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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02798406
Other study ID # 2401BT-002P
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date October 6, 2016
Est. completion date June 30, 2021

Study information

Verified date July 2021
Source DNAtrix, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


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.


Recruitment information / eligibility

Status Completed
Enrollment 49
Est. completion date June 30, 2021
Est. primary completion date March 17, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

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.
pembrolizumab
Sequential intravenous administration every three weeks beginning 7-9 days after Day 0/DNX-2401

Locations

Country Name City State
Canada University Health Network Toronto Ontario
United States Lehigh Valley Health Network Allentown Pennsylvania
United States Texas Oncology Austin-Midtown Austin Texas
United States UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina
United States Northwestern University Chicago Illinois
United States Cleveland Clinic Cleveland Ohio
United States Ohio State University James Cancer Center Columbus Ohio
United States MD Anderson Cancer Center Houston Texas
United States University of Arkansas for Medical Sciences (UAMS) Little Rock Arkansas
United States UCLA Medical Center Los Angeles California
United States University of Minnesota Neurosurgery Minneapolis Minnesota
United States Rutgers Cancer Institute of New Jersey New Brunswick New Jersey
United States Memorial Sloan Kettering Cancer Center New York New York
United States Weill-Cornell Medicine New York-Presbyterian New York New York
United States Huntsman Cancer Institute Salt Lake City Utah

Sponsors (2)

Lead Sponsor Collaborator
DNAtrix, Inc. Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Objective response rate (ORR) Interval tumor size reduction as measured from periodic MRI 3.5 years
Secondary Overall survival (OS) Months alive following treatment as measured during periodic study visits 3.5 years
Secondary Time to tumor response Months to response following treatment as measured during periodic MRIs 3.5 years
Secondary Duration of response Months of sustained response as measured during periodic study visits 3.5 years
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