Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects

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