We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02503774
Previous Study | Return to List | Next Study

MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors

This study is currently recruiting participants.
Verified October 2017 by MedImmune LLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT02503774
First Posted: July 21, 2015
Last Update Posted: October 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
MedImmune LLC
July 6, 2015
July 21, 2015
October 26, 2017
July 24, 2015
February 15, 2021   (Final data collection date for primary outcome measure)
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).
Same as current
Complete list of historical versions of study NCT02503774 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors
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
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
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Solid Tumours
  • Biological: MEDI9447
    Subjects will receive MEDI9447 until disease progression
  • Biological: MEDI4736 and MEDI9447
    Subjects will receive MEDI9447 and MEDI4736 until disease progression
  • Experimental: Monotherapy
    MEDI9447 only
    Intervention: Biological: MEDI9447
  • Experimental: Combination
    MEDI9447 and MEDI4736
    Intervention: Biological: MEDI4736 and MEDI9447
Hay CM, Sult E, Huang Q, Mulgrew K, Fuhrmann SR, McGlinchey KA, Hammond SA, Rothstein R, Rios-Doria J, Poon E, Holoweckyj N, Durham NM, Leow CC, Diedrich G, Damschroder M, Herbst R, Hollingsworth RE, Sachsenmeier KF. Targeting CD73 in the tumor microenvironment with MEDI9447. Oncoimmunology. 2016 Jul 11;5(8):e1208875. doi: 10.1080/2162402X.2016.1208875. eCollection 2016 Aug.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
188
February 15, 2021
February 15, 2021   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 101 Years   (Adult, Senior)
No
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
Australia,   United States
 
 
NCT02503774
D6070C00001
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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://
MedImmune LLC
MedImmune LLC
Not Provided
Study Director: MedImmune LLC MedImmune LLC
MedImmune LLC
October 2017

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