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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02705482




Registration number
NCT02705482
Ethics application status
Date submitted
22/09/2015
Date registered
4/03/2016
Date last updated
24/10/2018

Titles & IDs
Public title
A Study to Evaluate MEDI0562 in Combination With Immune Therapeutic Agents in Adult Subjects With Advanced Solid Tumors
Scientific title
A Phase 1 Multicenter, Open-label, Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Antitumor Activity of MEDI0562 in Combination With Immune Therapeutic Agents in Adult Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
D6060C00002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Select Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - MEDI0562
Other interventions - Tremelimumab
Other interventions - Durvalumab

Experimental: Arm A: MEDI0562 and durvalumab - MEDI0562 and durvalumab

Experimental: Arm B: MEDI0562 and tremelimumab - MEDI0562 and tremelimumab


Other interventions: MEDI0562
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease (PD), or development of other reason for treatment discontinuation.

Other interventions: Tremelimumab
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease (PD), or development of other reason for treatment discontinuation.

Other interventions: Durvalumab
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease (PD), or development of other reason for treatment discontinuation.

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

Outcomes
Primary outcome [1] 0 0
Safety as defined by the presence of adverse events (AE), serious adverse events (SAE), and dose limiting toxicities (DLT). - The primary endpoint is safety as assessed by presence of adverse event (AE), serious adverse event (SAE), and dose limiting toxicity (DLT).
Timepoint [1] 0 0
From time of informed consent through 12 weeks after ending treatment with investigational product
Secondary outcome [1] 0 0
Preliminary Antitumor Activity:Best Overall Response - The endpoints for assessment of antitumor activity include Best Overall Response (BOR) and will be based on all post-baseline disease assessments that occur prior to the initiation of subsequent anticancer therapy
Timepoint [1] 0 0
At approximately 3 time points through Day 113.
Secondary outcome [2] 0 0
Pharmacokinetics of MEDI0562/durvalumab or MEDI0562/tremelimumab: Cmax - The endpoints for assessment of PK of MEDI0562 and durvalumab or tremelimumab include individual MEDI0562, durvalumab, and tremelimumab concentrations at different time points after administration. PK parameters that may be modeled on these data include, but are not limited to, maximum observed concentration (Cmax).
Timepoint [2] 0 0
To be assessed at approximately 12 clinic visits through Day 113
Secondary outcome [3] 0 0
Immunogenicity - The endpoints for assessment of immunogenicity of MEDI0562, durvalumab, and tremelimumab include the number and percentage of subjects who develop detectable anti drug antibodies (ADAs).
Timepoint [3] 0 0
At approximately 8 time points through Day 113.
Secondary outcome [4] 0 0
Pharmacodynamic Activity - The endpoints for assessment of pharmacodynamic activity include induction of proliferation markers in various lymphocyte populations and assessment of tumor-infiltrating lymphocytes (TILs) in tumor biopsy specimens.
Timepoint [4] 0 0
At approximately 12 time points through Day 113.
Secondary outcome [5] 0 0
Preliminary Antitumor Activity: Disease Control - The endpoints for assessment of antitumor activity include disease control and is defined as CR, PR, or SD according to RECIST v1.1
Timepoint [5] 0 0
At approximately 3 time points through Day 113.
Secondary outcome [6] 0 0
Preliminary Antitumor Activity: Duration of Response - The endpoints for assessment of antitumor activity include duration of response (DoR) and is defined as the duration from the first documentation of OR to the first documentation of disease progression or death due to any cause.
Timepoint [6] 0 0
At approximately 3 time points through Day 113.
Secondary outcome [7] 0 0
Preliminary Antitumor Activity: Progression-free Survival - The endpoints for assessment of antitumor activity include progression-free survival (PFS) and is defined as the duration measured from the start of treatment with investigational product to the first documentation of disease progression or death due to any cause
Timepoint [7] 0 0
At approximately 3 time points through Day 113.
Secondary outcome [8] 0 0
Preliminary Antitumor Activity: Overall Survival - The endpoints for assessment of antitumor activity include overall survival (OS) and is defined as the time from the start of treatment with Investigational Product until death due to any cause.
Timepoint [8] 0 0
At approximately 3 time points through Day 113.
Secondary outcome [9] 0 0
Pharmacokinetics of MEDI0562/durvalumab or MEDI0562/tremelimumab: AUC - The endpoints for assessment of PK of MEDI0562 and durvalumab or tremelimumab include individual MEDI0562, durvalumab, and tremelimumab concentrations at different time points after administration. PK parameters that may be modeled on these data include area under the concentration-time curve (AUC).
Timepoint [9] 0 0
To be assessed at approximately 12 clinic visits through Day 113
Secondary outcome [10] 0 0
Pharmacokinetics of MEDI0562/durvalumab or MEDI0562/tremelimumab: Clearance - The endpoints for assessment of PK of MEDI0562 and durvalumab or tremelimumab include individual MEDI0562, durvalumab, and tremelimumab concentrations at different time points after administration. PK parameters that may be modeled on these data include clearance (CL).
Timepoint [10] 0 0
To be assessed at approximately 12 clinic visits through Day 113
Secondary outcome [11] 0 0
Pharmacokinetics of MEDI0562/durvalumab or MEDI0562/tremelimumab: t½ - The endpoints for assessment of PK of MEDI0562 and durvalumab or tremelimumab include individual MEDI0562, durvalumab, and tremelimumab concentrations at different time points after administration. PK parameters that may be modeled on these data include terminal phase half-life (t½).
Timepoint [11] 0 0
To be assessed at approximately 12 clinic visits through Day 113
Secondary outcome [12] 0 0
Preliminary Antitumor Activity: Objective Response - The endpoints for assessment of antitumor activity include objective response (OR) and is defined as confirmed CR or confirmed PR based on RECIST v1.1
Timepoint [12] 0 0
At approximately 3 time points through Day 113.
Secondary outcome [13] 0 0
Preliminary Antitumor Activity: Time to Response - The endpoints for assessment of Time to Response TTR and is defined as the time of first treatment to a subsequently confirmed CR or confirmed PR based on RECIST v1.1
Timepoint [13] 0 0
At approximately 3 time points through Day 113.
Secondary outcome [14] 0 0
Preliminary Antitumor Activity: Percent Change from Baseline - The endpoints for assessment percent change from baseline in target lesion sum of diameters will be calculated at each adequate post baseline disease assessment with recorded measurement for all target lesions defined at baseline.
Timepoint [14] 0 0
At approximately 3 time points through Day 113.

Eligibility
Key inclusion criteria
Subjects must meet all of the following criteria:

1. Written and signed informed consent.

2. Age = 18 years at the time of study entry.

3. Subjects 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 3 prior lines of systemic therapy for recurrent or metastatic.

4. Subjects in the dose-escalation phase, must have histologic documentation of advanced
solid tumors, excluding primary CNS tumors and hematologic malignancies.

5. Subjects in the dose-expansion phase, must have recurrent or metastatic disease solid
tumors according to treatment arm as specified in the protocol.

6. Subjects who have received prior therapy with regimens containing CTLA 4, PD L1, or PD
1 antagonists are permitted to enroll if additional protocol criteria are met.

7. Subjects must have at least 1 lesion that is measurable using RECIST guidelines.

8. Subjects must consent to provide archived tumor specimens for correlative biomarker
studies. In the setting where archival material is unavailable or unsuitable for use,
subjects must consent and undergo fresh tumor biopsy.

9. All subjects are encouraged to consent to and provide both pretreatment and on
treatment tumor biopsies.

10. ECOG Performance score of 0 or 1, unless protocol exceptions are met.

11. In the opinion of the investigator likely to complete = 8 weeks of treatment.

12. Adequate hematologic, renal and hepatic function as determined by blood laboratory
values.

13. At the time of Day 1 of the study, subjects with CNS metastases must have been treated
and must be asymptomatic and meet the following:

1. No concurrent treatment, inclusive of, but not limited to surgery, radiation,
and/or corticosteroids

2. At least 42 days without progression of CNS metastases as evidenced by magnetic
resonance imaging (MRI) or computed tomography (CT) after last day of treatment

3. At least 14 days since last dose of corticosteroids Note: Subjects with
leptomeningeal disease or cord compression are excluded from the study.

14. Female subjects of childbearing potential who are sexually active with a
non-sterilized male partner must use at least 1 highly effective method of
contraception from screening, and must agree to continue using such precautions for
180 days after the final dose of investigational product.

15. Non-sterilized male subjects who are sexually active with a female partner of
childbearing potential must use male condom plus, if locally available, spermicide
from Day 1 and for 180 days after receipt of the final dose of investigational
product.
Minimum age
18 Years
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any of the following would exclude the subject from participation in the study:

1. Prior treatment with TNFRSF agonists

2. Prior treatment with IMT for certain disease types may be restricted per protocol.

3. History of severe allergic reactions to any unknown allergens or any components of the
study drug formulations

4. Active or prior documented autoimmune disease within the past 2 years.

5. Concurrent enrollment in another clinical study, unless it is an observational
clinical study or the follow up period of an interventional study

6. Receipt of any conventional or investigational anticancer therapy not otherwise
specified above within 28 days prior to the first dose

7. Any concurrent chemotherapy, IMT, or biologic or hormonal therapy for cancer
treatment.

8. Unresolved toxicities from prior anticancer therapy.

9. Systemic therapeutic anticoagulation or daily aspirin dose exceeding 325 mg/per day.

10. Current or prior use of immunosuppressive medication within 14 days prior to the first
dose of MEDI0562 with exceptions as per protocol.

11. History of primary immunodeficiency, solid organ transplantation, or tuberculosis

12. Test results indicating active infection with human immunodeficiency virus (HIV) or
hepatitis B or C defined by positive serologic testing and confirmatory viral nucleic
acid testing

13. Pregnant or breastfeeding women

14. Major surgery within 4 weeks prior to first dose of MEDI0562 or still recovering from
prior surgery.

15. Other invasive malignancy within 2 years with the exception of protocol specified
criteria

16. Any uncontrolled intercurent illness or condition that, in the opinion of the
investigator, would interfere with evaluation of the investigational product or
interpretation of subject safety or study results.

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
Recruiting
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 - Clayton
Recruitment hospital [2] 0 0
Research Site - Kogarah
Recruitment hospital [3] 0 0
Research Site - Macquarie University
Recruitment hospital [4] 0 0
Research Site - Waratah
Recruitment hospital [5] 0 0
Research Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2109 - Macquarie University
Recruitment postcode(s) [4] 0 0
2298 - Waratah
Recruitment postcode(s) [5] 0 0
4068 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
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
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New Mexico
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
France
State/province [12] 0 0
Bordeaux Cedex
Country [13] 0 0
France
State/province [13] 0 0
Dijon
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Montpellier
Country [16] 0 0
France
State/province [16] 0 0
Villejuif
Country [17] 0 0
Netherlands
State/province [17] 0 0
Amsterdam
Country [18] 0 0
Spain
State/province [18] 0 0
Barcelona
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Spain
State/province [20] 0 0
Sevilla
Country [21] 0 0
Spain
State/province [21] 0 0
Valencia
Country [22] 0 0
United Kingdom
State/province [22] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate MEDI0562 in combination with immune therapeutic
agents in adult subjects with select advanced solid tumors.
Trial website
https://clinicaltrials.gov/show/NCT02705482
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02705482