Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects (CAPTIVE)
Brain Cancer, Brain Neoplasm, Glioma
About this trial
This is an interventional treatment trial for Brain Cancer focused on measuring 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
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
Sites / Locations
- University of Arkansas for Medical Sciences (UAMS)
- UCLA Medical Center
- Northwestern University
- University of Minnesota Neurosurgery
- Rutgers Cancer Institute of New Jersey
- Memorial Sloan Kettering Cancer Center
- Weill-Cornell Medicine New York-Presbyterian
- UNC Lineberger Comprehensive Cancer Center
- Cleveland Clinic
- Ohio State University James Cancer Center
- Lehigh Valley Health Network
- Texas Oncology Austin-Midtown
- MD Anderson Cancer Center
- Huntsman Cancer Institute
- University Health Network
Arms of the Study
Arm 1
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.