We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors

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.
 
ClinicalTrials.gov Identifier: NCT03530397
Recruitment Status : Recruiting
First Posted : May 21, 2018
Last Update Posted : October 3, 2022
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Tracking Information
First Submitted Date  ICMJE March 28, 2018
First Posted Date  ICMJE May 21, 2018
Last Update Posted Date October 3, 2022
Actual Study Start Date  ICMJE April 24, 2018
Estimated Primary Completion Date March 20, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2021)
  • The number of subjects experiencing treatment related adverse events (AEs) (Dose-escalation phase) [ 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
  • Preliminary anti-tumor activitiy of MEDI5752 (versus pembrolizumab, where applicable) 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.
  • The number of subjects experiencing dose-limiting toxicities (DLTs) (Dose-escalation phase) [ 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.
  • The number of subjects experiencing abnormal laboratory evaluations (Dose-escalation phase) [ Time Frame: From the time of informed consent through 114 days following termination of treatment with investigational product ]
    The primary endpoint is as assessed as the number of subjects experiencing changes in laboratory parameters from baseline.
  • The number of subjects experiencing changes from baseline in vital signs reported as adverse events (Dose-escalation phase) [ 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 clinically significant changes in vital signs from baseline.
  • The number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events (Dose-escalation phase) [ 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 the number of subjects experiencing clinically significant changes in ECG parameters from baseline.
  • The number of subjects experiencing treatment related serious adverse events (SAEs) (Dose-escalation phase) [ 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 18, 2018)
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2022)
  • 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)
  • 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)
  • 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)
  • 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)
  • Ability of MEDI5752 to generate immune response in subjects with advanced solid tumors [ 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)
  • PD-L1 Expression in subjects with advanced solid tumors [ Time Frame: To be assessed at baseline ]
    The endpoint for the PD-L1 expression will be determined by Immunohistochemistry characterization.
  • 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.
  • 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.
  • 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.
  • 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.
  • The number of subjects experiencing treatment related adverse events (AEs) (Dose-expansion phase) [ Time Frame: From the time of informed consent through 114 days following termination of treatment with investigational product ]
    The secondary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v4.03
  • The number of subjects experiencing abnormal laboratory evaluations (Dose-expansion phase) [ Time Frame: From the time of informed consent through 114 days following termination of treatment with investigational product ]
    The secondary endpoint is as assessed by the number of subjects experiencing changes in laboratory parameters from baseline.
  • The number of subjects experiencing Changes from baseline in vital signs reported as adverse events (Dose-expansion phase) [ Time Frame: From the time of informed consent through 114 days following termination of treatment with investigational product ]
    The secondary endpoint is as assessed by the number of subjects experiencing clinically significant changes in vital signs from baseline.
  • The number of subjects experiencing abnormal ECGs reported as adverse events (Dose-expansion phase) [ Time Frame: From the time of informed consent through 14 days following termination of treatment with investigational product ]
    The secondary endpoint is as assessed by the number of subjects experiencing clinically significant changes in ECG parameters from baseline.
  • The number of subjects experiencing treatment related serious adverse events (SAEs) (Dose-expansion phase) [ Time Frame: From the time of informed consent through 114 days following termination of treatment with investigational product ]
    The secondary endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v4.03
Original Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2018)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors
Official Title  ICMJE 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.
Brief Summary The purpose of this study is to evaluate MEDI5752 and carboplatin and pemetrexed or paclitaxel or nab-paclitaxel in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.
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 and carboplatin and pemetrexed or paclitaxel or nab-paclitaxel in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Selected Advanced Solid Tumors
Intervention  ICMJE
  • 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
  • Biological: Pembrolizumab
    Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation
  • Drug: Paclitaxel or Nab-Paclitaxel
    Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation
Study Arms  ICMJE
  • Experimental: Arm A: MEDI5752
    MEDI5752
    Intervention: Biological: MEDI5752
  • Experimental: Arm B: MEDI5752 and chemotherapy
    MEDI5752, pemetrexed, carboplatin and paclitaxel.
    Interventions:
    • Biological: MEDI5752
    • Drug: Pemetrexed
    • Drug: Carboplatin
    • Drug: Paclitaxel or Nab-Paclitaxel
  • Active Comparator: Arm C: Pembrolizumab and chemotherapy
    pembrolizumab, pemetrexed, and carboplatin
    Interventions:
    • Drug: Pemetrexed
    • Drug: Carboplatin
    • Biological: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 1, 2022)
366
Original Estimated Enrollment  ICMJE
 (submitted: May 18, 2018)
263
Estimated Study Completion Date  ICMJE March 20, 2024
Estimated Primary Completion Date March 20, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 or carboplatin 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

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 21 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
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Australia,   France,   Italy,   Korea, Republic of,   Netherlands,   Portugal,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03530397
Other Study ID Numbers  ICMJE D7980C00001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Current Responsible Party MedImmune LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE MedImmune LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Deepa Subramaniam, MD, MSc AstraZeneca
PRS Account MedImmune LLC
Verification Date September 2022

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