Clinical trial NCT02798406: Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain Cancer
Brain Neoplasm
Glioma
Glioblastoma
Gliosarcoma
Malignant Brain Tumor
Neoplasm, Neuroepithelial
Neuroectodermal Tumors
Neoplasm by Histologic Type
Neoplasm, Nerve Tissue
Nervous System Diseases
Keywords: brain
Central Nervous System (CNS) diseases
Central Nervous System (CNS) neoplasms
CNS
conditionally replicative adenovirus
DNX-2401
pembrolizumab
KEYTRUDA
MK-3475
SCH 900475
lambrolizumab
neoplasm, germ cell and embryonal
neoplasm, granular and epithelial
Alcyone
Alcyone Lifesciences
AMC
cannula
MEMS cannula
DNX-2401 + pembrolizumab
Delta-24
Delta-24-RGD
Checkpoint inhibitor
anti-PD1/PD-L1
immunotherapy
monoclonal antibody
KEYNOTE-192
Lead sponsor: DNAtrix, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-06-14
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 3.5 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 3.5 years
measure: Time to tumor response
timeFrame: 3.5 years
measure: Duration of response
timeFrame: 3.5 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences (UAMS)
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota Neurosurgery
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill-Cornell Medicine New York-Presbyterian
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University James Cancer Center
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology Austin-Midtown
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: DNAtrix, Inc.
name: Nancy Gady, BS
role: STUDY_DIRECTOR
References: