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A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03530397
Recruitment Status : Recruiting
First Posted : May 21, 2018
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

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.

Condition or disease Intervention/treatment Phase
Selected Advanced Solid Tumors Biological: MEDI5752 Biological: Durvalumab Drug: Pemetrexed Drug: Carboplatin Biological: Pembrolizumab Phase 1

Detailed Description:
This is a phase 1, first-time-in-human, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety and tolerability, and efficacy, pharmacokinetics and Immunogenicity of MEDI5752 in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 275 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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.
Actual Study Start Date : April 24, 2018
Estimated Primary Completion Date : September 8, 2022
Estimated Study Completion Date : September 8, 2022

Arm Intervention/treatment
Experimental: Arm A: MEDI5752
MEDI5752
Biological: MEDI5752
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation.

Active Comparator: Arm B: durvalumab
durvalumab
Biological: Durvalumab
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation

Experimental: Arm C: MEDI5752 and chemotherapy
MEDI5752, pemetrexed and carboplatin.
Biological: MEDI5752
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation.

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

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

Active Comparator: Arm D: Pembrolizumab and chemotherapy
pembrolizumab, pemetrexed, and carboplatin
Drug: Pemetrexed
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation

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

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




Primary Outcome Measures :
  1. The number of subjects experiencing treatment related adverse events (AEs). [ Time Frame: From the time of informed consent through 114 days following termination of treatment with investigational product ]
    The primary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v4.03

  2. Preliminary anti-tumor activitiy of MEDI5752 using Objective Response based on RECIST v1.1 (Dose-Expansion Phase) [ Time Frame: 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 ]
    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.

  3. The number of subjects experiencing dose-limiting toxicities (DLTs) [ Time Frame: Up to 21 days following the first dose ]
    The primary endpoint is as assessed by the number of subjects experiencing dose limiting toxicities (DLTs) as defined by the protocol.

  4. Change from baseline in laboratory evaluations. [ Time Frame: From the time of informed consent through 30 days following termination of treatment with investigational product ]
    The primary endpoint is as assessed by the change in laboratory parameters from baseline.

  5. Change from baseline in vital signs [ Time Frame: From the time of informed consent through 14 days following termination of treatment with investigational product ]
    The primary endpoint is as assessed by the change in vital signs from baseline.

  6. Change from baseline in ECGs [ Time Frame: From the time of informed consent through 14 days following termination of treatment with investigational product ]
    The primary endpoint is as assessed by the change in ECG parameters from baseline.

  7. The number of subjects experiencing treatment related serious adverse events (SAEs). [ Time Frame: From the time of informed consent through 114 days following termination of treatment with investigational product ]
    The primary endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v4.03.


Secondary Outcome Measures :
  1. Pharmacokinetics of MEDI5752: Cmax [ Time Frame: 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 ]
    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)

  2. Pharmacokinetics of MEDI5752: AUC [ Time Frame: 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 ]
    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)

  3. Pharmacokinetics of MEDI5752: Clearance [ Time Frame: 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 ]
    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)

  4. Pharmacokinetics of MEDI5752: t 1/2 [ Time Frame: 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. ]
    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)

  5. Immunogenicity of MEDI5752 [ Time Frame: 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. ]
    The endpoints for the immunogenicity of MEDI5752 include the number of subjects who develop detectable anti-drug antibodies (ADAs)

  6. PD-L1 Expression in subjects with advanced solid tumors [ Time Frame: To be assessed at at baseline ]
    The endpoint for the PD-L1 expression will be determined by Immunohistochemistry characterization.

  7. Preliminary Antitumor Activity: Duration of Response [ Time Frame: 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 ]
    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.

  8. Preliminary Antitumor Activity: Disease Control [ Time Frame: 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 ]
    The endpoints for assessment of antitumor activity include disease control (DC) and is defined as CR, PR, or SD according to RECIST v1.1.

  9. Preliminary Antitumor Activity: Progression Free Survival [ Time Frame: 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 ]
    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.

  10. Preliminary Antitumor Activity: Overall Survival [ Time Frame: 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 ]
    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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 of these treatments totaling at least 28 days before the first dose.

5. Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception 6. 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 7. Subjects must have at least one measurable lesion 8. Adequate organ and marrow function 9. Written informed consent and any locally required authorization

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03530397


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Australia
Research Site Not yet recruiting
Heidelberg, Australia, 3084
Research Site Recruiting
Melbourne, Australia, 3000
Research Site Recruiting
Melbourne, Australia, 3004
Research Site Recruiting
Randwick, Australia, 2031
Italy
Research Site Not yet recruiting
Meldola, Italy, 47014
Research Site Not yet recruiting
Milano, Italy, 20133
Research Site Not yet recruiting
Parma, Italy, 43100
Research Site Not yet recruiting
Ravenna, Italy, 48121
Korea, Republic of
Research Site Not yet recruiting
Cheongju-si, Korea, Republic of, 28644
Research Site Not yet recruiting
Incheon, Korea, Republic of, 21565
Research Site Recruiting
Seoul, Korea, Republic of, 03080
Research Site Recruiting
Seoul, Korea, Republic of, 03722
Research Site Recruiting
Seoul, Korea, Republic of, 05505
Research Site Recruiting
Seoul, Korea, Republic of, 06351
Portugal
Research Site Not yet recruiting
Porto, Portugal, 4200-072
Spain
Research Site Not yet recruiting
A Coruna, Spain, 15006
Research Site Not yet recruiting
Barcelona, Spain, 08028
Research Site Not yet recruiting
Barcelona, Spain, 08035
Research Site Not yet recruiting
Barcelona, Spain, 08916
Research Site Not yet recruiting
Majadahonda, Spain, 28222
Research Site Not yet recruiting
Malaga, Spain, 29010
Research Site Not yet recruiting
Pamplona, Spain, 31008
Taiwan
Research Site Not yet recruiting
Taichung, Taiwan, 40705
Research Site Not yet recruiting
Tainan, Taiwan, 70403
Research Site Not yet recruiting
Taipei, Taiwan, 10048
Sponsors and Collaborators
MedImmune LLC
Investigators
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Principal Investigator: Pablo Martinez, MD, PhD AstraZeneca

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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT03530397     History of Changes
Other Study ID Numbers: D7980C00001
First Posted: May 21, 2018    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by MedImmune LLC:
Advanced solid tumors
MEDI5752
durvalumab
immuno-oncology
Cancer
PD-1/CTLA-4 Bispecific
PD-1
CTLA-4
Bispecific
Chemotherapy
Pemetrexed
Carboplatin
Pembrolizumab

Additional relevant MeSH terms:
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Carboplatin
Pembrolizumab
Pemetrexed
Durvalumab
Antibodies, Monoclonal
Antineoplastic Agents
Antineoplastic Agents, Immunological
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Immunologic Factors
Physiological Effects of Drugs