In support of the US marketing application for 5-ALA, this single arm trial is being
conducted to establish the efficacy and safety of Gliolan (5-ALA) in patients with newly
diagnosed or recurrent malignant gliomas. The hypothesis of the study is Gliolan (5-ALA), as
an adjunct to tumor resection, is safe and that real-time tissue fluorescence correlates with
malignant histopathology. The primary objective in this single arm study is to define the
positive predictive value (PPV) of Gliolan-induced PPIX fluorescence for malignant tumor at
the time of initial resection and first use of FGS by taking a biopsy of tissue presenting
with red fluorescence when observed during the course of resection of new or recurrent
malignant gliomas. The functionality and performance reliability of the blue light excitation
microscope platforms will be assessed.

This is a multi-institutional, consortium-based, non-interventional prospective blinded
endpoints clinical study to determine whether high activity of Cytochrome C Oxidase (CcO) in
tumor specimens from subjects with newly diagnosed primary GBM is associated with shortened
OS (primary outcome) and PFS (secondary outcome) times.

The main purpose of this study is to compare how long patients with glioblastoma (GBM, a
malignant brain cancer) live after receiving nivolumab every two weeks in addition to
radiation therapy (RT), and then every four weeks, compared with patients receiving standard
therapy with temozolomide in addition to RT.

The main purpose of this study is to compare how long patients with glioblastoma (GBM, a
malignant brain cancer) live after receiving temozolomide plus radiation therapy compared
with patients receiving nivolumab in addition to temozolomide plus radiation therapy.

This feasibility study will assess the effects of the Nativis Voyager therapy in patients
with recurrent GBM who have either failed standard of care or are intolerant to therapy. The
study will enroll and treat up to 64 subjects of which 32 will be treated with the Voyager
therapy alone (monotherapy) and 32 will be treated with Voyager plus concurrent
chemotherapy. Safety and clinical utility will be evaluated.