Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects

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.

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