Clinical Trials /

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

NCT03889275

Description:

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

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of MEDI5395 in Combination With Durvalumab in Subjects With Select Advanced Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: D6450C00001
  • NCT ID: NCT03889275

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
MEDI5395Sequential
DurvalumabInfinziSequential

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
SequentialExperimentalMEDI5395 and durvalumab administered sequentially
  • MEDI5395
  • Durvalumab
ConcurrentExperimentalMEDI5395 and durvalumab administered concurrently
  • MEDI5395
  • Durvalumab

Eligibility 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

          -  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 will require varying washout times
             prior to the first dose of MEDI5395

          -  Unresolved toxicities from prior anticancer therapy

          -  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
             hepatitis B/C with undetectable virus load and are on medications may be permitted).

          -  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.
      
Maximum Eligible Age:101 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:The occurrence of DLTs will be used to establish the maximum tolerated dose (MTD) of MEDI5395.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Estimated to be from the time of informed consent for approximately 2.5 years
Safety Issue:
Description:The ORR is defined as the proportion of subjects with confirmed response (CR) or confirmed partial response (PR).
Measure:Disease Control Rate (DCR)
Time Frame:Estimated to be from the time of informed consent for approximately 2.5 years
Safety Issue:
Description:The DCR will be estimated by the proportion of disease control. Disease control is defined as CR, PR or stable disease.
Measure:Duration of Response (DoR)
Time Frame:Estimated to be from the time of informed consent for approximately 2.5 years
Safety Issue:
Description: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.
Measure:Time To Response (TTR)
Time Frame:Estimated to be from the time of informed consent for approximately 2.5 years
Safety Issue:
Description: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.
Measure:Progression Free Survival (PFS)
Time Frame:Estimated to be from the time of informed consent for approximately 2.5 years
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Estimated to be from the time of informed consent for approximately 2.5 years
Safety Issue:
Description:OS will be measured from the start of treatment with investigational product until death due to any cause.
Measure:MEDI5395 viral genome copies in blood collected over time
Time Frame:Estimated to be from the time of informed consent for approximately 6 months
Safety Issue:
Description:MEDI5395 concentrations in blood will be tabulated by dose cohort along with descriptive statistics.
Measure: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
Safety Issue:
Description:GM-CSF protein concentrations in blood will be tabulated by dose cohort along with descriptive statistics.
Measure: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
Safety Issue:
Description:Immunogenic response to MEDI5395 will be assessed by summarizing the number of subjects who develop detectable anti-MEDI5395 neutralizing antibodies
Measure: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
Safety Issue:
Description:Immunogenic response to MEDI5395 will be assessed by summarizing the percentage of subjects who develop detectable anti-MEDI5395 neutralizing antibodies
Measure: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
Safety Issue:
Description:CD8 T cell infiltration and PD-L1 expression in tumors pre and post dosing will be assessed using validated IHC assays.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MedImmune LLC

Trial Keywords

  • solid tumors
  • immunotherapy
  • oncolytic virus
  • NDV-GMCSF

Last Updated

November 28, 2019