclitaxelArm A1

Purpose

The objective of this study is to evaluate the safety, tolerability, and antitumor activity of oleclumab (MEDI9447) in combination with or without durvalumab plus chemotherapy in subjects with metastatic pancreatic cancer.

Detailed Description

      This is a Phase 1b/2, multicenter, open-label, dose-escalation, and dose-expansion study to
      assess the safety, preliminary antitumor activity, immunogenicity, and PK of oleclumab with
      or without durvalumab in combination with chemotherapy administered in subjects with
      metastatic PDAC. Subjects with previously untreated metastatic PDAC (1L metastatic PDAC) with
      be enrolled in Cohort A. Subjects with metastatic PDAC previously treated with
      gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, or oxaliplatin, 2L
      metastatic PDAC) will be enrolled in Cohort B. The study consists of 2 parts, dose escalation
      (part 1) and dose expansion (Part 2).
    

Trial Arms

NameTypeDescriptionInterventions
Arm A1Active Comparatorgemcitabine and nab-paclitaxel
  • gemcitabine
  • nab-paclitaxel
Arm A2Experimentaloleclumab (MEDI9447), gemcitabine and nab-paclitaxel
  • oleclumab
  • gemcitabine
  • nab-paclitaxel
Arm A3Experimentaloleclumab (MEDI9447), durvalumab (MEDI4736), and gemcitabine/nab-paclitaxel
  • oleclumab
  • durvalumab
  • gemcitabine
  • nab-paclitaxel
Arm B1Active ComparatormFOLFOX (oxaliplatin, leucovorin, 5-FU)
    Arm B2Experimentaloleclumab (MEDI9447) and mFOLFOX (oxaliplatin, leucovorin, 5-FU)
    • oleclumab
    Arm B3Experimentaloleclumab (MEDI9447), durvalumab (MEDI4736), and mFOLFOX (oxaliplatin, leucovorin, 5-FU)
    • oleclumab
    • durvalumab

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Age ≥ 18
    
              2. Written and signed informed consent must be obtained
    
              3. ECOG Performance Status 0 or 1
    
              4. Weight ≥ 35 kg
    
              5. Subjects must have histologically or cytologically, confirmed pancreatic
                 adenocarcinoma:
    
                 Cohort A: Subjects with previously untreated metastatic pancreatic adenocarcinoma (1st
                 line metastatic disease) not previously treated with systemic therapies.
    
                 Cohort B: Subjects with metastatic pancreatic adenocarcinoma previously treated with
                 gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, oxaliplatin)
                 2nd line metastatic disease
    
              6. Subjects must have at least 1 measurable lesion according to RECIST v1.1
    
              7. All subjects must consent to providing archival tumor specimens
    
            Exclusion Criteria:
    
              1. Receipt of any conventional or investigational anticancer therapy within 21 days or
                 palliative radiotherapy within 14 days prior to the scheduled first dose of study
                 treatment.
    
              2. Prior receipt of any immune-related therapy
    
              3. Concurrent enrollment in another therapeutic clinical study. Enrollment in
                 observational studies will be allowed
    
              4. Subjects with a history of venous thrombosis within the past 3 months
    
              5. Subjects with prior history of myocardial infarction, transient ischemic attack, or
                 stroke in the last 3 months prior to start of treatment
    
              6. Active or prior documented autoimmune or inflammatory disorders within the past 3
                 years prior to the start of treatment
    
              7. Other invasive malignancy within 2 years.
    
              8. Any history of leptomeningeal disease or cord compression.
    
              9. Current or prior use of immunosuppressive medication within 14 days prior to the first
                 dose
          
    Maximum Eligible Age:101 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Incidence of Adverse Events as a measure of safety in dose escalation phase
    Time Frame:From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximately 1 year
    Safety Issue:
    Description:The primary endpoint is safety as assessed by the presence of adverse events and serious adverse events

    Secondary Outcome Measures

    Measure:Incidence of Adverse Events as a measure of safety in dose expansion phase
    Time Frame:From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximately 1 year
    Safety Issue:
    Description:Safety as assessed by the presence of adverse events and serious adverse events
    Measure:Objective Response (OR) rate as a measure of antitumor activity in dose escalation phase
    Time Frame:From start of treatment until documentation of disease progression or initiation of subsequent anticancer therapy or study completion, about 2 years after the last subject dosed, which ever comes first
    Safety Issue:
    Description:Best overall response of confirmed CR or confirmed PR according to RECIST version 1.1 in Part 1 (dose escalation)
    Measure:Overall Survival (OS)
    Time Frame:From time randomization until death or study completion, about 2 years after the last subject dosed
    Safety Issue:
    Description:The time from randomization until death due to any cause in Part 2 (dose expansion)
    Measure:Progression-Free Survival (PFS)
    Time Frame:From start of treatment until death or study completion, about 2 years after the last subject dosed, which ever comes first
    Safety Issue:
    Description:The time from randomization until the first documentation of disease progression or death due to any cause, whichever occurs first in Part 2 (dose expansion)
    Measure:Duration of Response (DoR)
    Time Frame:From time of informed consent through study completion, about 2 years after the last subject dosed
    Safety Issue:
    Description:The duration from the first documentation of OR to the first documented disease progression or death due to any cause, whichever occurs first in Part 2 (dose expansion)
    Measure:Disease control (DC)
    Time Frame:During treatment through study completion, about 2 years after the last subject dosed
    Safety Issue:
    Description:CR, PR, or SD (if subjects maintain SD for ≥ 8 weeks [± 3 days]) in Part 1 (dose escalation) in Part 2 (dose expansion)
    Measure:Development of detectable anti-drug antibody (ADA) to oleclumab (MEDI9447)
    Time Frame:From start of treatment through 12 weeks post last dose of investigational product
    Safety Issue:
    Description:Immunogenicity of oleclumab
    Measure:Development of detectable anti-drug antibody(ADA) to durvalumab
    Time Frame:From start of treatment through 12 weeks post last dose of investigational product
    Safety Issue:
    Description:Immunogenicity of durvalumab
    Measure:Serum oleclumab (MEDI9447) concentration levels
    Time Frame:During treatment through 12 weeks post last dose of investigational product
    Safety Issue:
    Description:Pharmacokinetics of oleclumab
    Measure:Serum durvalumab concentration levels
    Time Frame:During treatment through 12 weeks post last dose of investigational product
    Safety Issue:
    Description:Pharmacokinetics of durvalumab
    Measure:Area under the curve (AUC) of selected chemo-therapies and /or their metabolites
    Time Frame:From start of treatment through the first 16 weeks of treatment
    Safety Issue:
    Description:Pharmacokinetics of gemcitabine and nab paclitaxel and their metabolites
    Measure:Maximun serum concentration (Cmax) of selected chemo-therapies and /or their metabolites
    Time Frame:From start of treatment through the first 16 weeks of treatment
    Safety Issue:
    Description:Pharmacokinetics of gemcitabine and nab paclitaxel and their metabolites
    Measure:Incidence of clinically significant ECG abnormalities as a measure of safety in dose expansion phase
    Time Frame:From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximately 1 year
    Safety Issue:
    Description:12 lead ECGs will be measured to identify clinical significant abnormalities including ECGs that demonstrate a QTcF value >500ms, 2 additional 12-lead ECGs should be obtained over a 30 minute time period to confirm prolongation based on the average QTcF value
    Measure:Incidence of clinically significant laboratory values as a measure of safety in dose expansion phase
    Time Frame:From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximately 1 year
    Safety Issue:
    Description:Assess the presence of clinically significant laboratory values from baseline

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:MedImmune LLC

    Trial Keywords

    • MEDI9447
    • oleclumab
    • immunotherapy
    • pancreatic cancer
    • durvalumab

    Last Updated