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A Study of MEDI5395 in Combination With Durvalumab in Subjects With Select Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03889275
Recruitment Status : Recruiting
First Posted : March 26, 2019
Last Update Posted : July 21, 2021
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Brief Summary:
The reason for the study is to find out if MEDI5395 and durvalumab will work and be safe for the treatment of solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Biological: MEDI5395 Biological: Durvalumab Phase 1

Detailed Description:
This is an Phase 1, first-in-human, open-label, dose-escalation, and dose-expansion study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary efficacy of MEDI5395 in combination with durvalumab in subjects with selected advanced solid tumors.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 188 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MEDI5395 in Combination With Durvalumab in Subjects With Select Advanced Solid Tumors.
Actual Study Start Date : October 24, 2019
Estimated Primary Completion Date : May 23, 2025
Estimated Study Completion Date : May 23, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Sequential
MEDI5395 and durvalumab administered sequentially
Biological: MEDI5395
Subjects will receive multiple doses of MEDI5395 over several days.

Biological: Durvalumab
Durvalumab will be administered periodically for a maximum of 2 years or until radiologically confirmed disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity
Other Name: Imfinzi

Experimental: Concurrent
MEDI5395 and durvalumab administered concurrently
Biological: MEDI5395
Subjects will receive multiple doses of MEDI5395 over several days.

Biological: Durvalumab
Durvalumab will be administered periodically for a maximum of 2 years or until radiologically confirmed disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity
Other Name: Imfinzi




Primary Outcome Measures :
  1. Number of subjects with adverse events (AEs) serious adverse events (SAEs) and dose limiting toxicities (DLTs). [ Time Frame: From the time of informed consent until 90 days after the last dose of investigational product (MEDI5395 or durvalumab) ]
    The occurrence of DLTs will be used to establish the maximum tolerated dose (MTD) of MEDI5395.


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Estimated to be from the time of informed consent for approximately 2.5 years ]
    The ORR is defined as the proportion of subjects with confirmed response (CR) or confirmed partial response (PR).

  2. Disease Control Rate (DCR) [ Time Frame: Estimated to be from the time of informed consent for approximately 2.5 years ]
    The DCR will be estimated by the proportion of disease control. Disease control is defined as CR, PR or stable disease.

  3. Duration of Response (DoR) [ Time Frame: Estimated to be from the time of informed consent for approximately 2.5 years ]
    The DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.

  4. Time To Response (TTR) [ Time Frame: Estimated to be from the time of informed consent for approximately 2.5 years ]
    The TTR is defined as the time from the start of treatment with any investigational product until the first documentation of a subsequently confirmed objective response.

  5. Progression Free Survival (PFS) [ Time Frame: Estimated to be from the time of informed consent for approximately 2.5 years ]
    PFS will be measured from the start of treatment with any investigational product until the first documentation of disease progression or death due to any cause, whichever occurs first.

  6. Overall Survival (OS) [ Time Frame: Estimated to be from the time of informed consent for approximately 2.5 years ]
    OS will be measured from the start of treatment with investigational product until death due to any cause.

  7. MEDI5395 viral genome copies in blood collected over time [ Time Frame: Estimated to be from the time of informed consent for approximately 6 months ]
    MEDI5395 concentrations in blood will be tabulated by dose cohort along with descriptive statistics.

  8. Granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations in blood collected over time [ Time Frame: Estimated to be from the time of informed consent for approximately 6 months ]
    GM-CSF protein concentrations in blood will be tabulated by dose cohort along with descriptive statistics.

  9. Number of subjects who develop detectable anti-MEDI5395 neutralizing antibodies [ Time Frame: Estimated to be from the time of informed consent until approximately 90 days after the last dose of last investigational product ]
    Immunogenic response to MEDI5395 will be assessed by summarizing the number of subjects who develop detectable anti-MEDI5395 neutralizing antibodies

  10. Percentage of subjects who develop detectable anti-MEDI5395 neutralizing antibodies [ Time Frame: Estimated to be from the time of informed consent until approximately 90 days after the last dose of last investigational product ]
    Immunogenic response to MEDI5395 will be assessed by summarizing the percentage of subjects who develop detectable anti-MEDI5395 neutralizing antibodies

  11. The number of cluster of differentiation 8 (CD8) positive cells and programmed death-ligand 1(PD-L1) expressing cells within biopsies will be assessed. [ Time Frame: Estimated to be from the time of informed consent until 4 weeks after the first dose of MEDI5395 ]
    CD8 T cell infiltration and PD-L1 expression in tumors pre and post dosing will be assessed using validated IHC assays.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 101 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • The subject must consent to take precautionary measures to prevent Newcastle Disease Virus (NDV) transmission to humans and birds
  • Subjects must have histologic documentation of advanced solid tumor and received and have progressed, are refractory, or are intolerant to standard therapy for the specific tumor type. All subjects are required to have had at least one prior line of treatment in the recurrent or metastatic setting
  • Subjects must have at least 1 measurable lesion and an additional non-lymph node non-target lesion that can be biopsied at acceptable risk as judged by the investigator. (Note: if a non-target lesion is not available or cannot be biopsied, a RECIST target, non-lymph node lesion, lesion ≥ 2 cm in longest diameter may be used for non-excisional biopsy
  • All subjects must consent to provide tumor tissue for correlative studies
  • ECOG performance status of 0 to 1
  • Adequate organ function
  • Use of highly effective contraception (females) or male condom plus spermicide (males)

Exclusion Criteria

  • Rapidly progressing disease defined as a subject that cannot tolerate a break of at least 8 weeks from systemic anticancer therapy.
  • Primary central nervous system (CNS) disease is excluded
  • Subjects who have received prior immunotherapy within 28 days prior to the first dose of MEDI5395
  • Unresolved toxicities from prior anticancer therapy that led to permanent discontinuation of prior immunotherapy or that required immunosuppression other than corticosteroids
  • History of severe allergic reactions to any of the study drug components
  • Infectious disease exclusions including tuberculosis, Human immunodeficiency virus (HIV), hepatitis A, B or C, active bacterial, fungal or viral infections plus receipt of live attenuated vaccine prior to first dose of MEDI5395. (NOTE: Subjects with evidence of fully recovered past hepatitis B infection who developed immunity OR hepatitis B/C with undetectable virus load and are on medications may be permitted).
  • Positive SARS-CoV-2 diagnostic test at screening
  • Any conditions requiring use of any systemic immunosuppressant including systemic corticosteroids, methotrexate, azathioprine, tumor necrosis factor (TNF) inhibitor, and/or interleukin 6 (IL-6) blockers
  • Active autoimmune disease or chronic inflammatory condition (Exceptions include vitiligo, alopecia, hypothyroidism on stable treatment, diverticulosis, controlled celiac disease and chronic skin conditions not requiring systemic therapy)
  • Active acquired immune-deficiency states
  • Subjects who are regularly exposed to poultry or birds
  • Current active hepatitis or biliary disease (except for Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease)
  • Clinically significant pulmonary disease and cardiac disease
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.

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): NCT03889275


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

Locations
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United States, Arizona
Research Site Recruiting
Phoenix, Arizona, United States, 85054
United States, California
Research Site Recruiting
La Jolla, California, United States, 92093
United States, Minnesota
Research Site Recruiting
Rochester, Minnesota, United States, 55905
United States, New York
Research Site Recruiting
Buffalo, New York, United States, 14263
Research Site Recruiting
New York, New York, United States, 10065
United States, North Carolina
Research Site Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
United States, Pennsylvania
Research Site Recruiting
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Research Site Recruiting
Providence, Rhode Island, United States, 02903
Spain
Research Site Not yet recruiting
Barcelona, Spain, 8035
Research Site Not yet recruiting
Madrid, Spain, 28027
United Kingdom
Research Site Withdrawn
Edgbaston, United Kingdom, B15 2GW
Research Site Not yet recruiting
Guildford, United Kingdom, GU2 7WG
Research Site Not yet recruiting
Leeds, United Kingdom, LS9 7TF
Research Site Recruiting
London, United Kingdom, SW3 6JJ
Sponsors and Collaborators
MedImmune LLC
Investigators
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Study Director: Medimmune LLC MedImmune LLC
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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT03889275    
Other Study ID Numbers: D6450C00001
First Posted: March 26, 2019    Key Record Dates
Last Update Posted: July 21, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedImmune LLC:
solid tumors
immunotherapy
oncolytic virus
NDV-GMCSF
Additional relevant MeSH terms:
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Neoplasms
Durvalumab
Antineoplastic Agents, Immunological
Antineoplastic Agents