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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03530397




Registration number
NCT03530397
Ethics application status
Date submitted
28/03/2018
Date registered
21/05/2018
Date last updated
22/05/2020

Titles & IDs
Public title
A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors
Scientific title
A Phase 1, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability Pharmacokinetics Immunogenicity, and Antitumor Activity of MEDI5752 in Subjects With Advanced Solid Tumors.
Secondary ID [1] 0 0
D7980C00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - MEDI5752
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Carboplatin
Other interventions - Pembrolizumab

Experimental: Arm A: MEDI5752 - MEDI5752

Experimental: Arm B: MEDI5752 and chemotherapy - MEDI5752, pemetrexed and carboplatin.

Active Comparator: Arm C: Pembrolizumab and chemotherapy - pembrolizumab, pemetrexed, and carboplatin


Other interventions: MEDI5752
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation.

Treatment: Drugs: Pemetrexed
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation

Treatment: Drugs: Carboplatin
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation

Other interventions: Pembrolizumab
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The number of subjects experiencing treatment related adverse events (AEs). - The primary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v4.03
Timepoint [1] 0 0
From the time of informed consent through 114 days following termination of treatment with investigational product
Primary outcome [2] 0 0
Preliminary anti-tumor activitiy of MEDI5752 using Objective Response based on RECIST v1.1 (Dose-Expansion Phase) - The primary endpoint of antitumor activity include Objective Response and will be based on all post baseline disease assessments that occur prior to initiation of subsequent anticancer therapy.
Timepoint [2] 0 0
From the first dose of study drug through the date of first documented progression, end of study, date of death, or two years after the last patient starts treatment, whichever should occur first
Primary outcome [3] 0 0
The number of subjects experiencing dose-limiting toxicities (DLTs) - The primary endpoint is as assessed by the number of subjects experiencing dose limiting toxicities (DLTs) as defined by the protocol.
Timepoint [3] 0 0
Up to 21 days following the first dose
Primary outcome [4] 0 0
Change from baseline in laboratory evaluations. - The primary endpoint is as assessed by the change in laboratory parameters from baseline.
Timepoint [4] 0 0
From the time of informed consent through 30 days following termination of treatment with investigational product
Primary outcome [5] 0 0
Change from baseline in vital signs - The primary endpoint is as assessed by the change in vital signs from baseline.
Timepoint [5] 0 0
From the time of informed consent through 14 days following termination of treatment with investigational product
Primary outcome [6] 0 0
Change from baseline in ECGs - The primary endpoint is as assessed by the change in ECG parameters from baseline.
Timepoint [6] 0 0
From the time of informed consent through 14 days following termination of treatment with investigational product
Primary outcome [7] 0 0
The number of subjects experiencing treatment related serious adverse events (SAEs). - The primary endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v4.03.
Timepoint [7] 0 0
From the time of informed consent through 114 days following termination of treatment with investigational product
Secondary outcome [1] 0 0
Pharmacokinetics of MEDI5752: Cmax - The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include maximum observed concentration (Cmax)
Timepoint [1] 0 0
To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment
Secondary outcome [2] 0 0
Pharmacokinetics of MEDI5752: AUC - The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include area under the concentration-time curve (AUC)
Timepoint [2] 0 0
To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment
Secondary outcome [3] 0 0
Pharmacokinetics of MEDI5752: Clearance - The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include clearance (CL)
Timepoint [3] 0 0
To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment
Secondary outcome [4] 0 0
Pharmacokinetics of MEDI5752: t 1/2 - The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. PK parameters that may be modeled on this data include terminal phase half life (t 1/2)
Timepoint [4] 0 0
To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment.
Secondary outcome [5] 0 0
Immunogenicity of MEDI5752 - The endpoints for the immunogenicity of MEDI5752 include the number of subjects who develop detectable anti-drug antibodies (ADAs)
Timepoint [5] 0 0
To be assessed at Day 1, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment.
Secondary outcome [6] 0 0
PD-L1 Expression in subjects with advanced solid tumors - The endpoint for the PD-L1 expression will be determined by Immunohistochemistry characterization.
Timepoint [6] 0 0
To be assessed at at baseline
Secondary outcome [7] 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 documentation of OR to the first documentation of disease progression or death due to any cause.
Timepoint [7] 0 0
From the date of response through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Secondary outcome [8] 0 0
Preliminary Antitumor Activity: Disease Control - The endpoints for assessment of antitumor activity include disease control (DC) and is defined as CR, PR, or SD according to RECIST v1.1.
Timepoint [8] 0 0
From the first dose of study drug through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Secondary outcome [9] 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 [9] 0 0
From the first dose of study drug through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Secondary outcome [10] 0 0
Preliminary Antitumor Activity: Overall Survival - The endpoints for assessment of antitumor activity include overall survival (OS) and is defined as the duration measured from the start of treatment with investigational product until death due to any cause.
Timepoint [10] 0 0
From the first dose of study drug through the end of study, or date of death, or two years after last subject starts treatment whichever should occur first

Eligibility
Key inclusion criteria
Inclusion Criteria

1. Age = 18 years at the time of screening

2. World Health Organization/Eastern Cooperative Oncology Group (ECOG) performance status
of 0 or 1 at enrollment

3. Life expectancy = 12 weeks

4. Histologically or cytologically-confirmed advanced solid tumors

5. Subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy or any
concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy
for cancer treatment may be eligible to enter the study following a washout period as
applicable

6. Females of childbearing potential who are sexually active with a nonsterilized male
partner must use at least one highly effective method of contraception

7. Nonsterilized males who are sexually active with a female partner of childbearing
potential must use a male condom with spermicide where locally available from Day 1
and for 90 days after the final dose of investigational product. Males receiving
pemetrexed must use contraception during study treatment and up to 6 months
thereafter.

8. Subjects must have at least one measurable lesion

9. Adequate organ and marrow function

10. Written informed consent and any locally required authorization

11. Subjects must provide tumor material as applicable
Minimum age
18 Years
Maximum age
120 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. Involvement in the planning and/or conduct of the study (applies to both MedImmune
staff and/or staff at the study site)

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

3. For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4:

1. Subjects must not have received anti-PD-1, anti-PD-L1, anti-CTLA-4 or any other
immunotherapy or immune-oncology (IO) agent within 28 days of commencing
treatment with investigational product.

2. Subject must not have experienced a toxicity that led to permanent
discontinuation of prior immunotherapy.

3. All AEs while receiving prior immunotherapy must have completely resolved or
resolved to Grade 1 prior to screening for this study.

4. Current or prior use of immunosuppressive medication within 14 days before the first
dose of investigational product is excluded.

5. Receipt of live attenuated vaccine within 30 days prior to the first dose of
investigational product.

6. Active or prior documented autoimmune or inflammatory disorders

7. History of active primary immunodeficiency:

8. History of organ transplant that requires use of immunosuppressive therapy

9. Known allergy or reaction to any component of the planned study treatment.

10. Untreated CNS metastatic disease, leptomeningeal disease, or cord compression

11. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to
NCI CTCAE v4.03 Grade 0 or 1, or to levels dictated in the inclusion/exclusion
criteria

12. Major surgical procedure (as defined by the investigator) within 28 days prior to the
first dose of Investigational Product or still recovering from prior surgery

13. Female subjects who are pregnant or breastfeeding, as well as male or female subjects
of reproductive potential who are not willing to employ one highly effective method of
birth control

14. Uncontrolled intercurrent illness, that would limit compliance with study requirement,
substantially increase risk of incurring AEs or compromise the ability of the subject
to give written informed consent.

15. Any condition that, in the opinion of the investigator, would interfere with
evaluation of the investigational product or interpretation of the subject's safety or
study results

16. Judgment by the investigator that the subject is unsuitable to participate in the
study and the subject is unlikely to comply with study procedures, restrictions, and
requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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 - Heidelberg
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment hospital [3] 0 0
Research Site - Randwick
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
France
State/province [5] 0 0
Villejuif Cedex
Country [6] 0 0
Italy
State/province [6] 0 0
Meldola
Country [7] 0 0
Italy
State/province [7] 0 0
Milano
Country [8] 0 0
Italy
State/province [8] 0 0
Napoli
Country [9] 0 0
Italy
State/province [9] 0 0
Parma
Country [10] 0 0
Italy
State/province [10] 0 0
Ravenna
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Cheongju-si
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Incheon
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Seoul
Country [14] 0 0
Netherlands
State/province [14] 0 0
Amsterdam
Country [15] 0 0
Portugal
State/province [15] 0 0
Lisboa
Country [16] 0 0
Portugal
State/province [16] 0 0
Porto
Country [17] 0 0
Spain
State/province [17] 0 0
A Coruna
Country [18] 0 0
Spain
State/province [18] 0 0
Barcelona
Country [19] 0 0
Spain
State/province [19] 0 0
Majadahonda
Country [20] 0 0
Spain
State/province [20] 0 0
Malaga
Country [21] 0 0
Spain
State/province [21] 0 0
Pamplona
Country [22] 0 0
Spain
State/province [22] 0 0
Valencia
Country [23] 0 0
Taiwan
State/province [23] 0 0
Taichung
Country [24] 0 0
Taiwan
State/province [24] 0 0
Tainan
Country [25] 0 0
Taiwan
State/province [25] 0 0
Taipei

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 MEDI5752 in adult subjects with advanced solid
tumors, when administered as a single agent or combined with chemotherapy.
Trial website
https://clinicaltrials.gov/show/NCT03530397
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Deepa Subramaniam, MD, MSc
Address 0 0
AstraZeneca
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/NCT03530397