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Trial record 1 of 1 for:    NCT02503774
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MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by MedImmune LLC
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT02503774
First received: July 6, 2015
Last updated: July 18, 2017
Last verified: July 2017
  Purpose
The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination with MEDI4736 in Adult Subjects with Select Advanced Solid Tumors

Condition Intervention Phase
Solid Tumours Biological: MEDI9447 Biological: MEDI4736 and MEDI9447 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
    The primary endpoint is safety as assessed by the presence of AEs, serious adverse events (SAEs).


Secondary Outcome Measures:
  • Composite measure of Preliminary antitumor activity [ Time Frame: From the time of informed consent through an average of 1 year ]
    Assessment of antitumor activity include OR, disease control (DC), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

  • Composite measure of Pharmacokinetics of MEDI9447 or MEDI9447/MEDI4736 [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
    Including Cmax and AUC of MEDI9447 administered as a single agent and the Cmax and AUC of both MEDI9447 and MEDI4736 when administered in combination.

  • Composite measure of Immunogenicity [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
    Immunogenicity of MEDI9447 and MEDI4736 include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).

  • Biomarker activity [ Time Frame: From time of informed consent through 12 weeks after last dose of investigational product ]
    Assessment of target expression in subject samples.


Estimated Enrollment: 188
Actual Study Start Date: July 24, 2015
Estimated Study Completion Date: April 24, 2023
Estimated Primary Completion Date: November 13, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Monotherapy
MEDI9447 only
Biological: MEDI9447
Subjects will receive MEDI9447 until disease progression
Experimental: Combination
MEDI9447 and MEDI4736
Biological: MEDI4736 and MEDI9447
Subjects will receive MEDI9447 and MEDI4736 until disease progression

  Eligibility

Ages Eligible for Study:   18 Years to 101 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult subjects; age ≥ 18
  2. Written and signed informed consent must be obtained
  3. Have histologic or cytologic documentation of solid tumor

    ◦ Must have received and have progressed, are refractory, or are intolerant to standard therapy appropriate for the specific tumor type. Depending on 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 that is measureable using RECIST guidelines
  5. Subjects must consent to provide archived tumor specimens or tumor biopsies for correlative biomarker studies.
  6. All subjects are encouraged to consent to and provide paired pretreatment and on-treatment tumor biopsies.
  7. In the dose-expansion phase, all subjects are encouraged to consent and provide paired on-treatment tumor biopsies
  8. Eastern Cooperative Oncology Group performance score of 0 or 1
  9. In the opinion of the investigator, likely to complete ≥ 56 days of treatment
  10. Adequate organ function as determined by: I.Absolute neutrophil count ≥ 1.5 × 109/L (1,500/mm3) II.Platelet count ≥ 75 × 109/L (75,000/mm3) III.Hemoglobin ≥ 9.0 g/dL IV.Prothrombin time-international normalized ratio and partial thromboplastin time ≤ 1.5 × ULN V.Calculated creatinine clearance* (CrCl) or 24 hour urine CrCl > 50 mL/minute VI.Total bilirubin ≤ 1.5 × ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ≤ 3 × UL VII.AST and ALT ≤ 2.5 × ULN VIII.Serum electrolytes within normal limits
  11. Female subjects of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 90 days (or 180 days) after the final dose of investigational product.
  12. Nonsterilized males who are sexually active with a female partner of childbearing potential must use condom plus spermicide from Day 1 through 90 days (or 180 days) after receipt of the last dose of investigational product.

Exclusion Criteria:

  1. Prior treatment with tumor necrosis factor receptor superfamily agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR). One cohort also excludes anti CTLA-4, anti PDL-1 and anti PDL-1.
  2. Subjects who have received prior therapy with regimens containing CTLA-4, PD-L1, or PD-1 antagonists are NOT permitted to enroll unless all of the following apply:

    • Dose of immunotherapy must have been administered at least 28 days or 5 half lives, whichever is shorter, prior to planned first dose of MEDI9447/MEDI4736
    • 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 required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day
  4. Known allergy or hypersensitivity to investigational product formulations
  5. History of more than one event of IRR requiring permanent discontinuation of IV drug treatment
  6. History of severe drug allergies or anaphylaxis to 2 or more food products or medicine (including known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid)
  7. Cardiac or peripheral vascular disease meeting any of the following criteria:

    • Past history of myocardial infarction in the prior 12 months
    • Past history of stroke or transient ischemic attack requiring medical therapy
    • Congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification
  8. Grade 3 or greater edema (eg, peripheral, pulmonary)
  9. History of Grade 3 or greater thromboembolic events or thromboembolic event of any grade with on going symptoms
  10. Subjects with active tuberculosis are ineligible. In settings where there is clinical or radiographic evidence of tuberculosis, active disease must be ruled out
  11. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn's disease], celiac disease, or other serious gastrointestinal chronic conditions associated with diarrhea, etc) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion are subjects s with vitiligo or alopecia or hypothyroidism.
  12. Untreated central nervous system (CNS) metastatic disease
  13. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study
  14. Receipt of any conventional or investigational anticancer therapy not otherwise specified above within 28 days prior to the first dose of Investigational product
  15. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
  16. Unresolved toxicities from prior anticancer therapy
  17. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of Investigational product
  18. History of primary immunodeficiency, solid organ transplantation
  19. Known positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or active hepatitis A or C
  20. Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational products
  21. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
  22. Major surgery within 28 days prior to first dose of Investigational Product or still recovering from prior surgery.
  23. Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, ductal carcinoma in situ of the breast that has been surgically cured
  24. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, uncontrolled hypertension, uncontrolled diabetes, or psychiatric illness/social situations that would limit compliance with study requirement
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02503774

Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locater Service 1-877-400-4656 AstraZeneca@emergingmed.com

Locations
United States, California
Research Site Recruiting
La Jolla, California, United States, 92093-0987
United States, Connecticut
Research Site Recruiting
New Haven, Connecticut, United States, 06510
United States, Florida
Research Site Recruiting
Gainesville, Florida, United States, 32610
United States, Georgia
Research Site Recruiting
Atlanta, Georgia, United States, 30318
United States, Missouri
Research Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Research Site Recruiting
Durham, North Carolina, United States, 27705-3827
United States, Ohio
Research Site Recruiting
Columbus, Ohio, United States, 43210
United States, Tennessee
Research Site Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Research Site Recruiting
Dallas, Texas, United States, 75230
Research Site Recruiting
Houston, Texas, United States, 77030
Australia
Research Site Recruiting
Camperdown, Australia, 2050
Research Site Recruiting
Parkville, Australia, 3050
Research Site Recruiting
St Leonards, Australia, 2065
Research Site Recruiting
Woolloongabba, Australia, 4068
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: MedImmune LLC MedImmune LLC
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02503774     History of Changes
Other Study ID Numbers: D6070C00001
Study First Received: July 6, 2015
Last Updated: July 18, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AZ's policy is to share data with researchers if the request is in scope of our policy. The policy and additional information can be found on astrazenecaclinicaltrials.com.
URL: http://

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MedImmune LLC:
Solid Tumours, MEDI9447, MEDI4736, durvalumab, CD73, PD-L1

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 27, 2017