CAPTIVE: Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects

Sponsor
DNAtrix, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02798406
Collaborator
Merck Sharp & Dohme LLC (Industry)
49
15
1
56.8
3.3
0.1

Study Details

Study Description

Brief Summary

Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant brain tumor in adults and can be resistant to conventional therapies. The purpose of this Phase II study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor responds to one injection of DNX-2401, a genetically modified oncolytic adenovirus, when delivered directly into the tumor followed by the administration of intravenous pembrolizumab (an immune checkpoint inhibitor) given every 3 weeks for up to 2 years or until disease progression.

Funding Source-FDA OOPD

Detailed Description

In the initial phase of the study, up to 12 evaluable subjects will be enrolled in 3 dose cohorts to determine the best dose of DNX-2401, as follows:

  • Cohort 1: Single dose DNX-2401 (5e8 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W)

  • Cohort 2: Single dose DNX-2401(5e9 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W)

  • Cohort 3: Single dose DNX-2401 (5e10 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W)

Following the initial phase, up to 36 additional subjects diagnosed with recurrent glioblastoma or gliosarcoma will be enrolled to receive a single of DNX-2401 determined in the initial phase administered intratumorally followed by intravenous pembrolizumab every 3 weeks.

All subjects will return to the clinic for study follow-up visits at regular intervals for safety monitoring, MRI scans and other assessments, for up to 2 years or until disease progression. All subjects will be followed closely for safety and survival.

Study Design

Study Type:
Interventional
Actual Enrollment :
49 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Multi-center, Open-label Study of a Conditionally Replicative Adenovirus (DNX-2401) With Pembrolizumab (KEYTRUDA®) for Recurrent Glioblastoma or Gliosarcoma (CAPTIVE/KEYNOTE-192)
Actual Study Start Date :
Oct 6, 2016
Actual Primary Completion Date :
Mar 17, 2021
Actual Study Completion Date :
Jun 30, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: DNX-2401 + pembrolizumab

Intratumoral dose (1.0 mL) of DNX-2401 followed 7-9 days later by intravenous pembrolizumab, 200 mg, given every three weeks through 105 weeks (2 yrs.) or until progressive disease or unacceptable toxicity.

Biological: DNX-2401
On Day 0, following brain tumor biopsy and confirmation of recurrent tumor, a single injection of DNX-2401 is administered directly into the brain tumor.
Other Names:
  • Oncolytic virus
  • Genetically-modified adenovirus
  • Delta-24
  • Delta-24-RGD
  • Biological: pembrolizumab
    Sequential intravenous administration every three weeks beginning 7-9 days after Day 0/DNX-2401
    Other Names:
  • KEYTRUDA
  • lambrolizumab
  • MK-3475
  • SCH 900475
  • Checkpoint inhibitor
  • monoclonal antibody
  • anti-PD1/PD-L1
  • Outcome Measures

    Primary Outcome Measures

    1. Objective response rate (ORR) [3.5 years]

      Interval tumor size reduction as measured from periodic MRI

    Secondary Outcome Measures

    1. Overall survival (OS) [3.5 years]

      Months alive following treatment as measured during periodic study visits

    2. Time to tumor response [3.5 years]

      Months to response following treatment as measured during periodic MRIs

    3. Duration of response [3.5 years]

      Months of sustained response as measured during periodic study visits

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • A single glioblastoma or gliosarcoma tumor with histopathological confirmation for first or presenting second recurrence of glioblastoma or gliosarcoma at the time of consent

    • Gross total or partial tumor resection is not possible or not planned

    • A single measurable tumor that is at least 10.0 mm longest diameter (LDi) X 10.0 mm shortest diameter (SDi) and this tumor does not exceed 40.0 mm in LDi or SDi on Screening MRI

    • Tumor recurrence or progression documented after previously failing surgical resection, chemotherapy or radiation

    • Karnofsky performance status ≥ 70 %

    • Prior anti-tumor therapies must have been completed within time periods specified in the protocol prior to DNX-2401 injection and toxic side effects must be mild, if present

    • Demonstrate adequate organ function via specified laboratory test results

    Exclusion Criteria:
    • Multiple (≥ 2) separate enhancing tumors

    • Tumor location on both sides of the brain and/or involvement that would present the risk of injecting DNX-2401 into the ventricles of the brain

    • Tumor location in the brain stem

    • Requires or, based upon history, may require treatment with high-dose systemic corticosteroids within 2 weeks of the start of intravenous pembrolizumab infusions and within 2 weeks following the first infusion of pembrolizumab

    • Uncontrolled blood-sugar levels defined as HbA1c > 7%

    • Previous treatment with any checkpoint inhibitor such as anti-PD1 or PD-L1 agents including pembrolizumab (KEYTRUDA) or any other checkpoint inhibitor(s) (e.g., ipilimumab, nivolumab, etc.)

    • History of (non-infectious) or current active pneumonitis that required steroids and/or a history of interstitial lung disease

    • Prior gene transfer therapy or prior therapy with a cytolytic virus of any type

    • Brain tumor that is not measurable on MRI or persons who are unable to have MRIs

    • Pregnant or nursing females

    Note: Other protocol-defined inclusion and exclusion criteria may apply as outlined in the relevant protocol version

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Arkansas for Medical Sciences (UAMS) Little Rock Arkansas United States 72205
    2 UCLA Medical Center Los Angeles California United States 90095
    3 Northwestern University Chicago Illinois United States 60611
    4 University of Minnesota Neurosurgery Minneapolis Minnesota United States 55455
    5 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08903
    6 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    7 Weill-Cornell Medicine New York-Presbyterian New York New York United States 10065
    8 UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27514
    9 Cleveland Clinic Cleveland Ohio United States 44195
    10 Ohio State University James Cancer Center Columbus Ohio United States 43210
    11 Lehigh Valley Health Network Allentown Pennsylvania United States 18103
    12 Texas Oncology Austin-Midtown Austin Texas United States 78705
    13 MD Anderson Cancer Center Houston Texas United States 77030
    14 Huntsman Cancer Institute Salt Lake City Utah United States 84112
    15 University Health Network Toronto Ontario Canada M5T 2S8

    Sponsors and Collaborators

    • DNAtrix, Inc.
    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Nancy Gady, BS, DNAtrix, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    DNAtrix, Inc.
    ClinicalTrials.gov Identifier:
    NCT02798406
    Other Study ID Numbers:
    • 2401BT-002P
    First Posted:
    Jun 14, 2016
    Last Update Posted:
    Jul 15, 2021
    Last Verified:
    Jul 1, 2021

    Study Results

    No Results Posted as of Jul 15, 2021