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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02221960




Registration number
NCT02221960
Ethics application status
Date submitted
19/08/2014
Date registered
21/08/2014
Date last updated
13/03/2019

Titles & IDs
Public title
A Phase 1 Study to Evaluate MEDI6383 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors
Scientific title
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
Secondary ID [1] 0 0
D6050C00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent or Metastatic Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - MEDI6383
Other interventions - MEDI6383 and MEDI4736

Experimental: Monotherapy Arm - MEDI6383

Experimental: Combination Arm - MEDI6383 and MEDI4736


Other interventions: MEDI6383
Subjects will receive MEDI6383 until disease progression or adverse event.

Other interventions: MEDI6383 and MEDI4736
Subjects will recieve MEDI6383 and MEDI4736 until disease progression or adverse event.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety - Primary endpoint will be the number (%) of subjects with adverse events and serious adverse events.
Timepoint [1] 0 0
From time of informed consent through 12 weeks after last dose of investigational product
Secondary outcome [1] 0 0
Preliminary Antitumor Activity - 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)
Timepoint [1] 0 0
Duration of Study
Secondary outcome [2] 0 0
Pharmacokinetics of MEDI6383 or MEDI6383/MEDI4736 - 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.
Timepoint [2] 0 0
From time of informed consent through 12 weeks after last dose of investigational product
Secondary outcome [3] 0 0
Biomarker Activity - The endpoints for assessment of pharmacodynamic activity include immunohistochemistry of tumor biopsies and assessment of tumor-infiltrating lymphocyte phenotypic markers
Timepoint [3] 0 0
From time of informed consent through 12 weeks after last dose of investigational product
Secondary outcome [4] 0 0
Immunogenicity - The endpoint for for the assessment of immunogenicity will include the number and percentage of subjects that develop anti-drug antibodies.
Timepoint [4] 0 0
From time of informed consent through 12 weeks after last dose of investigational product

Eligibility
Key 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
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

-

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
MedImmune LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate MEDI6383 when given alone or together with MEDI4736 in adult subjects with
recurrent or metastatic solid tumors.
Trial website
https://clinicaltrials.gov/show/NCT02221960
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medimmune Medimmune
Address 0 0
MedImmune LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications