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Trial record 1 of 1 for:    NCT02221960
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A Phase 1 Study to Evaluate MEDI6383 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02221960
Recruitment Status : Completed
First Posted : August 21, 2014
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Tracking Information
First Submitted Date  ICMJE August 19, 2014
First Posted Date  ICMJE August 21, 2014
Last Update Posted Date March 13, 2019
Actual Study Start Date  ICMJE September 15, 2014
Actual Primary Completion Date July 3, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 19, 2014)
Safety [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
Primary endpoint will be the number (%) of subjects with adverse events and serious adverse events.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2015)
  • Preliminary Antitumor Activity [ Time Frame: Duration of Study ]
    The endpoints for assessment of antitumor activity include objective response (OR), disease control (DC), duration of response (DoR), progression-free survival (PFS), and 3-year overall survival (OS)
  • Pharmacokinetics of MEDI6383 or MEDI6383/MEDI4736 [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
    When MEDI6383 is administered alone, the endpoints for assessment of PK of MEDI6383 include individual subject MEDI6383 concentrations in serum at different time points after MEDI6383 administration. When MEDI6383 is administered together with MEDI4736, the endpoints for assessment of PK of MEDI6383 and MEDI4736 include individual subject MEDI6383 and MEDI4736 concentrations in serum at different time points after MEDI6383 and MEDI4736 administration. PK Parameters that may be modeled may include Cmax, Area Under the concentration-time curve, Clearance, and terminal half-live.
  • Biomarker Activity [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
    The endpoints for assessment of pharmacodynamic activity include immunohistochemistry of tumor biopsies and assessment of tumor-infiltrating lymphocyte phenotypic markers
  • Immunogenicity [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
    The endpoint for for the assessment of immunogenicity will include the number and percentage of subjects that develop anti-drug antibodies.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 19, 2014)
  • Preliminary Antitumor Activity [ Time Frame: Duration of Study ]
    The endpoints for assessment of antitumor activity include objective response (OR), disease control (DC), duration of response (DoR), progression-free survival (PFS), and 3-year overall survival (OS)
  • Pharmokinetics of MEDI6383 [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
    The endpoints for assessment of PK of MEDI6383 include individual subject MEDI6383 concentrations in serum at different time points after MEDI6383 administration.
  • Biomarker Activity [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
    The endpoints for assessment of pharmacodynamic activity include immunohistochemistry of tumor biopsies and assessment of tumor-infiltrating lymphocyte phenotypic markers
  • Immunogenicity [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
    The endpoint for for the assessment of immunogenicity will include the number and percentage of subjects that develop anti-drug antibodies.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study to Evaluate MEDI6383 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors
Official Title  ICMJE A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI6383 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors
Brief Summary To evaluate MEDI6383 when given alone or together with MEDI4736 in adult subjects with recurrent or metastatic solid tumors.
Detailed Description This is a Phase 1, multicenter, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and antitumor activity of MEDI6383 alone and in combination with MEDI4736 in adult subjects with recurrent or metastatic solid tumors.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent or Metastatic Solid Tumors
Intervention  ICMJE
  • Biological: MEDI6383
    Subjects will receive MEDI6383 until disease progression or adverse event.
  • Biological: MEDI6383 and MEDI4736
    Subjects will recieve MEDI6383 and MEDI4736 until disease progression or adverse event.
Study Arms  ICMJE
  • Experimental: Monotherapy Arm
    MEDI6383
    Intervention: Biological: MEDI6383
  • Experimental: Combination Arm
    MEDI6383 and MEDI4736
    Intervention: Biological: MEDI6383 and MEDI4736
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 19, 2017)
39
Original Estimated Enrollment  ICMJE
 (submitted: August 19, 2014)
116
Actual Study Completion Date  ICMJE July 3, 2017
Actual Primary Completion Date July 3, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male and female subjects; age ≥ 18
  2. Written informed consent must be obtained
  3. Subjects must meet the following criteria:

    1. Have recurrent or metastatic solid tumors
    2. Must have received and have progressed, are refractory, or are intolerant to standard therapy appropriate for the specific tumor type. Subjects should not have received more than 5 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies
  4. Subjects must have at least 1 lesion
  5. Subjects must consent to provide archived tumor specimens and / or tumor biopsy for correlative biomarker studies.
  6. Eastern Cooperative Oncology Group performance score of 0 or 1
  7. In the opinion of the invesgator likely to complete ≥ 8 weeks of treatment.
  8. Adequate organ function as determined by:

    i. Absolute neutrophil count ≥ 1.5 x 109/L (1,500/mm3) ii.Platelet count ≥ 100 x 109/L (100,000/mm3) iii.Hemoglobin ≥ 9.0 g/dL within first 2 weeks prior to first dose of investigational product iv.Calculated creatinine clearance* (CrCl) or 24 hour urine CrCl > 50 mL/min v.Total bilirubin ≤ 1.5× ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ≤ 3× ULN vi.Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5× ULN vii.Serum Electrolytes within normal limits

  9. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of highly effective contraception from screening, and must agree to continue using such precautions for 90 days after the final dose of investigational product; 10) Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1 through 90 days after receipt of the final dose of investigational product

Exclusion Criteria:

  1. Prior treatment with TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR) .
  2. Subjects who have received prior therapy with regimens containing CTLA-4, PDL-1, or PD-1 antagonists are NOT permitted to enroll unless all of the following apply:

    • Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
    • All AEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or baseline prior to screening for this study.
  3. Must not have experienced a ≥ Grade 3 AE or neurologic or ocular AE of any grade while receiving prior immunotherapy
  4. History of severe allergic reactions to any unknown allergens or any components of the study drug formulations
  5. Active or prior documented autoimmune disease within the past 2 years.
  6. Untreated central nervous system metastatic disease l
  7. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study
  8. Receipt of anticancer therapy within 28 days prior to the first dose of Investigational Product
  9. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
  10. Unresolved toxicities from prior anticancer therapy
  11. Systemic anticoagulation or daily aspirin dose exceeding 325 mg per day
  12. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI6383. )
  13. History of primary immunodeficiency, solid organ transplantation, or tuberculosis
  14. True positive test results for human immunodeficiency virus (HIV) or hepatitis B or C
  15. Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational products )
  16. Pregnant or breastfeeding women
  17. Major surgery (as defined by the investigator) within 4 weeks prior to first dose of MEDI6383 or still recovering from prior surgery. Local surgery of isolated lesions for palliative intent is acceptable
  18. Other invasive malignancy within 2 years

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02221960
Other Study ID Numbers  ICMJE D6050C00001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MedImmune LLC
Study Sponsor  ICMJE MedImmune LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medimmune Medimmune MedImmune LLC
PRS Account MedImmune LLC
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP