A Phase 2 Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Patients With Recurrent Gliomas

This is an open-label, multicenter, Phase 2 study to evaluate the efficacy and safety of oral
selinexor in patients with recurrent gliomas.

Initially, the study included 2 arms: an exploratory Surgical Arm (Arm A) with sequential
enrollment for patients who require surgery and a medical arm (Arm B) for patients who are
not eligible for surgery.

Enrollment in Arm B was stopped to explore alternative dosing in Protocol Versions ≥ 4.0 to
potentially improve tolerability. Four arms (Arms C, D, E, and F) were added to the Medical
Arm in Protocol Version 4.0. Arms E and F were eliminated in protocol version 6.0 and no
patients were ever enrolled in these arms.

Patients in the primary population enrolled under Protocol Version 4.0 or above will be
randomized to Arm C and Arm D (approximately 30 patients per arm) to explore alternative
dosing to potentially improve tolerability.

After screening and registration/randomization in the study, patients enrolling in Arm A or
randomized to Arm C will receive 60 mg selinexor orally twice weekly. Patients randomized to
Arm D will receive 80 mg selinexor orally weekly.

Patients will be treated until progression of disease or the development of unacceptable
toxicities. All patients will then undergo the End of Treatment (EOT) visit.

Inclusion Criteria:

- Pathologically confirmed GBM (including all histologic variants) at first diagnosis
with radiographic evidence of recurrent disease after treatment with radiotherapy and
temozolomide;

- 18 years of age or older

- Patients enrolling in the medical arm (Arms C and D) must be on a stable or decreasing
dose of corticosteroids (or none) for at least 5 days prior to the baseline MRI;

- Measurable disease (according to RANO guidelines)

- Surgical arm (Arm A) must be predicted pre-operatively to have sufficiently sized
tumor to be resected and provide tissue samples for exploratory assessments.

Exclusion Criteria:

- Markedly decreased visual acuity if attributed to other causes than GBM.

- Known active hepatitis A, B, or C

- Patients with coagulation problems and medically significant bleeding in the month
prior to start of treatment (e.g., peptic ulcer, epistaxis, spontaneous bleeding).
Prior history of DVT or PE is not exclusionary.

- Patients must not have significantly diseased or obstructed gastrointestinal tract,
malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral
medications.

- Prior treatment with bevacizumab or other direct VEGF/ VEGFR inhibitors. For any
question of the definition of a direct VEGF/VEGFR inhibitor, consult Sponsor.

- Arms C and D only: body surface area < 1.2 m².

- < 24 days from prior temozolomide, < 6 weeks from nitrosourea, < 4 weeks from other
chemotherapy or investigational agents prior to start of treatment within study.